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New Risk Factors for Alzheimer’s Disease?
Vision and hearing deficits, poorly fitting dentures, and increased serum proinflammatory cytokines all may be risk factors for Alzheimer’s disease, according to three studies published in the July 12 online issue of Neurology.
Alzheimer’s disease and dementia risk were associated with health deficits that are usually seen in the elderly but were not previously known to predict dementia, according to a study by Xiaowei Song, PhD, of Dalhousie University, Halifax, Canada, and colleagues.
The investigators created an index combining 19 such deficits—including problems with vision, hearing, denture fit, chest or skin, stomach or bladder, sinuses, broken bones, and feet or ankles—and applied it to 7,239 participants who were age 65 or older and free of dementia at baseline. After adjustment for age, sex, education, and baseline cognition, participants’ index scores were significantly associated with Alzheimer’s disease and dementia of all types at five and 10 years. In addition, their risk of dementia increased by 3.2% with each deficit included in the index.
Both lower and higher levels of hemoglobin were associated with Alzheimer’s disease and cognitive decline in a study by Raj C. Shah, MD, of Rush University Medical Center in Chicago, and colleagues. They gave annual cognitive assessments and clinical evaluations for Alzheimer’s disease to 881 community-dwelling, elderly participants for a mean of 3.3 years.
With adjustment for age, sex, and education, higher and lower levels of hemoglobin were associated with Alzheimer’s disease risk, with a hazard ratio of 1.06 for the quadratic of hemoglobin. Participants who had anemia or clinically high hemoglobin had a 60% increased risk of Alzheimer’s disease dementia, compared with participants who had clinically normal hemoglobin.
Increased serum proinflammatory cytokines predicted such “sickness behaviors” as increased anxiety, depression, and apathy in patients with Alzheimer’s disease, according to a study by Clive Holmes, PhD, of the University of Southampton, Southampton, UK, and colleagues. The investigators took blood samples from and performed cognitive assessments on 300 patients with mild to severe Alzheimer’s disease at baseline and two, four, and six months. Increased levels of serum tumor necrosis factor and IL-6 at baseline were associated with an approximately twofold increased frequency of neuropsychiatric symptoms characteristic of sickness behavior, independent of a history of delirium, at six months.
Despite these findings, “much uncertainty remains” about the value of nontraditional Alzheimer’s disease risk factors, emphasized Jean François Dartigues, MD, PhD, and Catherine Féart, PhD, both of the University of Victor Segalen of Bordeaux, Bordeaux, France, in an accompanying editorial. They suggested that “the studied factors could be a nonspecific consequence of aging phenomenon” and that health-related behaviors, nutritional factors, physical activities, or leisure activities could have affected the studies’ results.
Nevertheless, they added, the studies “suggest a new vision of preventive or curative treatments which, instead of targeting specific etiologic mechanisms, would aim at improving general health. Perhaps increasing adaptation to age-related changes would reduce the risk of Alzheimer’s disease dementia or its impact on the patient, caregivers, and society.”
Holmes C, Cunningham C, Zotova E, et al. Proinflammatory cytokines, sickness behavior, and Alzheimer disease. Neurology. 2011;77(3):212-218.
Shah RC, Buchman AS, Wilson RS, et al. Hemoglobin level in older persons and incident Alzheimer disease: prospective cohort analysis. Neurology. 2011;77(3):219-226.
Song X, Mitnitski A, Rockwood K. Nontraditional risk factors combine to predict Alzheimer disease and dementia. Neurology. 2011;77(3):227-234.
Dartigues JF, Féart C. Risk factors for Alzheimer disease: aging beyond age? Neurology. 2011;77(3):206-207.
Reducing Tonic-Clonic Seizures Can Minimize Risk of SUDEP
Clinicians can minimize the risk of sudden unexpected death in epilepsy (SUDEP) through such measures as reducing tonic-clonic seizures, choosing drugs carefully, changing treatments gradually, acting on ictal warning signs, and supervising and counseling patients, according to a seminar published online July 6 in Lancet. The seminar, by Simon Shorvon, FRCP, of the UCL Institute of Neurology in London, and Torbjorn Tomson, MD, of the Karolinska Institute in Stockholm, reviewed current research on and provided advice about minimizing SUDEP risk.
Almost all studies indicate that this risk is high in patients with a high number of tonic-clonic seizures, the authors noted. They suggested reducing these seizures through optimum treatment, good drug compliance, and advice on such lifestyle choices as alcohol intake and sleep. Ictal warning signs for tonic-clonic seizures include prolonged seizures that are associated with marked cyanosis, severe bradycardia or apnea, and postictal EEG suppression; complex partial seizures with marked atonia; and seizures in patients with pre-existing cardiac or respiratory impairment.
Patients who experience tonic-clonic seizures require supervision, the authors noted. They recommended attending to these patients continuously until the full restoration of consciousness, contacting emergency services for high-risk seizures, and supervising high-risk patients at night through attendance and use of alarms.
Clinicians should be cautious in using antiepileptic drugs (AEDs) with potential cardiorespiratory adverse effects, according to the researchers. When clinicians switch AEDs, they should introduce the new drug before withdrawing the old one and provide patients with “access to immediate advice in the event of worsening seizures,” the investigators stated.
Although some clinicians believe that informing all patients with epilepsy about the risk of SUDEP will cause unnecessary stress and anxiety, the authors recommended informing most patients about the risk to facilitate its minimization. However, they further suggested putting the risk in perspective—for example, by pointing out that, on an annual basis, it is similar to that of dying in a motor vehicle accident.
SUDEP probably has several mechanisms, and “most research has focused on seizure-related respiratory depression, cardiac arrhythmia, cerebral depression, and autonomic dysfunction,” the authors noted. Along with tonic-clonic seizures, risk factors for the event include male sex, long-duration epilepsy, and antiepileptic polytherapy.
Shorvon S, Tomson T. Sudden unexpected death in epilepsy. Lancet. 2011 Jul 5; [Epub ahead of print].
How Cost-Effective Are Disease-Modifying Therapies in MS?
Disease-modifying therapies (DMTs) for relapsing-remitting or secondary progressive multiple sclerosis (MS) do not appear to be cost-effective in the United States, according to findings published online July 20 by Neurology.
Katia Noyes, PhD, MPH, of the University of Rochester, New York, and colleagues calculated the cost-effectiveness of four DMTs in a nationally representative cohort of 1,121 patients with MS. The investigators generated 10-year disease progression paths for this cohort; looked at data on drug effectiveness, patient health preferences, health care use, lost productivity, and medical costs; measured health gains in quality-adjusted life-years (QALYs) and relapse-free years; and calculated incremental cost-effectiveness ratios (ICERs). The DMTs studied were glatiramer acetate, intramuscular interferon beta-1a, subcutaneous interferon beta-1a, and interferon beta-1b.
DMT therapy for 10 years resulted in modest QALY gains (0.082 for glatiramer acetate and 0.126 to 0.192 for the interferons), compared with basic supportive therapy. In addition, DMT therapy resulted in more relapse-free years throughout the course of a decade; patients on basic therapy averaged 5.051 relapse-free years, compared with 5.879 relapse-free years for glatiramer acetate and 5.620 to 6.074 relapse-free years for the interferons.
However, the ICERs of all four DMTs far exceeded $800,000 per QALY gained. The interferons had similar ICERs, at $901,319/QALY for intramuscular interferon beta-1a, $1,487,306/QALY for subcutaneous interferon beta-1a, and $1,123,162/QALY for interferon beta-1b. The ICER for glatiramer acetate was significantly higher, at $2,178,555/QALY. “While there is no formal cost-effectiveness threshold in the US, these estimates are an order of magnitude greater than the cost-effectiveness of many commonly accepted therapies for chronic illness,” the researchers commented.
The researchers added that cutting DMT costs by two-thirds would make the therapies’ cost-effectiveness comparable to that of other accepted interventions, however. In addition, the investigators noted that starting DMT earlier was associated with a more favorable ICER, compared with initiating treatment at any disease state, and that early treatment “may defer the substantial costs associated with late-stage MS and disability.”
Noyes K, Bajorska A, Chappel A, et al. Cost-effectiveness of disease-modifying therapy for multiple sclerosis: a population-based study. Neurology. 2011 Jul 20; [Epub ahead of print].
New Risk Factors for Alzheimer’s Disease?
Vision and hearing deficits, poorly fitting dentures, and increased serum proinflammatory cytokines all may be risk factors for Alzheimer’s disease, according to three studies published in the July 12 online issue of Neurology.
Alzheimer’s disease and dementia risk were associated with health deficits that are usually seen in the elderly but were not previously known to predict dementia, according to a study by Xiaowei Song, PhD, of Dalhousie University, Halifax, Canada, and colleagues.
The investigators created an index combining 19 such deficits—including problems with vision, hearing, denture fit, chest or skin, stomach or bladder, sinuses, broken bones, and feet or ankles—and applied it to 7,239 participants who were age 65 or older and free of dementia at baseline. After adjustment for age, sex, education, and baseline cognition, participants’ index scores were significantly associated with Alzheimer’s disease and dementia of all types at five and 10 years. In addition, their risk of dementia increased by 3.2% with each deficit included in the index.
Both lower and higher levels of hemoglobin were associated with Alzheimer’s disease and cognitive decline in a study by Raj C. Shah, MD, of Rush University Medical Center in Chicago, and colleagues. They gave annual cognitive assessments and clinical evaluations for Alzheimer’s disease to 881 community-dwelling, elderly participants for a mean of 3.3 years.
With adjustment for age, sex, and education, higher and lower levels of hemoglobin were associated with Alzheimer’s disease risk, with a hazard ratio of 1.06 for the quadratic of hemoglobin. Participants who had anemia or clinically high hemoglobin had a 60% increased risk of Alzheimer’s disease dementia, compared with participants who had clinically normal hemoglobin.
Increased serum proinflammatory cytokines predicted such “sickness behaviors” as increased anxiety, depression, and apathy in patients with Alzheimer’s disease, according to a study by Clive Holmes, PhD, of the University of Southampton, Southampton, UK, and colleagues. The investigators took blood samples from and performed cognitive assessments on 300 patients with mild to severe Alzheimer’s disease at baseline and two, four, and six months. Increased levels of serum tumor necrosis factor and IL-6 at baseline were associated with an approximately twofold increased frequency of neuropsychiatric symptoms characteristic of sickness behavior, independent of a history of delirium, at six months.
Despite these findings, “much uncertainty remains” about the value of nontraditional Alzheimer’s disease risk factors, emphasized Jean François Dartigues, MD, PhD, and Catherine Féart, PhD, both of the University of Victor Segalen of Bordeaux, Bordeaux, France, in an accompanying editorial. They suggested that “the studied factors could be a nonspecific consequence of aging phenomenon” and that health-related behaviors, nutritional factors, physical activities, or leisure activities could have affected the studies’ results.
Nevertheless, they added, the studies “suggest a new vision of preventive or curative treatments which, instead of targeting specific etiologic mechanisms, would aim at improving general health. Perhaps increasing adaptation to age-related changes would reduce the risk of Alzheimer’s disease dementia or its impact on the patient, caregivers, and society.”
Holmes C, Cunningham C, Zotova E, et al. Proinflammatory cytokines, sickness behavior, and Alzheimer disease. Neurology. 2011;77(3):212-218.
Shah RC, Buchman AS, Wilson RS, et al. Hemoglobin level in older persons and incident Alzheimer disease: prospective cohort analysis. Neurology. 2011;77(3):219-226.
Song X, Mitnitski A, Rockwood K. Nontraditional risk factors combine to predict Alzheimer disease and dementia. Neurology. 2011;77(3):227-234.
Dartigues JF, Féart C. Risk factors for Alzheimer disease: aging beyond age? Neurology. 2011;77(3):206-207.
Reducing Tonic-Clonic Seizures Can Minimize Risk of SUDEP
Clinicians can minimize the risk of sudden unexpected death in epilepsy (SUDEP) through such measures as reducing tonic-clonic seizures, choosing drugs carefully, changing treatments gradually, acting on ictal warning signs, and supervising and counseling patients, according to a seminar published online July 6 in Lancet. The seminar, by Simon Shorvon, FRCP, of the UCL Institute of Neurology in London, and Torbjorn Tomson, MD, of the Karolinska Institute in Stockholm, reviewed current research on and provided advice about minimizing SUDEP risk.
Almost all studies indicate that this risk is high in patients with a high number of tonic-clonic seizures, the authors noted. They suggested reducing these seizures through optimum treatment, good drug compliance, and advice on such lifestyle choices as alcohol intake and sleep. Ictal warning signs for tonic-clonic seizures include prolonged seizures that are associated with marked cyanosis, severe bradycardia or apnea, and postictal EEG suppression; complex partial seizures with marked atonia; and seizures in patients with pre-existing cardiac or respiratory impairment.
Patients who experience tonic-clonic seizures require supervision, the authors noted. They recommended attending to these patients continuously until the full restoration of consciousness, contacting emergency services for high-risk seizures, and supervising high-risk patients at night through attendance and use of alarms.
Clinicians should be cautious in using antiepileptic drugs (AEDs) with potential cardiorespiratory adverse effects, according to the researchers. When clinicians switch AEDs, they should introduce the new drug before withdrawing the old one and provide patients with “access to immediate advice in the event of worsening seizures,” the investigators stated.
Although some clinicians believe that informing all patients with epilepsy about the risk of SUDEP will cause unnecessary stress and anxiety, the authors recommended informing most patients about the risk to facilitate its minimization. However, they further suggested putting the risk in perspective—for example, by pointing out that, on an annual basis, it is similar to that of dying in a motor vehicle accident.
SUDEP probably has several mechanisms, and “most research has focused on seizure-related respiratory depression, cardiac arrhythmia, cerebral depression, and autonomic dysfunction,” the authors noted. Along with tonic-clonic seizures, risk factors for the event include male sex, long-duration epilepsy, and antiepileptic polytherapy.
Shorvon S, Tomson T. Sudden unexpected death in epilepsy. Lancet. 2011 Jul 5; [Epub ahead of print].
How Cost-Effective Are Disease-Modifying Therapies in MS?
Disease-modifying therapies (DMTs) for relapsing-remitting or secondary progressive multiple sclerosis (MS) do not appear to be cost-effective in the United States, according to findings published online July 20 by Neurology.
Katia Noyes, PhD, MPH, of the University of Rochester, New York, and colleagues calculated the cost-effectiveness of four DMTs in a nationally representative cohort of 1,121 patients with MS. The investigators generated 10-year disease progression paths for this cohort; looked at data on drug effectiveness, patient health preferences, health care use, lost productivity, and medical costs; measured health gains in quality-adjusted life-years (QALYs) and relapse-free years; and calculated incremental cost-effectiveness ratios (ICERs). The DMTs studied were glatiramer acetate, intramuscular interferon beta-1a, subcutaneous interferon beta-1a, and interferon beta-1b.
DMT therapy for 10 years resulted in modest QALY gains (0.082 for glatiramer acetate and 0.126 to 0.192 for the interferons), compared with basic supportive therapy. In addition, DMT therapy resulted in more relapse-free years throughout the course of a decade; patients on basic therapy averaged 5.051 relapse-free years, compared with 5.879 relapse-free years for glatiramer acetate and 5.620 to 6.074 relapse-free years for the interferons.
However, the ICERs of all four DMTs far exceeded $800,000 per QALY gained. The interferons had similar ICERs, at $901,319/QALY for intramuscular interferon beta-1a, $1,487,306/QALY for subcutaneous interferon beta-1a, and $1,123,162/QALY for interferon beta-1b. The ICER for glatiramer acetate was significantly higher, at $2,178,555/QALY. “While there is no formal cost-effectiveness threshold in the US, these estimates are an order of magnitude greater than the cost-effectiveness of many commonly accepted therapies for chronic illness,” the researchers commented.
The researchers added that cutting DMT costs by two-thirds would make the therapies’ cost-effectiveness comparable to that of other accepted interventions, however. In addition, the investigators noted that starting DMT earlier was associated with a more favorable ICER, compared with initiating treatment at any disease state, and that early treatment “may defer the substantial costs associated with late-stage MS and disability.”
Noyes K, Bajorska A, Chappel A, et al. Cost-effectiveness of disease-modifying therapy for multiple sclerosis: a population-based study. Neurology. 2011 Jul 20; [Epub ahead of print].
New Risk Factors for Alzheimer’s Disease?
Vision and hearing deficits, poorly fitting dentures, and increased serum proinflammatory cytokines all may be risk factors for Alzheimer’s disease, according to three studies published in the July 12 online issue of Neurology.
Alzheimer’s disease and dementia risk were associated with health deficits that are usually seen in the elderly but were not previously known to predict dementia, according to a study by Xiaowei Song, PhD, of Dalhousie University, Halifax, Canada, and colleagues.
The investigators created an index combining 19 such deficits—including problems with vision, hearing, denture fit, chest or skin, stomach or bladder, sinuses, broken bones, and feet or ankles—and applied it to 7,239 participants who were age 65 or older and free of dementia at baseline. After adjustment for age, sex, education, and baseline cognition, participants’ index scores were significantly associated with Alzheimer’s disease and dementia of all types at five and 10 years. In addition, their risk of dementia increased by 3.2% with each deficit included in the index.
Both lower and higher levels of hemoglobin were associated with Alzheimer’s disease and cognitive decline in a study by Raj C. Shah, MD, of Rush University Medical Center in Chicago, and colleagues. They gave annual cognitive assessments and clinical evaluations for Alzheimer’s disease to 881 community-dwelling, elderly participants for a mean of 3.3 years.
With adjustment for age, sex, and education, higher and lower levels of hemoglobin were associated with Alzheimer’s disease risk, with a hazard ratio of 1.06 for the quadratic of hemoglobin. Participants who had anemia or clinically high hemoglobin had a 60% increased risk of Alzheimer’s disease dementia, compared with participants who had clinically normal hemoglobin.
Increased serum proinflammatory cytokines predicted such “sickness behaviors” as increased anxiety, depression, and apathy in patients with Alzheimer’s disease, according to a study by Clive Holmes, PhD, of the University of Southampton, Southampton, UK, and colleagues. The investigators took blood samples from and performed cognitive assessments on 300 patients with mild to severe Alzheimer’s disease at baseline and two, four, and six months. Increased levels of serum tumor necrosis factor and IL-6 at baseline were associated with an approximately twofold increased frequency of neuropsychiatric symptoms characteristic of sickness behavior, independent of a history of delirium, at six months.
Despite these findings, “much uncertainty remains” about the value of nontraditional Alzheimer’s disease risk factors, emphasized Jean François Dartigues, MD, PhD, and Catherine Féart, PhD, both of the University of Victor Segalen of Bordeaux, Bordeaux, France, in an accompanying editorial. They suggested that “the studied factors could be a nonspecific consequence of aging phenomenon” and that health-related behaviors, nutritional factors, physical activities, or leisure activities could have affected the studies’ results.
Nevertheless, they added, the studies “suggest a new vision of preventive or curative treatments which, instead of targeting specific etiologic mechanisms, would aim at improving general health. Perhaps increasing adaptation to age-related changes would reduce the risk of Alzheimer’s disease dementia or its impact on the patient, caregivers, and society.”
Holmes C, Cunningham C, Zotova E, et al. Proinflammatory cytokines, sickness behavior, and Alzheimer disease. Neurology. 2011;77(3):212-218.
Shah RC, Buchman AS, Wilson RS, et al. Hemoglobin level in older persons and incident Alzheimer disease: prospective cohort analysis. Neurology. 2011;77(3):219-226.
Song X, Mitnitski A, Rockwood K. Nontraditional risk factors combine to predict Alzheimer disease and dementia. Neurology. 2011;77(3):227-234.
Dartigues JF, Féart C. Risk factors for Alzheimer disease: aging beyond age? Neurology. 2011;77(3):206-207.
Reducing Tonic-Clonic Seizures Can Minimize Risk of SUDEP
Clinicians can minimize the risk of sudden unexpected death in epilepsy (SUDEP) through such measures as reducing tonic-clonic seizures, choosing drugs carefully, changing treatments gradually, acting on ictal warning signs, and supervising and counseling patients, according to a seminar published online July 6 in Lancet. The seminar, by Simon Shorvon, FRCP, of the UCL Institute of Neurology in London, and Torbjorn Tomson, MD, of the Karolinska Institute in Stockholm, reviewed current research on and provided advice about minimizing SUDEP risk.
Almost all studies indicate that this risk is high in patients with a high number of tonic-clonic seizures, the authors noted. They suggested reducing these seizures through optimum treatment, good drug compliance, and advice on such lifestyle choices as alcohol intake and sleep. Ictal warning signs for tonic-clonic seizures include prolonged seizures that are associated with marked cyanosis, severe bradycardia or apnea, and postictal EEG suppression; complex partial seizures with marked atonia; and seizures in patients with pre-existing cardiac or respiratory impairment.
Patients who experience tonic-clonic seizures require supervision, the authors noted. They recommended attending to these patients continuously until the full restoration of consciousness, contacting emergency services for high-risk seizures, and supervising high-risk patients at night through attendance and use of alarms.
Clinicians should be cautious in using antiepileptic drugs (AEDs) with potential cardiorespiratory adverse effects, according to the researchers. When clinicians switch AEDs, they should introduce the new drug before withdrawing the old one and provide patients with “access to immediate advice in the event of worsening seizures,” the investigators stated.
Although some clinicians believe that informing all patients with epilepsy about the risk of SUDEP will cause unnecessary stress and anxiety, the authors recommended informing most patients about the risk to facilitate its minimization. However, they further suggested putting the risk in perspective—for example, by pointing out that, on an annual basis, it is similar to that of dying in a motor vehicle accident.
SUDEP probably has several mechanisms, and “most research has focused on seizure-related respiratory depression, cardiac arrhythmia, cerebral depression, and autonomic dysfunction,” the authors noted. Along with tonic-clonic seizures, risk factors for the event include male sex, long-duration epilepsy, and antiepileptic polytherapy.
Shorvon S, Tomson T. Sudden unexpected death in epilepsy. Lancet. 2011 Jul 5; [Epub ahead of print].
How Cost-Effective Are Disease-Modifying Therapies in MS?
Disease-modifying therapies (DMTs) for relapsing-remitting or secondary progressive multiple sclerosis (MS) do not appear to be cost-effective in the United States, according to findings published online July 20 by Neurology.
Katia Noyes, PhD, MPH, of the University of Rochester, New York, and colleagues calculated the cost-effectiveness of four DMTs in a nationally representative cohort of 1,121 patients with MS. The investigators generated 10-year disease progression paths for this cohort; looked at data on drug effectiveness, patient health preferences, health care use, lost productivity, and medical costs; measured health gains in quality-adjusted life-years (QALYs) and relapse-free years; and calculated incremental cost-effectiveness ratios (ICERs). The DMTs studied were glatiramer acetate, intramuscular interferon beta-1a, subcutaneous interferon beta-1a, and interferon beta-1b.
DMT therapy for 10 years resulted in modest QALY gains (0.082 for glatiramer acetate and 0.126 to 0.192 for the interferons), compared with basic supportive therapy. In addition, DMT therapy resulted in more relapse-free years throughout the course of a decade; patients on basic therapy averaged 5.051 relapse-free years, compared with 5.879 relapse-free years for glatiramer acetate and 5.620 to 6.074 relapse-free years for the interferons.
However, the ICERs of all four DMTs far exceeded $800,000 per QALY gained. The interferons had similar ICERs, at $901,319/QALY for intramuscular interferon beta-1a, $1,487,306/QALY for subcutaneous interferon beta-1a, and $1,123,162/QALY for interferon beta-1b. The ICER for glatiramer acetate was significantly higher, at $2,178,555/QALY. “While there is no formal cost-effectiveness threshold in the US, these estimates are an order of magnitude greater than the cost-effectiveness of many commonly accepted therapies for chronic illness,” the researchers commented.
The researchers added that cutting DMT costs by two-thirds would make the therapies’ cost-effectiveness comparable to that of other accepted interventions, however. In addition, the investigators noted that starting DMT earlier was associated with a more favorable ICER, compared with initiating treatment at any disease state, and that early treatment “may defer the substantial costs associated with late-stage MS and disability.”
Noyes K, Bajorska A, Chappel A, et al. Cost-effectiveness of disease-modifying therapy for multiple sclerosis: a population-based study. Neurology. 2011 Jul 20; [Epub ahead of print].