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New and Noteworthy Information—August 2015
Incident stroke is associated with an acute decline in cognitive function and accelerated and persistent cognitive decline over six years, according to a study published July 7 in JAMA. Researchers used data from 23,572 cognitively healthy participants age 45 or older from the Reasons for Geographic and Racial Differences in Stroke study. Participants resided in the United States, were enrolled in the study from 2003 through 2007, and were followed up through March 31, 2013. In all, 515 participants survived expert-adjudicated incident stroke, and 23,057 remained stroke-free. Stroke was associated with acute decline in global cognition, new learning, and verbal memory. Participants with stroke, compared with those without stroke, had faster declines in global cognition and executive function, but not in new learning and verbal memory, compared with prestroke changes.
Childhood adversities are associated with migraine, and greater numbers of adversities are associated with increasing odds of migraine, according to a study published online ahead of print June 23 in Headache. Researchers used a representative sample of 10,358 men and 12,638 women and performed gender-specific logistic regression analyses to determine the association between number and type of self-reported childhood adversities and migraine, while controlling for sociodemographics, comorbid adversities, health behaviors, depression, and anxiety. Overall, 6.5% of men and 14.2% of women reported migraines. Physical abuse, witnessing parental domestic violence, and sexual abuse were significantly associated with migraine for both genders, even after controlling for variables. Men reporting all three adversities had more than three times the odds of migraine, compared with those without childhood adversities.
Full truncal vagotomy is associated with a decreased risk for subsequent Parkinson’s disease, suggesting that the vagal nerve may be involved in the pathogenesis of Parkinson’s disease, according to a study published online ahead of print May 29 in Annals of Neurology. Researchers constructed cohorts of all patients in Denmark who underwent vagotomy from 1977 through 1995, and a matched general population cohort. Investigators used Cox regression analysis to compute hazard ratios for Parkinson’s disease, adjusting for potential confounders. Risk of Parkinson’s disease was decreased in patients who underwent truncal vagotomy, compared with superselective vagotomy. Risk of Parkinson’s disease also was decreased following truncal vagotomy when compared with the general population cohort. In patients who underwent superselective vagotomy, risk of Parkinson’s disease was similar to that of the general population.
In women with acute ischemic stroke treated with alteplase, uric acid reduced infarct growth in selected patients and was better than placebo for reaching excellent outcome, according to a study published online ahead of print July 9 in Stroke. Researchers reanalyzed 2014 data from the randomized, double-blind URICO-ICTUS trial of patients admitted to Spanish stroke centers. Participants included 206 women and 205 men. All participants received therapies to remove the clots, while half in each gender group also received either 1,000 mg of uric acid IV or placebo. Uric acid doubled the effect of placebo to achieve excellent outcome in women, but not in men. The interactions between treatment and serum uric acid levels or allantoin–uric acid ratio on infarct growth were significant only in women.
Women with epilepsy are at a heightened risk for adverse outcomes during their delivery hospitalizations, according to a study published online ahead of print July 6 in JAMA Neurology. Researchers examined a retrospective cohort study of pregnant women identified through delivery hospitalization records from the 2007 through 2011 Nationwide Inpatient Sample. Investigators obtained a weighted sample of delivery hospitalizations from 69,385 women with epilepsy and 20,449,532 women without epilepsy. Women with epilepsy had a risk of death during delivery hospitalization of 80 deaths per 100,000 pregnancies, compared with six deaths per 100,000 pregnancies among controls. Women with epilepsy also were at increased risk for pre-eclampsia, preterm labor, and stillbirth. They also had increased health care utilization, including an increased risk of cesarean delivery and prolonged hospital stay.
Eight-hour sleep duration may help consolidate newly learned procedural and declarative memories and ensure full access to them during periods of subjective stress, according to a study published online ahead of print June 22 in Sleep. For this study, 15 healthy young men learned object locations and a finger tapping sequence in the evening. Participants either had the opportunity to sleep for eight hours or could sleep between the hours of 3:00 am and 7:00 am. Retrieval of both memory tasks was tested in the morning after each sleep condition, both before and after stress exposure. Post-sleep memory changes did not differ between sleep conditions. Men who received less sleep, however, had reduced recall ability after exposure to stress, while post-stress recall was not affected in those who received a full night of sleep.
Cognitive impairment may manifest in the preclinical phase of Alzheimer’s disease substantially earlier than previously established, according to a study published online ahead of print June 24 in Neurology. A composite cognitive test score based on tests of episodic memory, executive function, and global cognition was constructed in a prospective population-based sample of 2,125 participants ages 65 and older. In all, 442 participants developed clinical Alzheimer’s disease over 18 years of follow-up. Lower composite cognitive test scores were associated with the development of Alzheimer’s disease. The magnitude of association between composite cognitive test score and development of Alzheimer’s disease dementia increased from an odds ratio of 3.39 at 13.0 to 17.9 years to an odds ratio of 9.84 at 0.1 to 0.9 years, per standard deviation increment.
Shared biological processes contribute to the risk of migraine and coronary artery disease, but this commonality is restricted to migraine without aura, according to a study published online ahead of print July 2 in Neurology Genetics. Researchers analyzed two large genome-wide association studies of migraine and heart disease. The migraine study involved 19,981 people with migraine and 56,667 people without migraine. Also included were 21,076 people with heart disease and 63,014 people without heart disease. Investigators found a significant overlap of genetic risk loci for migraine and coronary artery disease. When stratified by migraine subtype, this overlap was limited to migraine without aura. The overlap was protective, in that patients with migraine had a lower load of coronary artery disease risk alleles than controls did.
Women with stimulant dependence have significant changes in gray matter volume after prolonged abstinence, but men do not, according to a study published online ahead of print July 14 in Radiology. For this prospective, parallel-group study, 127 age- and sex-matched participants underwent T1-weighted spoiled gradient-echo inversion recovery MRI of the brain at 3 T. Compared with female control subjects, women with stimulant dependence had significantly lower gray matter volume in various brain regions. There were no significant differences in gray matter volume between male control subjects and men with stimulant dependence. Dependence symptom count negatively correlated with gray matter volume in the nucleus accumbens in women. Behavioral approach and impulsivity correlated negatively with frontal and temporal gray matter volume changes in women with stimulant dependence.
The FDA has approved Fycompa (perampanel) CIII for adjunctive therapy in the treatment of primary generalized tonic-clonic seizures. The approval is based on a phase III, randomized, double-blind, placebo-controlled clinical trial of 162 patients taking one to three antiepileptic drugs. Patients treated with Fycompa achieved a 76% median reduction in primary generalized tonic-clonic seizure frequency. In addition, 64% of patients treated with Fycompa had a 50% or greater reduction in primary generalized tonic-clonic seizure frequency versus 40% with placebo. The most frequently reported adverse events in patients treated with Fycompa were dizziness, fatigue, headache, somnolence, and irritability. The adverse event profile was similar to that in the controlled phase III partial-onset seizure trials of the drug. Eisai, headquartered in Woodcliff Lake, New Jersey, manufactures Fycompa.
Imaging biomarkers, including white matter disruption, may help explain some of the heterogeneity in postinjury outcome among children with traumatic brain injury (TBI), according to a study published July 15 in Journal of Neuroscience. Researchers used high angular resolution diffusion-weighted imaging to evaluate the structural integrity of the corpus callosum following brain injury in a sample of 32 children with moderate-to-severe TBI at one to five months post injury, and in healthy control children. A subset of children with TBI had markedly impaired functioning and structural integrity in the corpus callosum. These impairments were associated with poor neurocognitive functioning. The children with impaired functioning also had significantly slower interhemispheric transfer times than the control group did, as measured using event-related potentials.
Longitudinal CSF biomarker patterns consistent with Alzheimer’s disease are first detectable during early middle age and are associated with later amyloid positivity and cognitive decline, according to a study published online ahead of print July 6 in JAMA Neurology. Cognitively normal middle-aged participants enrolled in the Adult Children Study at Washington University underwent serial CSF collection and longitudinal clinical assessment at three-year intervals. A subset of patients underwent longitudinal amyloid PET imaging with Pittsburgh compound B (PiB) in the same period. The researchers found no consistent longitudinal patterns in Aβ40. Longitudinal reductions in Aβ42 were observed in some individuals as early as middle age, and low Aβ42 levels were associated with the development of cortical PiB-positive amyloid plaques. The patterns were more apparent in at-risk carriers of the ε4 allele.
Men with high exposure to formaldehyde at work had an almost three times greater rate of amyotrophic lateral sclerosis (ALS) mortality than men with no exposure, according to a study published online ahead of print July 13 in the Journal of Neurology Neurosurgery & Psychiatry. Researchers examined data for 794,541 men and 674,694 women included in the National Longitudinal Mortality Study who were 25 or older when surveyed. They used a formaldehyde exposure matrix constructed by industrial hygienists at the National Cancer Institute. Exposure to formaldehyde differed between males and females. All men with high-intensity exposure were funeral directors. Few women had high-exposure jobs, and there were no ALS deaths among women with such jobs. Participants with exposure were poorer and less educated than those without exposure.
—Kimberly Williams
Incident stroke is associated with an acute decline in cognitive function and accelerated and persistent cognitive decline over six years, according to a study published July 7 in JAMA. Researchers used data from 23,572 cognitively healthy participants age 45 or older from the Reasons for Geographic and Racial Differences in Stroke study. Participants resided in the United States, were enrolled in the study from 2003 through 2007, and were followed up through March 31, 2013. In all, 515 participants survived expert-adjudicated incident stroke, and 23,057 remained stroke-free. Stroke was associated with acute decline in global cognition, new learning, and verbal memory. Participants with stroke, compared with those without stroke, had faster declines in global cognition and executive function, but not in new learning and verbal memory, compared with prestroke changes.
Childhood adversities are associated with migraine, and greater numbers of adversities are associated with increasing odds of migraine, according to a study published online ahead of print June 23 in Headache. Researchers used a representative sample of 10,358 men and 12,638 women and performed gender-specific logistic regression analyses to determine the association between number and type of self-reported childhood adversities and migraine, while controlling for sociodemographics, comorbid adversities, health behaviors, depression, and anxiety. Overall, 6.5% of men and 14.2% of women reported migraines. Physical abuse, witnessing parental domestic violence, and sexual abuse were significantly associated with migraine for both genders, even after controlling for variables. Men reporting all three adversities had more than three times the odds of migraine, compared with those without childhood adversities.
Full truncal vagotomy is associated with a decreased risk for subsequent Parkinson’s disease, suggesting that the vagal nerve may be involved in the pathogenesis of Parkinson’s disease, according to a study published online ahead of print May 29 in Annals of Neurology. Researchers constructed cohorts of all patients in Denmark who underwent vagotomy from 1977 through 1995, and a matched general population cohort. Investigators used Cox regression analysis to compute hazard ratios for Parkinson’s disease, adjusting for potential confounders. Risk of Parkinson’s disease was decreased in patients who underwent truncal vagotomy, compared with superselective vagotomy. Risk of Parkinson’s disease also was decreased following truncal vagotomy when compared with the general population cohort. In patients who underwent superselective vagotomy, risk of Parkinson’s disease was similar to that of the general population.
In women with acute ischemic stroke treated with alteplase, uric acid reduced infarct growth in selected patients and was better than placebo for reaching excellent outcome, according to a study published online ahead of print July 9 in Stroke. Researchers reanalyzed 2014 data from the randomized, double-blind URICO-ICTUS trial of patients admitted to Spanish stroke centers. Participants included 206 women and 205 men. All participants received therapies to remove the clots, while half in each gender group also received either 1,000 mg of uric acid IV or placebo. Uric acid doubled the effect of placebo to achieve excellent outcome in women, but not in men. The interactions between treatment and serum uric acid levels or allantoin–uric acid ratio on infarct growth were significant only in women.
Women with epilepsy are at a heightened risk for adverse outcomes during their delivery hospitalizations, according to a study published online ahead of print July 6 in JAMA Neurology. Researchers examined a retrospective cohort study of pregnant women identified through delivery hospitalization records from the 2007 through 2011 Nationwide Inpatient Sample. Investigators obtained a weighted sample of delivery hospitalizations from 69,385 women with epilepsy and 20,449,532 women without epilepsy. Women with epilepsy had a risk of death during delivery hospitalization of 80 deaths per 100,000 pregnancies, compared with six deaths per 100,000 pregnancies among controls. Women with epilepsy also were at increased risk for pre-eclampsia, preterm labor, and stillbirth. They also had increased health care utilization, including an increased risk of cesarean delivery and prolonged hospital stay.
Eight-hour sleep duration may help consolidate newly learned procedural and declarative memories and ensure full access to them during periods of subjective stress, according to a study published online ahead of print June 22 in Sleep. For this study, 15 healthy young men learned object locations and a finger tapping sequence in the evening. Participants either had the opportunity to sleep for eight hours or could sleep between the hours of 3:00 am and 7:00 am. Retrieval of both memory tasks was tested in the morning after each sleep condition, both before and after stress exposure. Post-sleep memory changes did not differ between sleep conditions. Men who received less sleep, however, had reduced recall ability after exposure to stress, while post-stress recall was not affected in those who received a full night of sleep.
Cognitive impairment may manifest in the preclinical phase of Alzheimer’s disease substantially earlier than previously established, according to a study published online ahead of print June 24 in Neurology. A composite cognitive test score based on tests of episodic memory, executive function, and global cognition was constructed in a prospective population-based sample of 2,125 participants ages 65 and older. In all, 442 participants developed clinical Alzheimer’s disease over 18 years of follow-up. Lower composite cognitive test scores were associated with the development of Alzheimer’s disease. The magnitude of association between composite cognitive test score and development of Alzheimer’s disease dementia increased from an odds ratio of 3.39 at 13.0 to 17.9 years to an odds ratio of 9.84 at 0.1 to 0.9 years, per standard deviation increment.
Shared biological processes contribute to the risk of migraine and coronary artery disease, but this commonality is restricted to migraine without aura, according to a study published online ahead of print July 2 in Neurology Genetics. Researchers analyzed two large genome-wide association studies of migraine and heart disease. The migraine study involved 19,981 people with migraine and 56,667 people without migraine. Also included were 21,076 people with heart disease and 63,014 people without heart disease. Investigators found a significant overlap of genetic risk loci for migraine and coronary artery disease. When stratified by migraine subtype, this overlap was limited to migraine without aura. The overlap was protective, in that patients with migraine had a lower load of coronary artery disease risk alleles than controls did.
Women with stimulant dependence have significant changes in gray matter volume after prolonged abstinence, but men do not, according to a study published online ahead of print July 14 in Radiology. For this prospective, parallel-group study, 127 age- and sex-matched participants underwent T1-weighted spoiled gradient-echo inversion recovery MRI of the brain at 3 T. Compared with female control subjects, women with stimulant dependence had significantly lower gray matter volume in various brain regions. There were no significant differences in gray matter volume between male control subjects and men with stimulant dependence. Dependence symptom count negatively correlated with gray matter volume in the nucleus accumbens in women. Behavioral approach and impulsivity correlated negatively with frontal and temporal gray matter volume changes in women with stimulant dependence.
The FDA has approved Fycompa (perampanel) CIII for adjunctive therapy in the treatment of primary generalized tonic-clonic seizures. The approval is based on a phase III, randomized, double-blind, placebo-controlled clinical trial of 162 patients taking one to three antiepileptic drugs. Patients treated with Fycompa achieved a 76% median reduction in primary generalized tonic-clonic seizure frequency. In addition, 64% of patients treated with Fycompa had a 50% or greater reduction in primary generalized tonic-clonic seizure frequency versus 40% with placebo. The most frequently reported adverse events in patients treated with Fycompa were dizziness, fatigue, headache, somnolence, and irritability. The adverse event profile was similar to that in the controlled phase III partial-onset seizure trials of the drug. Eisai, headquartered in Woodcliff Lake, New Jersey, manufactures Fycompa.
Imaging biomarkers, including white matter disruption, may help explain some of the heterogeneity in postinjury outcome among children with traumatic brain injury (TBI), according to a study published July 15 in Journal of Neuroscience. Researchers used high angular resolution diffusion-weighted imaging to evaluate the structural integrity of the corpus callosum following brain injury in a sample of 32 children with moderate-to-severe TBI at one to five months post injury, and in healthy control children. A subset of children with TBI had markedly impaired functioning and structural integrity in the corpus callosum. These impairments were associated with poor neurocognitive functioning. The children with impaired functioning also had significantly slower interhemispheric transfer times than the control group did, as measured using event-related potentials.
Longitudinal CSF biomarker patterns consistent with Alzheimer’s disease are first detectable during early middle age and are associated with later amyloid positivity and cognitive decline, according to a study published online ahead of print July 6 in JAMA Neurology. Cognitively normal middle-aged participants enrolled in the Adult Children Study at Washington University underwent serial CSF collection and longitudinal clinical assessment at three-year intervals. A subset of patients underwent longitudinal amyloid PET imaging with Pittsburgh compound B (PiB) in the same period. The researchers found no consistent longitudinal patterns in Aβ40. Longitudinal reductions in Aβ42 were observed in some individuals as early as middle age, and low Aβ42 levels were associated with the development of cortical PiB-positive amyloid plaques. The patterns were more apparent in at-risk carriers of the ε4 allele.
Men with high exposure to formaldehyde at work had an almost three times greater rate of amyotrophic lateral sclerosis (ALS) mortality than men with no exposure, according to a study published online ahead of print July 13 in the Journal of Neurology Neurosurgery & Psychiatry. Researchers examined data for 794,541 men and 674,694 women included in the National Longitudinal Mortality Study who were 25 or older when surveyed. They used a formaldehyde exposure matrix constructed by industrial hygienists at the National Cancer Institute. Exposure to formaldehyde differed between males and females. All men with high-intensity exposure were funeral directors. Few women had high-exposure jobs, and there were no ALS deaths among women with such jobs. Participants with exposure were poorer and less educated than those without exposure.
—Kimberly Williams
Incident stroke is associated with an acute decline in cognitive function and accelerated and persistent cognitive decline over six years, according to a study published July 7 in JAMA. Researchers used data from 23,572 cognitively healthy participants age 45 or older from the Reasons for Geographic and Racial Differences in Stroke study. Participants resided in the United States, were enrolled in the study from 2003 through 2007, and were followed up through March 31, 2013. In all, 515 participants survived expert-adjudicated incident stroke, and 23,057 remained stroke-free. Stroke was associated with acute decline in global cognition, new learning, and verbal memory. Participants with stroke, compared with those without stroke, had faster declines in global cognition and executive function, but not in new learning and verbal memory, compared with prestroke changes.
Childhood adversities are associated with migraine, and greater numbers of adversities are associated with increasing odds of migraine, according to a study published online ahead of print June 23 in Headache. Researchers used a representative sample of 10,358 men and 12,638 women and performed gender-specific logistic regression analyses to determine the association between number and type of self-reported childhood adversities and migraine, while controlling for sociodemographics, comorbid adversities, health behaviors, depression, and anxiety. Overall, 6.5% of men and 14.2% of women reported migraines. Physical abuse, witnessing parental domestic violence, and sexual abuse were significantly associated with migraine for both genders, even after controlling for variables. Men reporting all three adversities had more than three times the odds of migraine, compared with those without childhood adversities.
Full truncal vagotomy is associated with a decreased risk for subsequent Parkinson’s disease, suggesting that the vagal nerve may be involved in the pathogenesis of Parkinson’s disease, according to a study published online ahead of print May 29 in Annals of Neurology. Researchers constructed cohorts of all patients in Denmark who underwent vagotomy from 1977 through 1995, and a matched general population cohort. Investigators used Cox regression analysis to compute hazard ratios for Parkinson’s disease, adjusting for potential confounders. Risk of Parkinson’s disease was decreased in patients who underwent truncal vagotomy, compared with superselective vagotomy. Risk of Parkinson’s disease also was decreased following truncal vagotomy when compared with the general population cohort. In patients who underwent superselective vagotomy, risk of Parkinson’s disease was similar to that of the general population.
In women with acute ischemic stroke treated with alteplase, uric acid reduced infarct growth in selected patients and was better than placebo for reaching excellent outcome, according to a study published online ahead of print July 9 in Stroke. Researchers reanalyzed 2014 data from the randomized, double-blind URICO-ICTUS trial of patients admitted to Spanish stroke centers. Participants included 206 women and 205 men. All participants received therapies to remove the clots, while half in each gender group also received either 1,000 mg of uric acid IV or placebo. Uric acid doubled the effect of placebo to achieve excellent outcome in women, but not in men. The interactions between treatment and serum uric acid levels or allantoin–uric acid ratio on infarct growth were significant only in women.
Women with epilepsy are at a heightened risk for adverse outcomes during their delivery hospitalizations, according to a study published online ahead of print July 6 in JAMA Neurology. Researchers examined a retrospective cohort study of pregnant women identified through delivery hospitalization records from the 2007 through 2011 Nationwide Inpatient Sample. Investigators obtained a weighted sample of delivery hospitalizations from 69,385 women with epilepsy and 20,449,532 women without epilepsy. Women with epilepsy had a risk of death during delivery hospitalization of 80 deaths per 100,000 pregnancies, compared with six deaths per 100,000 pregnancies among controls. Women with epilepsy also were at increased risk for pre-eclampsia, preterm labor, and stillbirth. They also had increased health care utilization, including an increased risk of cesarean delivery and prolonged hospital stay.
Eight-hour sleep duration may help consolidate newly learned procedural and declarative memories and ensure full access to them during periods of subjective stress, according to a study published online ahead of print June 22 in Sleep. For this study, 15 healthy young men learned object locations and a finger tapping sequence in the evening. Participants either had the opportunity to sleep for eight hours or could sleep between the hours of 3:00 am and 7:00 am. Retrieval of both memory tasks was tested in the morning after each sleep condition, both before and after stress exposure. Post-sleep memory changes did not differ between sleep conditions. Men who received less sleep, however, had reduced recall ability after exposure to stress, while post-stress recall was not affected in those who received a full night of sleep.
Cognitive impairment may manifest in the preclinical phase of Alzheimer’s disease substantially earlier than previously established, according to a study published online ahead of print June 24 in Neurology. A composite cognitive test score based on tests of episodic memory, executive function, and global cognition was constructed in a prospective population-based sample of 2,125 participants ages 65 and older. In all, 442 participants developed clinical Alzheimer’s disease over 18 years of follow-up. Lower composite cognitive test scores were associated with the development of Alzheimer’s disease. The magnitude of association between composite cognitive test score and development of Alzheimer’s disease dementia increased from an odds ratio of 3.39 at 13.0 to 17.9 years to an odds ratio of 9.84 at 0.1 to 0.9 years, per standard deviation increment.
Shared biological processes contribute to the risk of migraine and coronary artery disease, but this commonality is restricted to migraine without aura, according to a study published online ahead of print July 2 in Neurology Genetics. Researchers analyzed two large genome-wide association studies of migraine and heart disease. The migraine study involved 19,981 people with migraine and 56,667 people without migraine. Also included were 21,076 people with heart disease and 63,014 people without heart disease. Investigators found a significant overlap of genetic risk loci for migraine and coronary artery disease. When stratified by migraine subtype, this overlap was limited to migraine without aura. The overlap was protective, in that patients with migraine had a lower load of coronary artery disease risk alleles than controls did.
Women with stimulant dependence have significant changes in gray matter volume after prolonged abstinence, but men do not, according to a study published online ahead of print July 14 in Radiology. For this prospective, parallel-group study, 127 age- and sex-matched participants underwent T1-weighted spoiled gradient-echo inversion recovery MRI of the brain at 3 T. Compared with female control subjects, women with stimulant dependence had significantly lower gray matter volume in various brain regions. There were no significant differences in gray matter volume between male control subjects and men with stimulant dependence. Dependence symptom count negatively correlated with gray matter volume in the nucleus accumbens in women. Behavioral approach and impulsivity correlated negatively with frontal and temporal gray matter volume changes in women with stimulant dependence.
The FDA has approved Fycompa (perampanel) CIII for adjunctive therapy in the treatment of primary generalized tonic-clonic seizures. The approval is based on a phase III, randomized, double-blind, placebo-controlled clinical trial of 162 patients taking one to three antiepileptic drugs. Patients treated with Fycompa achieved a 76% median reduction in primary generalized tonic-clonic seizure frequency. In addition, 64% of patients treated with Fycompa had a 50% or greater reduction in primary generalized tonic-clonic seizure frequency versus 40% with placebo. The most frequently reported adverse events in patients treated with Fycompa were dizziness, fatigue, headache, somnolence, and irritability. The adverse event profile was similar to that in the controlled phase III partial-onset seizure trials of the drug. Eisai, headquartered in Woodcliff Lake, New Jersey, manufactures Fycompa.
Imaging biomarkers, including white matter disruption, may help explain some of the heterogeneity in postinjury outcome among children with traumatic brain injury (TBI), according to a study published July 15 in Journal of Neuroscience. Researchers used high angular resolution diffusion-weighted imaging to evaluate the structural integrity of the corpus callosum following brain injury in a sample of 32 children with moderate-to-severe TBI at one to five months post injury, and in healthy control children. A subset of children with TBI had markedly impaired functioning and structural integrity in the corpus callosum. These impairments were associated with poor neurocognitive functioning. The children with impaired functioning also had significantly slower interhemispheric transfer times than the control group did, as measured using event-related potentials.
Longitudinal CSF biomarker patterns consistent with Alzheimer’s disease are first detectable during early middle age and are associated with later amyloid positivity and cognitive decline, according to a study published online ahead of print July 6 in JAMA Neurology. Cognitively normal middle-aged participants enrolled in the Adult Children Study at Washington University underwent serial CSF collection and longitudinal clinical assessment at three-year intervals. A subset of patients underwent longitudinal amyloid PET imaging with Pittsburgh compound B (PiB) in the same period. The researchers found no consistent longitudinal patterns in Aβ40. Longitudinal reductions in Aβ42 were observed in some individuals as early as middle age, and low Aβ42 levels were associated with the development of cortical PiB-positive amyloid plaques. The patterns were more apparent in at-risk carriers of the ε4 allele.
Men with high exposure to formaldehyde at work had an almost three times greater rate of amyotrophic lateral sclerosis (ALS) mortality than men with no exposure, according to a study published online ahead of print July 13 in the Journal of Neurology Neurosurgery & Psychiatry. Researchers examined data for 794,541 men and 674,694 women included in the National Longitudinal Mortality Study who were 25 or older when surveyed. They used a formaldehyde exposure matrix constructed by industrial hygienists at the National Cancer Institute. Exposure to formaldehyde differed between males and females. All men with high-intensity exposure were funeral directors. Few women had high-exposure jobs, and there were no ALS deaths among women with such jobs. Participants with exposure were poorer and less educated than those without exposure.
—Kimberly Williams
New and Noteworthy Information—July 2015
Cognitive behavioral therapy for insomnia (CBT-I) is an effective treatment for adults with chronic insomnia, according to a review published online ahead of print June 9 in Annals of Internal Medicine. Researchers analyzed 20 randomized controlled trials that included 1,162 participants, of whom 64% were female, with a mean age of 56. Approaches to CBT-I incorporated techniques such as cognitive therapy, stimulus control, sleep restriction, sleep hygiene, and relaxation. At the post-treatment time point, sleep onset latency improved by an average of 19.03 minutes, wake after sleep onset improved by 26.00 minutes, total sleep time improved by 7.61 minutes, and sleep efficiency improved by 9.91%. These changes seemed to be sustained at later time points. These findings provide evidence that the psychologic approach to chronic insomnia is safer and better tolerated than medication.
Lifelong cognitive activity may support better cognitive performance by a mechanism that is independent of brain β-amyloid burden, brain glucose metabolism, or hippocampal volume, according to a study published online ahead of print June 10 in Neurology. Researchers evaluated self-reported histories of recent and past cognitive activity, self-reported history of recent physical activity, and objective recent walking activity in 186 clinically normal individuals with an average age of 74. The researchers analyzed the data with backward elimination general linear models. Greater cognitive activity was correlated with greater estimated IQ and education and better neuropsychologic testing performance. Evidence did not support an association of Pittsburgh compound B retention, 18F-fluorodeoxyglucose uptake, or hippocampal volume with past or current levels of cognitive activity, nor with current physical activity.
Among people who have had organ transplants, taking calcineurin daily to prevent organ rejection may protect against Alzheimer’s disease, according to a study published online ahead of print June 8 in Journal of Alzheimer’s Disease. Researchers analyzed data from the medical records of 2,644 patients who received organ transplants and must take calcineurin inhibitor-based medications for the rest of their lives. The participants were separated into groups by age at the time of last visit or death, gender, and ethnicity. Eight participants showed evidence of dementia. Two of these participants were younger than 65, five were between ages 65 and 74, and one person was between ages 75 and 84. The prevalence of dementia and Alzheimer’s disease in the study population was significantly lower than that in the general population.
Academic performance may decline after pediatric epilepsy surgery, according to a study published in the June issue of Epilepsy & Behavior. Investigators examined 136 children with a mean age of 14.3 who underwent resective epilepsy surgery. Academic functioning was assessed before and after surgery using standardized tests of reading, reading comprehension, arithmetic, and spelling. At baseline, 65% of the children displayed low achievement, and 28% had underachievement in at least one academic domain. Performance in reading, numeral operations, and spelling significantly declined after surgery among all patients. Seizure freedom at follow-up did not influence this relationship. Reading comprehension and IQ remained unchanged after surgery. The researchers found similar results when examining patients with a baseline IQ of 70 or greater and when controlling for IQ.
Incident stroke does not explain racial differences in cognitive decline or affect cognition differently by race, according to a study published online ahead of print May 21 in Stroke. Included in this study were 4,908 black and white participants who were age 65 or older and free of stroke and cognitive impairment. Researchers examined longitudinal changes in global cognition by race, before and after adjusting the data. In all, 7.5% of blacks and 6.7% of whites had incident stroke during a mean of 4.1 years of follow-up. Blacks had greater cognitive decline than whites, and the difference persisted after adjustments for cumulative incidence of stroke. Stroke was associated with a decrease in global cognition similar to that associated with approximately 7.9 years of cognitive aging.
Type 2 diabetes may protect against amyotrophic lateral sclerosis (ALS), according to a study published online ahead of print June 1 in JAMA Neurology. The population-based, nested case–control study included 3,650 Danish residents who received a diagnosis of ALS between January 1, 1982, and December 31, 2009, and 365,000 age- and sex-matched controls. The estimated odds ratio for ALS among individuals with diabetes was 0.61. Researchers found a significant modification by age at ALS diagnosis and age at first mention of diabetes in the hospital registers. The protective association with diabetes was stronger with increasing age at ALS diagnosis, and the odds ratio for first mention of diabetes was 1.66 before age 40, but 0.52 for older ages.
The FDA has approved Qudexy XR (topiramate) extended-release capsules for use as initial monotherapy in patients age two and older with partial-onset seizures or primary generalized tonic–clonic seizures. The capsules are engineered to deliver a consistent pharmacokinetic profile. Qudexy XR is approved for administration by sprinkling the contents onto soft food, which may aid the treatment of young children who have difficulty swallowing whole capsules or tablets. Qudexy XR previously was approved for use as initial monotherapy in patients age 10 and older with partial-onset seizures or primary generalized tonic–clonic seizures. The drug is also approved as an adjunctive therapy in patients age two or older with partial-onset seizures, primary generalized tonic–clonic seizures, or seizures associated with Lennox-Gastaut syndrome.
—Kimberly Williams
Cognitive behavioral therapy for insomnia (CBT-I) is an effective treatment for adults with chronic insomnia, according to a review published online ahead of print June 9 in Annals of Internal Medicine. Researchers analyzed 20 randomized controlled trials that included 1,162 participants, of whom 64% were female, with a mean age of 56. Approaches to CBT-I incorporated techniques such as cognitive therapy, stimulus control, sleep restriction, sleep hygiene, and relaxation. At the post-treatment time point, sleep onset latency improved by an average of 19.03 minutes, wake after sleep onset improved by 26.00 minutes, total sleep time improved by 7.61 minutes, and sleep efficiency improved by 9.91%. These changes seemed to be sustained at later time points. These findings provide evidence that the psychologic approach to chronic insomnia is safer and better tolerated than medication.
Lifelong cognitive activity may support better cognitive performance by a mechanism that is independent of brain β-amyloid burden, brain glucose metabolism, or hippocampal volume, according to a study published online ahead of print June 10 in Neurology. Researchers evaluated self-reported histories of recent and past cognitive activity, self-reported history of recent physical activity, and objective recent walking activity in 186 clinically normal individuals with an average age of 74. The researchers analyzed the data with backward elimination general linear models. Greater cognitive activity was correlated with greater estimated IQ and education and better neuropsychologic testing performance. Evidence did not support an association of Pittsburgh compound B retention, 18F-fluorodeoxyglucose uptake, or hippocampal volume with past or current levels of cognitive activity, nor with current physical activity.
Among people who have had organ transplants, taking calcineurin daily to prevent organ rejection may protect against Alzheimer’s disease, according to a study published online ahead of print June 8 in Journal of Alzheimer’s Disease. Researchers analyzed data from the medical records of 2,644 patients who received organ transplants and must take calcineurin inhibitor-based medications for the rest of their lives. The participants were separated into groups by age at the time of last visit or death, gender, and ethnicity. Eight participants showed evidence of dementia. Two of these participants were younger than 65, five were between ages 65 and 74, and one person was between ages 75 and 84. The prevalence of dementia and Alzheimer’s disease in the study population was significantly lower than that in the general population.
Academic performance may decline after pediatric epilepsy surgery, according to a study published in the June issue of Epilepsy & Behavior. Investigators examined 136 children with a mean age of 14.3 who underwent resective epilepsy surgery. Academic functioning was assessed before and after surgery using standardized tests of reading, reading comprehension, arithmetic, and spelling. At baseline, 65% of the children displayed low achievement, and 28% had underachievement in at least one academic domain. Performance in reading, numeral operations, and spelling significantly declined after surgery among all patients. Seizure freedom at follow-up did not influence this relationship. Reading comprehension and IQ remained unchanged after surgery. The researchers found similar results when examining patients with a baseline IQ of 70 or greater and when controlling for IQ.
Incident stroke does not explain racial differences in cognitive decline or affect cognition differently by race, according to a study published online ahead of print May 21 in Stroke. Included in this study were 4,908 black and white participants who were age 65 or older and free of stroke and cognitive impairment. Researchers examined longitudinal changes in global cognition by race, before and after adjusting the data. In all, 7.5% of blacks and 6.7% of whites had incident stroke during a mean of 4.1 years of follow-up. Blacks had greater cognitive decline than whites, and the difference persisted after adjustments for cumulative incidence of stroke. Stroke was associated with a decrease in global cognition similar to that associated with approximately 7.9 years of cognitive aging.
Type 2 diabetes may protect against amyotrophic lateral sclerosis (ALS), according to a study published online ahead of print June 1 in JAMA Neurology. The population-based, nested case–control study included 3,650 Danish residents who received a diagnosis of ALS between January 1, 1982, and December 31, 2009, and 365,000 age- and sex-matched controls. The estimated odds ratio for ALS among individuals with diabetes was 0.61. Researchers found a significant modification by age at ALS diagnosis and age at first mention of diabetes in the hospital registers. The protective association with diabetes was stronger with increasing age at ALS diagnosis, and the odds ratio for first mention of diabetes was 1.66 before age 40, but 0.52 for older ages.
The FDA has approved Qudexy XR (topiramate) extended-release capsules for use as initial monotherapy in patients age two and older with partial-onset seizures or primary generalized tonic–clonic seizures. The capsules are engineered to deliver a consistent pharmacokinetic profile. Qudexy XR is approved for administration by sprinkling the contents onto soft food, which may aid the treatment of young children who have difficulty swallowing whole capsules or tablets. Qudexy XR previously was approved for use as initial monotherapy in patients age 10 and older with partial-onset seizures or primary generalized tonic–clonic seizures. The drug is also approved as an adjunctive therapy in patients age two or older with partial-onset seizures, primary generalized tonic–clonic seizures, or seizures associated with Lennox-Gastaut syndrome.
—Kimberly Williams
Cognitive behavioral therapy for insomnia (CBT-I) is an effective treatment for adults with chronic insomnia, according to a review published online ahead of print June 9 in Annals of Internal Medicine. Researchers analyzed 20 randomized controlled trials that included 1,162 participants, of whom 64% were female, with a mean age of 56. Approaches to CBT-I incorporated techniques such as cognitive therapy, stimulus control, sleep restriction, sleep hygiene, and relaxation. At the post-treatment time point, sleep onset latency improved by an average of 19.03 minutes, wake after sleep onset improved by 26.00 minutes, total sleep time improved by 7.61 minutes, and sleep efficiency improved by 9.91%. These changes seemed to be sustained at later time points. These findings provide evidence that the psychologic approach to chronic insomnia is safer and better tolerated than medication.
Lifelong cognitive activity may support better cognitive performance by a mechanism that is independent of brain β-amyloid burden, brain glucose metabolism, or hippocampal volume, according to a study published online ahead of print June 10 in Neurology. Researchers evaluated self-reported histories of recent and past cognitive activity, self-reported history of recent physical activity, and objective recent walking activity in 186 clinically normal individuals with an average age of 74. The researchers analyzed the data with backward elimination general linear models. Greater cognitive activity was correlated with greater estimated IQ and education and better neuropsychologic testing performance. Evidence did not support an association of Pittsburgh compound B retention, 18F-fluorodeoxyglucose uptake, or hippocampal volume with past or current levels of cognitive activity, nor with current physical activity.
Among people who have had organ transplants, taking calcineurin daily to prevent organ rejection may protect against Alzheimer’s disease, according to a study published online ahead of print June 8 in Journal of Alzheimer’s Disease. Researchers analyzed data from the medical records of 2,644 patients who received organ transplants and must take calcineurin inhibitor-based medications for the rest of their lives. The participants were separated into groups by age at the time of last visit or death, gender, and ethnicity. Eight participants showed evidence of dementia. Two of these participants were younger than 65, five were between ages 65 and 74, and one person was between ages 75 and 84. The prevalence of dementia and Alzheimer’s disease in the study population was significantly lower than that in the general population.
Academic performance may decline after pediatric epilepsy surgery, according to a study published in the June issue of Epilepsy & Behavior. Investigators examined 136 children with a mean age of 14.3 who underwent resective epilepsy surgery. Academic functioning was assessed before and after surgery using standardized tests of reading, reading comprehension, arithmetic, and spelling. At baseline, 65% of the children displayed low achievement, and 28% had underachievement in at least one academic domain. Performance in reading, numeral operations, and spelling significantly declined after surgery among all patients. Seizure freedom at follow-up did not influence this relationship. Reading comprehension and IQ remained unchanged after surgery. The researchers found similar results when examining patients with a baseline IQ of 70 or greater and when controlling for IQ.
Incident stroke does not explain racial differences in cognitive decline or affect cognition differently by race, according to a study published online ahead of print May 21 in Stroke. Included in this study were 4,908 black and white participants who were age 65 or older and free of stroke and cognitive impairment. Researchers examined longitudinal changes in global cognition by race, before and after adjusting the data. In all, 7.5% of blacks and 6.7% of whites had incident stroke during a mean of 4.1 years of follow-up. Blacks had greater cognitive decline than whites, and the difference persisted after adjustments for cumulative incidence of stroke. Stroke was associated with a decrease in global cognition similar to that associated with approximately 7.9 years of cognitive aging.
Type 2 diabetes may protect against amyotrophic lateral sclerosis (ALS), according to a study published online ahead of print June 1 in JAMA Neurology. The population-based, nested case–control study included 3,650 Danish residents who received a diagnosis of ALS between January 1, 1982, and December 31, 2009, and 365,000 age- and sex-matched controls. The estimated odds ratio for ALS among individuals with diabetes was 0.61. Researchers found a significant modification by age at ALS diagnosis and age at first mention of diabetes in the hospital registers. The protective association with diabetes was stronger with increasing age at ALS diagnosis, and the odds ratio for first mention of diabetes was 1.66 before age 40, but 0.52 for older ages.
The FDA has approved Qudexy XR (topiramate) extended-release capsules for use as initial monotherapy in patients age two and older with partial-onset seizures or primary generalized tonic–clonic seizures. The capsules are engineered to deliver a consistent pharmacokinetic profile. Qudexy XR is approved for administration by sprinkling the contents onto soft food, which may aid the treatment of young children who have difficulty swallowing whole capsules or tablets. Qudexy XR previously was approved for use as initial monotherapy in patients age 10 and older with partial-onset seizures or primary generalized tonic–clonic seizures. The drug is also approved as an adjunctive therapy in patients age two or older with partial-onset seizures, primary generalized tonic–clonic seizures, or seizures associated with Lennox-Gastaut syndrome.
—Kimberly Williams
New and Noteworthy Information—June 2015
Persistently high depressive symptoms are associated with increased stroke risk, according to a study published May 13 in Journal of the American Heart Association. This research included health information from 16,178 men and women age 50 or older who participated in the Health and Retirement Study between 1998 and 2010. Participants were interviewed every two years about depressive symptoms, history of stroke, and stroke risk factors, among other health measures. Stroke risk was elevated among participants with stable high (hazard ratio [HR], 2.14) or remitted (HR, 1.66) depressive symptoms, compared with participants with stable low or no depressive symptoms. Stable high depressive symptoms predicted stroke among all subgroups. Remitted depressive symptoms predicted increased stroke risk among women (HR, 1.86) and non-Hispanic white participants (HR, 1.66).
Chronic traumatic encephalopathy (CTE) is associated with altered and accelerated deposition of amyloid β, according to a study published online ahead of print May 6 in Acta Neuropathologica. Researchers studied a heterogeneous cohort of deceased athletes and military veterans with neuropathologically diagnosed CTE. The investigators found that amyloid β deposition was present in 52% of subjects with CTE. Moreover, amyloid β deposition in CTE occurred at an accelerated rate and with altered dynamics in CTE, compared with a normal aging population. In addition, amyloid β deposition was significantly associated with the presence of the APOE e4 allele, older age at symptom onset, and older age at death. Neuritic plaques were significantly associated with increased CTE tauopathy stage, comorbid Lewy body disease, and dementia.
Low-dose tetrahydrocannabinol (THC) does not significantly reduce dementia-related neuropsychiatric symptoms at 21 days, though it is well tolerated, according to a study published online ahead of print May 13 in Neurology. In a double-blind, placebo-controlled study, investigators randomly assigned patients with dementia and clinically relevant neuropsychiatric symptoms to receive 1.5 mg of THC or matched placebo three times daily for three weeks. Neuropsychiatric symptoms were reduced during both treatment conditions. The difference in reduction from baseline between THC and placebo was not significant. Changes in scores for agitation, quality of life, or activities of daily living also were not significantly different between treatment arms. The number of patients experiencing mild or moderate adverse events was similar in both groups. No effects on vital signs, weight, or episodic memory were observed.
Exposure to elevated levels of fine particulate matter is associated with smaller total cerebral brain volume, according to a study published in the May issue of Stroke. Researchers analyzed 943 adults in the Framingham Offspring Study who were relatively healthy and free of dementia and stroke. Investigators evaluated associations between exposure to fine particulate matter and total cerebral brain volume, hippocampal volume, white matter hyperintensity volume, and covert brain infarcts. A 2-μg/m3 increase in fine particulate matter was associated with –0.32% smaller total cerebral brain volume and 1.46 higher odds of covert brain infarcts. Living further away from a major roadway was associated with 0.10 greater log-transformed white matter hyperintensity volume for an interquartile range difference in distance, but no clear pattern of association was observed for extensive white matter.
Higher occupational attainment is associated with longer survival in autopsy-confirmed frontotemporal lobar degeneration, according to a study published online ahead of print April 22 in Neurology. Researchers performed a retrospective chart review of 83 demographically matched patients with autopsy-confirmed frontotemporal lobar degeneration or Alzheimer’s disease. They used linear regression to test for associations among occupational attainment, education, and patient survival. Median survival was 81 months among patients with frontotemporal lobar degeneration and 95 months among patients with Alzheimer’s disease. Years of education and occupational attainment were similar for both groups. Higher occupational attainment was associated with longer survival in frontotemporal lobar degeneration, but not in Alzheimer’s disease. The findings support the theory that education, occupation, and mental activity create cognitive reserve and protect against disease.
Obesity is a major risk factor for the incidence and chronicity of excessive daytime sleepiness (EDS), and weight loss is associated with its remission, according to a study published March 1 in Sleep. Investigators followed up 1,395 people from a random, general population sample of 1,741 participants in the Penn State Adult Cohort after 7.5 years. The incidence of EDS was 8.2%. Of people with EDS, 62% had remission. Significant interactions between depression and polysomnographic parameters on incident EDS showed that in depressed individuals, incident EDS was associated with sleep disturbances. In individuals without depression, incident EDS was associated with increased physiologic sleep propensity. Diabetes, allergy or asthma, anemia, and sleep complaints also predicted EDS. “EDS has huge implications for public health and policy,” stated the researchers.
Patients with celiac disease have an increased risk of neuropathy, according to a study published online ahead of print May 11 in JAMA Neurology. Between October 27, 2006, and February 12, 2008, researchers collected data on small-intestinal biopsies performed in pathology departments between June 16, 1969, and February 4, 2008. Investigators compared the risk of neuropathy in 28,232 patients with celiac disease with that of 139,473 age- and sex-matched controls. Celiac disease was associated with a 2.5-fold increased risk of subsequent neuropathy. In addition, the investigators found an increased risk of chronic inflammatory demyelinating neuropathy, autonomic neuropathy, and mononeuritis multiplex in patients with celiac disease. They found no association, however, between celiac disease and acute inflammatory demyelinating polyneuropathy. Physicians should screen patients with neuropathy for celiac disease, said the researchers.
A professional life that stimulates verbal intelligence and executive function may help to sustain good cognitive function in people age 75 and older, according to a study published online ahead of print April 29 in Neurology. For the study, 1,054 people age 75 or older underwent the Mini-Mental State Examination every one-and-a-half years for eight years. In multivariate mixed-model analyses, a high level of mentally demanding work tasks stimulating verbal intelligence was significantly associated with better cognitive functioning at baseline and a lower rate of cognitive decline during the eight-year follow-up period, compared with a low level of these tasks. The rate of cognitive decline in old age was also significantly lower in individuals who had a high level of mentally demanding work tasks stimulating executive function.
In Get With the Guidelines-Stroke hospitals, electronic health records are not associated with higher-quality care or better clinical outcomes for stroke care, according to a study published May 12 in Journal of the American College of Cardiology. Researchers studied 626,473 patients from 1,236 US hospitals in Get With the Guidelines-Stroke from 2007 through 2010. They used the American Hospital Association annual survey to determine the presence of electronic health records. Hospitals with electronic health records were larger and were more often teaching hospitals and stroke centers. After controlling for patient and hospital characteristics, patients admitted to hospitals with electronic health records had similar odds of receiving “all-or-none care.” The odds of having a length of stay greater than four days was slightly lower at hospitals with electronic health records.
Off-label use of the Lariat device for left atrial appendage exclusion to prevent stroke in patients with atrial fibrillation entails significant risks of adverse events, according to a study published online ahead of print May 4 in JAMA Internal Medicine. Investigators searched PubMed, EMBASE, CINAHL, and the Cochrane Library from January 2007 through August 2014 to identify all studies reporting use of the Lariat device in three or more patients. They queried the FDA MAUDE database for adverse events reports related to Lariat use. Five reports of Lariat device use in 309 participants were identified. The FDA MAUDE database contained 35 unique reports of adverse events with use of the Lariat device. Among these reports were five adverse event reports that noted pericardial effusion and death and an additional 23 that reported urgent cardiac surgery, but not death.
Insomnia is linked to functional and cognitive impairment among patients with shift work disorder, according to a study published April 15 in Journal of Clinical Sleep Medicine. The analysis included 34 night workers, 26 of whom were diagnosed with shift work disorder. Participants underwent an overnight laboratory protocol including a multiple sleep latency test (MSLT), an event-related brain potential (ERP) task, and various questionnaires. Participants reporting insomnia without sleepiness were the most impaired on the Endicott Work Productivity Scale (EWPS) and significantly more impaired than controls. Participants reporting insomnia and sleepiness were not statistically different from controls. Neither MSLT nor the Epworth Sleepiness Scale correlated with EWPS scores or ERP amplitudes. The mean of the Insomnia Severity Indices measurements, however, correlated with the EWPS.
The measurement of grip strength is a simple, inexpensive risk-stratifying method for all-cause death, cardiovascular death, and cardiovascular disease, according to a study published online ahead of print May 13 in Lancet. In the Prospective Urban-Rural Epidemiology study, researchers enrolled households that each included at least one member between ages 35 and 70. The investigators measured participants’ grip strength with a Jamar dynamometer. Median follow-up was four years. Grip strength was inversely associated with all-cause mortality, cardiovascular mortality, noncardiovascular mortality, myocardial infarction, and stroke. Grip strength was a stronger predictor of all-cause and cardiovascular mortality than systolic blood pressure was. The researchers found no significant association between grip strength and incident diabetes, risk of hospital admission for pneumonia or chronic obstructive pulmonary disease, injury from fall, or fracture.
Sleep deprivation is particularly problematic for decision-making involving uncertainty and unexpected change, according to a study published in the May issue of Sleep. Twenty-six subjects were randomized to 62 hours of total sleep deprivation or to a control condition. Researchers conducted performance testing at baseline, after two nights of total sleep deprivation or rested control, and following two nights of recovery sleep. Participants performed a decision task that involved initial learning of response sets and subsequent reversal of contingencies. Working memory and psychomotor vigilance tests also were administered. Sleep-deprived subjects had difficulty with initial learning of stimuli sets and profound impairment adapting to reversal. Skin conductance responses to outcome feedback were diminished, indicating blunted affective reactions to feedback accompanying sleep deprivation. Sleep deprivation did not significantly affect working memory scanning performance.
—Kimberly Williams
Persistently high depressive symptoms are associated with increased stroke risk, according to a study published May 13 in Journal of the American Heart Association. This research included health information from 16,178 men and women age 50 or older who participated in the Health and Retirement Study between 1998 and 2010. Participants were interviewed every two years about depressive symptoms, history of stroke, and stroke risk factors, among other health measures. Stroke risk was elevated among participants with stable high (hazard ratio [HR], 2.14) or remitted (HR, 1.66) depressive symptoms, compared with participants with stable low or no depressive symptoms. Stable high depressive symptoms predicted stroke among all subgroups. Remitted depressive symptoms predicted increased stroke risk among women (HR, 1.86) and non-Hispanic white participants (HR, 1.66).
Chronic traumatic encephalopathy (CTE) is associated with altered and accelerated deposition of amyloid β, according to a study published online ahead of print May 6 in Acta Neuropathologica. Researchers studied a heterogeneous cohort of deceased athletes and military veterans with neuropathologically diagnosed CTE. The investigators found that amyloid β deposition was present in 52% of subjects with CTE. Moreover, amyloid β deposition in CTE occurred at an accelerated rate and with altered dynamics in CTE, compared with a normal aging population. In addition, amyloid β deposition was significantly associated with the presence of the APOE e4 allele, older age at symptom onset, and older age at death. Neuritic plaques were significantly associated with increased CTE tauopathy stage, comorbid Lewy body disease, and dementia.
Low-dose tetrahydrocannabinol (THC) does not significantly reduce dementia-related neuropsychiatric symptoms at 21 days, though it is well tolerated, according to a study published online ahead of print May 13 in Neurology. In a double-blind, placebo-controlled study, investigators randomly assigned patients with dementia and clinically relevant neuropsychiatric symptoms to receive 1.5 mg of THC or matched placebo three times daily for three weeks. Neuropsychiatric symptoms were reduced during both treatment conditions. The difference in reduction from baseline between THC and placebo was not significant. Changes in scores for agitation, quality of life, or activities of daily living also were not significantly different between treatment arms. The number of patients experiencing mild or moderate adverse events was similar in both groups. No effects on vital signs, weight, or episodic memory were observed.
Exposure to elevated levels of fine particulate matter is associated with smaller total cerebral brain volume, according to a study published in the May issue of Stroke. Researchers analyzed 943 adults in the Framingham Offspring Study who were relatively healthy and free of dementia and stroke. Investigators evaluated associations between exposure to fine particulate matter and total cerebral brain volume, hippocampal volume, white matter hyperintensity volume, and covert brain infarcts. A 2-μg/m3 increase in fine particulate matter was associated with –0.32% smaller total cerebral brain volume and 1.46 higher odds of covert brain infarcts. Living further away from a major roadway was associated with 0.10 greater log-transformed white matter hyperintensity volume for an interquartile range difference in distance, but no clear pattern of association was observed for extensive white matter.
Higher occupational attainment is associated with longer survival in autopsy-confirmed frontotemporal lobar degeneration, according to a study published online ahead of print April 22 in Neurology. Researchers performed a retrospective chart review of 83 demographically matched patients with autopsy-confirmed frontotemporal lobar degeneration or Alzheimer’s disease. They used linear regression to test for associations among occupational attainment, education, and patient survival. Median survival was 81 months among patients with frontotemporal lobar degeneration and 95 months among patients with Alzheimer’s disease. Years of education and occupational attainment were similar for both groups. Higher occupational attainment was associated with longer survival in frontotemporal lobar degeneration, but not in Alzheimer’s disease. The findings support the theory that education, occupation, and mental activity create cognitive reserve and protect against disease.
Obesity is a major risk factor for the incidence and chronicity of excessive daytime sleepiness (EDS), and weight loss is associated with its remission, according to a study published March 1 in Sleep. Investigators followed up 1,395 people from a random, general population sample of 1,741 participants in the Penn State Adult Cohort after 7.5 years. The incidence of EDS was 8.2%. Of people with EDS, 62% had remission. Significant interactions between depression and polysomnographic parameters on incident EDS showed that in depressed individuals, incident EDS was associated with sleep disturbances. In individuals without depression, incident EDS was associated with increased physiologic sleep propensity. Diabetes, allergy or asthma, anemia, and sleep complaints also predicted EDS. “EDS has huge implications for public health and policy,” stated the researchers.
Patients with celiac disease have an increased risk of neuropathy, according to a study published online ahead of print May 11 in JAMA Neurology. Between October 27, 2006, and February 12, 2008, researchers collected data on small-intestinal biopsies performed in pathology departments between June 16, 1969, and February 4, 2008. Investigators compared the risk of neuropathy in 28,232 patients with celiac disease with that of 139,473 age- and sex-matched controls. Celiac disease was associated with a 2.5-fold increased risk of subsequent neuropathy. In addition, the investigators found an increased risk of chronic inflammatory demyelinating neuropathy, autonomic neuropathy, and mononeuritis multiplex in patients with celiac disease. They found no association, however, between celiac disease and acute inflammatory demyelinating polyneuropathy. Physicians should screen patients with neuropathy for celiac disease, said the researchers.
A professional life that stimulates verbal intelligence and executive function may help to sustain good cognitive function in people age 75 and older, according to a study published online ahead of print April 29 in Neurology. For the study, 1,054 people age 75 or older underwent the Mini-Mental State Examination every one-and-a-half years for eight years. In multivariate mixed-model analyses, a high level of mentally demanding work tasks stimulating verbal intelligence was significantly associated with better cognitive functioning at baseline and a lower rate of cognitive decline during the eight-year follow-up period, compared with a low level of these tasks. The rate of cognitive decline in old age was also significantly lower in individuals who had a high level of mentally demanding work tasks stimulating executive function.
In Get With the Guidelines-Stroke hospitals, electronic health records are not associated with higher-quality care or better clinical outcomes for stroke care, according to a study published May 12 in Journal of the American College of Cardiology. Researchers studied 626,473 patients from 1,236 US hospitals in Get With the Guidelines-Stroke from 2007 through 2010. They used the American Hospital Association annual survey to determine the presence of electronic health records. Hospitals with electronic health records were larger and were more often teaching hospitals and stroke centers. After controlling for patient and hospital characteristics, patients admitted to hospitals with electronic health records had similar odds of receiving “all-or-none care.” The odds of having a length of stay greater than four days was slightly lower at hospitals with electronic health records.
Off-label use of the Lariat device for left atrial appendage exclusion to prevent stroke in patients with atrial fibrillation entails significant risks of adverse events, according to a study published online ahead of print May 4 in JAMA Internal Medicine. Investigators searched PubMed, EMBASE, CINAHL, and the Cochrane Library from January 2007 through August 2014 to identify all studies reporting use of the Lariat device in three or more patients. They queried the FDA MAUDE database for adverse events reports related to Lariat use. Five reports of Lariat device use in 309 participants were identified. The FDA MAUDE database contained 35 unique reports of adverse events with use of the Lariat device. Among these reports were five adverse event reports that noted pericardial effusion and death and an additional 23 that reported urgent cardiac surgery, but not death.
Insomnia is linked to functional and cognitive impairment among patients with shift work disorder, according to a study published April 15 in Journal of Clinical Sleep Medicine. The analysis included 34 night workers, 26 of whom were diagnosed with shift work disorder. Participants underwent an overnight laboratory protocol including a multiple sleep latency test (MSLT), an event-related brain potential (ERP) task, and various questionnaires. Participants reporting insomnia without sleepiness were the most impaired on the Endicott Work Productivity Scale (EWPS) and significantly more impaired than controls. Participants reporting insomnia and sleepiness were not statistically different from controls. Neither MSLT nor the Epworth Sleepiness Scale correlated with EWPS scores or ERP amplitudes. The mean of the Insomnia Severity Indices measurements, however, correlated with the EWPS.
The measurement of grip strength is a simple, inexpensive risk-stratifying method for all-cause death, cardiovascular death, and cardiovascular disease, according to a study published online ahead of print May 13 in Lancet. In the Prospective Urban-Rural Epidemiology study, researchers enrolled households that each included at least one member between ages 35 and 70. The investigators measured participants’ grip strength with a Jamar dynamometer. Median follow-up was four years. Grip strength was inversely associated with all-cause mortality, cardiovascular mortality, noncardiovascular mortality, myocardial infarction, and stroke. Grip strength was a stronger predictor of all-cause and cardiovascular mortality than systolic blood pressure was. The researchers found no significant association between grip strength and incident diabetes, risk of hospital admission for pneumonia or chronic obstructive pulmonary disease, injury from fall, or fracture.
Sleep deprivation is particularly problematic for decision-making involving uncertainty and unexpected change, according to a study published in the May issue of Sleep. Twenty-six subjects were randomized to 62 hours of total sleep deprivation or to a control condition. Researchers conducted performance testing at baseline, after two nights of total sleep deprivation or rested control, and following two nights of recovery sleep. Participants performed a decision task that involved initial learning of response sets and subsequent reversal of contingencies. Working memory and psychomotor vigilance tests also were administered. Sleep-deprived subjects had difficulty with initial learning of stimuli sets and profound impairment adapting to reversal. Skin conductance responses to outcome feedback were diminished, indicating blunted affective reactions to feedback accompanying sleep deprivation. Sleep deprivation did not significantly affect working memory scanning performance.
—Kimberly Williams
Persistently high depressive symptoms are associated with increased stroke risk, according to a study published May 13 in Journal of the American Heart Association. This research included health information from 16,178 men and women age 50 or older who participated in the Health and Retirement Study between 1998 and 2010. Participants were interviewed every two years about depressive symptoms, history of stroke, and stroke risk factors, among other health measures. Stroke risk was elevated among participants with stable high (hazard ratio [HR], 2.14) or remitted (HR, 1.66) depressive symptoms, compared with participants with stable low or no depressive symptoms. Stable high depressive symptoms predicted stroke among all subgroups. Remitted depressive symptoms predicted increased stroke risk among women (HR, 1.86) and non-Hispanic white participants (HR, 1.66).
Chronic traumatic encephalopathy (CTE) is associated with altered and accelerated deposition of amyloid β, according to a study published online ahead of print May 6 in Acta Neuropathologica. Researchers studied a heterogeneous cohort of deceased athletes and military veterans with neuropathologically diagnosed CTE. The investigators found that amyloid β deposition was present in 52% of subjects with CTE. Moreover, amyloid β deposition in CTE occurred at an accelerated rate and with altered dynamics in CTE, compared with a normal aging population. In addition, amyloid β deposition was significantly associated with the presence of the APOE e4 allele, older age at symptom onset, and older age at death. Neuritic plaques were significantly associated with increased CTE tauopathy stage, comorbid Lewy body disease, and dementia.
Low-dose tetrahydrocannabinol (THC) does not significantly reduce dementia-related neuropsychiatric symptoms at 21 days, though it is well tolerated, according to a study published online ahead of print May 13 in Neurology. In a double-blind, placebo-controlled study, investigators randomly assigned patients with dementia and clinically relevant neuropsychiatric symptoms to receive 1.5 mg of THC or matched placebo three times daily for three weeks. Neuropsychiatric symptoms were reduced during both treatment conditions. The difference in reduction from baseline between THC and placebo was not significant. Changes in scores for agitation, quality of life, or activities of daily living also were not significantly different between treatment arms. The number of patients experiencing mild or moderate adverse events was similar in both groups. No effects on vital signs, weight, or episodic memory were observed.
Exposure to elevated levels of fine particulate matter is associated with smaller total cerebral brain volume, according to a study published in the May issue of Stroke. Researchers analyzed 943 adults in the Framingham Offspring Study who were relatively healthy and free of dementia and stroke. Investigators evaluated associations between exposure to fine particulate matter and total cerebral brain volume, hippocampal volume, white matter hyperintensity volume, and covert brain infarcts. A 2-μg/m3 increase in fine particulate matter was associated with –0.32% smaller total cerebral brain volume and 1.46 higher odds of covert brain infarcts. Living further away from a major roadway was associated with 0.10 greater log-transformed white matter hyperintensity volume for an interquartile range difference in distance, but no clear pattern of association was observed for extensive white matter.
Higher occupational attainment is associated with longer survival in autopsy-confirmed frontotemporal lobar degeneration, according to a study published online ahead of print April 22 in Neurology. Researchers performed a retrospective chart review of 83 demographically matched patients with autopsy-confirmed frontotemporal lobar degeneration or Alzheimer’s disease. They used linear regression to test for associations among occupational attainment, education, and patient survival. Median survival was 81 months among patients with frontotemporal lobar degeneration and 95 months among patients with Alzheimer’s disease. Years of education and occupational attainment were similar for both groups. Higher occupational attainment was associated with longer survival in frontotemporal lobar degeneration, but not in Alzheimer’s disease. The findings support the theory that education, occupation, and mental activity create cognitive reserve and protect against disease.
Obesity is a major risk factor for the incidence and chronicity of excessive daytime sleepiness (EDS), and weight loss is associated with its remission, according to a study published March 1 in Sleep. Investigators followed up 1,395 people from a random, general population sample of 1,741 participants in the Penn State Adult Cohort after 7.5 years. The incidence of EDS was 8.2%. Of people with EDS, 62% had remission. Significant interactions between depression and polysomnographic parameters on incident EDS showed that in depressed individuals, incident EDS was associated with sleep disturbances. In individuals without depression, incident EDS was associated with increased physiologic sleep propensity. Diabetes, allergy or asthma, anemia, and sleep complaints also predicted EDS. “EDS has huge implications for public health and policy,” stated the researchers.
Patients with celiac disease have an increased risk of neuropathy, according to a study published online ahead of print May 11 in JAMA Neurology. Between October 27, 2006, and February 12, 2008, researchers collected data on small-intestinal biopsies performed in pathology departments between June 16, 1969, and February 4, 2008. Investigators compared the risk of neuropathy in 28,232 patients with celiac disease with that of 139,473 age- and sex-matched controls. Celiac disease was associated with a 2.5-fold increased risk of subsequent neuropathy. In addition, the investigators found an increased risk of chronic inflammatory demyelinating neuropathy, autonomic neuropathy, and mononeuritis multiplex in patients with celiac disease. They found no association, however, between celiac disease and acute inflammatory demyelinating polyneuropathy. Physicians should screen patients with neuropathy for celiac disease, said the researchers.
A professional life that stimulates verbal intelligence and executive function may help to sustain good cognitive function in people age 75 and older, according to a study published online ahead of print April 29 in Neurology. For the study, 1,054 people age 75 or older underwent the Mini-Mental State Examination every one-and-a-half years for eight years. In multivariate mixed-model analyses, a high level of mentally demanding work tasks stimulating verbal intelligence was significantly associated with better cognitive functioning at baseline and a lower rate of cognitive decline during the eight-year follow-up period, compared with a low level of these tasks. The rate of cognitive decline in old age was also significantly lower in individuals who had a high level of mentally demanding work tasks stimulating executive function.
In Get With the Guidelines-Stroke hospitals, electronic health records are not associated with higher-quality care or better clinical outcomes for stroke care, according to a study published May 12 in Journal of the American College of Cardiology. Researchers studied 626,473 patients from 1,236 US hospitals in Get With the Guidelines-Stroke from 2007 through 2010. They used the American Hospital Association annual survey to determine the presence of electronic health records. Hospitals with electronic health records were larger and were more often teaching hospitals and stroke centers. After controlling for patient and hospital characteristics, patients admitted to hospitals with electronic health records had similar odds of receiving “all-or-none care.” The odds of having a length of stay greater than four days was slightly lower at hospitals with electronic health records.
Off-label use of the Lariat device for left atrial appendage exclusion to prevent stroke in patients with atrial fibrillation entails significant risks of adverse events, according to a study published online ahead of print May 4 in JAMA Internal Medicine. Investigators searched PubMed, EMBASE, CINAHL, and the Cochrane Library from January 2007 through August 2014 to identify all studies reporting use of the Lariat device in three or more patients. They queried the FDA MAUDE database for adverse events reports related to Lariat use. Five reports of Lariat device use in 309 participants were identified. The FDA MAUDE database contained 35 unique reports of adverse events with use of the Lariat device. Among these reports were five adverse event reports that noted pericardial effusion and death and an additional 23 that reported urgent cardiac surgery, but not death.
Insomnia is linked to functional and cognitive impairment among patients with shift work disorder, according to a study published April 15 in Journal of Clinical Sleep Medicine. The analysis included 34 night workers, 26 of whom were diagnosed with shift work disorder. Participants underwent an overnight laboratory protocol including a multiple sleep latency test (MSLT), an event-related brain potential (ERP) task, and various questionnaires. Participants reporting insomnia without sleepiness were the most impaired on the Endicott Work Productivity Scale (EWPS) and significantly more impaired than controls. Participants reporting insomnia and sleepiness were not statistically different from controls. Neither MSLT nor the Epworth Sleepiness Scale correlated with EWPS scores or ERP amplitudes. The mean of the Insomnia Severity Indices measurements, however, correlated with the EWPS.
The measurement of grip strength is a simple, inexpensive risk-stratifying method for all-cause death, cardiovascular death, and cardiovascular disease, according to a study published online ahead of print May 13 in Lancet. In the Prospective Urban-Rural Epidemiology study, researchers enrolled households that each included at least one member between ages 35 and 70. The investigators measured participants’ grip strength with a Jamar dynamometer. Median follow-up was four years. Grip strength was inversely associated with all-cause mortality, cardiovascular mortality, noncardiovascular mortality, myocardial infarction, and stroke. Grip strength was a stronger predictor of all-cause and cardiovascular mortality than systolic blood pressure was. The researchers found no significant association between grip strength and incident diabetes, risk of hospital admission for pneumonia or chronic obstructive pulmonary disease, injury from fall, or fracture.
Sleep deprivation is particularly problematic for decision-making involving uncertainty and unexpected change, according to a study published in the May issue of Sleep. Twenty-six subjects were randomized to 62 hours of total sleep deprivation or to a control condition. Researchers conducted performance testing at baseline, after two nights of total sleep deprivation or rested control, and following two nights of recovery sleep. Participants performed a decision task that involved initial learning of response sets and subsequent reversal of contingencies. Working memory and psychomotor vigilance tests also were administered. Sleep-deprived subjects had difficulty with initial learning of stimuli sets and profound impairment adapting to reversal. Skin conductance responses to outcome feedback were diminished, indicating blunted affective reactions to feedback accompanying sleep deprivation. Sleep deprivation did not significantly affect working memory scanning performance.
—Kimberly Williams
New and Noteworthy Information—May 2015
Chronic disease burden increases the risk of mild cognitive impairment (MCI), but certain lifestyle factors reduce the risk of MCI in people ages 85 and older, according to a study published online ahead of print April 8 in Neurology. Participants in the population-based prospective study were evaluated at baseline and at 15 monthly intervals to determine incident MCI. At baseline, lifestyle factors in midlife and late life were assessed, and vascular and comorbid conditions were abstracted from participants’ medical records. The risk of MCI was increased for participants with APOE ε4 allele or current depressive symptoms. The risk of MCI was reduced for participants who reported engagement in artistic, craft, and social activities in both midlife and late life, and those who reported the use of a computer in late life.
A new blood test may identify biomarkers for Parkinson’s disease more accurately than before, according to a study published online ahead of print March 18 in Movement Disorders. Researchers used a digital gene expression platform to quantify 175 mRNA markers with low coefficients of variation. They compared whole-blood transcript levels in mouse models overexpressing wild-type LRRK2, overexpressing G2019S LRRK2, lacking LRRK2, and wild-type controls. The investigators then studied a cohort of 34 symptomatic patients with Parkinson’s disease and 32 asymptomatic controls. The expression profiles distinguished the four mouse groups with different genetic backgrounds. Significant differences in blood transcript levels were found between individuals differing in LRRK2 genotype and between patients with Parkinson’s disease and controls. Thus, whole-blood mRNA signatures may correlate with LRRK2 genotype and Parkinson’s disease state.
There is a relationship between Alzheimer’s disease-related white matter alterations and impaired cognitive-motor control, according to a study published January 1 in Journal of Alzheimer’s Disease. Using diffusion-weighted MRI, researchers examined changes in white matter integrity associated with normal aging and increased Alzheimer’s disease risk, and assessed the relationship between these white matter alterations and cognitive-motor performance. The investigators found significant age-related declines in white matter integrity, which were more widespread in patients at high risk of Alzheimer’s disease, compared with those at low risk. Furthermore, an analysis of mean diffusivity measures within isolated white matter clusters revealed a stepwise decline in white matter integrity across young, low Alzheimer’s disease risk, and high Alzheimer’s disease risk groups. Investigators also observed that lower white matter integrity was associated with poorer cognitive-motor performance.
Researchers have developed mild cognitive impairment (MCI) risk scores using variables that are easily assessable in the clinical setting and that may be useful in routine patient care, according to a study published April 7 in Neurology. Investigators randomly selected people between ages 70 and 89 on October 1, 2004, for a population-based sample in a longitudinal cohort study. At baseline and subsequent visits, participants were evaluated for demographic, clinical, and neuropsychologic measures and were classified as cognitively normal, having MCI, or having dementia. Of 1,449 cognitively normal participants, 401 developed MCI. Both men and women in the highest versus lowest sex-specific quartiles of the augmented model’s risk scores had an approximately sevenfold higher risk of developing MCI. The presence of APOE ε4 carrier status improved the model.
The progression of dysfunctional tau protein may be the primary cause of cognitive decline and memory loss in Alzheimer’s disease, according to a study published online ahead of print March 23 in Brain. Researchers evaluated the correspondence of Thal amyloid phase to Braak tangle stage and ante mortem clinical characteristics in a large autopsy cohort. In the brain bank cohort of patients with a high likelihood of Alzheimer’s disease, samples with lower Thal amyloid phases were older at death, had a lower Braak tangle stage, and were less frequently APOE ε4 positive. Regression modeling in these samples with Alzheimer’s disease showed that Braak tangle stage, but not Thal amyloid phase, predicted age at onset, disease duration, and final Mini-Mental State Examination score.
A panel of blood biomarkers distinguishes accurately between patients with isolated concussion and uninjured individuals within the first eight hours after an accident, according to a study published online ahead of print in March 20 in Journal of Neurotrauma. Adult patients were enrolled in a study within 24 hours of concussion. Controls included uninjured people and patients with orthopedic injury. The investigators identified copeptin, galectin 3, matrix metalloproteinase 9, and occludin as biomarkers of concussion. A 3.4-fold decrease in plasma concentration of copeptin was found in patients with mild traumatic brain injury (mTBI) within eight hours after accident, compared with uninjured controls. Plasma levels of all biomarkers but copeptin increased by 3.6 to 4.5 times during the same time postinjury. The levels of at least two biomarkers were altered beyond their cutoff values in 90% of patients with mTBI.
Exploding head syndrome is relatively common in younger individuals, according to a study published online ahead of print March 13 in Journal of Sleep Research. Researchers assessed 211 undergraduate students for exploding head syndrome and isolated sleep paralysis using semistructured diagnostic interviews. A total of 18% of the sample population had exploding head syndrome during their lifetimes, and 16.60% of the population had recurrent cases of the syndrome. Exploding head syndrome affected both genders at equal rates, and investigators found it in 36.89% of participants who had been diagnosed with isolated sleep paralysis. Furthermore, exploding head syndrome episodes were accompanied by clinically significant levels of fear. For a minority of participants (2.80%), the fear was associated with clinically significant distress or impairment.
A distinctive pattern of abnormal protein deposits in the brain could help identify athletes with brain disorders, according to a study published online ahead of print April 6 in Proceedings of the National Academy of Science. Investigators used [F-18]FDDNP PET to detect brain patterns of neuropathology distribution in 14 retired professional football players with suspected chronic traumatic encephalopathy and compared results with those of 28 cognitively intact controls and 24 patients with Alzheimer’s dementia. The [F-18]FDDNP PET imaging results in retired players suggested the presence of the neuropathologic patterns consistent with models of concussion in which brainstem white matter tracts undergo early axonal damage and cumulative axonal injuries along subcortical, limbic, and cortical regions that support mood, emotions, and behavior. The pattern was distinct from that observed in Alzheimer’s disease.
A blood test could help identify women with fragile X syndrome who are at risk of dysexecutive and social anxiety symptoms, according to a study published online ahead of print March 25 in Neurology. Thirty-five women with FMR1 premutation between ages 22 and 55 and 35 age- and IQ-matched controls completed a range of executive function tests and self-reported symptoms of psychiatric disorders. The researchers found that FMR1 intron 1 methylation levels could help dichotomize women with the premutation into categories of greater and lesser risk. FMR1 intron 1 methylation and activation ratio were significantly correlated with the likelihood of probable dysexecutive or psychiatric symptoms. The significant relationships between methylation and social anxiety were mediated by executive function performance, but only in women with the premutation.
Targeted temperature management at 33 °C or 36 °C helps maintain good quality of life in patients with cardiac arrest, according to a study published online ahead of print April 6 in JAMA Neurology. Investigators studied 939 unconscious adults with cardiac arrest at 36 intensive care units. Patients were assigned to temperature management at 33 °C or 36 °C for 36 hours. Cognitive function was measured by Mini-Mental State Examination (MMSE). The median MMSE score was 14 for patients assigned to 33 °C and 17 for patients assigned to 36 °C. Approximately 19% of the 33 °C group and 18% of the 36 °C group reported needing help with everyday activities, and 66.5% in the 33 °C group versus 61.8% in the 36 °C group reported making a complete mental recovery.
Biracial population eligibility for r-tPA is similar by gender, according to a study published in the March issue of Stroke. The study included 1,837 patients with ischemic stroke who were age 18 or older and presented to 16 emergency departments in 2005. Eligibility for r-tPA and individual exclusion criteria were determined using 2013 American Heart Association and European Cooperative Acute Stroke Study III guidelines. The mean age was 72.2 for women and 66.1 for men. Eligibility for r-tPA was similar by sex, and adjusting the data for age did not alter this result. More women than men had severe hypertension, and the investigators found no gender differences in blood pressure treatment rates among patients with severe hypertension. More women were older than 80 and had an NIH Stroke Scale score greater than 25.
The brains of patients with traumatic brain injury (TBI) may appear to be older than their chronological age, according to a study published in the April issue of Annals of Neurology. A predictive model of normal aging was defined using machine learning in 1,537 healthy individuals, based on MRI-derived estimates of gray matter and white matter. Investigators used this aging model to estimate brain age for 99 patients with TBI and 113 healthy controls. Brains with TBI were estimated to be older, with a mean predicted age difference between chronological and estimated brain age of 4.66 years for gray matter and 5.97 years for white matter. The predicted age difference correlated strongly with the time since TBI, indicating that brain tissue loss increases throughout the chronic postinjury phase.
A combination of mental practice and physical therapy may help stroke survivors regain the strength of their motor behaviors, according to a study published March 30 in Frontiers in Human Neuroscience. The researchers recorded fMRI signals from 17 young healthy controls and 13 older stroke survivors. Participants with stroke underwent mental practice or both mental practice and physical therapy within 14 to 51 days following stroke. Investigators discovered that network activity was in the frequency range of 0.06 to 0.08 Hz for all brain regions studied and for controls and participants with stroke. Information flow between brain regions was reduced significantly for stroke survivors. The flow did not increase significantly after mental practice alone, but the flow among the regions during mental practice and physical therapy increased significantly.
—Kimberly Williams
Chronic disease burden increases the risk of mild cognitive impairment (MCI), but certain lifestyle factors reduce the risk of MCI in people ages 85 and older, according to a study published online ahead of print April 8 in Neurology. Participants in the population-based prospective study were evaluated at baseline and at 15 monthly intervals to determine incident MCI. At baseline, lifestyle factors in midlife and late life were assessed, and vascular and comorbid conditions were abstracted from participants’ medical records. The risk of MCI was increased for participants with APOE ε4 allele or current depressive symptoms. The risk of MCI was reduced for participants who reported engagement in artistic, craft, and social activities in both midlife and late life, and those who reported the use of a computer in late life.
A new blood test may identify biomarkers for Parkinson’s disease more accurately than before, according to a study published online ahead of print March 18 in Movement Disorders. Researchers used a digital gene expression platform to quantify 175 mRNA markers with low coefficients of variation. They compared whole-blood transcript levels in mouse models overexpressing wild-type LRRK2, overexpressing G2019S LRRK2, lacking LRRK2, and wild-type controls. The investigators then studied a cohort of 34 symptomatic patients with Parkinson’s disease and 32 asymptomatic controls. The expression profiles distinguished the four mouse groups with different genetic backgrounds. Significant differences in blood transcript levels were found between individuals differing in LRRK2 genotype and between patients with Parkinson’s disease and controls. Thus, whole-blood mRNA signatures may correlate with LRRK2 genotype and Parkinson’s disease state.
There is a relationship between Alzheimer’s disease-related white matter alterations and impaired cognitive-motor control, according to a study published January 1 in Journal of Alzheimer’s Disease. Using diffusion-weighted MRI, researchers examined changes in white matter integrity associated with normal aging and increased Alzheimer’s disease risk, and assessed the relationship between these white matter alterations and cognitive-motor performance. The investigators found significant age-related declines in white matter integrity, which were more widespread in patients at high risk of Alzheimer’s disease, compared with those at low risk. Furthermore, an analysis of mean diffusivity measures within isolated white matter clusters revealed a stepwise decline in white matter integrity across young, low Alzheimer’s disease risk, and high Alzheimer’s disease risk groups. Investigators also observed that lower white matter integrity was associated with poorer cognitive-motor performance.
Researchers have developed mild cognitive impairment (MCI) risk scores using variables that are easily assessable in the clinical setting and that may be useful in routine patient care, according to a study published April 7 in Neurology. Investigators randomly selected people between ages 70 and 89 on October 1, 2004, for a population-based sample in a longitudinal cohort study. At baseline and subsequent visits, participants were evaluated for demographic, clinical, and neuropsychologic measures and were classified as cognitively normal, having MCI, or having dementia. Of 1,449 cognitively normal participants, 401 developed MCI. Both men and women in the highest versus lowest sex-specific quartiles of the augmented model’s risk scores had an approximately sevenfold higher risk of developing MCI. The presence of APOE ε4 carrier status improved the model.
The progression of dysfunctional tau protein may be the primary cause of cognitive decline and memory loss in Alzheimer’s disease, according to a study published online ahead of print March 23 in Brain. Researchers evaluated the correspondence of Thal amyloid phase to Braak tangle stage and ante mortem clinical characteristics in a large autopsy cohort. In the brain bank cohort of patients with a high likelihood of Alzheimer’s disease, samples with lower Thal amyloid phases were older at death, had a lower Braak tangle stage, and were less frequently APOE ε4 positive. Regression modeling in these samples with Alzheimer’s disease showed that Braak tangle stage, but not Thal amyloid phase, predicted age at onset, disease duration, and final Mini-Mental State Examination score.
A panel of blood biomarkers distinguishes accurately between patients with isolated concussion and uninjured individuals within the first eight hours after an accident, according to a study published online ahead of print in March 20 in Journal of Neurotrauma. Adult patients were enrolled in a study within 24 hours of concussion. Controls included uninjured people and patients with orthopedic injury. The investigators identified copeptin, galectin 3, matrix metalloproteinase 9, and occludin as biomarkers of concussion. A 3.4-fold decrease in plasma concentration of copeptin was found in patients with mild traumatic brain injury (mTBI) within eight hours after accident, compared with uninjured controls. Plasma levels of all biomarkers but copeptin increased by 3.6 to 4.5 times during the same time postinjury. The levels of at least two biomarkers were altered beyond their cutoff values in 90% of patients with mTBI.
Exploding head syndrome is relatively common in younger individuals, according to a study published online ahead of print March 13 in Journal of Sleep Research. Researchers assessed 211 undergraduate students for exploding head syndrome and isolated sleep paralysis using semistructured diagnostic interviews. A total of 18% of the sample population had exploding head syndrome during their lifetimes, and 16.60% of the population had recurrent cases of the syndrome. Exploding head syndrome affected both genders at equal rates, and investigators found it in 36.89% of participants who had been diagnosed with isolated sleep paralysis. Furthermore, exploding head syndrome episodes were accompanied by clinically significant levels of fear. For a minority of participants (2.80%), the fear was associated with clinically significant distress or impairment.
A distinctive pattern of abnormal protein deposits in the brain could help identify athletes with brain disorders, according to a study published online ahead of print April 6 in Proceedings of the National Academy of Science. Investigators used [F-18]FDDNP PET to detect brain patterns of neuropathology distribution in 14 retired professional football players with suspected chronic traumatic encephalopathy and compared results with those of 28 cognitively intact controls and 24 patients with Alzheimer’s dementia. The [F-18]FDDNP PET imaging results in retired players suggested the presence of the neuropathologic patterns consistent with models of concussion in which brainstem white matter tracts undergo early axonal damage and cumulative axonal injuries along subcortical, limbic, and cortical regions that support mood, emotions, and behavior. The pattern was distinct from that observed in Alzheimer’s disease.
A blood test could help identify women with fragile X syndrome who are at risk of dysexecutive and social anxiety symptoms, according to a study published online ahead of print March 25 in Neurology. Thirty-five women with FMR1 premutation between ages 22 and 55 and 35 age- and IQ-matched controls completed a range of executive function tests and self-reported symptoms of psychiatric disorders. The researchers found that FMR1 intron 1 methylation levels could help dichotomize women with the premutation into categories of greater and lesser risk. FMR1 intron 1 methylation and activation ratio were significantly correlated with the likelihood of probable dysexecutive or psychiatric symptoms. The significant relationships between methylation and social anxiety were mediated by executive function performance, but only in women with the premutation.
Targeted temperature management at 33 °C or 36 °C helps maintain good quality of life in patients with cardiac arrest, according to a study published online ahead of print April 6 in JAMA Neurology. Investigators studied 939 unconscious adults with cardiac arrest at 36 intensive care units. Patients were assigned to temperature management at 33 °C or 36 °C for 36 hours. Cognitive function was measured by Mini-Mental State Examination (MMSE). The median MMSE score was 14 for patients assigned to 33 °C and 17 for patients assigned to 36 °C. Approximately 19% of the 33 °C group and 18% of the 36 °C group reported needing help with everyday activities, and 66.5% in the 33 °C group versus 61.8% in the 36 °C group reported making a complete mental recovery.
Biracial population eligibility for r-tPA is similar by gender, according to a study published in the March issue of Stroke. The study included 1,837 patients with ischemic stroke who were age 18 or older and presented to 16 emergency departments in 2005. Eligibility for r-tPA and individual exclusion criteria were determined using 2013 American Heart Association and European Cooperative Acute Stroke Study III guidelines. The mean age was 72.2 for women and 66.1 for men. Eligibility for r-tPA was similar by sex, and adjusting the data for age did not alter this result. More women than men had severe hypertension, and the investigators found no gender differences in blood pressure treatment rates among patients with severe hypertension. More women were older than 80 and had an NIH Stroke Scale score greater than 25.
The brains of patients with traumatic brain injury (TBI) may appear to be older than their chronological age, according to a study published in the April issue of Annals of Neurology. A predictive model of normal aging was defined using machine learning in 1,537 healthy individuals, based on MRI-derived estimates of gray matter and white matter. Investigators used this aging model to estimate brain age for 99 patients with TBI and 113 healthy controls. Brains with TBI were estimated to be older, with a mean predicted age difference between chronological and estimated brain age of 4.66 years for gray matter and 5.97 years for white matter. The predicted age difference correlated strongly with the time since TBI, indicating that brain tissue loss increases throughout the chronic postinjury phase.
A combination of mental practice and physical therapy may help stroke survivors regain the strength of their motor behaviors, according to a study published March 30 in Frontiers in Human Neuroscience. The researchers recorded fMRI signals from 17 young healthy controls and 13 older stroke survivors. Participants with stroke underwent mental practice or both mental practice and physical therapy within 14 to 51 days following stroke. Investigators discovered that network activity was in the frequency range of 0.06 to 0.08 Hz for all brain regions studied and for controls and participants with stroke. Information flow between brain regions was reduced significantly for stroke survivors. The flow did not increase significantly after mental practice alone, but the flow among the regions during mental practice and physical therapy increased significantly.
—Kimberly Williams
Chronic disease burden increases the risk of mild cognitive impairment (MCI), but certain lifestyle factors reduce the risk of MCI in people ages 85 and older, according to a study published online ahead of print April 8 in Neurology. Participants in the population-based prospective study were evaluated at baseline and at 15 monthly intervals to determine incident MCI. At baseline, lifestyle factors in midlife and late life were assessed, and vascular and comorbid conditions were abstracted from participants’ medical records. The risk of MCI was increased for participants with APOE ε4 allele or current depressive symptoms. The risk of MCI was reduced for participants who reported engagement in artistic, craft, and social activities in both midlife and late life, and those who reported the use of a computer in late life.
A new blood test may identify biomarkers for Parkinson’s disease more accurately than before, according to a study published online ahead of print March 18 in Movement Disorders. Researchers used a digital gene expression platform to quantify 175 mRNA markers with low coefficients of variation. They compared whole-blood transcript levels in mouse models overexpressing wild-type LRRK2, overexpressing G2019S LRRK2, lacking LRRK2, and wild-type controls. The investigators then studied a cohort of 34 symptomatic patients with Parkinson’s disease and 32 asymptomatic controls. The expression profiles distinguished the four mouse groups with different genetic backgrounds. Significant differences in blood transcript levels were found between individuals differing in LRRK2 genotype and between patients with Parkinson’s disease and controls. Thus, whole-blood mRNA signatures may correlate with LRRK2 genotype and Parkinson’s disease state.
There is a relationship between Alzheimer’s disease-related white matter alterations and impaired cognitive-motor control, according to a study published January 1 in Journal of Alzheimer’s Disease. Using diffusion-weighted MRI, researchers examined changes in white matter integrity associated with normal aging and increased Alzheimer’s disease risk, and assessed the relationship between these white matter alterations and cognitive-motor performance. The investigators found significant age-related declines in white matter integrity, which were more widespread in patients at high risk of Alzheimer’s disease, compared with those at low risk. Furthermore, an analysis of mean diffusivity measures within isolated white matter clusters revealed a stepwise decline in white matter integrity across young, low Alzheimer’s disease risk, and high Alzheimer’s disease risk groups. Investigators also observed that lower white matter integrity was associated with poorer cognitive-motor performance.
Researchers have developed mild cognitive impairment (MCI) risk scores using variables that are easily assessable in the clinical setting and that may be useful in routine patient care, according to a study published April 7 in Neurology. Investigators randomly selected people between ages 70 and 89 on October 1, 2004, for a population-based sample in a longitudinal cohort study. At baseline and subsequent visits, participants were evaluated for demographic, clinical, and neuropsychologic measures and were classified as cognitively normal, having MCI, or having dementia. Of 1,449 cognitively normal participants, 401 developed MCI. Both men and women in the highest versus lowest sex-specific quartiles of the augmented model’s risk scores had an approximately sevenfold higher risk of developing MCI. The presence of APOE ε4 carrier status improved the model.
The progression of dysfunctional tau protein may be the primary cause of cognitive decline and memory loss in Alzheimer’s disease, according to a study published online ahead of print March 23 in Brain. Researchers evaluated the correspondence of Thal amyloid phase to Braak tangle stage and ante mortem clinical characteristics in a large autopsy cohort. In the brain bank cohort of patients with a high likelihood of Alzheimer’s disease, samples with lower Thal amyloid phases were older at death, had a lower Braak tangle stage, and were less frequently APOE ε4 positive. Regression modeling in these samples with Alzheimer’s disease showed that Braak tangle stage, but not Thal amyloid phase, predicted age at onset, disease duration, and final Mini-Mental State Examination score.
A panel of blood biomarkers distinguishes accurately between patients with isolated concussion and uninjured individuals within the first eight hours after an accident, according to a study published online ahead of print in March 20 in Journal of Neurotrauma. Adult patients were enrolled in a study within 24 hours of concussion. Controls included uninjured people and patients with orthopedic injury. The investigators identified copeptin, galectin 3, matrix metalloproteinase 9, and occludin as biomarkers of concussion. A 3.4-fold decrease in plasma concentration of copeptin was found in patients with mild traumatic brain injury (mTBI) within eight hours after accident, compared with uninjured controls. Plasma levels of all biomarkers but copeptin increased by 3.6 to 4.5 times during the same time postinjury. The levels of at least two biomarkers were altered beyond their cutoff values in 90% of patients with mTBI.
Exploding head syndrome is relatively common in younger individuals, according to a study published online ahead of print March 13 in Journal of Sleep Research. Researchers assessed 211 undergraduate students for exploding head syndrome and isolated sleep paralysis using semistructured diagnostic interviews. A total of 18% of the sample population had exploding head syndrome during their lifetimes, and 16.60% of the population had recurrent cases of the syndrome. Exploding head syndrome affected both genders at equal rates, and investigators found it in 36.89% of participants who had been diagnosed with isolated sleep paralysis. Furthermore, exploding head syndrome episodes were accompanied by clinically significant levels of fear. For a minority of participants (2.80%), the fear was associated with clinically significant distress or impairment.
A distinctive pattern of abnormal protein deposits in the brain could help identify athletes with brain disorders, according to a study published online ahead of print April 6 in Proceedings of the National Academy of Science. Investigators used [F-18]FDDNP PET to detect brain patterns of neuropathology distribution in 14 retired professional football players with suspected chronic traumatic encephalopathy and compared results with those of 28 cognitively intact controls and 24 patients with Alzheimer’s dementia. The [F-18]FDDNP PET imaging results in retired players suggested the presence of the neuropathologic patterns consistent with models of concussion in which brainstem white matter tracts undergo early axonal damage and cumulative axonal injuries along subcortical, limbic, and cortical regions that support mood, emotions, and behavior. The pattern was distinct from that observed in Alzheimer’s disease.
A blood test could help identify women with fragile X syndrome who are at risk of dysexecutive and social anxiety symptoms, according to a study published online ahead of print March 25 in Neurology. Thirty-five women with FMR1 premutation between ages 22 and 55 and 35 age- and IQ-matched controls completed a range of executive function tests and self-reported symptoms of psychiatric disorders. The researchers found that FMR1 intron 1 methylation levels could help dichotomize women with the premutation into categories of greater and lesser risk. FMR1 intron 1 methylation and activation ratio were significantly correlated with the likelihood of probable dysexecutive or psychiatric symptoms. The significant relationships between methylation and social anxiety were mediated by executive function performance, but only in women with the premutation.
Targeted temperature management at 33 °C or 36 °C helps maintain good quality of life in patients with cardiac arrest, according to a study published online ahead of print April 6 in JAMA Neurology. Investigators studied 939 unconscious adults with cardiac arrest at 36 intensive care units. Patients were assigned to temperature management at 33 °C or 36 °C for 36 hours. Cognitive function was measured by Mini-Mental State Examination (MMSE). The median MMSE score was 14 for patients assigned to 33 °C and 17 for patients assigned to 36 °C. Approximately 19% of the 33 °C group and 18% of the 36 °C group reported needing help with everyday activities, and 66.5% in the 33 °C group versus 61.8% in the 36 °C group reported making a complete mental recovery.
Biracial population eligibility for r-tPA is similar by gender, according to a study published in the March issue of Stroke. The study included 1,837 patients with ischemic stroke who were age 18 or older and presented to 16 emergency departments in 2005. Eligibility for r-tPA and individual exclusion criteria were determined using 2013 American Heart Association and European Cooperative Acute Stroke Study III guidelines. The mean age was 72.2 for women and 66.1 for men. Eligibility for r-tPA was similar by sex, and adjusting the data for age did not alter this result. More women than men had severe hypertension, and the investigators found no gender differences in blood pressure treatment rates among patients with severe hypertension. More women were older than 80 and had an NIH Stroke Scale score greater than 25.
The brains of patients with traumatic brain injury (TBI) may appear to be older than their chronological age, according to a study published in the April issue of Annals of Neurology. A predictive model of normal aging was defined using machine learning in 1,537 healthy individuals, based on MRI-derived estimates of gray matter and white matter. Investigators used this aging model to estimate brain age for 99 patients with TBI and 113 healthy controls. Brains with TBI were estimated to be older, with a mean predicted age difference between chronological and estimated brain age of 4.66 years for gray matter and 5.97 years for white matter. The predicted age difference correlated strongly with the time since TBI, indicating that brain tissue loss increases throughout the chronic postinjury phase.
A combination of mental practice and physical therapy may help stroke survivors regain the strength of their motor behaviors, according to a study published March 30 in Frontiers in Human Neuroscience. The researchers recorded fMRI signals from 17 young healthy controls and 13 older stroke survivors. Participants with stroke underwent mental practice or both mental practice and physical therapy within 14 to 51 days following stroke. Investigators discovered that network activity was in the frequency range of 0.06 to 0.08 Hz for all brain regions studied and for controls and participants with stroke. Information flow between brain regions was reduced significantly for stroke survivors. The flow did not increase significantly after mental practice alone, but the flow among the regions during mental practice and physical therapy increased significantly.
—Kimberly Williams
New and Noteworthy Information—April 2015
Gout is inversely associated with the risk of developing Alzheimer’s disease, and uric acid may play a neuroprotective role, according to a study published March 4 in Annals of the Rheumatic Diseases. Researchers conducted a study using data from the Health Improvement Network, an electronic medical record database that is representative of the United Kingdom’s general population. Investigators identified 309 new cases of Alzheimer’s disease among 59,224 patients with gout (average age, 65) and 1,942 cases of Alzheimer’s disease among 238,805 people in the comparison group over a five-year follow up. After accounting for age, sex, BMI, socioeconomic status, lifestyle factors, prior heart conditions, and use of heart drugs, people with a history of gout had a 24% lower risk of developing Alzheimer’s disease.
In patients with ST-segment elevation myocardial infarction who are undergoing primary percutaneous coronary intervention (PCI), routine manual thrombectomy may not reduce the risk of cardiovascular death, compared with PCI alone, according to a study published online ahead of print March 16 in New England Journal of Medicine. In a randomized controlled trial that involved 10,732 patients at 87 hospitals in 20 countries, half of participants received PCI alone and half received PCI with manual thrombectomy. Death from cardiovascular causes, recurrent myocardial infarction, cardiogenic shock, or heart failure occurred within 180 days in 6.9% of the thrombectomy group and 7% of the PCI-alone group. “The message from this study is that thrombectomy should not be used as a routine strategy,” the researchers stated.
A broad range of pre-existing mental disorders are associated with the subsequent onset of severe or frequent headaches, according to a study published in the January issue of Journal of Pain. Researchers evaluated data from 19 World Health Organization World Mental Health Surveys completed by more than 50,000 subjects. The investigators looked at the association between pre-existing mood, anxiety, impulse control, and substance use disorders with subsequent onset of frequent or severe headaches. After adjusting for sex, age, and mental disorder comorbidity, the researchers found that mood, anxiety, and impulse control disorders increased the likelihood of developing severe and frequent headaches by 40%. Respondents with early-onset pre-existing mental disorders had a 21% higher risk for developing headaches than people with later-onset mental disorders.
Early symptoms of post-traumatic stress, such as anxiety, emotional numbness, flashbacks, and irritability, are the strongest predictors of later disability, according to a study published online ahead of print March 4 in Brain. The trial included 38 service members diagnosed with blast-related concussive traumatic brain injury and 34 service members without brain injury who volunteered to serve as controls. Early assessments of service members were conducted in Afghanistan during the first week after injury. Follow-up mental health assessments were conducted with standard interviews at six to 12 months afterward. Sixty-three percent of patients with brain injury were classified as moderately disabled, compared with 20% of people in the control group. The remaining 37% of the brain injury group were considered to have a good recovery.
Among teenagers, heavy marijuana use is associated with an abnormally shaped hippocampus and poor performance on long-term memory tasks, according to a study published online ahead of print March 11 in Hippocampus. Researchers examined 97 people, including matched groups of healthy controls, subjects with a marijuana use disorder, people with schizophrenia and no history of substance use disorders, and people with schizophrenia and a marijuana use disorder. Participants had started using marijuana daily between ages 16 and 17 and continued for about three years. Overall, the longer participants used marijuana, the more abnormal the shape of their hippocampus became. Young adults with schizophrenia who abused cannabis as teens also performed about 26% more poorly on memory tests than young adults with schizophrenia who never abused cannabis.
The combination of enalapril and folic acid, compared with enalapril alone, significantly reduces the risk of a first stroke in adults with hypertension, according to a study published online ahead of print March 15 in JAMA. Researchers randomized 20,702 adults with hypertension and no history of stroke or heart attack to daily treatment with a single-pill combination containing 10 mg of enalapril and 0.8 mg of folic acid or to a tablet containing 10 mg of enalapril alone. During a median treatment duration of 4.5 years, first stroke occurred in 282 participants in the enalapril–folic acid group, compared with 355 participants in the enalapril group. Analyses also showed significant reductions in the risk of ischemic stroke and cardiovascular events among participants in the enalapril– folic acid group.
Responsive direct cortical stimulation safely and effectively reduces seizures in adults with medically refractory partial onset seizures, according to a study published February 24 in Neurology. The results are part of an ongoing, seven-year, multicenter, prospective, open-label study to evaluate the long-term efficacy and safety of the RNS System. A total of 256 participants were implanted with the neurostimulator and leads. Seizure frequency decreased in the majority of participants treated with responsive stimulation. The median percent reduction in seizures was 44% at one year and 53% at two years postimplant. The median percent reduction in seizures was 60% at the beginning of year three and 66% at the beginning of year six. The responder rates at the same time points were 58% and 59%, respectively.
Persistent insomnia is associated with increased risk for all-cause and cardiopulmonary mortality and a steeper increase in inflammation, according to a study published March 12 in American Journal of Medicine. Researchers assessed the persistence of insomnia complaints in 1,409 adult participants from the Tucson Epidemiological Study of Airway Obstructive Disease. The study began in 1972 and included multiple follow-up surveys until 1996 and continuous mortality follow-up data until 2011. Using data from the survey from 1972 through 1973 and from the 1990 through 1992 follow-up survey, the researchers found that serum C-reactive protein (CRP) levels increased over time in people with persistent insomnia. In those subjects for whom CRP data were available, persistent insomnia was associated with a 58% increase in mortality risk, after adjustments for confounding factors.
Prolonged sleep is a potentially useful marker to determine increased future stroke risk in a healthy aging population, according to a study published online ahead of print February 25 in Neurology. Researchers followed 9,692 people with a mean age of 62 who had never had a stroke. Participants were asked about their sleeping habits once and then again four years later. The participants were followed for an average of 9.5 years, and 346 people had a stroke. Of the 986 people who slept more than eight hours per night, 52 had a stroke, compared with 211 of the 6,684 people who slept an average amount. The relationship between long sleep and stroke remained the same after researchers accounted for high cholesterol, high blood pressure, physical activity, and BMI.
Higher levels of physical activity may reduce the effects of white matter hyperintensity burden on motor function in healthy older adults, according to a study published online ahead of print March 11 in Neurology. Researchers examined 167 people (average age, 80) who wore movement monitors on their wrists for as long as 11 days to measure exercise and nonexercise activity. Participants also took 11 motor performance tests. For the people in the top 10% of activity, greater amounts of brain damage did not influence scores on the movement tests. However, for people in the less active half of the population, greater amounts of brain damage were associated with lower scores on the movement tests. For all participants, the average score on the movement tests was 1.04.
Patients with Parkinson’s disease have reduced low- and high-contrast visual acuity, compared with controls, according to a study published January 1 in Journal of Parkinson’s Disease. Thirty-two patients with Parkinson’s disease and 71 control subjects underwent a neurologic examination, which included the Unified Parkinson’s Disease Rating Scale and vision testing using the Variable Contrast Acuity Chart displayed on an iPad. The chart was displayed at low and high contrast at distances of 40 cm and 2 m. Based on the number of letters correctly identified, patients with Parkinson’s disease saw about 10% fewer letters than control subjects in the low-contrast tests at either distance and in the high-contrast tests at 2 m. Researchers found no significant difference between Parkinson’s disease and control subjects in the high-contrast testing at 40 cm.
Statins may not lower the risk for Parkinson’s disease, according to a study published online ahead of print January 14 in Movement Disorders. The researchers examined blood cholesterol levels, medications, and Parkinson’s disease status in participants in the ongoing, long-term Atherosclerosis Risk in Communities study. Cholesterol readings were taken at three-year intervals between 1987 and 1998. Statin use before 1998 was associated with significantly higher risk of Parkinson’s disease after 1998. Higher total cholesterol, however, was associated with lower risk for Parkinson’s disease after adjustment for statin use and confounders. Compared with the lowest tertile of average total cholesterol, the odds ratios for Parkinson’s disease were 0.56 for the second tertile and 0.43 for the third tertile. These data are inconsistent with the hypothesis that statins protect against Parkinson’s disease.
—Kimberly Williams
Gout is inversely associated with the risk of developing Alzheimer’s disease, and uric acid may play a neuroprotective role, according to a study published March 4 in Annals of the Rheumatic Diseases. Researchers conducted a study using data from the Health Improvement Network, an electronic medical record database that is representative of the United Kingdom’s general population. Investigators identified 309 new cases of Alzheimer’s disease among 59,224 patients with gout (average age, 65) and 1,942 cases of Alzheimer’s disease among 238,805 people in the comparison group over a five-year follow up. After accounting for age, sex, BMI, socioeconomic status, lifestyle factors, prior heart conditions, and use of heart drugs, people with a history of gout had a 24% lower risk of developing Alzheimer’s disease.
In patients with ST-segment elevation myocardial infarction who are undergoing primary percutaneous coronary intervention (PCI), routine manual thrombectomy may not reduce the risk of cardiovascular death, compared with PCI alone, according to a study published online ahead of print March 16 in New England Journal of Medicine. In a randomized controlled trial that involved 10,732 patients at 87 hospitals in 20 countries, half of participants received PCI alone and half received PCI with manual thrombectomy. Death from cardiovascular causes, recurrent myocardial infarction, cardiogenic shock, or heart failure occurred within 180 days in 6.9% of the thrombectomy group and 7% of the PCI-alone group. “The message from this study is that thrombectomy should not be used as a routine strategy,” the researchers stated.
A broad range of pre-existing mental disorders are associated with the subsequent onset of severe or frequent headaches, according to a study published in the January issue of Journal of Pain. Researchers evaluated data from 19 World Health Organization World Mental Health Surveys completed by more than 50,000 subjects. The investigators looked at the association between pre-existing mood, anxiety, impulse control, and substance use disorders with subsequent onset of frequent or severe headaches. After adjusting for sex, age, and mental disorder comorbidity, the researchers found that mood, anxiety, and impulse control disorders increased the likelihood of developing severe and frequent headaches by 40%. Respondents with early-onset pre-existing mental disorders had a 21% higher risk for developing headaches than people with later-onset mental disorders.
Early symptoms of post-traumatic stress, such as anxiety, emotional numbness, flashbacks, and irritability, are the strongest predictors of later disability, according to a study published online ahead of print March 4 in Brain. The trial included 38 service members diagnosed with blast-related concussive traumatic brain injury and 34 service members without brain injury who volunteered to serve as controls. Early assessments of service members were conducted in Afghanistan during the first week after injury. Follow-up mental health assessments were conducted with standard interviews at six to 12 months afterward. Sixty-three percent of patients with brain injury were classified as moderately disabled, compared with 20% of people in the control group. The remaining 37% of the brain injury group were considered to have a good recovery.
Among teenagers, heavy marijuana use is associated with an abnormally shaped hippocampus and poor performance on long-term memory tasks, according to a study published online ahead of print March 11 in Hippocampus. Researchers examined 97 people, including matched groups of healthy controls, subjects with a marijuana use disorder, people with schizophrenia and no history of substance use disorders, and people with schizophrenia and a marijuana use disorder. Participants had started using marijuana daily between ages 16 and 17 and continued for about three years. Overall, the longer participants used marijuana, the more abnormal the shape of their hippocampus became. Young adults with schizophrenia who abused cannabis as teens also performed about 26% more poorly on memory tests than young adults with schizophrenia who never abused cannabis.
The combination of enalapril and folic acid, compared with enalapril alone, significantly reduces the risk of a first stroke in adults with hypertension, according to a study published online ahead of print March 15 in JAMA. Researchers randomized 20,702 adults with hypertension and no history of stroke or heart attack to daily treatment with a single-pill combination containing 10 mg of enalapril and 0.8 mg of folic acid or to a tablet containing 10 mg of enalapril alone. During a median treatment duration of 4.5 years, first stroke occurred in 282 participants in the enalapril–folic acid group, compared with 355 participants in the enalapril group. Analyses also showed significant reductions in the risk of ischemic stroke and cardiovascular events among participants in the enalapril– folic acid group.
Responsive direct cortical stimulation safely and effectively reduces seizures in adults with medically refractory partial onset seizures, according to a study published February 24 in Neurology. The results are part of an ongoing, seven-year, multicenter, prospective, open-label study to evaluate the long-term efficacy and safety of the RNS System. A total of 256 participants were implanted with the neurostimulator and leads. Seizure frequency decreased in the majority of participants treated with responsive stimulation. The median percent reduction in seizures was 44% at one year and 53% at two years postimplant. The median percent reduction in seizures was 60% at the beginning of year three and 66% at the beginning of year six. The responder rates at the same time points were 58% and 59%, respectively.
Persistent insomnia is associated with increased risk for all-cause and cardiopulmonary mortality and a steeper increase in inflammation, according to a study published March 12 in American Journal of Medicine. Researchers assessed the persistence of insomnia complaints in 1,409 adult participants from the Tucson Epidemiological Study of Airway Obstructive Disease. The study began in 1972 and included multiple follow-up surveys until 1996 and continuous mortality follow-up data until 2011. Using data from the survey from 1972 through 1973 and from the 1990 through 1992 follow-up survey, the researchers found that serum C-reactive protein (CRP) levels increased over time in people with persistent insomnia. In those subjects for whom CRP data were available, persistent insomnia was associated with a 58% increase in mortality risk, after adjustments for confounding factors.
Prolonged sleep is a potentially useful marker to determine increased future stroke risk in a healthy aging population, according to a study published online ahead of print February 25 in Neurology. Researchers followed 9,692 people with a mean age of 62 who had never had a stroke. Participants were asked about their sleeping habits once and then again four years later. The participants were followed for an average of 9.5 years, and 346 people had a stroke. Of the 986 people who slept more than eight hours per night, 52 had a stroke, compared with 211 of the 6,684 people who slept an average amount. The relationship between long sleep and stroke remained the same after researchers accounted for high cholesterol, high blood pressure, physical activity, and BMI.
Higher levels of physical activity may reduce the effects of white matter hyperintensity burden on motor function in healthy older adults, according to a study published online ahead of print March 11 in Neurology. Researchers examined 167 people (average age, 80) who wore movement monitors on their wrists for as long as 11 days to measure exercise and nonexercise activity. Participants also took 11 motor performance tests. For the people in the top 10% of activity, greater amounts of brain damage did not influence scores on the movement tests. However, for people in the less active half of the population, greater amounts of brain damage were associated with lower scores on the movement tests. For all participants, the average score on the movement tests was 1.04.
Patients with Parkinson’s disease have reduced low- and high-contrast visual acuity, compared with controls, according to a study published January 1 in Journal of Parkinson’s Disease. Thirty-two patients with Parkinson’s disease and 71 control subjects underwent a neurologic examination, which included the Unified Parkinson’s Disease Rating Scale and vision testing using the Variable Contrast Acuity Chart displayed on an iPad. The chart was displayed at low and high contrast at distances of 40 cm and 2 m. Based on the number of letters correctly identified, patients with Parkinson’s disease saw about 10% fewer letters than control subjects in the low-contrast tests at either distance and in the high-contrast tests at 2 m. Researchers found no significant difference between Parkinson’s disease and control subjects in the high-contrast testing at 40 cm.
Statins may not lower the risk for Parkinson’s disease, according to a study published online ahead of print January 14 in Movement Disorders. The researchers examined blood cholesterol levels, medications, and Parkinson’s disease status in participants in the ongoing, long-term Atherosclerosis Risk in Communities study. Cholesterol readings were taken at three-year intervals between 1987 and 1998. Statin use before 1998 was associated with significantly higher risk of Parkinson’s disease after 1998. Higher total cholesterol, however, was associated with lower risk for Parkinson’s disease after adjustment for statin use and confounders. Compared with the lowest tertile of average total cholesterol, the odds ratios for Parkinson’s disease were 0.56 for the second tertile and 0.43 for the third tertile. These data are inconsistent with the hypothesis that statins protect against Parkinson’s disease.
—Kimberly Williams
Gout is inversely associated with the risk of developing Alzheimer’s disease, and uric acid may play a neuroprotective role, according to a study published March 4 in Annals of the Rheumatic Diseases. Researchers conducted a study using data from the Health Improvement Network, an electronic medical record database that is representative of the United Kingdom’s general population. Investigators identified 309 new cases of Alzheimer’s disease among 59,224 patients with gout (average age, 65) and 1,942 cases of Alzheimer’s disease among 238,805 people in the comparison group over a five-year follow up. After accounting for age, sex, BMI, socioeconomic status, lifestyle factors, prior heart conditions, and use of heart drugs, people with a history of gout had a 24% lower risk of developing Alzheimer’s disease.
In patients with ST-segment elevation myocardial infarction who are undergoing primary percutaneous coronary intervention (PCI), routine manual thrombectomy may not reduce the risk of cardiovascular death, compared with PCI alone, according to a study published online ahead of print March 16 in New England Journal of Medicine. In a randomized controlled trial that involved 10,732 patients at 87 hospitals in 20 countries, half of participants received PCI alone and half received PCI with manual thrombectomy. Death from cardiovascular causes, recurrent myocardial infarction, cardiogenic shock, or heart failure occurred within 180 days in 6.9% of the thrombectomy group and 7% of the PCI-alone group. “The message from this study is that thrombectomy should not be used as a routine strategy,” the researchers stated.
A broad range of pre-existing mental disorders are associated with the subsequent onset of severe or frequent headaches, according to a study published in the January issue of Journal of Pain. Researchers evaluated data from 19 World Health Organization World Mental Health Surveys completed by more than 50,000 subjects. The investigators looked at the association between pre-existing mood, anxiety, impulse control, and substance use disorders with subsequent onset of frequent or severe headaches. After adjusting for sex, age, and mental disorder comorbidity, the researchers found that mood, anxiety, and impulse control disorders increased the likelihood of developing severe and frequent headaches by 40%. Respondents with early-onset pre-existing mental disorders had a 21% higher risk for developing headaches than people with later-onset mental disorders.
Early symptoms of post-traumatic stress, such as anxiety, emotional numbness, flashbacks, and irritability, are the strongest predictors of later disability, according to a study published online ahead of print March 4 in Brain. The trial included 38 service members diagnosed with blast-related concussive traumatic brain injury and 34 service members without brain injury who volunteered to serve as controls. Early assessments of service members were conducted in Afghanistan during the first week after injury. Follow-up mental health assessments were conducted with standard interviews at six to 12 months afterward. Sixty-three percent of patients with brain injury were classified as moderately disabled, compared with 20% of people in the control group. The remaining 37% of the brain injury group were considered to have a good recovery.
Among teenagers, heavy marijuana use is associated with an abnormally shaped hippocampus and poor performance on long-term memory tasks, according to a study published online ahead of print March 11 in Hippocampus. Researchers examined 97 people, including matched groups of healthy controls, subjects with a marijuana use disorder, people with schizophrenia and no history of substance use disorders, and people with schizophrenia and a marijuana use disorder. Participants had started using marijuana daily between ages 16 and 17 and continued for about three years. Overall, the longer participants used marijuana, the more abnormal the shape of their hippocampus became. Young adults with schizophrenia who abused cannabis as teens also performed about 26% more poorly on memory tests than young adults with schizophrenia who never abused cannabis.
The combination of enalapril and folic acid, compared with enalapril alone, significantly reduces the risk of a first stroke in adults with hypertension, according to a study published online ahead of print March 15 in JAMA. Researchers randomized 20,702 adults with hypertension and no history of stroke or heart attack to daily treatment with a single-pill combination containing 10 mg of enalapril and 0.8 mg of folic acid or to a tablet containing 10 mg of enalapril alone. During a median treatment duration of 4.5 years, first stroke occurred in 282 participants in the enalapril–folic acid group, compared with 355 participants in the enalapril group. Analyses also showed significant reductions in the risk of ischemic stroke and cardiovascular events among participants in the enalapril– folic acid group.
Responsive direct cortical stimulation safely and effectively reduces seizures in adults with medically refractory partial onset seizures, according to a study published February 24 in Neurology. The results are part of an ongoing, seven-year, multicenter, prospective, open-label study to evaluate the long-term efficacy and safety of the RNS System. A total of 256 participants were implanted with the neurostimulator and leads. Seizure frequency decreased in the majority of participants treated with responsive stimulation. The median percent reduction in seizures was 44% at one year and 53% at two years postimplant. The median percent reduction in seizures was 60% at the beginning of year three and 66% at the beginning of year six. The responder rates at the same time points were 58% and 59%, respectively.
Persistent insomnia is associated with increased risk for all-cause and cardiopulmonary mortality and a steeper increase in inflammation, according to a study published March 12 in American Journal of Medicine. Researchers assessed the persistence of insomnia complaints in 1,409 adult participants from the Tucson Epidemiological Study of Airway Obstructive Disease. The study began in 1972 and included multiple follow-up surveys until 1996 and continuous mortality follow-up data until 2011. Using data from the survey from 1972 through 1973 and from the 1990 through 1992 follow-up survey, the researchers found that serum C-reactive protein (CRP) levels increased over time in people with persistent insomnia. In those subjects for whom CRP data were available, persistent insomnia was associated with a 58% increase in mortality risk, after adjustments for confounding factors.
Prolonged sleep is a potentially useful marker to determine increased future stroke risk in a healthy aging population, according to a study published online ahead of print February 25 in Neurology. Researchers followed 9,692 people with a mean age of 62 who had never had a stroke. Participants were asked about their sleeping habits once and then again four years later. The participants were followed for an average of 9.5 years, and 346 people had a stroke. Of the 986 people who slept more than eight hours per night, 52 had a stroke, compared with 211 of the 6,684 people who slept an average amount. The relationship between long sleep and stroke remained the same after researchers accounted for high cholesterol, high blood pressure, physical activity, and BMI.
Higher levels of physical activity may reduce the effects of white matter hyperintensity burden on motor function in healthy older adults, according to a study published online ahead of print March 11 in Neurology. Researchers examined 167 people (average age, 80) who wore movement monitors on their wrists for as long as 11 days to measure exercise and nonexercise activity. Participants also took 11 motor performance tests. For the people in the top 10% of activity, greater amounts of brain damage did not influence scores on the movement tests. However, for people in the less active half of the population, greater amounts of brain damage were associated with lower scores on the movement tests. For all participants, the average score on the movement tests was 1.04.
Patients with Parkinson’s disease have reduced low- and high-contrast visual acuity, compared with controls, according to a study published January 1 in Journal of Parkinson’s Disease. Thirty-two patients with Parkinson’s disease and 71 control subjects underwent a neurologic examination, which included the Unified Parkinson’s Disease Rating Scale and vision testing using the Variable Contrast Acuity Chart displayed on an iPad. The chart was displayed at low and high contrast at distances of 40 cm and 2 m. Based on the number of letters correctly identified, patients with Parkinson’s disease saw about 10% fewer letters than control subjects in the low-contrast tests at either distance and in the high-contrast tests at 2 m. Researchers found no significant difference between Parkinson’s disease and control subjects in the high-contrast testing at 40 cm.
Statins may not lower the risk for Parkinson’s disease, according to a study published online ahead of print January 14 in Movement Disorders. The researchers examined blood cholesterol levels, medications, and Parkinson’s disease status in participants in the ongoing, long-term Atherosclerosis Risk in Communities study. Cholesterol readings were taken at three-year intervals between 1987 and 1998. Statin use before 1998 was associated with significantly higher risk of Parkinson’s disease after 1998. Higher total cholesterol, however, was associated with lower risk for Parkinson’s disease after adjustment for statin use and confounders. Compared with the lowest tertile of average total cholesterol, the odds ratios for Parkinson’s disease were 0.56 for the second tertile and 0.43 for the third tertile. These data are inconsistent with the hypothesis that statins protect against Parkinson’s disease.
—Kimberly Williams
New and Noteworthy Information—March 2015
Moderate physical activity is associated with a lower risk of coronary heart disease, venous thromboembolic events, and cerebrovascular disease in women, according to a study published online ahead of print February 16 in Circulation. Participants included 1.1 million women in the United Kingdom with no history of cancer, heart disease, stroke, blood clots, or diabetes who joined the Million Women study between 1996 and 2001. Their average age when they joined the study was 56. Women who performed strenuous physical activity two to three times per week were 20% less likely to develop heart disease, strokes, or blood clots, compared with participants who reported little or no activity. More frequent physical activity did not result in further reductions in the risk of heart disease.
The FDA has approved Rytary, an extended-release oral capsule formulation of carbidopa–levodopa, for the treatment of Parkinson’s disease, post-encephalitic parkinsonism, and parkinsonism that may follow carbon monoxide intoxication or manganese intoxication. Rytary contains immediate-release and extended-release beads that contain carbidopa and levodopa in a 1:4 ratio, and provides initial and extended levodopa plasma concentrations after a single dose. In a trial of 393 randomized patients with advanced Parkinson’s disease, treatment with Rytary reduced the percentage of off time during waking hours from baseline to the end of the study, versus immediate-release carbidopa–levodopa. Rytary may be swallowed whole or opened, and the beads may be sprinkled on applesauce and consumed immediately. The drug is manufactured by Impax Pharmaceuticals (Hayward, California).
The FDA has approved Duopa, an enteral suspension of carbidopa and levodopa, as an orphan drug for the treatment of motor fluctuations in people with advanced Parkinson’s disease. The approval of Duopa is based on a phase III, 12-week, double-blind, double-placebo, active control, parallel-group, multicenter trial that compared the efficacy and safety of Duopa with that of oral, immediate-release carbidopa–levodopa tablets in patients with advanced Parkinson’s disease. Duopa significantly reduced daily mean off time at 12 weeks by four hours, which resulted in an average of 1.9 fewer hours of off time, when compared with carbidopa–levodopa tablets. Duopa is administered using a small, portable infusion pump that delivers carbidopa and levodopa directly into the small intestine continuously for 16 hours via a surgically-placed tube. The drug is manufactured by AbbVie (North Chicago, Illinois).
A link exists between brain structure and postconcussive symptoms among young male athletes who are otherwise healthy, according to a study published in the February issue of the Journal of Pediatrics. Researchers used advanced imaging technology and cognitive testing to assess 29 ice hockey players between ages 14 and 23, some of whom had a sports-related concussion. As the severity of the athletes’ concussion symptoms increased, the cortex became thinner in areas of the brain where it should be dense for players of these ages. Investigators believe that injury to a developing brain may be more severe than injury to an adult brain. “Years of playing contact sports and repeatedly getting your head knocked around probably is not good for the brain, especially in young children whose brains are still maturing,” the researchers stated.
Children whose urine drug screens tested positive for tetrahydrocannabinol (THC) met multiple sleep latency tests (MSLT) criteria for narcolepsy or had multiple sleep-onset REM periods, according to a study published January 15 in Journal of Clinical Sleep Medicine. The 10-year retrospective study included 383 children who underwent drug screens on the morning before MSLT. Of children with urine drug screens that were positive for marijuana, 43% had MSLT results consistent with narcolepsy or abnormal REM sleep patterns. Approximately 24% of children who tested negative for marijuana had MSLT results consistent with narcolepsy. No child younger than 13 had a positive urine drug screen. Males were more likely to have a positive urine drug screen and MSLT findings that were consistent with narcolepsy, compared with other groups.
Low plasma levels of APOE are associated with increased risk of future Alzheimer’s disease and all dementia in the general population, independent of ε2, ε3, and ε4 APOE genotype, according to a study published in the February issue of Annals of Neurology. The study included 75,708 participants. Multifactorially adjusted hazard ratios for lowest versus highest APOE tertile were 2.68 and 1.80 for Alzheimer’s disease and all dementia, respectively. After further adjustment for APOE genotype, plasma APOE tertiles remained associated with Alzheimer’s disease and all dementia. Researchers determined that the low level of APOE in the blood reflects a low level of APOE in the brain, indicating that β-amyloid is less effectively removed. Plasma levels of APOE may be a new, easily accessible preclinical biomarker, said the authors.
Women with Alzheimer’s disease had stable cognition for a year when they received leuprolide acetate, according to a study published in the January 1 issue of Journal of Alzheimer’s Disease. The clinical trial followed 109 women with mild to moderate Alzheimer’s disease who were randomized to low-dose leuprolide acetate, high-dose leuprolide acetate, or placebo. Among patients taking an acetylcholinesterase inhibitor, researchers saw a statistically significant benefit in the high-dose leuprolide acetate group, compared with the other groups, as determined by the Alzheimer’s Disease Assessment Scale-cognitive subscale. Mean decline was 0.18 for the high-dose group, 4.21 for the low-dose group, and 3.30 for the placebo group. “This is the first time any therapy has been shown to stabilize memory loss over a year,” the researchers said.
The rate of favorable seizure outcome or seizure freedom after resective epilepsy surgery is significant and remains stable for more than 15 years, according to a study published online ahead of print January 19 in Epilepsy & Behavior. The findings were based on a telephone survey of 253 patients who underwent resection to treat localization-related epilepsy during an 18-year period. The mean age at the time of surgery was 35.4, with a range from five months to 71. Investigators found that 92% of patients surveyed considered epilepsy surgery worthwhile, 32% were seizure-free, and 75% had favorable results. Favorable and seizure-free outcome rates remained stable after surgery over long-term follow-up. Compared with baseline, patients were more likely to be driving and taking antidepressant medication, but less likely to be employed full-time after surgery.
Nearly one in five adults with epilepsy has symptoms of attention deficit hyperactivity disorder (ADHD), which are associated with increased psychosocial morbidity and lowered quality of life, according to a study published online ahead of print January 15 in Epilepsia. In the study, researchers mailed a survey to a national sample of adult patients with epilepsy, as part of the Epilepsy Comorbidities and Health study. The relationship of ADHD symptoms to quality of life outcomes was examined using statistical analyses, which also looked at sociodemographics, depression, anxiety, seizure frequency, and number of antiepileptic drugs. Nearly one-fifth (18.4%) of 1,361 respondents with active epilepsy were classified as experiencing significant ADHD symptoms. “This study reinforces the fact that we have to broaden our view of what epilepsy entails,” said the investigators.
Triheptanoin corrects the bioenergetic profile in the brain of patients with Huntington’s disease early in the course of the disease, according to a study published online ahead of print January 7 in Neurology. Researchers used MRI brain scans to analyze the energy profile before, during, and after the brain was visually stimulated in nine people in the early stages of Huntington’s disease and 13 people without the disease. In the people without the disease, the brain’s metabolism increased during the stimulation, then returned to the normal level. In people with Huntington’s disease, there was no change in metabolism. For the second part of the study, participants with Huntington’s disease received triheptanoin. When these participants underwent the visual stimulation test again, their brain metabolism was normal.
A common gut microbe may curb the risk of developing multiple sclerosis (MS) in women, according to a study published online ahead of print January 19 in the Journal of Neurology, Neurosurgery & Psychiatry. Researchers tested 550 people with confirmed MS and a comparison group of 299 healthy people, matched for age and sex, for antibodies to H. pylori between 2007 and 2011. The prevalence of the infection was significantly lower in participants with MS than in the comparison group, but only among women, in whom it was 30% lower. Among men, a positive test result was linked to higher rates of disability, but a positive test was associated with lower disability among women. The researchers found no evidence of any link between the presence of the infection and relapse rate.
Among patients with relapsing-remitting multiple sclerosis (MS), nonmyeloablative hematopoietic stem cell transplantation is associated with improvement in neurologic disability and other clinical outcomes, according to a study published January 20 in JAMA. In a case series of patients with relapsing-remitting MS or secondary progressive MS, participants received transplantation and were followed up for five years. In all, 41 patients (50%) had significant improvement in Expanded Disability Status Scale score at two years, and 23 patients (64%) had significant improvement at four years. Receipt of hematopoietic stem cell transplantation was associated with improvement in physical function, cognitive function, and quality of life. In addition, treatment was associated with a reduction in the volume of brain lesions associated with MS seen on MRI.
Insomnia in childhood and adolescence partially results from genetic factors, according to a study published in the January issue of Sleep. The study group included 1,412 twin pairs between the ages of 8 and 18. Participants were followed-up at three time points. The average ages at each of the four stages of the study were 8, 10, 14, and 15. The results showed that clinically significant insomnia was moderately heritable at all stages of the longitudinal study. Genetic factors contributed 33% to 38% of the insomnia ratings at the first two stages of the study, when participants were an average age of 8 to 10. “Insomnia in youth is moderately related to genetic factors, but the specific genetic factors may change with age,” stated the investigators.
People with epilepsy who sleep on their stomach may be at a higher risk of sudden unexpected death, according to a literature review published online ahead of print January 21 in Neurology. Researchers found that 73% of the deaths occurred while individuals were sleeping on their stomachs, compared with 27% of deaths that occurred during other sleep positions. In a subgroup of 88 people, researchers found that people younger than 40 were four times more likely to be found on their stomach at the time of sudden death than people older than 40. A total of 86% of those under 40 slept on their stomach, compared with 60% of people older than 40. Eleven sudden deaths occurred while the participants were being monitored with video EEG.
—Kimberly D. Williams
Moderate physical activity is associated with a lower risk of coronary heart disease, venous thromboembolic events, and cerebrovascular disease in women, according to a study published online ahead of print February 16 in Circulation. Participants included 1.1 million women in the United Kingdom with no history of cancer, heart disease, stroke, blood clots, or diabetes who joined the Million Women study between 1996 and 2001. Their average age when they joined the study was 56. Women who performed strenuous physical activity two to three times per week were 20% less likely to develop heart disease, strokes, or blood clots, compared with participants who reported little or no activity. More frequent physical activity did not result in further reductions in the risk of heart disease.
The FDA has approved Rytary, an extended-release oral capsule formulation of carbidopa–levodopa, for the treatment of Parkinson’s disease, post-encephalitic parkinsonism, and parkinsonism that may follow carbon monoxide intoxication or manganese intoxication. Rytary contains immediate-release and extended-release beads that contain carbidopa and levodopa in a 1:4 ratio, and provides initial and extended levodopa plasma concentrations after a single dose. In a trial of 393 randomized patients with advanced Parkinson’s disease, treatment with Rytary reduced the percentage of off time during waking hours from baseline to the end of the study, versus immediate-release carbidopa–levodopa. Rytary may be swallowed whole or opened, and the beads may be sprinkled on applesauce and consumed immediately. The drug is manufactured by Impax Pharmaceuticals (Hayward, California).
The FDA has approved Duopa, an enteral suspension of carbidopa and levodopa, as an orphan drug for the treatment of motor fluctuations in people with advanced Parkinson’s disease. The approval of Duopa is based on a phase III, 12-week, double-blind, double-placebo, active control, parallel-group, multicenter trial that compared the efficacy and safety of Duopa with that of oral, immediate-release carbidopa–levodopa tablets in patients with advanced Parkinson’s disease. Duopa significantly reduced daily mean off time at 12 weeks by four hours, which resulted in an average of 1.9 fewer hours of off time, when compared with carbidopa–levodopa tablets. Duopa is administered using a small, portable infusion pump that delivers carbidopa and levodopa directly into the small intestine continuously for 16 hours via a surgically-placed tube. The drug is manufactured by AbbVie (North Chicago, Illinois).
A link exists between brain structure and postconcussive symptoms among young male athletes who are otherwise healthy, according to a study published in the February issue of the Journal of Pediatrics. Researchers used advanced imaging technology and cognitive testing to assess 29 ice hockey players between ages 14 and 23, some of whom had a sports-related concussion. As the severity of the athletes’ concussion symptoms increased, the cortex became thinner in areas of the brain where it should be dense for players of these ages. Investigators believe that injury to a developing brain may be more severe than injury to an adult brain. “Years of playing contact sports and repeatedly getting your head knocked around probably is not good for the brain, especially in young children whose brains are still maturing,” the researchers stated.
Children whose urine drug screens tested positive for tetrahydrocannabinol (THC) met multiple sleep latency tests (MSLT) criteria for narcolepsy or had multiple sleep-onset REM periods, according to a study published January 15 in Journal of Clinical Sleep Medicine. The 10-year retrospective study included 383 children who underwent drug screens on the morning before MSLT. Of children with urine drug screens that were positive for marijuana, 43% had MSLT results consistent with narcolepsy or abnormal REM sleep patterns. Approximately 24% of children who tested negative for marijuana had MSLT results consistent with narcolepsy. No child younger than 13 had a positive urine drug screen. Males were more likely to have a positive urine drug screen and MSLT findings that were consistent with narcolepsy, compared with other groups.
Low plasma levels of APOE are associated with increased risk of future Alzheimer’s disease and all dementia in the general population, independent of ε2, ε3, and ε4 APOE genotype, according to a study published in the February issue of Annals of Neurology. The study included 75,708 participants. Multifactorially adjusted hazard ratios for lowest versus highest APOE tertile were 2.68 and 1.80 for Alzheimer’s disease and all dementia, respectively. After further adjustment for APOE genotype, plasma APOE tertiles remained associated with Alzheimer’s disease and all dementia. Researchers determined that the low level of APOE in the blood reflects a low level of APOE in the brain, indicating that β-amyloid is less effectively removed. Plasma levels of APOE may be a new, easily accessible preclinical biomarker, said the authors.
Women with Alzheimer’s disease had stable cognition for a year when they received leuprolide acetate, according to a study published in the January 1 issue of Journal of Alzheimer’s Disease. The clinical trial followed 109 women with mild to moderate Alzheimer’s disease who were randomized to low-dose leuprolide acetate, high-dose leuprolide acetate, or placebo. Among patients taking an acetylcholinesterase inhibitor, researchers saw a statistically significant benefit in the high-dose leuprolide acetate group, compared with the other groups, as determined by the Alzheimer’s Disease Assessment Scale-cognitive subscale. Mean decline was 0.18 for the high-dose group, 4.21 for the low-dose group, and 3.30 for the placebo group. “This is the first time any therapy has been shown to stabilize memory loss over a year,” the researchers said.
The rate of favorable seizure outcome or seizure freedom after resective epilepsy surgery is significant and remains stable for more than 15 years, according to a study published online ahead of print January 19 in Epilepsy & Behavior. The findings were based on a telephone survey of 253 patients who underwent resection to treat localization-related epilepsy during an 18-year period. The mean age at the time of surgery was 35.4, with a range from five months to 71. Investigators found that 92% of patients surveyed considered epilepsy surgery worthwhile, 32% were seizure-free, and 75% had favorable results. Favorable and seizure-free outcome rates remained stable after surgery over long-term follow-up. Compared with baseline, patients were more likely to be driving and taking antidepressant medication, but less likely to be employed full-time after surgery.
Nearly one in five adults with epilepsy has symptoms of attention deficit hyperactivity disorder (ADHD), which are associated with increased psychosocial morbidity and lowered quality of life, according to a study published online ahead of print January 15 in Epilepsia. In the study, researchers mailed a survey to a national sample of adult patients with epilepsy, as part of the Epilepsy Comorbidities and Health study. The relationship of ADHD symptoms to quality of life outcomes was examined using statistical analyses, which also looked at sociodemographics, depression, anxiety, seizure frequency, and number of antiepileptic drugs. Nearly one-fifth (18.4%) of 1,361 respondents with active epilepsy were classified as experiencing significant ADHD symptoms. “This study reinforces the fact that we have to broaden our view of what epilepsy entails,” said the investigators.
Triheptanoin corrects the bioenergetic profile in the brain of patients with Huntington’s disease early in the course of the disease, according to a study published online ahead of print January 7 in Neurology. Researchers used MRI brain scans to analyze the energy profile before, during, and after the brain was visually stimulated in nine people in the early stages of Huntington’s disease and 13 people without the disease. In the people without the disease, the brain’s metabolism increased during the stimulation, then returned to the normal level. In people with Huntington’s disease, there was no change in metabolism. For the second part of the study, participants with Huntington’s disease received triheptanoin. When these participants underwent the visual stimulation test again, their brain metabolism was normal.
A common gut microbe may curb the risk of developing multiple sclerosis (MS) in women, according to a study published online ahead of print January 19 in the Journal of Neurology, Neurosurgery & Psychiatry. Researchers tested 550 people with confirmed MS and a comparison group of 299 healthy people, matched for age and sex, for antibodies to H. pylori between 2007 and 2011. The prevalence of the infection was significantly lower in participants with MS than in the comparison group, but only among women, in whom it was 30% lower. Among men, a positive test result was linked to higher rates of disability, but a positive test was associated with lower disability among women. The researchers found no evidence of any link between the presence of the infection and relapse rate.
Among patients with relapsing-remitting multiple sclerosis (MS), nonmyeloablative hematopoietic stem cell transplantation is associated with improvement in neurologic disability and other clinical outcomes, according to a study published January 20 in JAMA. In a case series of patients with relapsing-remitting MS or secondary progressive MS, participants received transplantation and were followed up for five years. In all, 41 patients (50%) had significant improvement in Expanded Disability Status Scale score at two years, and 23 patients (64%) had significant improvement at four years. Receipt of hematopoietic stem cell transplantation was associated with improvement in physical function, cognitive function, and quality of life. In addition, treatment was associated with a reduction in the volume of brain lesions associated with MS seen on MRI.
Insomnia in childhood and adolescence partially results from genetic factors, according to a study published in the January issue of Sleep. The study group included 1,412 twin pairs between the ages of 8 and 18. Participants were followed-up at three time points. The average ages at each of the four stages of the study were 8, 10, 14, and 15. The results showed that clinically significant insomnia was moderately heritable at all stages of the longitudinal study. Genetic factors contributed 33% to 38% of the insomnia ratings at the first two stages of the study, when participants were an average age of 8 to 10. “Insomnia in youth is moderately related to genetic factors, but the specific genetic factors may change with age,” stated the investigators.
People with epilepsy who sleep on their stomach may be at a higher risk of sudden unexpected death, according to a literature review published online ahead of print January 21 in Neurology. Researchers found that 73% of the deaths occurred while individuals were sleeping on their stomachs, compared with 27% of deaths that occurred during other sleep positions. In a subgroup of 88 people, researchers found that people younger than 40 were four times more likely to be found on their stomach at the time of sudden death than people older than 40. A total of 86% of those under 40 slept on their stomach, compared with 60% of people older than 40. Eleven sudden deaths occurred while the participants were being monitored with video EEG.
—Kimberly D. Williams
Moderate physical activity is associated with a lower risk of coronary heart disease, venous thromboembolic events, and cerebrovascular disease in women, according to a study published online ahead of print February 16 in Circulation. Participants included 1.1 million women in the United Kingdom with no history of cancer, heart disease, stroke, blood clots, or diabetes who joined the Million Women study between 1996 and 2001. Their average age when they joined the study was 56. Women who performed strenuous physical activity two to three times per week were 20% less likely to develop heart disease, strokes, or blood clots, compared with participants who reported little or no activity. More frequent physical activity did not result in further reductions in the risk of heart disease.
The FDA has approved Rytary, an extended-release oral capsule formulation of carbidopa–levodopa, for the treatment of Parkinson’s disease, post-encephalitic parkinsonism, and parkinsonism that may follow carbon monoxide intoxication or manganese intoxication. Rytary contains immediate-release and extended-release beads that contain carbidopa and levodopa in a 1:4 ratio, and provides initial and extended levodopa plasma concentrations after a single dose. In a trial of 393 randomized patients with advanced Parkinson’s disease, treatment with Rytary reduced the percentage of off time during waking hours from baseline to the end of the study, versus immediate-release carbidopa–levodopa. Rytary may be swallowed whole or opened, and the beads may be sprinkled on applesauce and consumed immediately. The drug is manufactured by Impax Pharmaceuticals (Hayward, California).
The FDA has approved Duopa, an enteral suspension of carbidopa and levodopa, as an orphan drug for the treatment of motor fluctuations in people with advanced Parkinson’s disease. The approval of Duopa is based on a phase III, 12-week, double-blind, double-placebo, active control, parallel-group, multicenter trial that compared the efficacy and safety of Duopa with that of oral, immediate-release carbidopa–levodopa tablets in patients with advanced Parkinson’s disease. Duopa significantly reduced daily mean off time at 12 weeks by four hours, which resulted in an average of 1.9 fewer hours of off time, when compared with carbidopa–levodopa tablets. Duopa is administered using a small, portable infusion pump that delivers carbidopa and levodopa directly into the small intestine continuously for 16 hours via a surgically-placed tube. The drug is manufactured by AbbVie (North Chicago, Illinois).
A link exists between brain structure and postconcussive symptoms among young male athletes who are otherwise healthy, according to a study published in the February issue of the Journal of Pediatrics. Researchers used advanced imaging technology and cognitive testing to assess 29 ice hockey players between ages 14 and 23, some of whom had a sports-related concussion. As the severity of the athletes’ concussion symptoms increased, the cortex became thinner in areas of the brain where it should be dense for players of these ages. Investigators believe that injury to a developing brain may be more severe than injury to an adult brain. “Years of playing contact sports and repeatedly getting your head knocked around probably is not good for the brain, especially in young children whose brains are still maturing,” the researchers stated.
Children whose urine drug screens tested positive for tetrahydrocannabinol (THC) met multiple sleep latency tests (MSLT) criteria for narcolepsy or had multiple sleep-onset REM periods, according to a study published January 15 in Journal of Clinical Sleep Medicine. The 10-year retrospective study included 383 children who underwent drug screens on the morning before MSLT. Of children with urine drug screens that were positive for marijuana, 43% had MSLT results consistent with narcolepsy or abnormal REM sleep patterns. Approximately 24% of children who tested negative for marijuana had MSLT results consistent with narcolepsy. No child younger than 13 had a positive urine drug screen. Males were more likely to have a positive urine drug screen and MSLT findings that were consistent with narcolepsy, compared with other groups.
Low plasma levels of APOE are associated with increased risk of future Alzheimer’s disease and all dementia in the general population, independent of ε2, ε3, and ε4 APOE genotype, according to a study published in the February issue of Annals of Neurology. The study included 75,708 participants. Multifactorially adjusted hazard ratios for lowest versus highest APOE tertile were 2.68 and 1.80 for Alzheimer’s disease and all dementia, respectively. After further adjustment for APOE genotype, plasma APOE tertiles remained associated with Alzheimer’s disease and all dementia. Researchers determined that the low level of APOE in the blood reflects a low level of APOE in the brain, indicating that β-amyloid is less effectively removed. Plasma levels of APOE may be a new, easily accessible preclinical biomarker, said the authors.
Women with Alzheimer’s disease had stable cognition for a year when they received leuprolide acetate, according to a study published in the January 1 issue of Journal of Alzheimer’s Disease. The clinical trial followed 109 women with mild to moderate Alzheimer’s disease who were randomized to low-dose leuprolide acetate, high-dose leuprolide acetate, or placebo. Among patients taking an acetylcholinesterase inhibitor, researchers saw a statistically significant benefit in the high-dose leuprolide acetate group, compared with the other groups, as determined by the Alzheimer’s Disease Assessment Scale-cognitive subscale. Mean decline was 0.18 for the high-dose group, 4.21 for the low-dose group, and 3.30 for the placebo group. “This is the first time any therapy has been shown to stabilize memory loss over a year,” the researchers said.
The rate of favorable seizure outcome or seizure freedom after resective epilepsy surgery is significant and remains stable for more than 15 years, according to a study published online ahead of print January 19 in Epilepsy & Behavior. The findings were based on a telephone survey of 253 patients who underwent resection to treat localization-related epilepsy during an 18-year period. The mean age at the time of surgery was 35.4, with a range from five months to 71. Investigators found that 92% of patients surveyed considered epilepsy surgery worthwhile, 32% were seizure-free, and 75% had favorable results. Favorable and seizure-free outcome rates remained stable after surgery over long-term follow-up. Compared with baseline, patients were more likely to be driving and taking antidepressant medication, but less likely to be employed full-time after surgery.
Nearly one in five adults with epilepsy has symptoms of attention deficit hyperactivity disorder (ADHD), which are associated with increased psychosocial morbidity and lowered quality of life, according to a study published online ahead of print January 15 in Epilepsia. In the study, researchers mailed a survey to a national sample of adult patients with epilepsy, as part of the Epilepsy Comorbidities and Health study. The relationship of ADHD symptoms to quality of life outcomes was examined using statistical analyses, which also looked at sociodemographics, depression, anxiety, seizure frequency, and number of antiepileptic drugs. Nearly one-fifth (18.4%) of 1,361 respondents with active epilepsy were classified as experiencing significant ADHD symptoms. “This study reinforces the fact that we have to broaden our view of what epilepsy entails,” said the investigators.
Triheptanoin corrects the bioenergetic profile in the brain of patients with Huntington’s disease early in the course of the disease, according to a study published online ahead of print January 7 in Neurology. Researchers used MRI brain scans to analyze the energy profile before, during, and after the brain was visually stimulated in nine people in the early stages of Huntington’s disease and 13 people without the disease. In the people without the disease, the brain’s metabolism increased during the stimulation, then returned to the normal level. In people with Huntington’s disease, there was no change in metabolism. For the second part of the study, participants with Huntington’s disease received triheptanoin. When these participants underwent the visual stimulation test again, their brain metabolism was normal.
A common gut microbe may curb the risk of developing multiple sclerosis (MS) in women, according to a study published online ahead of print January 19 in the Journal of Neurology, Neurosurgery & Psychiatry. Researchers tested 550 people with confirmed MS and a comparison group of 299 healthy people, matched for age and sex, for antibodies to H. pylori between 2007 and 2011. The prevalence of the infection was significantly lower in participants with MS than in the comparison group, but only among women, in whom it was 30% lower. Among men, a positive test result was linked to higher rates of disability, but a positive test was associated with lower disability among women. The researchers found no evidence of any link between the presence of the infection and relapse rate.
Among patients with relapsing-remitting multiple sclerosis (MS), nonmyeloablative hematopoietic stem cell transplantation is associated with improvement in neurologic disability and other clinical outcomes, according to a study published January 20 in JAMA. In a case series of patients with relapsing-remitting MS or secondary progressive MS, participants received transplantation and were followed up for five years. In all, 41 patients (50%) had significant improvement in Expanded Disability Status Scale score at two years, and 23 patients (64%) had significant improvement at four years. Receipt of hematopoietic stem cell transplantation was associated with improvement in physical function, cognitive function, and quality of life. In addition, treatment was associated with a reduction in the volume of brain lesions associated with MS seen on MRI.
Insomnia in childhood and adolescence partially results from genetic factors, according to a study published in the January issue of Sleep. The study group included 1,412 twin pairs between the ages of 8 and 18. Participants were followed-up at three time points. The average ages at each of the four stages of the study were 8, 10, 14, and 15. The results showed that clinically significant insomnia was moderately heritable at all stages of the longitudinal study. Genetic factors contributed 33% to 38% of the insomnia ratings at the first two stages of the study, when participants were an average age of 8 to 10. “Insomnia in youth is moderately related to genetic factors, but the specific genetic factors may change with age,” stated the investigators.
People with epilepsy who sleep on their stomach may be at a higher risk of sudden unexpected death, according to a literature review published online ahead of print January 21 in Neurology. Researchers found that 73% of the deaths occurred while individuals were sleeping on their stomachs, compared with 27% of deaths that occurred during other sleep positions. In a subgroup of 88 people, researchers found that people younger than 40 were four times more likely to be found on their stomach at the time of sudden death than people older than 40. A total of 86% of those under 40 slept on their stomach, compared with 60% of people older than 40. Eleven sudden deaths occurred while the participants were being monitored with video EEG.
—Kimberly D. Williams
New and Noteworthy Information—February 2015
The human papillomavirus (HPV) vaccination is not associated with the development of multiple sclerosis (MS) or other demyelinating diseases, according to a study published January 6 in JAMA. Researchers examined Danish and Swedish girls and women between ages 10 and 44. Participants were followed up from 2006 to 2013. A total of 3,983,824 girls and women were eligible for inclusion in this study. Of these individuals, 789,082 were vaccinated, and 1,927,581 HPV vaccine doses were administered. At follow-up, 4,322 cases of MS and 3,300 cases of other demyelinating diseases were identified, of which 73 and 90, respectively, occurred within the risk period of two years following vaccination. “These findings do not support concerns about a causal relationship between HPV vaccination and demyelinating diseases,” the researchers stated.
No evidence of disease activity (NEDA) is a difficult outcome for patients with multiple sclerosis (MS) to sustain in the long term, even with treatment, according to a study published online ahead of print December 22 in JAMA Neurology. Researchers investigated the sustainability of NEDA over seven years in a group of 219 patients with MS. Patients had seven years of follow-up that included yearly brain MRI and biannual clinic visits. Investigators found that of 215 patients, 99 (46%) had NEDA for clinical and MRI measures at one year. At two years, 60 of 218 patients (27.5%) maintained NEDA, and 17 of 216 patients (7.9%) sustained NEDA after seven years. There was no difference in NEDA status for patients with early MS, compared with patients with more established disease.
Pharnext announced the proof of concept of its pleotherapy research and development approach based on a proprietary network pharmacology platform that identifies synergistic combinations of drugs already approved for other diseases. According to two reports published online December 10, 2014, in the Orphanet Journal of Rare Diseases, Pharnext’s lead pleodrug, PXT-3003, has shown positive results in preclinical and phase 2 clinical studies. The first paper shows consistent and synergistic preclinical data for PXT-3003 in two Charcot–Marie–Tooth disease type 1A (CMT 1A) rodent models. The second paper presents positive phase 2 results of PXT-3003 in 80 patients with mild to moderate CMT 1A.
Patients with acute ischemic stroke admitted to tertiary stroke centers during July had similar outcomes to patients admitted during other months, despite receiving slightly less frequent thrombolysis and stroke unit care, according to a study published online ahead of print December 19 in the Journal of Stroke and Cerebrovascular Diseases. Researchers examined 10,319 patients with acute ischemic stroke between July 1, 2003 and March 31, 2008. The research team evaluated referrals to long-term care facilities, length of hospital stay, hospital readmissions or emergency department visits within 30 days of hospital discharge, and hospital readmissions within 30 days from discharge due to stroke. “Ischemic stroke patients admitted in July were less likely to receive clot-busting drugs or be admitted to stroke units, but ultimately patients did just as well regardless of the month,” stated the investigators.
Insomnia symptoms are an important factor for explaining the mechanism by which alcohol use increases suicide risk, according to a study published December 15 in the Journal of Clinical Sleep Medicine. The study included 375 undergraduate students at a large, public university in the southeastern United States. Participants completed an online questionnaire that examined insomnia symptoms, nightmares, alcohol use, and suicide risk. Alcohol use was significantly associated with suicide risk among women. In addition, further analysis revealed that insomnia symptoms explained a significant proportion of the relationship between alcohol and suicide risk. Investigators found no direct effect of alcohol use on suicide risk in men, but they observed a significant indirect effect of alcohol use increasing suicide risk through insomnia symptoms.
The virtual supermarket (VSM) application correctly identifies 87.30% of patients with mild cognitive impairment (MCI), a level of diagnostic accuracy similar to that of standardized neuropsychologic tests, according to a study published online ahead of print November 25 in the Journal of Alzheimer’s Disease. Two groups, one of healthy older adults and one of patients with MCI, were recruited from day centers for people with cognitive disorders. Participants used the VSM application and underwent a battery of neuropsychologic tests. The VSM application accurately distinguished between patients with MCI and healthy older adults, but it was unable to differentiate between MCI subtypes. Overall, the VSM application is a valid method of screening for MCI in an older adult population, but it cannot be used for MCI subtype assessment.
—Kimberly D. Williams
The human papillomavirus (HPV) vaccination is not associated with the development of multiple sclerosis (MS) or other demyelinating diseases, according to a study published January 6 in JAMA. Researchers examined Danish and Swedish girls and women between ages 10 and 44. Participants were followed up from 2006 to 2013. A total of 3,983,824 girls and women were eligible for inclusion in this study. Of these individuals, 789,082 were vaccinated, and 1,927,581 HPV vaccine doses were administered. At follow-up, 4,322 cases of MS and 3,300 cases of other demyelinating diseases were identified, of which 73 and 90, respectively, occurred within the risk period of two years following vaccination. “These findings do not support concerns about a causal relationship between HPV vaccination and demyelinating diseases,” the researchers stated.
No evidence of disease activity (NEDA) is a difficult outcome for patients with multiple sclerosis (MS) to sustain in the long term, even with treatment, according to a study published online ahead of print December 22 in JAMA Neurology. Researchers investigated the sustainability of NEDA over seven years in a group of 219 patients with MS. Patients had seven years of follow-up that included yearly brain MRI and biannual clinic visits. Investigators found that of 215 patients, 99 (46%) had NEDA for clinical and MRI measures at one year. At two years, 60 of 218 patients (27.5%) maintained NEDA, and 17 of 216 patients (7.9%) sustained NEDA after seven years. There was no difference in NEDA status for patients with early MS, compared with patients with more established disease.
Pharnext announced the proof of concept of its pleotherapy research and development approach based on a proprietary network pharmacology platform that identifies synergistic combinations of drugs already approved for other diseases. According to two reports published online December 10, 2014, in the Orphanet Journal of Rare Diseases, Pharnext’s lead pleodrug, PXT-3003, has shown positive results in preclinical and phase 2 clinical studies. The first paper shows consistent and synergistic preclinical data for PXT-3003 in two Charcot–Marie–Tooth disease type 1A (CMT 1A) rodent models. The second paper presents positive phase 2 results of PXT-3003 in 80 patients with mild to moderate CMT 1A.
Patients with acute ischemic stroke admitted to tertiary stroke centers during July had similar outcomes to patients admitted during other months, despite receiving slightly less frequent thrombolysis and stroke unit care, according to a study published online ahead of print December 19 in the Journal of Stroke and Cerebrovascular Diseases. Researchers examined 10,319 patients with acute ischemic stroke between July 1, 2003 and March 31, 2008. The research team evaluated referrals to long-term care facilities, length of hospital stay, hospital readmissions or emergency department visits within 30 days of hospital discharge, and hospital readmissions within 30 days from discharge due to stroke. “Ischemic stroke patients admitted in July were less likely to receive clot-busting drugs or be admitted to stroke units, but ultimately patients did just as well regardless of the month,” stated the investigators.
Insomnia symptoms are an important factor for explaining the mechanism by which alcohol use increases suicide risk, according to a study published December 15 in the Journal of Clinical Sleep Medicine. The study included 375 undergraduate students at a large, public university in the southeastern United States. Participants completed an online questionnaire that examined insomnia symptoms, nightmares, alcohol use, and suicide risk. Alcohol use was significantly associated with suicide risk among women. In addition, further analysis revealed that insomnia symptoms explained a significant proportion of the relationship between alcohol and suicide risk. Investigators found no direct effect of alcohol use on suicide risk in men, but they observed a significant indirect effect of alcohol use increasing suicide risk through insomnia symptoms.
The virtual supermarket (VSM) application correctly identifies 87.30% of patients with mild cognitive impairment (MCI), a level of diagnostic accuracy similar to that of standardized neuropsychologic tests, according to a study published online ahead of print November 25 in the Journal of Alzheimer’s Disease. Two groups, one of healthy older adults and one of patients with MCI, were recruited from day centers for people with cognitive disorders. Participants used the VSM application and underwent a battery of neuropsychologic tests. The VSM application accurately distinguished between patients with MCI and healthy older adults, but it was unable to differentiate between MCI subtypes. Overall, the VSM application is a valid method of screening for MCI in an older adult population, but it cannot be used for MCI subtype assessment.
—Kimberly D. Williams
The human papillomavirus (HPV) vaccination is not associated with the development of multiple sclerosis (MS) or other demyelinating diseases, according to a study published January 6 in JAMA. Researchers examined Danish and Swedish girls and women between ages 10 and 44. Participants were followed up from 2006 to 2013. A total of 3,983,824 girls and women were eligible for inclusion in this study. Of these individuals, 789,082 were vaccinated, and 1,927,581 HPV vaccine doses were administered. At follow-up, 4,322 cases of MS and 3,300 cases of other demyelinating diseases were identified, of which 73 and 90, respectively, occurred within the risk period of two years following vaccination. “These findings do not support concerns about a causal relationship between HPV vaccination and demyelinating diseases,” the researchers stated.
No evidence of disease activity (NEDA) is a difficult outcome for patients with multiple sclerosis (MS) to sustain in the long term, even with treatment, according to a study published online ahead of print December 22 in JAMA Neurology. Researchers investigated the sustainability of NEDA over seven years in a group of 219 patients with MS. Patients had seven years of follow-up that included yearly brain MRI and biannual clinic visits. Investigators found that of 215 patients, 99 (46%) had NEDA for clinical and MRI measures at one year. At two years, 60 of 218 patients (27.5%) maintained NEDA, and 17 of 216 patients (7.9%) sustained NEDA after seven years. There was no difference in NEDA status for patients with early MS, compared with patients with more established disease.
Pharnext announced the proof of concept of its pleotherapy research and development approach based on a proprietary network pharmacology platform that identifies synergistic combinations of drugs already approved for other diseases. According to two reports published online December 10, 2014, in the Orphanet Journal of Rare Diseases, Pharnext’s lead pleodrug, PXT-3003, has shown positive results in preclinical and phase 2 clinical studies. The first paper shows consistent and synergistic preclinical data for PXT-3003 in two Charcot–Marie–Tooth disease type 1A (CMT 1A) rodent models. The second paper presents positive phase 2 results of PXT-3003 in 80 patients with mild to moderate CMT 1A.
Patients with acute ischemic stroke admitted to tertiary stroke centers during July had similar outcomes to patients admitted during other months, despite receiving slightly less frequent thrombolysis and stroke unit care, according to a study published online ahead of print December 19 in the Journal of Stroke and Cerebrovascular Diseases. Researchers examined 10,319 patients with acute ischemic stroke between July 1, 2003 and March 31, 2008. The research team evaluated referrals to long-term care facilities, length of hospital stay, hospital readmissions or emergency department visits within 30 days of hospital discharge, and hospital readmissions within 30 days from discharge due to stroke. “Ischemic stroke patients admitted in July were less likely to receive clot-busting drugs or be admitted to stroke units, but ultimately patients did just as well regardless of the month,” stated the investigators.
Insomnia symptoms are an important factor for explaining the mechanism by which alcohol use increases suicide risk, according to a study published December 15 in the Journal of Clinical Sleep Medicine. The study included 375 undergraduate students at a large, public university in the southeastern United States. Participants completed an online questionnaire that examined insomnia symptoms, nightmares, alcohol use, and suicide risk. Alcohol use was significantly associated with suicide risk among women. In addition, further analysis revealed that insomnia symptoms explained a significant proportion of the relationship between alcohol and suicide risk. Investigators found no direct effect of alcohol use on suicide risk in men, but they observed a significant indirect effect of alcohol use increasing suicide risk through insomnia symptoms.
The virtual supermarket (VSM) application correctly identifies 87.30% of patients with mild cognitive impairment (MCI), a level of diagnostic accuracy similar to that of standardized neuropsychologic tests, according to a study published online ahead of print November 25 in the Journal of Alzheimer’s Disease. Two groups, one of healthy older adults and one of patients with MCI, were recruited from day centers for people with cognitive disorders. Participants used the VSM application and underwent a battery of neuropsychologic tests. The VSM application accurately distinguished between patients with MCI and healthy older adults, but it was unable to differentiate between MCI subtypes. Overall, the VSM application is a valid method of screening for MCI in an older adult population, but it cannot be used for MCI subtype assessment.
—Kimberly D. Williams
New and Noteworthy Information—January 2015
Diabetes prevention and glucose control in midlife may protect against late-life cognitive decline, according to a study published December 2 in Annals of Internal Medicine. Researchers analyzed data from the Atherosclerosis Risk in Communities Study (ARIC). The investigators compared the amount of cognitive decline associated with aging with the amount of decline found in the ARIC participants. The study authors determined that participants with poorly controlled diabetes had 19% more cognitive decline than expected. They also observed declines for participants with controlled diabetes and prediabetes. “Knowing that the risk for cognitive impairments begins with diabetes and other risk factors in midlife can be a strong motivator for patients and their doctors to adopt and maintain long-term healthy practices,” stated the researchers.
The likelihood of receiving a clinical cognitive evaluation in elderly individuals with dementia depends on patient-specific factors such as severity of cognitive impairment and current marital status, according to a study published online ahead of print November 26 in Neurology. The investigation was part of the Health and Retirement Study. Eight hundred forty-five people age 70 and older were evaluated for dementia, and 297 met the criteria for dementia. Of those people, 45% had seen a doctor about their memory problems, compared with 5% of those with memory and thinking problems that did not meet the criteria for dementia, and 1% of those with normal memory and thinking skills. People who were married were more than twice as likely to undergo screening as people who were not married.
Stimwave Technologies (Miami Beach, Florida) has received FDA clearance to market the Stimwave Freedom Spinal Cord Stimulator System, a wireless, microtechnology neuromodulation device for the relief of chronic back pain and leg pain. The device, a long-term implant, is between 2 and 11 cm long and can be inserted through a standard needle. The Stimwave Freedom Spinal Cord Stimulator System also eliminates the need for long wires to be tunneled through the body and connected to the battery source. Patients who receive the system can undergo whole-body 3-T or 1.5-T MRI without removing the implant. The Stimwave technology is also fixed in place by an anchor that allows it to move only when the body moves. The device contains no internal batteries or toxic materials.
Chronic impairment of glymphatic pathway function after traumatic brain injury (TBI) may be a key factor that renders the post-traumatic brain vulnerable to tau aggregation and the onset of neurodegeneration, according to a study published December 3 in Journal of Neuroscience. Previously, investigators defined a network of paravascular channels called the glymphatic pathway that facilitates the clearance of solutes such as amyloid-β from the brain. The researchers demonstrated that extracellular tau in mice is cleared from the brain along the paravascular pathways. After TBI, glymphatic pathway function was reduced by 60%, and this impairment persisted for at least one month after injury. Knockout of the gene encoding the astroglial water channel aquaporin-4 exacerbated glymphatic pathway dysfunction after TBI and promoted the development of neurofibrillary pathology and neurodegeneration in the post-traumatic brain.
In patients with transient ischemic attack (TIA), CT evidence of acute ischemia alone or acute ischemia with chronic ischemia is associated with increased subsequent stroke risk within 90 days, according to a study published online ahead of print December 4 in Stroke. Of 2,028 patients who received CT scans within 24 hours of a TIA, 814 (40.1%) had brain damage resulting from ischemia. In addition, 3.4% of the people in the study group had a subsequent stroke within 90 days, and 25% of patients with CT scans showing three types of damage to their brain had strokes. “These findings should prompt physicians to be more aggressive in managing patients with TIA or nondisabling stroke who are diagnosed with acute ischemia, especially if there is additional chronic ischemia and microangiopathy,” the researchers said.
People who have sleep apnea or spend less time in deep sleep may be more likely to have changes in the brain that are associated with dementia, according to a study published December 10 in Neurology. A total of 167 Japanese–American men had sleep tests in their homes at an average age of 84. All men were followed until they died at an average of six years later. Autopsies were conducted on their brains to look for microinfarcts. Of the 41 men who spent the least sleep time with low blood oxygen levels, four had microinfarcts in the brain. Fourteen of the 42 men with the most sleep time with low blood oxygen levels had the abnormalities; thus, they were nearly four times more likely to develop brain damage.
Brains affected by autism share a pattern of increased immune responses, according to a data analysis published December 10 in Nature Communications. The researchers examined gene expression in samples from two tissue banks, comparing gene expression in people with autism with that in controls without the condition. Data from 104 brain samples from 72 individuals were analyzed. The investigators focused their analysis on microglial cells. In the brains with autism, the microglial cells appeared to be perpetually activated, and their genes for inflammation responses were activated. The results highlight “the lack of current understanding about how innate immunity controls neural circuits,” stated the study authors. Given the known genetic contributors to autism, inflammation is unlikely to be its root cause, they added.
Compared with placebo, progesterone did not improve outcomes when administered to patients with acute traumatic brain injury (TBI), according to a study published online ahead of print December 10 in the New England Journal of Medicine. Patients were randomly assigned to IV progesterone or placebo, and study treatment was initiated within four hours after injury and administered for 96 hours. The trial was stopped for futility. The researchers found no significant difference between the progesterone group and the placebo group in the proportion of patients with a favorable outcome. Favorable outcomes occurred in 51% of patients who received progesterone and in 56% of those who received placebo. Mortality after six months was 18.8% for participants receiving progesterone and 15.7% for those receiving placebo. Phlebitis was more common in the progesterone group.
Learning-related brain activity in patients with Parkinson’s disease improves as much in response to placebo as to medication, according to a study published in the December issue of Nature Neuroscience. For the study, researchers used functional MRI to scan the brains of 18 patients with Parkinson’s disease as they played a computer game that measures reward learning. In the game, participants discover through trial and error which of two symbols is more likely to lead to a better outcome. Participants played the game when they were not taking medication, when they took medication, and when they took placebo. The researchers found that the dopamine-rich areas of the brain associated with reward learning became equally active when patients took either the real medication or the placebo.
Oral fingolimod may improve outcomes for patients with acute and anterior cerebral circulation occlusion stroke, according to a study published online ahead of print December 8 in Proceedings of the National Academy of Sciences. The researchers conducted an open-label, evaluator-blinded, parallel-group clinical pilot trial of 22 patients with anterior cerebral circulation occlusion, among whom stroke onset had occurred more than 4.5 hours previously. Participants received standard management alone or standard management plus 0.5 mg of oral fingolimod per day for three consecutive days. Patients receiving fingolimod had lower circulating lymphocyte counts, milder neurologic deficits, and better recovery of neurologic functions. Neurologic rehabilitation was faster among participants who received fingolimod. In addition, enlargement of lesion size was less pronounced between baseline and day seven among patients who received fingolimod.
Migraine headache may double the risk of Bell’s palsy, according to a study published online ahead of print December 17 in Neurology. Two groups of 136,704 people age 18 and older, one group with migraine and one without, were followed for an average of three years. During that time, 671 people in the migraine group and 365 people in the control group were diagnosed with Bell’s palsy. Participants with migraine were twice as likely to develop Bell’s palsy, even after researchers accounted for other factors that could increase the risk of the condition, such as sex, high blood pressure, and diabetes. “Infection, inflammation, or heart and vascular problems could be shared causes for these diseases,” stated the researchers.
Struggling to balance on one leg for 20 seconds or longer is linked to an increased risk for small blood vessel damage in the brain and reduced cognitive function in healthy people with no clinical symptoms, according to a study published online ahead of print December 18 in Stroke. Investigators examined 841 women and 546 men with an average age of 67. To measure one-leg standing time, participants stood with their eyes open and raised one leg. In all, 34.5% of participants with more than two lacunar infarction lesions had trouble balancing, 16% of people with one lacunar infarction lesion had trouble balancing, 30% of participants with more than two microbleed lesions had trouble balancing, and 15.3% of people with one microbleed lesion had trouble balancing.
—Kimberly D. Williams
Diabetes prevention and glucose control in midlife may protect against late-life cognitive decline, according to a study published December 2 in Annals of Internal Medicine. Researchers analyzed data from the Atherosclerosis Risk in Communities Study (ARIC). The investigators compared the amount of cognitive decline associated with aging with the amount of decline found in the ARIC participants. The study authors determined that participants with poorly controlled diabetes had 19% more cognitive decline than expected. They also observed declines for participants with controlled diabetes and prediabetes. “Knowing that the risk for cognitive impairments begins with diabetes and other risk factors in midlife can be a strong motivator for patients and their doctors to adopt and maintain long-term healthy practices,” stated the researchers.
The likelihood of receiving a clinical cognitive evaluation in elderly individuals with dementia depends on patient-specific factors such as severity of cognitive impairment and current marital status, according to a study published online ahead of print November 26 in Neurology. The investigation was part of the Health and Retirement Study. Eight hundred forty-five people age 70 and older were evaluated for dementia, and 297 met the criteria for dementia. Of those people, 45% had seen a doctor about their memory problems, compared with 5% of those with memory and thinking problems that did not meet the criteria for dementia, and 1% of those with normal memory and thinking skills. People who were married were more than twice as likely to undergo screening as people who were not married.
Stimwave Technologies (Miami Beach, Florida) has received FDA clearance to market the Stimwave Freedom Spinal Cord Stimulator System, a wireless, microtechnology neuromodulation device for the relief of chronic back pain and leg pain. The device, a long-term implant, is between 2 and 11 cm long and can be inserted through a standard needle. The Stimwave Freedom Spinal Cord Stimulator System also eliminates the need for long wires to be tunneled through the body and connected to the battery source. Patients who receive the system can undergo whole-body 3-T or 1.5-T MRI without removing the implant. The Stimwave technology is also fixed in place by an anchor that allows it to move only when the body moves. The device contains no internal batteries or toxic materials.
Chronic impairment of glymphatic pathway function after traumatic brain injury (TBI) may be a key factor that renders the post-traumatic brain vulnerable to tau aggregation and the onset of neurodegeneration, according to a study published December 3 in Journal of Neuroscience. Previously, investigators defined a network of paravascular channels called the glymphatic pathway that facilitates the clearance of solutes such as amyloid-β from the brain. The researchers demonstrated that extracellular tau in mice is cleared from the brain along the paravascular pathways. After TBI, glymphatic pathway function was reduced by 60%, and this impairment persisted for at least one month after injury. Knockout of the gene encoding the astroglial water channel aquaporin-4 exacerbated glymphatic pathway dysfunction after TBI and promoted the development of neurofibrillary pathology and neurodegeneration in the post-traumatic brain.
In patients with transient ischemic attack (TIA), CT evidence of acute ischemia alone or acute ischemia with chronic ischemia is associated with increased subsequent stroke risk within 90 days, according to a study published online ahead of print December 4 in Stroke. Of 2,028 patients who received CT scans within 24 hours of a TIA, 814 (40.1%) had brain damage resulting from ischemia. In addition, 3.4% of the people in the study group had a subsequent stroke within 90 days, and 25% of patients with CT scans showing three types of damage to their brain had strokes. “These findings should prompt physicians to be more aggressive in managing patients with TIA or nondisabling stroke who are diagnosed with acute ischemia, especially if there is additional chronic ischemia and microangiopathy,” the researchers said.
People who have sleep apnea or spend less time in deep sleep may be more likely to have changes in the brain that are associated with dementia, according to a study published December 10 in Neurology. A total of 167 Japanese–American men had sleep tests in their homes at an average age of 84. All men were followed until they died at an average of six years later. Autopsies were conducted on their brains to look for microinfarcts. Of the 41 men who spent the least sleep time with low blood oxygen levels, four had microinfarcts in the brain. Fourteen of the 42 men with the most sleep time with low blood oxygen levels had the abnormalities; thus, they were nearly four times more likely to develop brain damage.
Brains affected by autism share a pattern of increased immune responses, according to a data analysis published December 10 in Nature Communications. The researchers examined gene expression in samples from two tissue banks, comparing gene expression in people with autism with that in controls without the condition. Data from 104 brain samples from 72 individuals were analyzed. The investigators focused their analysis on microglial cells. In the brains with autism, the microglial cells appeared to be perpetually activated, and their genes for inflammation responses were activated. The results highlight “the lack of current understanding about how innate immunity controls neural circuits,” stated the study authors. Given the known genetic contributors to autism, inflammation is unlikely to be its root cause, they added.
Compared with placebo, progesterone did not improve outcomes when administered to patients with acute traumatic brain injury (TBI), according to a study published online ahead of print December 10 in the New England Journal of Medicine. Patients were randomly assigned to IV progesterone or placebo, and study treatment was initiated within four hours after injury and administered for 96 hours. The trial was stopped for futility. The researchers found no significant difference between the progesterone group and the placebo group in the proportion of patients with a favorable outcome. Favorable outcomes occurred in 51% of patients who received progesterone and in 56% of those who received placebo. Mortality after six months was 18.8% for participants receiving progesterone and 15.7% for those receiving placebo. Phlebitis was more common in the progesterone group.
Learning-related brain activity in patients with Parkinson’s disease improves as much in response to placebo as to medication, according to a study published in the December issue of Nature Neuroscience. For the study, researchers used functional MRI to scan the brains of 18 patients with Parkinson’s disease as they played a computer game that measures reward learning. In the game, participants discover through trial and error which of two symbols is more likely to lead to a better outcome. Participants played the game when they were not taking medication, when they took medication, and when they took placebo. The researchers found that the dopamine-rich areas of the brain associated with reward learning became equally active when patients took either the real medication or the placebo.
Oral fingolimod may improve outcomes for patients with acute and anterior cerebral circulation occlusion stroke, according to a study published online ahead of print December 8 in Proceedings of the National Academy of Sciences. The researchers conducted an open-label, evaluator-blinded, parallel-group clinical pilot trial of 22 patients with anterior cerebral circulation occlusion, among whom stroke onset had occurred more than 4.5 hours previously. Participants received standard management alone or standard management plus 0.5 mg of oral fingolimod per day for three consecutive days. Patients receiving fingolimod had lower circulating lymphocyte counts, milder neurologic deficits, and better recovery of neurologic functions. Neurologic rehabilitation was faster among participants who received fingolimod. In addition, enlargement of lesion size was less pronounced between baseline and day seven among patients who received fingolimod.
Migraine headache may double the risk of Bell’s palsy, according to a study published online ahead of print December 17 in Neurology. Two groups of 136,704 people age 18 and older, one group with migraine and one without, were followed for an average of three years. During that time, 671 people in the migraine group and 365 people in the control group were diagnosed with Bell’s palsy. Participants with migraine were twice as likely to develop Bell’s palsy, even after researchers accounted for other factors that could increase the risk of the condition, such as sex, high blood pressure, and diabetes. “Infection, inflammation, or heart and vascular problems could be shared causes for these diseases,” stated the researchers.
Struggling to balance on one leg for 20 seconds or longer is linked to an increased risk for small blood vessel damage in the brain and reduced cognitive function in healthy people with no clinical symptoms, according to a study published online ahead of print December 18 in Stroke. Investigators examined 841 women and 546 men with an average age of 67. To measure one-leg standing time, participants stood with their eyes open and raised one leg. In all, 34.5% of participants with more than two lacunar infarction lesions had trouble balancing, 16% of people with one lacunar infarction lesion had trouble balancing, 30% of participants with more than two microbleed lesions had trouble balancing, and 15.3% of people with one microbleed lesion had trouble balancing.
—Kimberly D. Williams
Diabetes prevention and glucose control in midlife may protect against late-life cognitive decline, according to a study published December 2 in Annals of Internal Medicine. Researchers analyzed data from the Atherosclerosis Risk in Communities Study (ARIC). The investigators compared the amount of cognitive decline associated with aging with the amount of decline found in the ARIC participants. The study authors determined that participants with poorly controlled diabetes had 19% more cognitive decline than expected. They also observed declines for participants with controlled diabetes and prediabetes. “Knowing that the risk for cognitive impairments begins with diabetes and other risk factors in midlife can be a strong motivator for patients and their doctors to adopt and maintain long-term healthy practices,” stated the researchers.
The likelihood of receiving a clinical cognitive evaluation in elderly individuals with dementia depends on patient-specific factors such as severity of cognitive impairment and current marital status, according to a study published online ahead of print November 26 in Neurology. The investigation was part of the Health and Retirement Study. Eight hundred forty-five people age 70 and older were evaluated for dementia, and 297 met the criteria for dementia. Of those people, 45% had seen a doctor about their memory problems, compared with 5% of those with memory and thinking problems that did not meet the criteria for dementia, and 1% of those with normal memory and thinking skills. People who were married were more than twice as likely to undergo screening as people who were not married.
Stimwave Technologies (Miami Beach, Florida) has received FDA clearance to market the Stimwave Freedom Spinal Cord Stimulator System, a wireless, microtechnology neuromodulation device for the relief of chronic back pain and leg pain. The device, a long-term implant, is between 2 and 11 cm long and can be inserted through a standard needle. The Stimwave Freedom Spinal Cord Stimulator System also eliminates the need for long wires to be tunneled through the body and connected to the battery source. Patients who receive the system can undergo whole-body 3-T or 1.5-T MRI without removing the implant. The Stimwave technology is also fixed in place by an anchor that allows it to move only when the body moves. The device contains no internal batteries or toxic materials.
Chronic impairment of glymphatic pathway function after traumatic brain injury (TBI) may be a key factor that renders the post-traumatic brain vulnerable to tau aggregation and the onset of neurodegeneration, according to a study published December 3 in Journal of Neuroscience. Previously, investigators defined a network of paravascular channels called the glymphatic pathway that facilitates the clearance of solutes such as amyloid-β from the brain. The researchers demonstrated that extracellular tau in mice is cleared from the brain along the paravascular pathways. After TBI, glymphatic pathway function was reduced by 60%, and this impairment persisted for at least one month after injury. Knockout of the gene encoding the astroglial water channel aquaporin-4 exacerbated glymphatic pathway dysfunction after TBI and promoted the development of neurofibrillary pathology and neurodegeneration in the post-traumatic brain.
In patients with transient ischemic attack (TIA), CT evidence of acute ischemia alone or acute ischemia with chronic ischemia is associated with increased subsequent stroke risk within 90 days, according to a study published online ahead of print December 4 in Stroke. Of 2,028 patients who received CT scans within 24 hours of a TIA, 814 (40.1%) had brain damage resulting from ischemia. In addition, 3.4% of the people in the study group had a subsequent stroke within 90 days, and 25% of patients with CT scans showing three types of damage to their brain had strokes. “These findings should prompt physicians to be more aggressive in managing patients with TIA or nondisabling stroke who are diagnosed with acute ischemia, especially if there is additional chronic ischemia and microangiopathy,” the researchers said.
People who have sleep apnea or spend less time in deep sleep may be more likely to have changes in the brain that are associated with dementia, according to a study published December 10 in Neurology. A total of 167 Japanese–American men had sleep tests in their homes at an average age of 84. All men were followed until they died at an average of six years later. Autopsies were conducted on their brains to look for microinfarcts. Of the 41 men who spent the least sleep time with low blood oxygen levels, four had microinfarcts in the brain. Fourteen of the 42 men with the most sleep time with low blood oxygen levels had the abnormalities; thus, they were nearly four times more likely to develop brain damage.
Brains affected by autism share a pattern of increased immune responses, according to a data analysis published December 10 in Nature Communications. The researchers examined gene expression in samples from two tissue banks, comparing gene expression in people with autism with that in controls without the condition. Data from 104 brain samples from 72 individuals were analyzed. The investigators focused their analysis on microglial cells. In the brains with autism, the microglial cells appeared to be perpetually activated, and their genes for inflammation responses were activated. The results highlight “the lack of current understanding about how innate immunity controls neural circuits,” stated the study authors. Given the known genetic contributors to autism, inflammation is unlikely to be its root cause, they added.
Compared with placebo, progesterone did not improve outcomes when administered to patients with acute traumatic brain injury (TBI), according to a study published online ahead of print December 10 in the New England Journal of Medicine. Patients were randomly assigned to IV progesterone or placebo, and study treatment was initiated within four hours after injury and administered for 96 hours. The trial was stopped for futility. The researchers found no significant difference between the progesterone group and the placebo group in the proportion of patients with a favorable outcome. Favorable outcomes occurred in 51% of patients who received progesterone and in 56% of those who received placebo. Mortality after six months was 18.8% for participants receiving progesterone and 15.7% for those receiving placebo. Phlebitis was more common in the progesterone group.
Learning-related brain activity in patients with Parkinson’s disease improves as much in response to placebo as to medication, according to a study published in the December issue of Nature Neuroscience. For the study, researchers used functional MRI to scan the brains of 18 patients with Parkinson’s disease as they played a computer game that measures reward learning. In the game, participants discover through trial and error which of two symbols is more likely to lead to a better outcome. Participants played the game when they were not taking medication, when they took medication, and when they took placebo. The researchers found that the dopamine-rich areas of the brain associated with reward learning became equally active when patients took either the real medication or the placebo.
Oral fingolimod may improve outcomes for patients with acute and anterior cerebral circulation occlusion stroke, according to a study published online ahead of print December 8 in Proceedings of the National Academy of Sciences. The researchers conducted an open-label, evaluator-blinded, parallel-group clinical pilot trial of 22 patients with anterior cerebral circulation occlusion, among whom stroke onset had occurred more than 4.5 hours previously. Participants received standard management alone or standard management plus 0.5 mg of oral fingolimod per day for three consecutive days. Patients receiving fingolimod had lower circulating lymphocyte counts, milder neurologic deficits, and better recovery of neurologic functions. Neurologic rehabilitation was faster among participants who received fingolimod. In addition, enlargement of lesion size was less pronounced between baseline and day seven among patients who received fingolimod.
Migraine headache may double the risk of Bell’s palsy, according to a study published online ahead of print December 17 in Neurology. Two groups of 136,704 people age 18 and older, one group with migraine and one without, were followed for an average of three years. During that time, 671 people in the migraine group and 365 people in the control group were diagnosed with Bell’s palsy. Participants with migraine were twice as likely to develop Bell’s palsy, even after researchers accounted for other factors that could increase the risk of the condition, such as sex, high blood pressure, and diabetes. “Infection, inflammation, or heart and vascular problems could be shared causes for these diseases,” stated the researchers.
Struggling to balance on one leg for 20 seconds or longer is linked to an increased risk for small blood vessel damage in the brain and reduced cognitive function in healthy people with no clinical symptoms, according to a study published online ahead of print December 18 in Stroke. Investigators examined 841 women and 546 men with an average age of 67. To measure one-leg standing time, participants stood with their eyes open and raised one leg. In all, 34.5% of participants with more than two lacunar infarction lesions had trouble balancing, 16% of people with one lacunar infarction lesion had trouble balancing, 30% of participants with more than two microbleed lesions had trouble balancing, and 15.3% of people with one microbleed lesion had trouble balancing.
—Kimberly D. Williams
New and Noteworthy Information—December 2014
Two-year folic acid and vitamin B12 supplementation did not improve performance in four cognitive domains in elderly people with elevated homocysteine levels, according to a study published online ahead of print November 12 in Neurology. A total of 2,919 participants with an average age of 74 took either a tablet with 400 μg of folic acid and 500 μg of vitamin B12, or a placebo every day for two years. Tests of memory and thinking skills were performed at the beginning and end of the study. All participants had high blood levels of homocysteine. “While the homocysteine levels decreased by more in the group taking the B vitamins than in the group taking the placebo, unfortunately, there was no difference between the two groups in the scores on the thinking and memory tests,” the researchers stated.
Among more than 43,000 children treated in 25 emergency departments for blunt head trauma, traumatic brain injury (TBI) was identified on CT scans in 7% of the patients, according to a study published November 13 in the New England Journal of Medicine. In children 12 and younger, falls were the most common cause of head injury—among those younger than 2, falls accounted for 77% of head injuries, and in those 2 to 12, falls accounted for 38% of injuries. In children ages 13 to 17, 24% of injuries were due to assault, 19% were sports-related, and 18% resulted from motor vehicle accidents. Among all cases, 98% had mild head trauma. During diagnosis and treatment, cranial CT scans were performed on 37% of the children, “many arguably unnecessarily,” according to the researchers.
Preadmission use of COX-2 inhibitors was associated with increased 30-day mortality after ischemic stroke, but not hemorrhagic stroke, according to a study published online ahead of print November 5 in Neurology. Researchers analyzed records of 100,243 patients hospitalized for a first stroke between 2004 and 2012 and deaths within one month after the stroke. The investigators examined whether participants were current, former, or nonusers of these drugs within two months of the stroke. Overall, people who were current users of COX-2 inhibitors were 19% more likely to die after stroke than were people who did not take the drugs. New users of the older COX-2 drugs were 42% more likely to die from stroke than were those who were not taking the drugs.
Once-daily, low-dose aspirin did not significantly reduce the risk of the composite outcome of cardiovascular death, nonfatal stroke, and nonfatal myocardial infarction among patients age 60 or older with atherosclerotic risk factors, according to a study published online ahead of print November 17 in JAMA. This study included 14,464 Japanese patients with hypertension, dyslipidemia, or diabetes mellitus who were randomized to aspirin (100 mg/d) or no aspirin in addition to ongoing medications. The researchers found no statistically significant difference between the two groups in time to the primary end point. The cumulative primary event rate was similar in participants in the aspirin group (2.77%) and those in the no-aspirin group (2.96%) five years after randomization. Aspirin significantly reduced the incidence of nonfatal heart attack and transient ischemic attack, and significantly increased the risk of extracranial hemorrhage requiring transfusion or hospitalization.
Overall symptom burden is the only independent predictor of prolonged symptoms after sport-related concussion, investigators reported online ahead of print November 7 in Neurology. The researchers conducted a prospective cohort study of 531 patients in a sports concussion clinic. Participants completed questionnaires that included the Post-Concussion Symptom Scale (PCSS). Patients ranged in age from 7 to 26 (mean age, 14.6). The mean PCSS score at the initial visit was 26, and mean time to presentation was 12 days. Only total score on symptom inventory was independently associated with symptoms lasting longer than 28 days. No other potential predictor variables were independently associated with symptom duration or were useful in developing the optimal regression decision tree. Most participants with an initial PCSS score of less than 13 had resolution of their symptoms within 28 days of injury.
The ketogenic diet and modified Atkins diet show modest efficacy, although in some patients the effect is “remarkable” in the treatment of refractory epilepsy in adults, according to a study published online ahead of print October 29 in Neurology. Researchers reviewed five studies on the ketogenic diet that included 47 people and five studies on the modified Atkins diet that included 85 people. The investigators found that across all studies, 32% of people treated with the ketogenic diet and 29% of those treated with the modified Atkins diet had a 50% or better reduction in their seizures. Nine percent in the ketogenic treatment group and 5% in the modified Atkins group had a greater than 90% reduction in seizures. “These studies show the diets are moderately to very effective as another option for people with epilepsy,” stated the study authors.
The evaluation of serum micro-RNAs may help to identify the severity of brain injury and the risk of developing adverse effects after traumatic brain injury (TBI), according to a study published November 7 in PLoS One. Researchers identified a unique and specific group of microRNAs, which were detected in blood immediately after injury to the brain in mice. The results suggest that the microRNAs can be measured in the blood as proxies for mild TBI. The microRNA panel identified in this study is unique and does not overlap with blood microRNAs of post-traumatic stress disorder, as previously reported. “This important finding is a step forward in identifying objective biomarkers for mild TBI that may be further validated to accurately and cost effectively identify mild TBI in service members and civilians with brain injuries,” said the investigators.
The FDA has approved Lemtrada (alemtuzumab) for the treatment of patients with relapsing forms of multiple sclerosis (MS). The approval comes nearly one year after the FDA declined to approve the drug, citing a lack of well-controlled data from clinical studies at the time indicating that the benefits had outweighed the risks. After an appeal by Genzyme (Cambridge, Massachusetts) and a new review by the FDA, the agency approved the drug based on two pivotal, randomized phase III, open-label, rater-blinded studies, comparing treatment with Lemtrada to interferon beta-1a, in patients with relapsing-remitting MS who were either new to treatment (CARE-MS I) or who had relapsed while on prior therapy (CARE-MS II). Lemtrada is recommended for patients who have had an inadequate response to two or more drugs indicated for the treatment of MS.
Angiotensin-converting enzyme inhibitors (ACEIs) exhibited a dose-dependent inverse association with amyotrophic lateral sclerosis (ALS), according to a study published online ahead of print November 10 in JAMA Neurology. Researchers included 729 patients diagnosed with ALS between January 2002 and December 2008. The patients were compared with 14,580 controls. Fifteen percent of patients with ALS reported ACEI use between two and five years before their ALS diagnosis, and 18% of the control group without ALS reported ACEI use. When compared with patients who did not use ACEIs, the adjusted odds ratios were 0.83 for the group prescribed ACEIs lower than 449.5 of the cumulative defined daily dose (cDDD) and 0.43 cDDD for the group with a cumulative ACEI use of greater than 449.5 cDDD.
Patients treated at hospitals with higher volumes of subarachnoid hemorrhage (SAH) cases have lower in-hospital mortality, independent of patient and hospital characteristics, according to a study published in the November Neurosurgery. In a large nationwide registry, researchers identified nearly 32,000 patients with SAH treated at 685 United States hospitals between 2003 and 2012. The median annual case volume per hospital was 8.5 patients. Mean in-hospital mortality was 25.7% but was lower with increasing annual SAH volume. Hospital SAH volume was independently associated with in-hospital mortality (adjusted odds ratio, 0.79 for quartile 4 vs quartile 1), independent of patient and other hospital characteristics. “Our results may have significant implications for regional stroke policies and procedures and affirm the recent recommendations that patients with SAH be treated at high-volume centers,” said study authors.
The use of a specialized ambulance—stroke emergency mobile unit (STEMO)—increases the percentage of patients receiving thrombolysis within 60 minutes, according to a study published online ahead of print November 17 in JAMA Neurology. A total of 3,213 emergency calls for suspected stroke occurred during weeks when STEMO was available, and 2,969 calls occurred during control weeks when STEMO was not available. Two hundred of 614 patients with stroke (32.6%) received thrombolysis when the STEMO was deployed, and 330 of 1,497 patients (22%) received thrombolysis in conventional care. Median onset to treatment was 24.5 minutes shorter after STEMO deployment, compared with conventional care. In all ischemic strokes, the rate of “golden hour” thrombolysis increased from 16 of the 1,497 patients (1.1%) during conventional care to 62 of 614 (10.1%) after STEMO deployment. Overall, golden hour thrombolysis entails no risk to the patients’ safety and is associated with better short-term outcomes, according to the researchers.
Granger causality (GC) analysis of intracranial EEG (iEEG) has the potential to increase understanding of preictal network activity and help improve surgical outcomes in cases of otherwise ambiguous iEEG onset, according to a study published online ahead of print November 4 in Epilepsia. In 10 retrospective and two prospective patients with epilepsy, iEEG was recorded at 500 or 1,000 Hz, using as many as 128 surface and depth electrodes. In all patients, the researchers found significant, widespread preictal GC network activity at peak frequencies from 80 to 250 Hz, beginning two to 42 seconds before visible electrographic onset. In the two prospective patients, GC source/sink comparisons supported the exclusion of early ictal regions that were not the dominant causal sources and contributed to planning of more limited surgical resections. Both groups of patients had a class 1 outcome at one year.
Tiny silent acute infarcts may be a cause of leukoaraiosis, a finding that points toward a potentially treatable form of dementia, investigators reported online ahead of print October 4 in Annals of Neurology. The study involved five patients with leukoaraiosis who underwent detailed MRI scanning of their brains every week for 16 consecutive weeks. The MRI scans revealed new tiny spots arising de novo in the cerebral white matter. The lesions were “clinically silent and had the signature features of acute ischemic stroke, according to the researchers. “With time, the characteristics of these lesions approached those of pre-existing leukoaraiosis,” the study authors stated.
—Kimberly D. Williams
Two-year folic acid and vitamin B12 supplementation did not improve performance in four cognitive domains in elderly people with elevated homocysteine levels, according to a study published online ahead of print November 12 in Neurology. A total of 2,919 participants with an average age of 74 took either a tablet with 400 μg of folic acid and 500 μg of vitamin B12, or a placebo every day for two years. Tests of memory and thinking skills were performed at the beginning and end of the study. All participants had high blood levels of homocysteine. “While the homocysteine levels decreased by more in the group taking the B vitamins than in the group taking the placebo, unfortunately, there was no difference between the two groups in the scores on the thinking and memory tests,” the researchers stated.
Among more than 43,000 children treated in 25 emergency departments for blunt head trauma, traumatic brain injury (TBI) was identified on CT scans in 7% of the patients, according to a study published November 13 in the New England Journal of Medicine. In children 12 and younger, falls were the most common cause of head injury—among those younger than 2, falls accounted for 77% of head injuries, and in those 2 to 12, falls accounted for 38% of injuries. In children ages 13 to 17, 24% of injuries were due to assault, 19% were sports-related, and 18% resulted from motor vehicle accidents. Among all cases, 98% had mild head trauma. During diagnosis and treatment, cranial CT scans were performed on 37% of the children, “many arguably unnecessarily,” according to the researchers.
Preadmission use of COX-2 inhibitors was associated with increased 30-day mortality after ischemic stroke, but not hemorrhagic stroke, according to a study published online ahead of print November 5 in Neurology. Researchers analyzed records of 100,243 patients hospitalized for a first stroke between 2004 and 2012 and deaths within one month after the stroke. The investigators examined whether participants were current, former, or nonusers of these drugs within two months of the stroke. Overall, people who were current users of COX-2 inhibitors were 19% more likely to die after stroke than were people who did not take the drugs. New users of the older COX-2 drugs were 42% more likely to die from stroke than were those who were not taking the drugs.
Once-daily, low-dose aspirin did not significantly reduce the risk of the composite outcome of cardiovascular death, nonfatal stroke, and nonfatal myocardial infarction among patients age 60 or older with atherosclerotic risk factors, according to a study published online ahead of print November 17 in JAMA. This study included 14,464 Japanese patients with hypertension, dyslipidemia, or diabetes mellitus who were randomized to aspirin (100 mg/d) or no aspirin in addition to ongoing medications. The researchers found no statistically significant difference between the two groups in time to the primary end point. The cumulative primary event rate was similar in participants in the aspirin group (2.77%) and those in the no-aspirin group (2.96%) five years after randomization. Aspirin significantly reduced the incidence of nonfatal heart attack and transient ischemic attack, and significantly increased the risk of extracranial hemorrhage requiring transfusion or hospitalization.
Overall symptom burden is the only independent predictor of prolonged symptoms after sport-related concussion, investigators reported online ahead of print November 7 in Neurology. The researchers conducted a prospective cohort study of 531 patients in a sports concussion clinic. Participants completed questionnaires that included the Post-Concussion Symptom Scale (PCSS). Patients ranged in age from 7 to 26 (mean age, 14.6). The mean PCSS score at the initial visit was 26, and mean time to presentation was 12 days. Only total score on symptom inventory was independently associated with symptoms lasting longer than 28 days. No other potential predictor variables were independently associated with symptom duration or were useful in developing the optimal regression decision tree. Most participants with an initial PCSS score of less than 13 had resolution of their symptoms within 28 days of injury.
The ketogenic diet and modified Atkins diet show modest efficacy, although in some patients the effect is “remarkable” in the treatment of refractory epilepsy in adults, according to a study published online ahead of print October 29 in Neurology. Researchers reviewed five studies on the ketogenic diet that included 47 people and five studies on the modified Atkins diet that included 85 people. The investigators found that across all studies, 32% of people treated with the ketogenic diet and 29% of those treated with the modified Atkins diet had a 50% or better reduction in their seizures. Nine percent in the ketogenic treatment group and 5% in the modified Atkins group had a greater than 90% reduction in seizures. “These studies show the diets are moderately to very effective as another option for people with epilepsy,” stated the study authors.
The evaluation of serum micro-RNAs may help to identify the severity of brain injury and the risk of developing adverse effects after traumatic brain injury (TBI), according to a study published November 7 in PLoS One. Researchers identified a unique and specific group of microRNAs, which were detected in blood immediately after injury to the brain in mice. The results suggest that the microRNAs can be measured in the blood as proxies for mild TBI. The microRNA panel identified in this study is unique and does not overlap with blood microRNAs of post-traumatic stress disorder, as previously reported. “This important finding is a step forward in identifying objective biomarkers for mild TBI that may be further validated to accurately and cost effectively identify mild TBI in service members and civilians with brain injuries,” said the investigators.
The FDA has approved Lemtrada (alemtuzumab) for the treatment of patients with relapsing forms of multiple sclerosis (MS). The approval comes nearly one year after the FDA declined to approve the drug, citing a lack of well-controlled data from clinical studies at the time indicating that the benefits had outweighed the risks. After an appeal by Genzyme (Cambridge, Massachusetts) and a new review by the FDA, the agency approved the drug based on two pivotal, randomized phase III, open-label, rater-blinded studies, comparing treatment with Lemtrada to interferon beta-1a, in patients with relapsing-remitting MS who were either new to treatment (CARE-MS I) or who had relapsed while on prior therapy (CARE-MS II). Lemtrada is recommended for patients who have had an inadequate response to two or more drugs indicated for the treatment of MS.
Angiotensin-converting enzyme inhibitors (ACEIs) exhibited a dose-dependent inverse association with amyotrophic lateral sclerosis (ALS), according to a study published online ahead of print November 10 in JAMA Neurology. Researchers included 729 patients diagnosed with ALS between January 2002 and December 2008. The patients were compared with 14,580 controls. Fifteen percent of patients with ALS reported ACEI use between two and five years before their ALS diagnosis, and 18% of the control group without ALS reported ACEI use. When compared with patients who did not use ACEIs, the adjusted odds ratios were 0.83 for the group prescribed ACEIs lower than 449.5 of the cumulative defined daily dose (cDDD) and 0.43 cDDD for the group with a cumulative ACEI use of greater than 449.5 cDDD.
Patients treated at hospitals with higher volumes of subarachnoid hemorrhage (SAH) cases have lower in-hospital mortality, independent of patient and hospital characteristics, according to a study published in the November Neurosurgery. In a large nationwide registry, researchers identified nearly 32,000 patients with SAH treated at 685 United States hospitals between 2003 and 2012. The median annual case volume per hospital was 8.5 patients. Mean in-hospital mortality was 25.7% but was lower with increasing annual SAH volume. Hospital SAH volume was independently associated with in-hospital mortality (adjusted odds ratio, 0.79 for quartile 4 vs quartile 1), independent of patient and other hospital characteristics. “Our results may have significant implications for regional stroke policies and procedures and affirm the recent recommendations that patients with SAH be treated at high-volume centers,” said study authors.
The use of a specialized ambulance—stroke emergency mobile unit (STEMO)—increases the percentage of patients receiving thrombolysis within 60 minutes, according to a study published online ahead of print November 17 in JAMA Neurology. A total of 3,213 emergency calls for suspected stroke occurred during weeks when STEMO was available, and 2,969 calls occurred during control weeks when STEMO was not available. Two hundred of 614 patients with stroke (32.6%) received thrombolysis when the STEMO was deployed, and 330 of 1,497 patients (22%) received thrombolysis in conventional care. Median onset to treatment was 24.5 minutes shorter after STEMO deployment, compared with conventional care. In all ischemic strokes, the rate of “golden hour” thrombolysis increased from 16 of the 1,497 patients (1.1%) during conventional care to 62 of 614 (10.1%) after STEMO deployment. Overall, golden hour thrombolysis entails no risk to the patients’ safety and is associated with better short-term outcomes, according to the researchers.
Granger causality (GC) analysis of intracranial EEG (iEEG) has the potential to increase understanding of preictal network activity and help improve surgical outcomes in cases of otherwise ambiguous iEEG onset, according to a study published online ahead of print November 4 in Epilepsia. In 10 retrospective and two prospective patients with epilepsy, iEEG was recorded at 500 or 1,000 Hz, using as many as 128 surface and depth electrodes. In all patients, the researchers found significant, widespread preictal GC network activity at peak frequencies from 80 to 250 Hz, beginning two to 42 seconds before visible electrographic onset. In the two prospective patients, GC source/sink comparisons supported the exclusion of early ictal regions that were not the dominant causal sources and contributed to planning of more limited surgical resections. Both groups of patients had a class 1 outcome at one year.
Tiny silent acute infarcts may be a cause of leukoaraiosis, a finding that points toward a potentially treatable form of dementia, investigators reported online ahead of print October 4 in Annals of Neurology. The study involved five patients with leukoaraiosis who underwent detailed MRI scanning of their brains every week for 16 consecutive weeks. The MRI scans revealed new tiny spots arising de novo in the cerebral white matter. The lesions were “clinically silent and had the signature features of acute ischemic stroke, according to the researchers. “With time, the characteristics of these lesions approached those of pre-existing leukoaraiosis,” the study authors stated.
—Kimberly D. Williams
Two-year folic acid and vitamin B12 supplementation did not improve performance in four cognitive domains in elderly people with elevated homocysteine levels, according to a study published online ahead of print November 12 in Neurology. A total of 2,919 participants with an average age of 74 took either a tablet with 400 μg of folic acid and 500 μg of vitamin B12, or a placebo every day for two years. Tests of memory and thinking skills were performed at the beginning and end of the study. All participants had high blood levels of homocysteine. “While the homocysteine levels decreased by more in the group taking the B vitamins than in the group taking the placebo, unfortunately, there was no difference between the two groups in the scores on the thinking and memory tests,” the researchers stated.
Among more than 43,000 children treated in 25 emergency departments for blunt head trauma, traumatic brain injury (TBI) was identified on CT scans in 7% of the patients, according to a study published November 13 in the New England Journal of Medicine. In children 12 and younger, falls were the most common cause of head injury—among those younger than 2, falls accounted for 77% of head injuries, and in those 2 to 12, falls accounted for 38% of injuries. In children ages 13 to 17, 24% of injuries were due to assault, 19% were sports-related, and 18% resulted from motor vehicle accidents. Among all cases, 98% had mild head trauma. During diagnosis and treatment, cranial CT scans were performed on 37% of the children, “many arguably unnecessarily,” according to the researchers.
Preadmission use of COX-2 inhibitors was associated with increased 30-day mortality after ischemic stroke, but not hemorrhagic stroke, according to a study published online ahead of print November 5 in Neurology. Researchers analyzed records of 100,243 patients hospitalized for a first stroke between 2004 and 2012 and deaths within one month after the stroke. The investigators examined whether participants were current, former, or nonusers of these drugs within two months of the stroke. Overall, people who were current users of COX-2 inhibitors were 19% more likely to die after stroke than were people who did not take the drugs. New users of the older COX-2 drugs were 42% more likely to die from stroke than were those who were not taking the drugs.
Once-daily, low-dose aspirin did not significantly reduce the risk of the composite outcome of cardiovascular death, nonfatal stroke, and nonfatal myocardial infarction among patients age 60 or older with atherosclerotic risk factors, according to a study published online ahead of print November 17 in JAMA. This study included 14,464 Japanese patients with hypertension, dyslipidemia, or diabetes mellitus who were randomized to aspirin (100 mg/d) or no aspirin in addition to ongoing medications. The researchers found no statistically significant difference between the two groups in time to the primary end point. The cumulative primary event rate was similar in participants in the aspirin group (2.77%) and those in the no-aspirin group (2.96%) five years after randomization. Aspirin significantly reduced the incidence of nonfatal heart attack and transient ischemic attack, and significantly increased the risk of extracranial hemorrhage requiring transfusion or hospitalization.
Overall symptom burden is the only independent predictor of prolonged symptoms after sport-related concussion, investigators reported online ahead of print November 7 in Neurology. The researchers conducted a prospective cohort study of 531 patients in a sports concussion clinic. Participants completed questionnaires that included the Post-Concussion Symptom Scale (PCSS). Patients ranged in age from 7 to 26 (mean age, 14.6). The mean PCSS score at the initial visit was 26, and mean time to presentation was 12 days. Only total score on symptom inventory was independently associated with symptoms lasting longer than 28 days. No other potential predictor variables were independently associated with symptom duration or were useful in developing the optimal regression decision tree. Most participants with an initial PCSS score of less than 13 had resolution of their symptoms within 28 days of injury.
The ketogenic diet and modified Atkins diet show modest efficacy, although in some patients the effect is “remarkable” in the treatment of refractory epilepsy in adults, according to a study published online ahead of print October 29 in Neurology. Researchers reviewed five studies on the ketogenic diet that included 47 people and five studies on the modified Atkins diet that included 85 people. The investigators found that across all studies, 32% of people treated with the ketogenic diet and 29% of those treated with the modified Atkins diet had a 50% or better reduction in their seizures. Nine percent in the ketogenic treatment group and 5% in the modified Atkins group had a greater than 90% reduction in seizures. “These studies show the diets are moderately to very effective as another option for people with epilepsy,” stated the study authors.
The evaluation of serum micro-RNAs may help to identify the severity of brain injury and the risk of developing adverse effects after traumatic brain injury (TBI), according to a study published November 7 in PLoS One. Researchers identified a unique and specific group of microRNAs, which were detected in blood immediately after injury to the brain in mice. The results suggest that the microRNAs can be measured in the blood as proxies for mild TBI. The microRNA panel identified in this study is unique and does not overlap with blood microRNAs of post-traumatic stress disorder, as previously reported. “This important finding is a step forward in identifying objective biomarkers for mild TBI that may be further validated to accurately and cost effectively identify mild TBI in service members and civilians with brain injuries,” said the investigators.
The FDA has approved Lemtrada (alemtuzumab) for the treatment of patients with relapsing forms of multiple sclerosis (MS). The approval comes nearly one year after the FDA declined to approve the drug, citing a lack of well-controlled data from clinical studies at the time indicating that the benefits had outweighed the risks. After an appeal by Genzyme (Cambridge, Massachusetts) and a new review by the FDA, the agency approved the drug based on two pivotal, randomized phase III, open-label, rater-blinded studies, comparing treatment with Lemtrada to interferon beta-1a, in patients with relapsing-remitting MS who were either new to treatment (CARE-MS I) or who had relapsed while on prior therapy (CARE-MS II). Lemtrada is recommended for patients who have had an inadequate response to two or more drugs indicated for the treatment of MS.
Angiotensin-converting enzyme inhibitors (ACEIs) exhibited a dose-dependent inverse association with amyotrophic lateral sclerosis (ALS), according to a study published online ahead of print November 10 in JAMA Neurology. Researchers included 729 patients diagnosed with ALS between January 2002 and December 2008. The patients were compared with 14,580 controls. Fifteen percent of patients with ALS reported ACEI use between two and five years before their ALS diagnosis, and 18% of the control group without ALS reported ACEI use. When compared with patients who did not use ACEIs, the adjusted odds ratios were 0.83 for the group prescribed ACEIs lower than 449.5 of the cumulative defined daily dose (cDDD) and 0.43 cDDD for the group with a cumulative ACEI use of greater than 449.5 cDDD.
Patients treated at hospitals with higher volumes of subarachnoid hemorrhage (SAH) cases have lower in-hospital mortality, independent of patient and hospital characteristics, according to a study published in the November Neurosurgery. In a large nationwide registry, researchers identified nearly 32,000 patients with SAH treated at 685 United States hospitals between 2003 and 2012. The median annual case volume per hospital was 8.5 patients. Mean in-hospital mortality was 25.7% but was lower with increasing annual SAH volume. Hospital SAH volume was independently associated with in-hospital mortality (adjusted odds ratio, 0.79 for quartile 4 vs quartile 1), independent of patient and other hospital characteristics. “Our results may have significant implications for regional stroke policies and procedures and affirm the recent recommendations that patients with SAH be treated at high-volume centers,” said study authors.
The use of a specialized ambulance—stroke emergency mobile unit (STEMO)—increases the percentage of patients receiving thrombolysis within 60 minutes, according to a study published online ahead of print November 17 in JAMA Neurology. A total of 3,213 emergency calls for suspected stroke occurred during weeks when STEMO was available, and 2,969 calls occurred during control weeks when STEMO was not available. Two hundred of 614 patients with stroke (32.6%) received thrombolysis when the STEMO was deployed, and 330 of 1,497 patients (22%) received thrombolysis in conventional care. Median onset to treatment was 24.5 minutes shorter after STEMO deployment, compared with conventional care. In all ischemic strokes, the rate of “golden hour” thrombolysis increased from 16 of the 1,497 patients (1.1%) during conventional care to 62 of 614 (10.1%) after STEMO deployment. Overall, golden hour thrombolysis entails no risk to the patients’ safety and is associated with better short-term outcomes, according to the researchers.
Granger causality (GC) analysis of intracranial EEG (iEEG) has the potential to increase understanding of preictal network activity and help improve surgical outcomes in cases of otherwise ambiguous iEEG onset, according to a study published online ahead of print November 4 in Epilepsia. In 10 retrospective and two prospective patients with epilepsy, iEEG was recorded at 500 or 1,000 Hz, using as many as 128 surface and depth electrodes. In all patients, the researchers found significant, widespread preictal GC network activity at peak frequencies from 80 to 250 Hz, beginning two to 42 seconds before visible electrographic onset. In the two prospective patients, GC source/sink comparisons supported the exclusion of early ictal regions that were not the dominant causal sources and contributed to planning of more limited surgical resections. Both groups of patients had a class 1 outcome at one year.
Tiny silent acute infarcts may be a cause of leukoaraiosis, a finding that points toward a potentially treatable form of dementia, investigators reported online ahead of print October 4 in Annals of Neurology. The study involved five patients with leukoaraiosis who underwent detailed MRI scanning of their brains every week for 16 consecutive weeks. The MRI scans revealed new tiny spots arising de novo in the cerebral white matter. The lesions were “clinically silent and had the signature features of acute ischemic stroke, according to the researchers. “With time, the characteristics of these lesions approached those of pre-existing leukoaraiosis,” the study authors stated.
—Kimberly D. Williams
New and Noteworthy Information—November 2014
Researchers found no long-term association of vaccines with multiple sclerosis (MS) or any other CNS demyelinating syndromes, according to a study published online ahead of print October 20 in JAMA Neurology. The investigators examined the relationship between vaccines and MS or other CNS demyelinating syndromes by using data from Kaiser Permanente Southern California members. The study authors identified 780 cases of CNS demyelinating syndromes and 3,885 controls; 92 cases and 459 controls were females between the ages of 9 and 26, which is the indicated age range for human papillomavirus (HPV) vaccination. The researchers found no associations between HepB vaccinations, HPV vaccination, or any vaccination and the risk of MS or CNS demyelinating syndromes for as long as three years later. Vaccination of any type was associated with increased risk of a CNS demyelinating syndrome onset within the first 30 days after vaccination only in patients younger than 50, but this association was not evident after 30 days.
Bariatric surgery is a potential risk factor for spontaneous intracranial hypotension, according to a study published online ahead of print October 22 in Neurology. Researchers compared a group of 338 patients with spontaneous intracranial hypotension to a control group of 245 people with unruptured intracranial aneurysms. Eleven of the 338 (3.3%) people with spontaneous intracranial hypotension had previously had bariatric surgery, compared with two of the 245 (0.8%) people with intracranial aneurysms. Of the 11 people with bariatric surgery and spontaneous intracranial hypotension, nine had no more symptoms after treatment, while symptoms persisted for two. The symptoms started from three months to 20 years after the bariatric surgery, and participants had lost an average of 116 pounds during that time.
Longitudinal measures of cortical atrophy were widely correlated with sleep quality, according to a study published September 9 in Neurology. The study included 147 adults, ages 20 and 84. Researchers examined the link between sleep difficulties, such as having trouble falling asleep or staying asleep at night, and brain volume. All participants underwent two MRI brain scans, an average of 3.5 years apart, before completing a questionnaire about their sleep habits. A total of 35% of the participants met the criteria for poor sleep quality, scoring an average of 8.5 out of 21 points on the sleep assessment. The researchers found that sleep difficulties were linked with a more rapid decline in brain volume during the course of the study in various brain regions, including within frontal, temporal, and parietal areas. The results were more pronounced in people older than 60.
An international group of researchers has established the first standardized guidelines for the collection of blood to test for early Alzheimer’s disease, as reported online ahead of print September 27 in Alzheimer’s & Dementia. These guidelines will be used in research for blood-based biomarkers of Alzheimer’s disease and will ensure that every laboratory is following the same protocol when collecting blood. The lack of readily available biomarkers is a significant hindrance toward progressing to effective therapeutic and preventative strategies for Alzheimer’s disease. Researchers have worked with representatives from the United States, Germany, Australia, England, and other countries to create these standards. “You can create a blood test in the lab, but if you don’t have a systemized way for collecting the blood, the test will never go into practice,” said the investigators.
A new study suggests a cause of amyotrophic lateral sclerosis (ALS), according to a study published online ahead of print October 14 in Proceedings of the National Academy of Sciences. Researchers used advanced biophysical methods to probe how different superoxide dismutase 1(SOD1) gene mutations in a genetic ALS hotspot affect SOD protein stability. Investigators examined how the aggregation dynamics of mutant SOD G93A differed from that of nonmutant SOD. They developed a method for gradually inducing SOD aggregation, which was measured with SAXS, a structural imaging system. The G93-mutant SODs appear to have looser, floppier structures that are more likely to drop their copper ions and are more likely to misfold and stick together in aggregates. “Our work supports a common theme whereby loss of protein stability leads to disease,” investigators said.
Long-term functional outcome and risk of fatal or disabling stroke are similar for stenting and endarterectomy for symptomatic carotid stenosis, according to a study published online ahead of print October 14 in the Lancet. Researchers followed 1,713 patients with carotid artery disease, of whom 855 were assigned to stenting and 858 to endarterectomy, for as long as 10 years. The median follow-up was 4.2 years. Both techniques were found to be equally good at preventing fatal and disabling strokes, but stented patients were slightly more likely to have minor strokes without long-term effects. The risk of any stroke in five years was 15.2% in the stenting group, compared with 9.4% in the endarterectomy group, but the additional strokes were minor and had no impact on long-term quality of life.
Researchers have found Class II evidence that serum metabolite profiles accurately distinguish patients with different subtypes and stages of multiple sclerosis (MS), according to a study published October 21 in Neurology. Investigators obtained serum samples from patients with primary progressive MS, secondary-progressive MS, and relapsing-remitting MS, patients with other neurodegenerative conditions, and from age-matched controls. Samples were analyzed by nuclear magnetic resonance, and partial least squares discriminant analysis models were derived to separate disease groups. The partial least squares discriminant analysis models for serum samples from patients with MS enabled reliable differentiation between relapsing-remitting MS and secondary-progressive MS. This approach identified significant differences between the metabolite profiles of each of the MS groups and the healthy controls, as well as predicting disease group membership with high sensitivity and specificity.
Parkinson’s disease pathogenic mutations have an age-dependent penetrance that could be ameliorated or exacerbated by modifier genes or environmental factors in different populations, according to a study published online ahead of print October 20 in JAMA Neurology. The investigators examined 49 previously published studies that included 709 participants and were found in ISI Web of Science and PubMed. They also analyzed extracted information about the number of mutation carriers within families and sporadic cases worldwide for pathogenic mutations in SNCA, LRRK2, VPS35, EIF4G1, and DNAJC13. The end-of-search date was January 31, 2014. In particular, penetrance of SNCA duplications were comparable to point mutations and driven by inclusion of SNCA p.A53T (mean age at onset, 45.9). Each penetrance estimate was given separately with 95% confidence intervals.
Spreading depolarizations can be measured after traumatic brain injury (TBI) by the placement of EEG electrodes on the scalp, according to a study published online ahead of print August 25 in Annals of Neurology. Eighteen patients requiring surgical treatment for TBI were monitored by invasive electrocorticography (ECoG) and noninvasive scalp EEG during intensive care. Spreading depolarizations were first identified in subdural recordings, and EEGs were then examined visually and quantitatively to identify correlates. A total of 455 spreading depolarizations occurred during 65.9 days of simultaneous ECoG and EEG monitoring. For 179 of 455 events (39%), depolarizations caused temporally isolated, transient depressions of spontaneous EEG amplitudes to 57% (median) of baseline power. For 62 of 179 (35%) events, isolated depressions showed a clear spread of depression between EEG channels with delays of 17 minutes (median).
A diet that includes walnuts may have a beneficial effect on reducing the risk, delaying the onset, and slowing the progression of, or preventing, Alzheimer’s disease, according to a study published October 21 in the Journal of Alzheimer’s Disease. The research group examined the effects of dietary supplementation on mice with 6% or 9% walnuts, which is equivalent to 1 ounce and 1.5 ounces per day, respectively, of walnuts in humans. The investigators found significant improvement in learning skills, memory, reducing anxiety, and motor development in mice fed a walnut-enriched diet. “These findings are very promising and help lay the groundwork for future human studies on walnuts and Alzheimer’s disease,” the investigators said.
Dopamine receptor agonist drugs are associated with impulse control disorders, such as pathologic gambling, hypersexuality, and compulsive shopping, according to a study that was published online ahead of print October 20 in JAMA Internal Medicine. Researchers conducted a retrospective disproportionality analysis that was based on the 2.7 million serious domestic and foreign adverse drug event reports between 2003 and 2012 that were extracted from the FDA Adverse Event Reporting System. The investigators identified 1,580 events indicating impulse control disorders from the United States and 21 other countries (710 for dopamine receptor agonist drugs and 870 for other drugs). The dopamine receptor agonist drugs had a strong signal associated with these impulse control disorders. The association was strongest for the dopamine agonists pramipexole and ropinirole, with preferential affinity for the dopamine D3 receptor. A signal was also seen for aripiprazole.
—Kimberly D. Williams
Researchers found no long-term association of vaccines with multiple sclerosis (MS) or any other CNS demyelinating syndromes, according to a study published online ahead of print October 20 in JAMA Neurology. The investigators examined the relationship between vaccines and MS or other CNS demyelinating syndromes by using data from Kaiser Permanente Southern California members. The study authors identified 780 cases of CNS demyelinating syndromes and 3,885 controls; 92 cases and 459 controls were females between the ages of 9 and 26, which is the indicated age range for human papillomavirus (HPV) vaccination. The researchers found no associations between HepB vaccinations, HPV vaccination, or any vaccination and the risk of MS or CNS demyelinating syndromes for as long as three years later. Vaccination of any type was associated with increased risk of a CNS demyelinating syndrome onset within the first 30 days after vaccination only in patients younger than 50, but this association was not evident after 30 days.
Bariatric surgery is a potential risk factor for spontaneous intracranial hypotension, according to a study published online ahead of print October 22 in Neurology. Researchers compared a group of 338 patients with spontaneous intracranial hypotension to a control group of 245 people with unruptured intracranial aneurysms. Eleven of the 338 (3.3%) people with spontaneous intracranial hypotension had previously had bariatric surgery, compared with two of the 245 (0.8%) people with intracranial aneurysms. Of the 11 people with bariatric surgery and spontaneous intracranial hypotension, nine had no more symptoms after treatment, while symptoms persisted for two. The symptoms started from three months to 20 years after the bariatric surgery, and participants had lost an average of 116 pounds during that time.
Longitudinal measures of cortical atrophy were widely correlated with sleep quality, according to a study published September 9 in Neurology. The study included 147 adults, ages 20 and 84. Researchers examined the link between sleep difficulties, such as having trouble falling asleep or staying asleep at night, and brain volume. All participants underwent two MRI brain scans, an average of 3.5 years apart, before completing a questionnaire about their sleep habits. A total of 35% of the participants met the criteria for poor sleep quality, scoring an average of 8.5 out of 21 points on the sleep assessment. The researchers found that sleep difficulties were linked with a more rapid decline in brain volume during the course of the study in various brain regions, including within frontal, temporal, and parietal areas. The results were more pronounced in people older than 60.
An international group of researchers has established the first standardized guidelines for the collection of blood to test for early Alzheimer’s disease, as reported online ahead of print September 27 in Alzheimer’s & Dementia. These guidelines will be used in research for blood-based biomarkers of Alzheimer’s disease and will ensure that every laboratory is following the same protocol when collecting blood. The lack of readily available biomarkers is a significant hindrance toward progressing to effective therapeutic and preventative strategies for Alzheimer’s disease. Researchers have worked with representatives from the United States, Germany, Australia, England, and other countries to create these standards. “You can create a blood test in the lab, but if you don’t have a systemized way for collecting the blood, the test will never go into practice,” said the investigators.
A new study suggests a cause of amyotrophic lateral sclerosis (ALS), according to a study published online ahead of print October 14 in Proceedings of the National Academy of Sciences. Researchers used advanced biophysical methods to probe how different superoxide dismutase 1(SOD1) gene mutations in a genetic ALS hotspot affect SOD protein stability. Investigators examined how the aggregation dynamics of mutant SOD G93A differed from that of nonmutant SOD. They developed a method for gradually inducing SOD aggregation, which was measured with SAXS, a structural imaging system. The G93-mutant SODs appear to have looser, floppier structures that are more likely to drop their copper ions and are more likely to misfold and stick together in aggregates. “Our work supports a common theme whereby loss of protein stability leads to disease,” investigators said.
Long-term functional outcome and risk of fatal or disabling stroke are similar for stenting and endarterectomy for symptomatic carotid stenosis, according to a study published online ahead of print October 14 in the Lancet. Researchers followed 1,713 patients with carotid artery disease, of whom 855 were assigned to stenting and 858 to endarterectomy, for as long as 10 years. The median follow-up was 4.2 years. Both techniques were found to be equally good at preventing fatal and disabling strokes, but stented patients were slightly more likely to have minor strokes without long-term effects. The risk of any stroke in five years was 15.2% in the stenting group, compared with 9.4% in the endarterectomy group, but the additional strokes were minor and had no impact on long-term quality of life.
Researchers have found Class II evidence that serum metabolite profiles accurately distinguish patients with different subtypes and stages of multiple sclerosis (MS), according to a study published October 21 in Neurology. Investigators obtained serum samples from patients with primary progressive MS, secondary-progressive MS, and relapsing-remitting MS, patients with other neurodegenerative conditions, and from age-matched controls. Samples were analyzed by nuclear magnetic resonance, and partial least squares discriminant analysis models were derived to separate disease groups. The partial least squares discriminant analysis models for serum samples from patients with MS enabled reliable differentiation between relapsing-remitting MS and secondary-progressive MS. This approach identified significant differences between the metabolite profiles of each of the MS groups and the healthy controls, as well as predicting disease group membership with high sensitivity and specificity.
Parkinson’s disease pathogenic mutations have an age-dependent penetrance that could be ameliorated or exacerbated by modifier genes or environmental factors in different populations, according to a study published online ahead of print October 20 in JAMA Neurology. The investigators examined 49 previously published studies that included 709 participants and were found in ISI Web of Science and PubMed. They also analyzed extracted information about the number of mutation carriers within families and sporadic cases worldwide for pathogenic mutations in SNCA, LRRK2, VPS35, EIF4G1, and DNAJC13. The end-of-search date was January 31, 2014. In particular, penetrance of SNCA duplications were comparable to point mutations and driven by inclusion of SNCA p.A53T (mean age at onset, 45.9). Each penetrance estimate was given separately with 95% confidence intervals.
Spreading depolarizations can be measured after traumatic brain injury (TBI) by the placement of EEG electrodes on the scalp, according to a study published online ahead of print August 25 in Annals of Neurology. Eighteen patients requiring surgical treatment for TBI were monitored by invasive electrocorticography (ECoG) and noninvasive scalp EEG during intensive care. Spreading depolarizations were first identified in subdural recordings, and EEGs were then examined visually and quantitatively to identify correlates. A total of 455 spreading depolarizations occurred during 65.9 days of simultaneous ECoG and EEG monitoring. For 179 of 455 events (39%), depolarizations caused temporally isolated, transient depressions of spontaneous EEG amplitudes to 57% (median) of baseline power. For 62 of 179 (35%) events, isolated depressions showed a clear spread of depression between EEG channels with delays of 17 minutes (median).
A diet that includes walnuts may have a beneficial effect on reducing the risk, delaying the onset, and slowing the progression of, or preventing, Alzheimer’s disease, according to a study published October 21 in the Journal of Alzheimer’s Disease. The research group examined the effects of dietary supplementation on mice with 6% or 9% walnuts, which is equivalent to 1 ounce and 1.5 ounces per day, respectively, of walnuts in humans. The investigators found significant improvement in learning skills, memory, reducing anxiety, and motor development in mice fed a walnut-enriched diet. “These findings are very promising and help lay the groundwork for future human studies on walnuts and Alzheimer’s disease,” the investigators said.
Dopamine receptor agonist drugs are associated with impulse control disorders, such as pathologic gambling, hypersexuality, and compulsive shopping, according to a study that was published online ahead of print October 20 in JAMA Internal Medicine. Researchers conducted a retrospective disproportionality analysis that was based on the 2.7 million serious domestic and foreign adverse drug event reports between 2003 and 2012 that were extracted from the FDA Adverse Event Reporting System. The investigators identified 1,580 events indicating impulse control disorders from the United States and 21 other countries (710 for dopamine receptor agonist drugs and 870 for other drugs). The dopamine receptor agonist drugs had a strong signal associated with these impulse control disorders. The association was strongest for the dopamine agonists pramipexole and ropinirole, with preferential affinity for the dopamine D3 receptor. A signal was also seen for aripiprazole.
—Kimberly D. Williams
Researchers found no long-term association of vaccines with multiple sclerosis (MS) or any other CNS demyelinating syndromes, according to a study published online ahead of print October 20 in JAMA Neurology. The investigators examined the relationship between vaccines and MS or other CNS demyelinating syndromes by using data from Kaiser Permanente Southern California members. The study authors identified 780 cases of CNS demyelinating syndromes and 3,885 controls; 92 cases and 459 controls were females between the ages of 9 and 26, which is the indicated age range for human papillomavirus (HPV) vaccination. The researchers found no associations between HepB vaccinations, HPV vaccination, or any vaccination and the risk of MS or CNS demyelinating syndromes for as long as three years later. Vaccination of any type was associated with increased risk of a CNS demyelinating syndrome onset within the first 30 days after vaccination only in patients younger than 50, but this association was not evident after 30 days.
Bariatric surgery is a potential risk factor for spontaneous intracranial hypotension, according to a study published online ahead of print October 22 in Neurology. Researchers compared a group of 338 patients with spontaneous intracranial hypotension to a control group of 245 people with unruptured intracranial aneurysms. Eleven of the 338 (3.3%) people with spontaneous intracranial hypotension had previously had bariatric surgery, compared with two of the 245 (0.8%) people with intracranial aneurysms. Of the 11 people with bariatric surgery and spontaneous intracranial hypotension, nine had no more symptoms after treatment, while symptoms persisted for two. The symptoms started from three months to 20 years after the bariatric surgery, and participants had lost an average of 116 pounds during that time.
Longitudinal measures of cortical atrophy were widely correlated with sleep quality, according to a study published September 9 in Neurology. The study included 147 adults, ages 20 and 84. Researchers examined the link between sleep difficulties, such as having trouble falling asleep or staying asleep at night, and brain volume. All participants underwent two MRI brain scans, an average of 3.5 years apart, before completing a questionnaire about their sleep habits. A total of 35% of the participants met the criteria for poor sleep quality, scoring an average of 8.5 out of 21 points on the sleep assessment. The researchers found that sleep difficulties were linked with a more rapid decline in brain volume during the course of the study in various brain regions, including within frontal, temporal, and parietal areas. The results were more pronounced in people older than 60.
An international group of researchers has established the first standardized guidelines for the collection of blood to test for early Alzheimer’s disease, as reported online ahead of print September 27 in Alzheimer’s & Dementia. These guidelines will be used in research for blood-based biomarkers of Alzheimer’s disease and will ensure that every laboratory is following the same protocol when collecting blood. The lack of readily available biomarkers is a significant hindrance toward progressing to effective therapeutic and preventative strategies for Alzheimer’s disease. Researchers have worked with representatives from the United States, Germany, Australia, England, and other countries to create these standards. “You can create a blood test in the lab, but if you don’t have a systemized way for collecting the blood, the test will never go into practice,” said the investigators.
A new study suggests a cause of amyotrophic lateral sclerosis (ALS), according to a study published online ahead of print October 14 in Proceedings of the National Academy of Sciences. Researchers used advanced biophysical methods to probe how different superoxide dismutase 1(SOD1) gene mutations in a genetic ALS hotspot affect SOD protein stability. Investigators examined how the aggregation dynamics of mutant SOD G93A differed from that of nonmutant SOD. They developed a method for gradually inducing SOD aggregation, which was measured with SAXS, a structural imaging system. The G93-mutant SODs appear to have looser, floppier structures that are more likely to drop their copper ions and are more likely to misfold and stick together in aggregates. “Our work supports a common theme whereby loss of protein stability leads to disease,” investigators said.
Long-term functional outcome and risk of fatal or disabling stroke are similar for stenting and endarterectomy for symptomatic carotid stenosis, according to a study published online ahead of print October 14 in the Lancet. Researchers followed 1,713 patients with carotid artery disease, of whom 855 were assigned to stenting and 858 to endarterectomy, for as long as 10 years. The median follow-up was 4.2 years. Both techniques were found to be equally good at preventing fatal and disabling strokes, but stented patients were slightly more likely to have minor strokes without long-term effects. The risk of any stroke in five years was 15.2% in the stenting group, compared with 9.4% in the endarterectomy group, but the additional strokes were minor and had no impact on long-term quality of life.
Researchers have found Class II evidence that serum metabolite profiles accurately distinguish patients with different subtypes and stages of multiple sclerosis (MS), according to a study published October 21 in Neurology. Investigators obtained serum samples from patients with primary progressive MS, secondary-progressive MS, and relapsing-remitting MS, patients with other neurodegenerative conditions, and from age-matched controls. Samples were analyzed by nuclear magnetic resonance, and partial least squares discriminant analysis models were derived to separate disease groups. The partial least squares discriminant analysis models for serum samples from patients with MS enabled reliable differentiation between relapsing-remitting MS and secondary-progressive MS. This approach identified significant differences between the metabolite profiles of each of the MS groups and the healthy controls, as well as predicting disease group membership with high sensitivity and specificity.
Parkinson’s disease pathogenic mutations have an age-dependent penetrance that could be ameliorated or exacerbated by modifier genes or environmental factors in different populations, according to a study published online ahead of print October 20 in JAMA Neurology. The investigators examined 49 previously published studies that included 709 participants and were found in ISI Web of Science and PubMed. They also analyzed extracted information about the number of mutation carriers within families and sporadic cases worldwide for pathogenic mutations in SNCA, LRRK2, VPS35, EIF4G1, and DNAJC13. The end-of-search date was January 31, 2014. In particular, penetrance of SNCA duplications were comparable to point mutations and driven by inclusion of SNCA p.A53T (mean age at onset, 45.9). Each penetrance estimate was given separately with 95% confidence intervals.
Spreading depolarizations can be measured after traumatic brain injury (TBI) by the placement of EEG electrodes on the scalp, according to a study published online ahead of print August 25 in Annals of Neurology. Eighteen patients requiring surgical treatment for TBI were monitored by invasive electrocorticography (ECoG) and noninvasive scalp EEG during intensive care. Spreading depolarizations were first identified in subdural recordings, and EEGs were then examined visually and quantitatively to identify correlates. A total of 455 spreading depolarizations occurred during 65.9 days of simultaneous ECoG and EEG monitoring. For 179 of 455 events (39%), depolarizations caused temporally isolated, transient depressions of spontaneous EEG amplitudes to 57% (median) of baseline power. For 62 of 179 (35%) events, isolated depressions showed a clear spread of depression between EEG channels with delays of 17 minutes (median).
A diet that includes walnuts may have a beneficial effect on reducing the risk, delaying the onset, and slowing the progression of, or preventing, Alzheimer’s disease, according to a study published October 21 in the Journal of Alzheimer’s Disease. The research group examined the effects of dietary supplementation on mice with 6% or 9% walnuts, which is equivalent to 1 ounce and 1.5 ounces per day, respectively, of walnuts in humans. The investigators found significant improvement in learning skills, memory, reducing anxiety, and motor development in mice fed a walnut-enriched diet. “These findings are very promising and help lay the groundwork for future human studies on walnuts and Alzheimer’s disease,” the investigators said.
Dopamine receptor agonist drugs are associated with impulse control disorders, such as pathologic gambling, hypersexuality, and compulsive shopping, according to a study that was published online ahead of print October 20 in JAMA Internal Medicine. Researchers conducted a retrospective disproportionality analysis that was based on the 2.7 million serious domestic and foreign adverse drug event reports between 2003 and 2012 that were extracted from the FDA Adverse Event Reporting System. The investigators identified 1,580 events indicating impulse control disorders from the United States and 21 other countries (710 for dopamine receptor agonist drugs and 870 for other drugs). The dopamine receptor agonist drugs had a strong signal associated with these impulse control disorders. The association was strongest for the dopamine agonists pramipexole and ropinirole, with preferential affinity for the dopamine D3 receptor. A signal was also seen for aripiprazole.
—Kimberly D. Williams