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Secondary CV prevention benefit from polypill promises global health benefit
Compared with separate medications in patients with a prior myocardial infarction, a single pill containing aspirin, a lipid-lowering agent, and an ACE inhibitor provided progressively greater protection from a second cardiovascular (CV) event over the course of a trial with several years of follow-up, according to results of a multinational trial.
“The curves began to separate at the very beginning of the trial, and they are continuing to separate, so we can begin to project the possibility that the results would be even more striking if we had an even longer follow-up,” said Valentin Fuster, MD, physician in chief, Mount Sinai Hospital, New York, who presented the results at the annual congress of the European Society of Cardiology.
By “striking,” Dr. Fuster was referring to a 24% reduction in the hazard ratio of major adverse CV events (MACE) for a trial in which patients were followed for a median of 3 years. The primary composite endpoint consisted of cardiovascular death, MI, stroke, and urgent revascularization (HR, 0.76; P = .02).
AS for the secondary composite endpoint, confined to CV death, MI, and stroke, use of the polypill linked to an even greater relative advantage over usual care (HR, 0.70; P = .005).
SECURE trial is latest test of polypill concept
A polypill strategy has been pursued for more than 15 years, according to Dr. Fuster. Other polypill studies have also generated positive results, but the latest trial, called SECURE, is the largest prospective randomized trial to evaluate a single pill combining multiple therapies for secondary prevention.
The degree of relative benefit has “huge implications for clinical care,” reported the ESC-invited commentator, Louise Bowman, MBBS, MD, professor of medicine and clinical trials, University of Oxford (England). She called the findings “in line with what was expected,” but she agreed that the results will drive practice change.
The SECURE trial, published online in the New England Journal of Medicine at the time of its presentation at the ESC congress, randomized 2,499 patients over the age of 65 years who had a MI within the previous 6 months and at least one other risk factor, such as diabetes mellitus, kidney dysfunction, or a prior coronary revascularization. They were enrolled at 113 participating study centers in seven European countries.
Multiple polypill versions permit dose titration
The polypill consisted of aspirin in a fixed dose of 100 mg, the HMG CoA reductase inhibitor atorvastatin, and the ACE inhibitor ramipril. For atorvastatin and ramipril, the target doses were 40 mg and 10 mg, respectively, but different versions of the polypill were available to permit titration to a tolerated dose. Usual care was provided by participating investigators according to ESC recommendations.
The average age of those enrolled was 76 years. Nearly one-third (31%) were women. At baseline, most had hypertension (77.9%), and the majority had diabetes (57.4%).
When the events in the primary endpoint were assessed individually, the polypill was associated with a 33% relative reduction in the risk of CV death (HR, 0.67; P = .03). The reductions in the risk of nonfatal MI (HR, 0.71) and stroke (HR, 0.70) were of the same general magnitude although they did not reach statistical significance. There was no meaningful reduction in urgent revascularization (HR, 0.96).
In addition, the reduction in all-cause mortality (HR, 0.97) was not significant.
The rate of adverse events over the course of the study was 32.7% in the polypill group and 31.6% in the usual-care group, which did not differ significantly. There was also no difference in types of adverse events, including bleeding and other adverse events of interest, according to Dr. Fuster.
Adherence, which was monitored at 6 and 24 months using the Morisky Medication Adherence Scale, was characterized as low, medium, or high. More patients in the polypill group reached high adherence at 6 months (70.6% vs. 62.7%) and at 24 months (74.1% vs. 63.2%). Conversely, fewer patients in the polypill group were deemed to have low adherence at both time points.
“Probably, adherence is the most important reason of how this works,” Dr. Fuster said. Although there were no substantial differences in lipid levels or in systolic or diastolic blood pressure between the two groups when compared at 24 months, there are several theories that might explain the lower event rates in the polypill group, including a more sustained anti-inflammatory effect from greater adherence.
One potential limitation was the open-label design, but Dr. Bowman said that this was unavoidable, given the difficulty of blinding and the fact that comparing a single pill with multiple pills was “the point of the study.” She noted that the 14% withdrawal rate over the course of the trial, which was attributed largely to the COVID-19 pandemic, and the lower than planned enrollment (2,500 vs. a projected 3,000 patients) are also limitations, prohibiting “a more robust result,” but she did not dispute the conclusions.
Polypill benefit documented in all subgroups
While acknowledging these limitations, Dr. Fuster emphasized the consistency of these results with prior polypill studies and within the study. Of the 16 predefined subgroups, such as those created with stratifications for age, sex, comorbidities, and country of treatment, all benefited to a similar degree.
“This really validates the importance of the study,” Dr. Fuster said.
In addition to the implications for risk management globally, Dr. Fuster and others, including Dr. Bowman, spoke of the potential of a relatively inexpensive polypill to improve care in resource-limited settings. Despite the move toward greater personalization of medicine, Dr. Fuster called “simplicity the key to global health” initiatives.
Salim Yusuf, MD, DPhil, a leader in international polypill research, agreed. He believes the supportive data for this approach are conclusive.
“There are four positive trials of the polypill now and collectively the data are overwhelmingly clear,” Dr. Yusuf, professor of medicine, McMaster University, Hamilton, Ont., said in an interview. “The polypill should be considered in secondary prevention as well as in primary prevention for high-risk individuals. We have estimated that, if it is used in even 50% of those who should get it, it would avoid 2 million premature deaths from CV disease and 6 million nonfatal events. The next step is to implement the findings.”
Dr. Fuster, Dr. Bowman, and Dr. Yusuf reported no potential conflicts of interest.
Compared with separate medications in patients with a prior myocardial infarction, a single pill containing aspirin, a lipid-lowering agent, and an ACE inhibitor provided progressively greater protection from a second cardiovascular (CV) event over the course of a trial with several years of follow-up, according to results of a multinational trial.
“The curves began to separate at the very beginning of the trial, and they are continuing to separate, so we can begin to project the possibility that the results would be even more striking if we had an even longer follow-up,” said Valentin Fuster, MD, physician in chief, Mount Sinai Hospital, New York, who presented the results at the annual congress of the European Society of Cardiology.
By “striking,” Dr. Fuster was referring to a 24% reduction in the hazard ratio of major adverse CV events (MACE) for a trial in which patients were followed for a median of 3 years. The primary composite endpoint consisted of cardiovascular death, MI, stroke, and urgent revascularization (HR, 0.76; P = .02).
AS for the secondary composite endpoint, confined to CV death, MI, and stroke, use of the polypill linked to an even greater relative advantage over usual care (HR, 0.70; P = .005).
SECURE trial is latest test of polypill concept
A polypill strategy has been pursued for more than 15 years, according to Dr. Fuster. Other polypill studies have also generated positive results, but the latest trial, called SECURE, is the largest prospective randomized trial to evaluate a single pill combining multiple therapies for secondary prevention.
The degree of relative benefit has “huge implications for clinical care,” reported the ESC-invited commentator, Louise Bowman, MBBS, MD, professor of medicine and clinical trials, University of Oxford (England). She called the findings “in line with what was expected,” but she agreed that the results will drive practice change.
The SECURE trial, published online in the New England Journal of Medicine at the time of its presentation at the ESC congress, randomized 2,499 patients over the age of 65 years who had a MI within the previous 6 months and at least one other risk factor, such as diabetes mellitus, kidney dysfunction, or a prior coronary revascularization. They were enrolled at 113 participating study centers in seven European countries.
Multiple polypill versions permit dose titration
The polypill consisted of aspirin in a fixed dose of 100 mg, the HMG CoA reductase inhibitor atorvastatin, and the ACE inhibitor ramipril. For atorvastatin and ramipril, the target doses were 40 mg and 10 mg, respectively, but different versions of the polypill were available to permit titration to a tolerated dose. Usual care was provided by participating investigators according to ESC recommendations.
The average age of those enrolled was 76 years. Nearly one-third (31%) were women. At baseline, most had hypertension (77.9%), and the majority had diabetes (57.4%).
When the events in the primary endpoint were assessed individually, the polypill was associated with a 33% relative reduction in the risk of CV death (HR, 0.67; P = .03). The reductions in the risk of nonfatal MI (HR, 0.71) and stroke (HR, 0.70) were of the same general magnitude although they did not reach statistical significance. There was no meaningful reduction in urgent revascularization (HR, 0.96).
In addition, the reduction in all-cause mortality (HR, 0.97) was not significant.
The rate of adverse events over the course of the study was 32.7% in the polypill group and 31.6% in the usual-care group, which did not differ significantly. There was also no difference in types of adverse events, including bleeding and other adverse events of interest, according to Dr. Fuster.
Adherence, which was monitored at 6 and 24 months using the Morisky Medication Adherence Scale, was characterized as low, medium, or high. More patients in the polypill group reached high adherence at 6 months (70.6% vs. 62.7%) and at 24 months (74.1% vs. 63.2%). Conversely, fewer patients in the polypill group were deemed to have low adherence at both time points.
“Probably, adherence is the most important reason of how this works,” Dr. Fuster said. Although there were no substantial differences in lipid levels or in systolic or diastolic blood pressure between the two groups when compared at 24 months, there are several theories that might explain the lower event rates in the polypill group, including a more sustained anti-inflammatory effect from greater adherence.
One potential limitation was the open-label design, but Dr. Bowman said that this was unavoidable, given the difficulty of blinding and the fact that comparing a single pill with multiple pills was “the point of the study.” She noted that the 14% withdrawal rate over the course of the trial, which was attributed largely to the COVID-19 pandemic, and the lower than planned enrollment (2,500 vs. a projected 3,000 patients) are also limitations, prohibiting “a more robust result,” but she did not dispute the conclusions.
Polypill benefit documented in all subgroups
While acknowledging these limitations, Dr. Fuster emphasized the consistency of these results with prior polypill studies and within the study. Of the 16 predefined subgroups, such as those created with stratifications for age, sex, comorbidities, and country of treatment, all benefited to a similar degree.
“This really validates the importance of the study,” Dr. Fuster said.
In addition to the implications for risk management globally, Dr. Fuster and others, including Dr. Bowman, spoke of the potential of a relatively inexpensive polypill to improve care in resource-limited settings. Despite the move toward greater personalization of medicine, Dr. Fuster called “simplicity the key to global health” initiatives.
Salim Yusuf, MD, DPhil, a leader in international polypill research, agreed. He believes the supportive data for this approach are conclusive.
“There are four positive trials of the polypill now and collectively the data are overwhelmingly clear,” Dr. Yusuf, professor of medicine, McMaster University, Hamilton, Ont., said in an interview. “The polypill should be considered in secondary prevention as well as in primary prevention for high-risk individuals. We have estimated that, if it is used in even 50% of those who should get it, it would avoid 2 million premature deaths from CV disease and 6 million nonfatal events. The next step is to implement the findings.”
Dr. Fuster, Dr. Bowman, and Dr. Yusuf reported no potential conflicts of interest.
Compared with separate medications in patients with a prior myocardial infarction, a single pill containing aspirin, a lipid-lowering agent, and an ACE inhibitor provided progressively greater protection from a second cardiovascular (CV) event over the course of a trial with several years of follow-up, according to results of a multinational trial.
“The curves began to separate at the very beginning of the trial, and they are continuing to separate, so we can begin to project the possibility that the results would be even more striking if we had an even longer follow-up,” said Valentin Fuster, MD, physician in chief, Mount Sinai Hospital, New York, who presented the results at the annual congress of the European Society of Cardiology.
By “striking,” Dr. Fuster was referring to a 24% reduction in the hazard ratio of major adverse CV events (MACE) for a trial in which patients were followed for a median of 3 years. The primary composite endpoint consisted of cardiovascular death, MI, stroke, and urgent revascularization (HR, 0.76; P = .02).
AS for the secondary composite endpoint, confined to CV death, MI, and stroke, use of the polypill linked to an even greater relative advantage over usual care (HR, 0.70; P = .005).
SECURE trial is latest test of polypill concept
A polypill strategy has been pursued for more than 15 years, according to Dr. Fuster. Other polypill studies have also generated positive results, but the latest trial, called SECURE, is the largest prospective randomized trial to evaluate a single pill combining multiple therapies for secondary prevention.
The degree of relative benefit has “huge implications for clinical care,” reported the ESC-invited commentator, Louise Bowman, MBBS, MD, professor of medicine and clinical trials, University of Oxford (England). She called the findings “in line with what was expected,” but she agreed that the results will drive practice change.
The SECURE trial, published online in the New England Journal of Medicine at the time of its presentation at the ESC congress, randomized 2,499 patients over the age of 65 years who had a MI within the previous 6 months and at least one other risk factor, such as diabetes mellitus, kidney dysfunction, or a prior coronary revascularization. They were enrolled at 113 participating study centers in seven European countries.
Multiple polypill versions permit dose titration
The polypill consisted of aspirin in a fixed dose of 100 mg, the HMG CoA reductase inhibitor atorvastatin, and the ACE inhibitor ramipril. For atorvastatin and ramipril, the target doses were 40 mg and 10 mg, respectively, but different versions of the polypill were available to permit titration to a tolerated dose. Usual care was provided by participating investigators according to ESC recommendations.
The average age of those enrolled was 76 years. Nearly one-third (31%) were women. At baseline, most had hypertension (77.9%), and the majority had diabetes (57.4%).
When the events in the primary endpoint were assessed individually, the polypill was associated with a 33% relative reduction in the risk of CV death (HR, 0.67; P = .03). The reductions in the risk of nonfatal MI (HR, 0.71) and stroke (HR, 0.70) were of the same general magnitude although they did not reach statistical significance. There was no meaningful reduction in urgent revascularization (HR, 0.96).
In addition, the reduction in all-cause mortality (HR, 0.97) was not significant.
The rate of adverse events over the course of the study was 32.7% in the polypill group and 31.6% in the usual-care group, which did not differ significantly. There was also no difference in types of adverse events, including bleeding and other adverse events of interest, according to Dr. Fuster.
Adherence, which was monitored at 6 and 24 months using the Morisky Medication Adherence Scale, was characterized as low, medium, or high. More patients in the polypill group reached high adherence at 6 months (70.6% vs. 62.7%) and at 24 months (74.1% vs. 63.2%). Conversely, fewer patients in the polypill group were deemed to have low adherence at both time points.
“Probably, adherence is the most important reason of how this works,” Dr. Fuster said. Although there were no substantial differences in lipid levels or in systolic or diastolic blood pressure between the two groups when compared at 24 months, there are several theories that might explain the lower event rates in the polypill group, including a more sustained anti-inflammatory effect from greater adherence.
One potential limitation was the open-label design, but Dr. Bowman said that this was unavoidable, given the difficulty of blinding and the fact that comparing a single pill with multiple pills was “the point of the study.” She noted that the 14% withdrawal rate over the course of the trial, which was attributed largely to the COVID-19 pandemic, and the lower than planned enrollment (2,500 vs. a projected 3,000 patients) are also limitations, prohibiting “a more robust result,” but she did not dispute the conclusions.
Polypill benefit documented in all subgroups
While acknowledging these limitations, Dr. Fuster emphasized the consistency of these results with prior polypill studies and within the study. Of the 16 predefined subgroups, such as those created with stratifications for age, sex, comorbidities, and country of treatment, all benefited to a similar degree.
“This really validates the importance of the study,” Dr. Fuster said.
In addition to the implications for risk management globally, Dr. Fuster and others, including Dr. Bowman, spoke of the potential of a relatively inexpensive polypill to improve care in resource-limited settings. Despite the move toward greater personalization of medicine, Dr. Fuster called “simplicity the key to global health” initiatives.
Salim Yusuf, MD, DPhil, a leader in international polypill research, agreed. He believes the supportive data for this approach are conclusive.
“There are four positive trials of the polypill now and collectively the data are overwhelmingly clear,” Dr. Yusuf, professor of medicine, McMaster University, Hamilton, Ont., said in an interview. “The polypill should be considered in secondary prevention as well as in primary prevention for high-risk individuals. We have estimated that, if it is used in even 50% of those who should get it, it would avoid 2 million premature deaths from CV disease and 6 million nonfatal events. The next step is to implement the findings.”
Dr. Fuster, Dr. Bowman, and Dr. Yusuf reported no potential conflicts of interest.
FROM ESC CONGRESS 2022
Call for Neurology Papers
Federal Practitioner invites VA, DoD, and PHS health care professionals and researchers to contribute to a future special issue on neurology. Topics of interest include epilepsy, headache and migraine, COVID-19 and neurology, Alzheimer and dementia, MS, and other neurological disorders.
Interested authors should submit an abstract to fedprac@mdedge.com with the subject line “Neurology Special Issue” for consideration. Once the editorial team confirms the article is eligible for consideration, authors will be asked to submit their manuscript in full through Editorial Manager.
Federal Practitioner never charges authors or readers. All submissions undergo a double-blinded peer review before publication. Accepted manuscripts are always available for free online at www.mdedge.com/fedprac and on PubMed Central.
Federal Practitioner welcomes original research, commentaries, clinical reviews, program profiles, case reports, and other evidence-based articles. The updated and complete submission guidelines, including details about the style and format, can be found here:
Federal Practitioner invites VA, DoD, and PHS health care professionals and researchers to contribute to a future special issue on neurology. Topics of interest include epilepsy, headache and migraine, COVID-19 and neurology, Alzheimer and dementia, MS, and other neurological disorders.
Interested authors should submit an abstract to fedprac@mdedge.com with the subject line “Neurology Special Issue” for consideration. Once the editorial team confirms the article is eligible for consideration, authors will be asked to submit their manuscript in full through Editorial Manager.
Federal Practitioner never charges authors or readers. All submissions undergo a double-blinded peer review before publication. Accepted manuscripts are always available for free online at www.mdedge.com/fedprac and on PubMed Central.
Federal Practitioner welcomes original research, commentaries, clinical reviews, program profiles, case reports, and other evidence-based articles. The updated and complete submission guidelines, including details about the style and format, can be found here:
Federal Practitioner invites VA, DoD, and PHS health care professionals and researchers to contribute to a future special issue on neurology. Topics of interest include epilepsy, headache and migraine, COVID-19 and neurology, Alzheimer and dementia, MS, and other neurological disorders.
Interested authors should submit an abstract to fedprac@mdedge.com with the subject line “Neurology Special Issue” for consideration. Once the editorial team confirms the article is eligible for consideration, authors will be asked to submit their manuscript in full through Editorial Manager.
Federal Practitioner never charges authors or readers. All submissions undergo a double-blinded peer review before publication. Accepted manuscripts are always available for free online at www.mdedge.com/fedprac and on PubMed Central.
Federal Practitioner welcomes original research, commentaries, clinical reviews, program profiles, case reports, and other evidence-based articles. The updated and complete submission guidelines, including details about the style and format, can be found here:
Large genetic study links 72 genes to autism spectrum disorders
according to a study published in Nature Genetics. The findings, based on analysis of more than 150,000 people’s genetics, arose from a collaboration of five research groups whose work included comparisons of ASD cohorts with separate cohorts of individuals with developmental delay or schizophrenia.
“We know that many genes, when mutated, contribute to autism,” and this study brought together “multiple types of mutations in a wide array of samples to get a much richer sense of the genes and genetic architecture involved in autism and other neurodevelopmental conditions,” co–senior author Joseph D. Buxbaum, PhD, director of the Seaver Autism Center for Research and Treatment at Mount Sinai and a professor at the Icahn School of Medicine at Mount Sinai, both in New York, said in a prepared statement. “This is significant in that we now have more insights as to the biology of the brain changes that underlie autism and more potential targets for treatment.”
Glen Elliott, PhD, MD, a clinical professor of psychiatry at Stanford (Calif.) University who was not involved in the study, said the paper is important paper for informing clinicians of where the basic research is headed. “We’re still in for a long road” before it bears fruit in terms of therapeutics. The value of studies like these, that investigate which genes are most associated with ASD, is that they may lead toward understanding the pathways in the brain that give rise to certain symptoms of ASD, which can then become therapeutic targets, Dr. Elliott said.
Investigating large cohorts
The researchers analyzed genetic exome sequencing data from 33 ASD cohorts with a total of 63,237 people and then compared these data with another cohort of people with developmental delay and a cohort of people with schizophrenia. The combined ASD cohorts included 15,036 individuals with ASD, 28,522 parents, and 5,492 unaffected siblings. The remaining participants were 5,591 people with ASD and 8,597 matched controls from case control studies.
In the ASD cohorts, the researchers identified 72 genes that were associated with ASD. De novo variants were eight times more likely in cases (4%) than in controls (0.5%). Ten genes occurred at least twice in ASD cases but never occurred in unaffected siblings.
Then the researchers integrated these ASD genetic data with a cohort of 91,605 people that included 31,058 people with developmental delay and their parents. Substantial overlap with gene mutations existed between these two cohorts: 70.1% of the genes related to developmental delay appeared linked to risk for ASD, and 86.6% of genes associated with ASD risk also had associations with developmental delay. Overall, the researchers identified 373 genes strongly associated with ASD and/or developmental delay and 664 genes with a likely association.
“Isolating genes that exert a greater effect on ASD than they do on other developmental delays has remained challenging due to the frequent comorbidity of these phenotypes,” wrote lead author Jack M. Fu, of Massachusetts General Hospital and Harvard Medical School, both in Boston, and colleagues. “Still, an estimated 13.4% of the transmission and de novo association–ASD genes show little evidence for association in the developmental delay cohort.”
ASD, developmental delay, and schizophrenia
When the researchers compared the cells where the genetic mutations occurred in fetal brains, they found that genes associated with developmental delay more often occurred in less differentiated cell types – less mature cells in the developmental process. Gene mutations associated with ASD, on the other hand, occurred in more mature cell types, particularly in maturing excitatory neurons and related cells.
”Our results are consistent with developmental delay-predominant genes being expressed earlier in development and in less differentiated cells than ASD-predominant genes,” they wrote.
The researchers also compared the specific gene mutations found in these two cohorts with a previously published set of 244 genes associated with schizophrenia. Of these, 234 genes are among those with a transmission and de novo association to ASD and/or developmental delay. Of the 72 genes linked to ASD, eight appear in the set of genes linked to schizophrenia, and 61 were associated with developmental delay, though these two subsets do not overlap each other much.
“The ASD-schizophrenia overlap was significantly enriched, while the developmental delay-schizophrenia overlap was not,” they reported. ”Together, these data suggest that one subset of ASD risk genes may overlap developmental delay while a different subset overlaps schizophrenia.”
Chasing therapy targets by backtracking through genes
The findings are a substantial step forward in understanding the potential genetic contribution to ASD, but they also highlight the challenges of eventually trying to use this information in a clinically meaningful way.
“Given the substantial overlap between the genes implicated in neurodevelopmental disorders writ large and those implicated directly in ASD, disentangling the relative impact of individual genes on neurodevelopment and phenotypic spectra is a daunting yet important challenge,” the researchers wrote. “To identify the key neurobiological features of ASD will likely require convergence of evidence from many ASD genes and studies.”
Dr. Elliott said the biggest takeaway from this study is a better understanding of how the paradigm has shifted away from finding “one gene” for autism or a cure based on genetics and more toward understanding the pathophysiology of symptoms that can point to therapies for better management of the condition.
“Basic researchers have completely changed the strategy for trying to understand the biology of major disorders,” including, in this case, autism, Dr. Elliott said. “The intent is to try to find the underlying systems [in the brain] by backtracking through genes. Meanwhile, given that scientists have made substantial progress in identifying genes that have specific effects on brain development, “the hope is that will mesh with this kind of research, to begin to identify systems that might ultimately be targets for treating.”
The end goal is to be able to offer targeted approaches, based on the pathways causing a symptom, which can be linked backward to a gene.
”So this is not going to offer an immediate cure – it’s probably not going to offer a cure at all – but it may actually lead to much more targeted medications than we currently have for specific types of symptoms within the autism spectrum,” Dr. Elliott said. “What they’re trying to do, ultimately, is to say, when this system is really badly affected because of a genetic abnormality, even though that genetic abnormality is very rare, it leads to these specific kinds of symptoms. If we can find out the neuroregulators underlying that change, then that would be the target, even if that gene were not present.”
The research was funded by the Simons Foundation for Autism Research Initiative, the SPARK project, the National Human Genome Research Institute Home, the National Institute of Mental Health, the National Institute of Child Health and Development, AMED, and the Beatrice and Samuel Seaver Foundation. Five authors reported financial disclosures linked to Desitin, Roche, BioMarin, BrigeBio Pharma, Illumina, Levo Therapeutics, and Microsoft.
according to a study published in Nature Genetics. The findings, based on analysis of more than 150,000 people’s genetics, arose from a collaboration of five research groups whose work included comparisons of ASD cohorts with separate cohorts of individuals with developmental delay or schizophrenia.
“We know that many genes, when mutated, contribute to autism,” and this study brought together “multiple types of mutations in a wide array of samples to get a much richer sense of the genes and genetic architecture involved in autism and other neurodevelopmental conditions,” co–senior author Joseph D. Buxbaum, PhD, director of the Seaver Autism Center for Research and Treatment at Mount Sinai and a professor at the Icahn School of Medicine at Mount Sinai, both in New York, said in a prepared statement. “This is significant in that we now have more insights as to the biology of the brain changes that underlie autism and more potential targets for treatment.”
Glen Elliott, PhD, MD, a clinical professor of psychiatry at Stanford (Calif.) University who was not involved in the study, said the paper is important paper for informing clinicians of where the basic research is headed. “We’re still in for a long road” before it bears fruit in terms of therapeutics. The value of studies like these, that investigate which genes are most associated with ASD, is that they may lead toward understanding the pathways in the brain that give rise to certain symptoms of ASD, which can then become therapeutic targets, Dr. Elliott said.
Investigating large cohorts
The researchers analyzed genetic exome sequencing data from 33 ASD cohorts with a total of 63,237 people and then compared these data with another cohort of people with developmental delay and a cohort of people with schizophrenia. The combined ASD cohorts included 15,036 individuals with ASD, 28,522 parents, and 5,492 unaffected siblings. The remaining participants were 5,591 people with ASD and 8,597 matched controls from case control studies.
In the ASD cohorts, the researchers identified 72 genes that were associated with ASD. De novo variants were eight times more likely in cases (4%) than in controls (0.5%). Ten genes occurred at least twice in ASD cases but never occurred in unaffected siblings.
Then the researchers integrated these ASD genetic data with a cohort of 91,605 people that included 31,058 people with developmental delay and their parents. Substantial overlap with gene mutations existed between these two cohorts: 70.1% of the genes related to developmental delay appeared linked to risk for ASD, and 86.6% of genes associated with ASD risk also had associations with developmental delay. Overall, the researchers identified 373 genes strongly associated with ASD and/or developmental delay and 664 genes with a likely association.
“Isolating genes that exert a greater effect on ASD than they do on other developmental delays has remained challenging due to the frequent comorbidity of these phenotypes,” wrote lead author Jack M. Fu, of Massachusetts General Hospital and Harvard Medical School, both in Boston, and colleagues. “Still, an estimated 13.4% of the transmission and de novo association–ASD genes show little evidence for association in the developmental delay cohort.”
ASD, developmental delay, and schizophrenia
When the researchers compared the cells where the genetic mutations occurred in fetal brains, they found that genes associated with developmental delay more often occurred in less differentiated cell types – less mature cells in the developmental process. Gene mutations associated with ASD, on the other hand, occurred in more mature cell types, particularly in maturing excitatory neurons and related cells.
”Our results are consistent with developmental delay-predominant genes being expressed earlier in development and in less differentiated cells than ASD-predominant genes,” they wrote.
The researchers also compared the specific gene mutations found in these two cohorts with a previously published set of 244 genes associated with schizophrenia. Of these, 234 genes are among those with a transmission and de novo association to ASD and/or developmental delay. Of the 72 genes linked to ASD, eight appear in the set of genes linked to schizophrenia, and 61 were associated with developmental delay, though these two subsets do not overlap each other much.
“The ASD-schizophrenia overlap was significantly enriched, while the developmental delay-schizophrenia overlap was not,” they reported. ”Together, these data suggest that one subset of ASD risk genes may overlap developmental delay while a different subset overlaps schizophrenia.”
Chasing therapy targets by backtracking through genes
The findings are a substantial step forward in understanding the potential genetic contribution to ASD, but they also highlight the challenges of eventually trying to use this information in a clinically meaningful way.
“Given the substantial overlap between the genes implicated in neurodevelopmental disorders writ large and those implicated directly in ASD, disentangling the relative impact of individual genes on neurodevelopment and phenotypic spectra is a daunting yet important challenge,” the researchers wrote. “To identify the key neurobiological features of ASD will likely require convergence of evidence from many ASD genes and studies.”
Dr. Elliott said the biggest takeaway from this study is a better understanding of how the paradigm has shifted away from finding “one gene” for autism or a cure based on genetics and more toward understanding the pathophysiology of symptoms that can point to therapies for better management of the condition.
“Basic researchers have completely changed the strategy for trying to understand the biology of major disorders,” including, in this case, autism, Dr. Elliott said. “The intent is to try to find the underlying systems [in the brain] by backtracking through genes. Meanwhile, given that scientists have made substantial progress in identifying genes that have specific effects on brain development, “the hope is that will mesh with this kind of research, to begin to identify systems that might ultimately be targets for treating.”
The end goal is to be able to offer targeted approaches, based on the pathways causing a symptom, which can be linked backward to a gene.
”So this is not going to offer an immediate cure – it’s probably not going to offer a cure at all – but it may actually lead to much more targeted medications than we currently have for specific types of symptoms within the autism spectrum,” Dr. Elliott said. “What they’re trying to do, ultimately, is to say, when this system is really badly affected because of a genetic abnormality, even though that genetic abnormality is very rare, it leads to these specific kinds of symptoms. If we can find out the neuroregulators underlying that change, then that would be the target, even if that gene were not present.”
The research was funded by the Simons Foundation for Autism Research Initiative, the SPARK project, the National Human Genome Research Institute Home, the National Institute of Mental Health, the National Institute of Child Health and Development, AMED, and the Beatrice and Samuel Seaver Foundation. Five authors reported financial disclosures linked to Desitin, Roche, BioMarin, BrigeBio Pharma, Illumina, Levo Therapeutics, and Microsoft.
according to a study published in Nature Genetics. The findings, based on analysis of more than 150,000 people’s genetics, arose from a collaboration of five research groups whose work included comparisons of ASD cohorts with separate cohorts of individuals with developmental delay or schizophrenia.
“We know that many genes, when mutated, contribute to autism,” and this study brought together “multiple types of mutations in a wide array of samples to get a much richer sense of the genes and genetic architecture involved in autism and other neurodevelopmental conditions,” co–senior author Joseph D. Buxbaum, PhD, director of the Seaver Autism Center for Research and Treatment at Mount Sinai and a professor at the Icahn School of Medicine at Mount Sinai, both in New York, said in a prepared statement. “This is significant in that we now have more insights as to the biology of the brain changes that underlie autism and more potential targets for treatment.”
Glen Elliott, PhD, MD, a clinical professor of psychiatry at Stanford (Calif.) University who was not involved in the study, said the paper is important paper for informing clinicians of where the basic research is headed. “We’re still in for a long road” before it bears fruit in terms of therapeutics. The value of studies like these, that investigate which genes are most associated with ASD, is that they may lead toward understanding the pathways in the brain that give rise to certain symptoms of ASD, which can then become therapeutic targets, Dr. Elliott said.
Investigating large cohorts
The researchers analyzed genetic exome sequencing data from 33 ASD cohorts with a total of 63,237 people and then compared these data with another cohort of people with developmental delay and a cohort of people with schizophrenia. The combined ASD cohorts included 15,036 individuals with ASD, 28,522 parents, and 5,492 unaffected siblings. The remaining participants were 5,591 people with ASD and 8,597 matched controls from case control studies.
In the ASD cohorts, the researchers identified 72 genes that were associated with ASD. De novo variants were eight times more likely in cases (4%) than in controls (0.5%). Ten genes occurred at least twice in ASD cases but never occurred in unaffected siblings.
Then the researchers integrated these ASD genetic data with a cohort of 91,605 people that included 31,058 people with developmental delay and their parents. Substantial overlap with gene mutations existed between these two cohorts: 70.1% of the genes related to developmental delay appeared linked to risk for ASD, and 86.6% of genes associated with ASD risk also had associations with developmental delay. Overall, the researchers identified 373 genes strongly associated with ASD and/or developmental delay and 664 genes with a likely association.
“Isolating genes that exert a greater effect on ASD than they do on other developmental delays has remained challenging due to the frequent comorbidity of these phenotypes,” wrote lead author Jack M. Fu, of Massachusetts General Hospital and Harvard Medical School, both in Boston, and colleagues. “Still, an estimated 13.4% of the transmission and de novo association–ASD genes show little evidence for association in the developmental delay cohort.”
ASD, developmental delay, and schizophrenia
When the researchers compared the cells where the genetic mutations occurred in fetal brains, they found that genes associated with developmental delay more often occurred in less differentiated cell types – less mature cells in the developmental process. Gene mutations associated with ASD, on the other hand, occurred in more mature cell types, particularly in maturing excitatory neurons and related cells.
”Our results are consistent with developmental delay-predominant genes being expressed earlier in development and in less differentiated cells than ASD-predominant genes,” they wrote.
The researchers also compared the specific gene mutations found in these two cohorts with a previously published set of 244 genes associated with schizophrenia. Of these, 234 genes are among those with a transmission and de novo association to ASD and/or developmental delay. Of the 72 genes linked to ASD, eight appear in the set of genes linked to schizophrenia, and 61 were associated with developmental delay, though these two subsets do not overlap each other much.
“The ASD-schizophrenia overlap was significantly enriched, while the developmental delay-schizophrenia overlap was not,” they reported. ”Together, these data suggest that one subset of ASD risk genes may overlap developmental delay while a different subset overlaps schizophrenia.”
Chasing therapy targets by backtracking through genes
The findings are a substantial step forward in understanding the potential genetic contribution to ASD, but they also highlight the challenges of eventually trying to use this information in a clinically meaningful way.
“Given the substantial overlap between the genes implicated in neurodevelopmental disorders writ large and those implicated directly in ASD, disentangling the relative impact of individual genes on neurodevelopment and phenotypic spectra is a daunting yet important challenge,” the researchers wrote. “To identify the key neurobiological features of ASD will likely require convergence of evidence from many ASD genes and studies.”
Dr. Elliott said the biggest takeaway from this study is a better understanding of how the paradigm has shifted away from finding “one gene” for autism or a cure based on genetics and more toward understanding the pathophysiology of symptoms that can point to therapies for better management of the condition.
“Basic researchers have completely changed the strategy for trying to understand the biology of major disorders,” including, in this case, autism, Dr. Elliott said. “The intent is to try to find the underlying systems [in the brain] by backtracking through genes. Meanwhile, given that scientists have made substantial progress in identifying genes that have specific effects on brain development, “the hope is that will mesh with this kind of research, to begin to identify systems that might ultimately be targets for treating.”
The end goal is to be able to offer targeted approaches, based on the pathways causing a symptom, which can be linked backward to a gene.
”So this is not going to offer an immediate cure – it’s probably not going to offer a cure at all – but it may actually lead to much more targeted medications than we currently have for specific types of symptoms within the autism spectrum,” Dr. Elliott said. “What they’re trying to do, ultimately, is to say, when this system is really badly affected because of a genetic abnormality, even though that genetic abnormality is very rare, it leads to these specific kinds of symptoms. If we can find out the neuroregulators underlying that change, then that would be the target, even if that gene were not present.”
The research was funded by the Simons Foundation for Autism Research Initiative, the SPARK project, the National Human Genome Research Institute Home, the National Institute of Mental Health, the National Institute of Child Health and Development, AMED, and the Beatrice and Samuel Seaver Foundation. Five authors reported financial disclosures linked to Desitin, Roche, BioMarin, BrigeBio Pharma, Illumina, Levo Therapeutics, and Microsoft.
FROM NATURE GENETICS
Blood biomarkers predict TBI disability and mortality
, new research suggests.
In new data from the TRACK-TBI study group, high levels of glial fibrillary acidic protein (GFAP) and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) proteins found in glial cells and neurons, respectively, correlated with death and severe injury. Investigators note that measuring these biomarkers may give a more accurate assessment of a patient’s prognosis following TBI.
This study is the “first report of the accuracy of a blood test that can be obtained rapidly on the day of injury to predict neurological recovery at 6 months after injury,” lead author Frederick Korley, MD, PhD, associate professor of emergency medicine at the University of Michigan, Ann Arbor, said in a news release.
The findings were published online in the Lancet Neurology.
Added value
The researchers measured GFAP and UCH-L1 in blood samples taken from 1,696 patients with TBI on the day of their injury, and they assessed patient recovery 6 months later.
The markers were measured using the i-STAT TBI Plasma test (Abbott Labs). The test was approved in 2021 by the U.S. Food and Drug Administration to determine which patients with mild TBI should undergo computed tomography scans.
About two-thirds of the study population were men, and the average age was 39 years. All patients were evaluated at Level I trauma centers for injuries caused primarily by traffic accidents or falls.
Six months following injury, 7% of the patients had died and 14% had an unfavorable outcome, ranging from vegetative state to severe disability requiring daily support. In addition, 67% had incomplete recovery, ranging from moderate disabilities requiring assistance outside of the home to minor disabling neurological or psychological deficits.
Day-of-injury GFAP and UCH-L1 levels had a high probability of predicting death (87% for GFAP and 89% for UCH-L1) and severe disability (86% for both GFAP and UCH-L1) at 6 months, the investigators reported.
The biomarkers were less accurate in predicting incomplete recovery (62% for GFAP and 61% for UCH-L1).
The researchers also assessed the added value of combining the blood biomarkers to current TBI prognostic models that take into account variables such as age, motor score, pupil reactivity, and CT characteristics.
In patients with a Glasgow Coma Scale (GCS) score of 3-12, adding GFAP and UCH-L1 alone or combined to each of the three International Mission for Prognosis and Analysis of Clinical Trials in TBI (IMPACT) models significantly increased their accuracy for predicting death (range, 90%-94%) and unfavorable outcome (range, 83%-89%).
In patients with milder TBI (GCS score, 13-15), adding GFAP and UCH-L1 to the UPFRONT prognostic model modestly increased accuracy for predicting incomplete recovery (69%).
‘Important’ findings
Commenting on the study, Cyrus A. Raji, MD, PhD, assistant professor of radiology and neurology, Washington University, St. Louis, said this “critical” study shows that these biomarkers can “predict key outcomes,” including mortality and severe disability. “Thus, in conjunction with clinical evaluations and related data such as neuroimaging, these tests may warrant translation to broader clinical practice, particularly in acute settings,” said Dr. Raji, who was not involved in the research.
Also weighing in, Heidi Fusco, MD, assistant director of the traumatic brain injury program at NYU Langone Rusk Rehabilitation, said the findings are “important.”
“Prognosis after brain injury often is based on the initial presentation, ongoing clinical exams, and neuroimaging; and the addition of biomarkers would contribute to creating a more objective prognostic model,” Dr. Fusco said.
She noted “it’s unclear” whether clinical hospital laboratories would be able to accommodate this type of laboratory drawing.
“It is imperative that clinicians still use the patient history [and] clinical and radiological exam when making clinical decisions for a patient and not just lab values. It would be best to incorporate the GFAP and UCH-L1 into a preexisting prognostic model,” Dr. Fusco said.
The study was funded by the U.S. National Institutes of Health, the National Institute of Neurologic Disorders and Stroke, the U.S. Department of Defense, One Mind, and U.S. Army Medical Research and Development Command. Dr. Korley reported having previously consulted for Abbott Laboratories and has received research funding from Abbott Laboratories, which makes the assays used in the study. Dr. Raji is a consultant for Brainreader ApS and Neurevolution. Dr. Fusco has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, new research suggests.
In new data from the TRACK-TBI study group, high levels of glial fibrillary acidic protein (GFAP) and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) proteins found in glial cells and neurons, respectively, correlated with death and severe injury. Investigators note that measuring these biomarkers may give a more accurate assessment of a patient’s prognosis following TBI.
This study is the “first report of the accuracy of a blood test that can be obtained rapidly on the day of injury to predict neurological recovery at 6 months after injury,” lead author Frederick Korley, MD, PhD, associate professor of emergency medicine at the University of Michigan, Ann Arbor, said in a news release.
The findings were published online in the Lancet Neurology.
Added value
The researchers measured GFAP and UCH-L1 in blood samples taken from 1,696 patients with TBI on the day of their injury, and they assessed patient recovery 6 months later.
The markers were measured using the i-STAT TBI Plasma test (Abbott Labs). The test was approved in 2021 by the U.S. Food and Drug Administration to determine which patients with mild TBI should undergo computed tomography scans.
About two-thirds of the study population were men, and the average age was 39 years. All patients were evaluated at Level I trauma centers for injuries caused primarily by traffic accidents or falls.
Six months following injury, 7% of the patients had died and 14% had an unfavorable outcome, ranging from vegetative state to severe disability requiring daily support. In addition, 67% had incomplete recovery, ranging from moderate disabilities requiring assistance outside of the home to minor disabling neurological or psychological deficits.
Day-of-injury GFAP and UCH-L1 levels had a high probability of predicting death (87% for GFAP and 89% for UCH-L1) and severe disability (86% for both GFAP and UCH-L1) at 6 months, the investigators reported.
The biomarkers were less accurate in predicting incomplete recovery (62% for GFAP and 61% for UCH-L1).
The researchers also assessed the added value of combining the blood biomarkers to current TBI prognostic models that take into account variables such as age, motor score, pupil reactivity, and CT characteristics.
In patients with a Glasgow Coma Scale (GCS) score of 3-12, adding GFAP and UCH-L1 alone or combined to each of the three International Mission for Prognosis and Analysis of Clinical Trials in TBI (IMPACT) models significantly increased their accuracy for predicting death (range, 90%-94%) and unfavorable outcome (range, 83%-89%).
In patients with milder TBI (GCS score, 13-15), adding GFAP and UCH-L1 to the UPFRONT prognostic model modestly increased accuracy for predicting incomplete recovery (69%).
‘Important’ findings
Commenting on the study, Cyrus A. Raji, MD, PhD, assistant professor of radiology and neurology, Washington University, St. Louis, said this “critical” study shows that these biomarkers can “predict key outcomes,” including mortality and severe disability. “Thus, in conjunction with clinical evaluations and related data such as neuroimaging, these tests may warrant translation to broader clinical practice, particularly in acute settings,” said Dr. Raji, who was not involved in the research.
Also weighing in, Heidi Fusco, MD, assistant director of the traumatic brain injury program at NYU Langone Rusk Rehabilitation, said the findings are “important.”
“Prognosis after brain injury often is based on the initial presentation, ongoing clinical exams, and neuroimaging; and the addition of biomarkers would contribute to creating a more objective prognostic model,” Dr. Fusco said.
She noted “it’s unclear” whether clinical hospital laboratories would be able to accommodate this type of laboratory drawing.
“It is imperative that clinicians still use the patient history [and] clinical and radiological exam when making clinical decisions for a patient and not just lab values. It would be best to incorporate the GFAP and UCH-L1 into a preexisting prognostic model,” Dr. Fusco said.
The study was funded by the U.S. National Institutes of Health, the National Institute of Neurologic Disorders and Stroke, the U.S. Department of Defense, One Mind, and U.S. Army Medical Research and Development Command. Dr. Korley reported having previously consulted for Abbott Laboratories and has received research funding from Abbott Laboratories, which makes the assays used in the study. Dr. Raji is a consultant for Brainreader ApS and Neurevolution. Dr. Fusco has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, new research suggests.
In new data from the TRACK-TBI study group, high levels of glial fibrillary acidic protein (GFAP) and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) proteins found in glial cells and neurons, respectively, correlated with death and severe injury. Investigators note that measuring these biomarkers may give a more accurate assessment of a patient’s prognosis following TBI.
This study is the “first report of the accuracy of a blood test that can be obtained rapidly on the day of injury to predict neurological recovery at 6 months after injury,” lead author Frederick Korley, MD, PhD, associate professor of emergency medicine at the University of Michigan, Ann Arbor, said in a news release.
The findings were published online in the Lancet Neurology.
Added value
The researchers measured GFAP and UCH-L1 in blood samples taken from 1,696 patients with TBI on the day of their injury, and they assessed patient recovery 6 months later.
The markers were measured using the i-STAT TBI Plasma test (Abbott Labs). The test was approved in 2021 by the U.S. Food and Drug Administration to determine which patients with mild TBI should undergo computed tomography scans.
About two-thirds of the study population were men, and the average age was 39 years. All patients were evaluated at Level I trauma centers for injuries caused primarily by traffic accidents or falls.
Six months following injury, 7% of the patients had died and 14% had an unfavorable outcome, ranging from vegetative state to severe disability requiring daily support. In addition, 67% had incomplete recovery, ranging from moderate disabilities requiring assistance outside of the home to minor disabling neurological or psychological deficits.
Day-of-injury GFAP and UCH-L1 levels had a high probability of predicting death (87% for GFAP and 89% for UCH-L1) and severe disability (86% for both GFAP and UCH-L1) at 6 months, the investigators reported.
The biomarkers were less accurate in predicting incomplete recovery (62% for GFAP and 61% for UCH-L1).
The researchers also assessed the added value of combining the blood biomarkers to current TBI prognostic models that take into account variables such as age, motor score, pupil reactivity, and CT characteristics.
In patients with a Glasgow Coma Scale (GCS) score of 3-12, adding GFAP and UCH-L1 alone or combined to each of the three International Mission for Prognosis and Analysis of Clinical Trials in TBI (IMPACT) models significantly increased their accuracy for predicting death (range, 90%-94%) and unfavorable outcome (range, 83%-89%).
In patients with milder TBI (GCS score, 13-15), adding GFAP and UCH-L1 to the UPFRONT prognostic model modestly increased accuracy for predicting incomplete recovery (69%).
‘Important’ findings
Commenting on the study, Cyrus A. Raji, MD, PhD, assistant professor of radiology and neurology, Washington University, St. Louis, said this “critical” study shows that these biomarkers can “predict key outcomes,” including mortality and severe disability. “Thus, in conjunction with clinical evaluations and related data such as neuroimaging, these tests may warrant translation to broader clinical practice, particularly in acute settings,” said Dr. Raji, who was not involved in the research.
Also weighing in, Heidi Fusco, MD, assistant director of the traumatic brain injury program at NYU Langone Rusk Rehabilitation, said the findings are “important.”
“Prognosis after brain injury often is based on the initial presentation, ongoing clinical exams, and neuroimaging; and the addition of biomarkers would contribute to creating a more objective prognostic model,” Dr. Fusco said.
She noted “it’s unclear” whether clinical hospital laboratories would be able to accommodate this type of laboratory drawing.
“It is imperative that clinicians still use the patient history [and] clinical and radiological exam when making clinical decisions for a patient and not just lab values. It would be best to incorporate the GFAP and UCH-L1 into a preexisting prognostic model,” Dr. Fusco said.
The study was funded by the U.S. National Institutes of Health, the National Institute of Neurologic Disorders and Stroke, the U.S. Department of Defense, One Mind, and U.S. Army Medical Research and Development Command. Dr. Korley reported having previously consulted for Abbott Laboratories and has received research funding from Abbott Laboratories, which makes the assays used in the study. Dr. Raji is a consultant for Brainreader ApS and Neurevolution. Dr. Fusco has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM THE LANCET NEUROLOGY
Digital therapy may ‘rewire’ the brain to improve tinnitus
, new research suggests. In a randomized controlled trial, results at 12 weeks showed patients with tinnitus reported clinically meaningful reductions in ratings of annoyance, inability to ignore, unpleasantness, and loudness after using a digital polytherapeutic app prototype that focuses on relief, relaxation, and attention-focused retraining. In addition, their improvements were significantly greater than for the control group, which received a common white noise app.
Researchers called the results “promising” for a condition that has no cure and few successful treatments. “What this therapy does is essentially rewire the brain in a way that de-emphasizes the sound of the tinnitus to a background noise that has no meaning or relevance to the listener,” lead author Grant Searchfield, PhD, associate professor of audiology at the University of Auckland, New Zealand, said in a press release.
The findings were published online in Frontiers in Neurology.
Worldwide problem
A recent study showed more than 740 million adults worldwide (nearly 15% of the population) have experienced at least one symptom of tinnitus – and about 120 million are severely affected. Tinnitus is the perception of a ringing, buzzing, whistling, or hissing noise in one or both ears when no external source of the sound is present. Often caused by damage to the auditory system, tinnitus can also be a symptom of a wide range of medical conditions and has been identified as a side effect of COVID-19 vaccination. In its most severe form, which is associated with hearing loss, tinnitus can also affect a patient’s mental, emotional, and social health.
For the current study, participants with tinnitus were randomly assigned to a popular app that uses white noise (control group, n = 30) or to the UpSilent app (n = 31). The UpSilent group received a smartphone app, Bluetooth bone conduction headphones, a Bluetooth neck pillow speaker for sleep, and written counseling materials. Participants in the control group received a widely available app called “White Noise” and in-ear wired headphones.
‘Quicker and more effective’
Both groups reported reductions in ratings of annoyance, inability to ignore, unpleasantness, and loudness at 12 weeks. But significantly more of the UpSilent group reported clinically meaningful improvement compared with the control group (65% vs. 43%, respectively; P = .049).
“Earlier trials have found white noise, goal-based counseling, goal-oriented games, and other technology-based therapies are effective for some people some of the time,” Dr. Searchfield said. “This is quicker and more effective, taking 12 weeks rather than 12 months for more individuals to gain some control,” he added.
The investigators noted that the study was not designed to determine which of the app’s functions of passive listening, active listening, or counseling contributed to symptom improvement.
The next step will be to refine the prototype and proceed to larger local and international trials with a view toward approval by the U.S. Food and Drug Administration, they reported.
The researchers hope the app will be clinically available in about 6 months.
The study was funded by Return on Science, Auckland UniServices. Dr. Searchfield is a founder and scientific officer for TrueSilence, a spinout company of the University of Auckland, and has a financial interest in TrueSilence. His coauthor has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, new research suggests. In a randomized controlled trial, results at 12 weeks showed patients with tinnitus reported clinically meaningful reductions in ratings of annoyance, inability to ignore, unpleasantness, and loudness after using a digital polytherapeutic app prototype that focuses on relief, relaxation, and attention-focused retraining. In addition, their improvements were significantly greater than for the control group, which received a common white noise app.
Researchers called the results “promising” for a condition that has no cure and few successful treatments. “What this therapy does is essentially rewire the brain in a way that de-emphasizes the sound of the tinnitus to a background noise that has no meaning or relevance to the listener,” lead author Grant Searchfield, PhD, associate professor of audiology at the University of Auckland, New Zealand, said in a press release.
The findings were published online in Frontiers in Neurology.
Worldwide problem
A recent study showed more than 740 million adults worldwide (nearly 15% of the population) have experienced at least one symptom of tinnitus – and about 120 million are severely affected. Tinnitus is the perception of a ringing, buzzing, whistling, or hissing noise in one or both ears when no external source of the sound is present. Often caused by damage to the auditory system, tinnitus can also be a symptom of a wide range of medical conditions and has been identified as a side effect of COVID-19 vaccination. In its most severe form, which is associated with hearing loss, tinnitus can also affect a patient’s mental, emotional, and social health.
For the current study, participants with tinnitus were randomly assigned to a popular app that uses white noise (control group, n = 30) or to the UpSilent app (n = 31). The UpSilent group received a smartphone app, Bluetooth bone conduction headphones, a Bluetooth neck pillow speaker for sleep, and written counseling materials. Participants in the control group received a widely available app called “White Noise” and in-ear wired headphones.
‘Quicker and more effective’
Both groups reported reductions in ratings of annoyance, inability to ignore, unpleasantness, and loudness at 12 weeks. But significantly more of the UpSilent group reported clinically meaningful improvement compared with the control group (65% vs. 43%, respectively; P = .049).
“Earlier trials have found white noise, goal-based counseling, goal-oriented games, and other technology-based therapies are effective for some people some of the time,” Dr. Searchfield said. “This is quicker and more effective, taking 12 weeks rather than 12 months for more individuals to gain some control,” he added.
The investigators noted that the study was not designed to determine which of the app’s functions of passive listening, active listening, or counseling contributed to symptom improvement.
The next step will be to refine the prototype and proceed to larger local and international trials with a view toward approval by the U.S. Food and Drug Administration, they reported.
The researchers hope the app will be clinically available in about 6 months.
The study was funded by Return on Science, Auckland UniServices. Dr. Searchfield is a founder and scientific officer for TrueSilence, a spinout company of the University of Auckland, and has a financial interest in TrueSilence. His coauthor has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, new research suggests. In a randomized controlled trial, results at 12 weeks showed patients with tinnitus reported clinically meaningful reductions in ratings of annoyance, inability to ignore, unpleasantness, and loudness after using a digital polytherapeutic app prototype that focuses on relief, relaxation, and attention-focused retraining. In addition, their improvements were significantly greater than for the control group, which received a common white noise app.
Researchers called the results “promising” for a condition that has no cure and few successful treatments. “What this therapy does is essentially rewire the brain in a way that de-emphasizes the sound of the tinnitus to a background noise that has no meaning or relevance to the listener,” lead author Grant Searchfield, PhD, associate professor of audiology at the University of Auckland, New Zealand, said in a press release.
The findings were published online in Frontiers in Neurology.
Worldwide problem
A recent study showed more than 740 million adults worldwide (nearly 15% of the population) have experienced at least one symptom of tinnitus – and about 120 million are severely affected. Tinnitus is the perception of a ringing, buzzing, whistling, or hissing noise in one or both ears when no external source of the sound is present. Often caused by damage to the auditory system, tinnitus can also be a symptom of a wide range of medical conditions and has been identified as a side effect of COVID-19 vaccination. In its most severe form, which is associated with hearing loss, tinnitus can also affect a patient’s mental, emotional, and social health.
For the current study, participants with tinnitus were randomly assigned to a popular app that uses white noise (control group, n = 30) or to the UpSilent app (n = 31). The UpSilent group received a smartphone app, Bluetooth bone conduction headphones, a Bluetooth neck pillow speaker for sleep, and written counseling materials. Participants in the control group received a widely available app called “White Noise” and in-ear wired headphones.
‘Quicker and more effective’
Both groups reported reductions in ratings of annoyance, inability to ignore, unpleasantness, and loudness at 12 weeks. But significantly more of the UpSilent group reported clinically meaningful improvement compared with the control group (65% vs. 43%, respectively; P = .049).
“Earlier trials have found white noise, goal-based counseling, goal-oriented games, and other technology-based therapies are effective for some people some of the time,” Dr. Searchfield said. “This is quicker and more effective, taking 12 weeks rather than 12 months for more individuals to gain some control,” he added.
The investigators noted that the study was not designed to determine which of the app’s functions of passive listening, active listening, or counseling contributed to symptom improvement.
The next step will be to refine the prototype and proceed to larger local and international trials with a view toward approval by the U.S. Food and Drug Administration, they reported.
The researchers hope the app will be clinically available in about 6 months.
The study was funded by Return on Science, Auckland UniServices. Dr. Searchfield is a founder and scientific officer for TrueSilence, a spinout company of the University of Auckland, and has a financial interest in TrueSilence. His coauthor has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM FRONTIERS IN NEUROLOGY
Incomplete recovery common 6 months after mild TBI
, new data from the TRACK-TBI study shows.
“Seeing that more than half of the GCS [Glasgow Coma Score] 15, CT-negative TBI cohort in our study were not back to their preinjury baseline at 6 months was surprising and impacts the millions of Americans who suffer from concussions annually,” said lead author Debbie Madhok, MD, with department of emergency medicine, University of California, San Francisco.
“These results highlight the importance of improving care pathways for concussion, particularly from the emergency department,” Dr. Madhok said.
The findings were published online in JAMA Network Open.
The short- and long-term outcomes in the large group of patients who come into the ED with TBI, a GCS of 15, and without acute intracranial traumatic injury (defined as a negative head CT scan) remain poorly understood, the investigators noted. To investigate further, they evaluated outcomes at 2 weeks and 6 months in 991 of these patients (mean age, 38 years; 64% men) from the TRACK-TBI study.
Among the 751 (76%) participants followed up at 2 weeks after the injury, only 204 (27%) had functional recovery – with a Glasgow Outcome Scale-Extended (GOS-E) score of 8. The remaining 547 (73%) had incomplete recovery (GOS-E scores < 8).
Among the 659 patients (66%) followed up at 6 months after the injury, 287 (44%) had functional recovery and 372 (56%) had incomplete recovery.
Most patients who failed to recover completely reported they had not returned to their preinjury life (88%). They described trouble returning to social activities outside the home and disruptions in family relationships and friendships.
The researchers noted that the study population had a high rate of preinjury psychiatric comorbidities, and these patients were more likely to have incomplete recovery than those without psychiatric comorbidities. This aligns with results from previous studies, they added.
The investigators also noted that patients with mild TBI without acute intracranial trauma are typically managed by ED personnel.
“These findings highlight the importance of ED clinicians being aware of the risk of incomplete recovery for patients with a mild TBI (that is, GCS score of 15 and negative head CT scan) and providing accurate education and timely referral information before ED discharge,” they wrote.
The study was funded by grants from the National Foundation of Emergency Medicine, the National Institute of Neurological Disorders and Stroke, and the U.S. Department of Defense Traumatic Brain Injury Endpoints Development Initiative. Dr. Madhok has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, new data from the TRACK-TBI study shows.
“Seeing that more than half of the GCS [Glasgow Coma Score] 15, CT-negative TBI cohort in our study were not back to their preinjury baseline at 6 months was surprising and impacts the millions of Americans who suffer from concussions annually,” said lead author Debbie Madhok, MD, with department of emergency medicine, University of California, San Francisco.
“These results highlight the importance of improving care pathways for concussion, particularly from the emergency department,” Dr. Madhok said.
The findings were published online in JAMA Network Open.
The short- and long-term outcomes in the large group of patients who come into the ED with TBI, a GCS of 15, and without acute intracranial traumatic injury (defined as a negative head CT scan) remain poorly understood, the investigators noted. To investigate further, they evaluated outcomes at 2 weeks and 6 months in 991 of these patients (mean age, 38 years; 64% men) from the TRACK-TBI study.
Among the 751 (76%) participants followed up at 2 weeks after the injury, only 204 (27%) had functional recovery – with a Glasgow Outcome Scale-Extended (GOS-E) score of 8. The remaining 547 (73%) had incomplete recovery (GOS-E scores < 8).
Among the 659 patients (66%) followed up at 6 months after the injury, 287 (44%) had functional recovery and 372 (56%) had incomplete recovery.
Most patients who failed to recover completely reported they had not returned to their preinjury life (88%). They described trouble returning to social activities outside the home and disruptions in family relationships and friendships.
The researchers noted that the study population had a high rate of preinjury psychiatric comorbidities, and these patients were more likely to have incomplete recovery than those without psychiatric comorbidities. This aligns with results from previous studies, they added.
The investigators also noted that patients with mild TBI without acute intracranial trauma are typically managed by ED personnel.
“These findings highlight the importance of ED clinicians being aware of the risk of incomplete recovery for patients with a mild TBI (that is, GCS score of 15 and negative head CT scan) and providing accurate education and timely referral information before ED discharge,” they wrote.
The study was funded by grants from the National Foundation of Emergency Medicine, the National Institute of Neurological Disorders and Stroke, and the U.S. Department of Defense Traumatic Brain Injury Endpoints Development Initiative. Dr. Madhok has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, new data from the TRACK-TBI study shows.
“Seeing that more than half of the GCS [Glasgow Coma Score] 15, CT-negative TBI cohort in our study were not back to their preinjury baseline at 6 months was surprising and impacts the millions of Americans who suffer from concussions annually,” said lead author Debbie Madhok, MD, with department of emergency medicine, University of California, San Francisco.
“These results highlight the importance of improving care pathways for concussion, particularly from the emergency department,” Dr. Madhok said.
The findings were published online in JAMA Network Open.
The short- and long-term outcomes in the large group of patients who come into the ED with TBI, a GCS of 15, and without acute intracranial traumatic injury (defined as a negative head CT scan) remain poorly understood, the investigators noted. To investigate further, they evaluated outcomes at 2 weeks and 6 months in 991 of these patients (mean age, 38 years; 64% men) from the TRACK-TBI study.
Among the 751 (76%) participants followed up at 2 weeks after the injury, only 204 (27%) had functional recovery – with a Glasgow Outcome Scale-Extended (GOS-E) score of 8. The remaining 547 (73%) had incomplete recovery (GOS-E scores < 8).
Among the 659 patients (66%) followed up at 6 months after the injury, 287 (44%) had functional recovery and 372 (56%) had incomplete recovery.
Most patients who failed to recover completely reported they had not returned to their preinjury life (88%). They described trouble returning to social activities outside the home and disruptions in family relationships and friendships.
The researchers noted that the study population had a high rate of preinjury psychiatric comorbidities, and these patients were more likely to have incomplete recovery than those without psychiatric comorbidities. This aligns with results from previous studies, they added.
The investigators also noted that patients with mild TBI without acute intracranial trauma are typically managed by ED personnel.
“These findings highlight the importance of ED clinicians being aware of the risk of incomplete recovery for patients with a mild TBI (that is, GCS score of 15 and negative head CT scan) and providing accurate education and timely referral information before ED discharge,” they wrote.
The study was funded by grants from the National Foundation of Emergency Medicine, the National Institute of Neurological Disorders and Stroke, and the U.S. Department of Defense Traumatic Brain Injury Endpoints Development Initiative. Dr. Madhok has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM JAMA NETWORK OPEN
How does not getting enough sleep affect the developing brain?
Children who do not get enough sleep for one night can be cranky, groggy, or meltdown prone the next day.
Over time, though, insufficient sleep may impair neurodevelopment in ways that can be measured on brain scans and tests long term, a new study shows.
Research published in The Lancet Child & Adolescent Health found that 9- and 10-year-olds who do not get at least 9 hours of sleep most nights tend to have less gray matter and smaller areas of the brain responsible for attention, memory, and inhibition control, relative to children who do get enough sleep.
The researchers also found a relationship between insufficient sleep and disrupted connections between the basal ganglia and cortical regions of the brain. These disruptions appeared to be linked to depression, thought problems, and impairments in crystallized intelligence, a type of intelligence that depends on memory.
The overall patterns persisted 2 years later, even as those who got enough sleep at baseline gradually slept less over time, while those who were not getting enough sleep to begin with continued to sleep about the same amount, the researchers reported.
The results bolster the case for delaying school start times, as California recently did, according one researcher who was not involved in the study.
The ABCD Study
To examine how insufficient sleep affects children’s mental health, cognition, brain function, and brain structure over 2 years, Ze Wang, PhD, professor of diagnostic radiology and nuclear medicine at the University of Maryland, Baltimore, and colleagues analyzed data from the ongoing Adolescent Brain Cognitive Development (ABCD) Study. The ABCD Study is tracking the biologic and behavioral development of more than 11,000 children in the United States who were recruited for the study when they were 9 or 10 years old.
For their new analysis, Dr. Wang’s group focused on 6,042 participants: 3,021 children with insufficient sleep who were matched with an equal number of participants who were similar in many respects, including sex, socioeconomic status, and puberty status, except they got at least 9 hours of sleep. They also looked at outcomes 2 years later from 749 of the matched pairs who had results available.
The investigators determined sleep duration based on how parents answered the question: “How many hours of sleep does your child get on most nights in the past 6 months?” Possible answers included at least 9 hours, 8-9 hours, 7-8 hours, 5-7 hours, or less than 5 hours. They also looked at functional and structural MRI scans, test results, and responses to questionnaires.
Negative effects of inadequate sleep were spread over “several different domains including brain structure, function, cognition, behavior, and mental health,” Dr. Wang said.
The strength of the relationship between sleep duration and the various outcomes was “modest” and based on group averages, he said. So, a given child who does not sleep for 9 hours most nights won’t necessarily perform worse than a child who gets enough sleep.
Still, modest effects may accumulate and have lasting consequences, Dr. Wang said.
Crystallized intelligence
The researchers looked at 42 behavioral outcomes, 32 of which were significantly different between the groups. Four outcomes in particular – depression, thought problems, performance on a picture-vocabulary test, and crystallized intelligence – were areas where insufficient sleep seemed to have a larger negative effect.
Sleep duration’s relationship with crystallized intelligence was twice that for fluid intelligence, which does not depend on memory.
“Sleep affects memory,” Dr. Wang said. “Crystallized intelligence depends on learned skills and knowledge, which are memory. In this sense, sleep is related to crystallized intelligence.”
One limitation of the study is that some parents may not accurately report how much sleep their child gets, Dr. Wang acknowledged. Children may be awake when parents think they are asleep, for example.
And although the results show getting 9 hours of sleep may help neurocognitive development, it’s also possible that excessive amounts of sleep could be problematic, the study authors wrote.
Further experiments are needed to prove that insufficient sleep – and not some other, unaccounted for factor – causes the observed impairments in neurodevelopment.
To promote healthy sleep, parents should keep a strict routine for their children, such as a regular bedtime and no electronic devices in the bedroom, Dr. Wang suggested. More physical activity during the day also should help.
If children have high levels of stress and depression, “finding the source is critical,” he said. Likewise, clinicians should consider how mental health can affect their patients’ sleep.
More to healthy sleep than duration
“This study both aligns with and advances existing research on the importance of sufficient sleep for child well-being,” said Ariel A. Williamson, PhD, DBSM, a psychologist and pediatric sleep expert in the department of child and adolescent psychiatry and behavioral sciences at Children’s Hospital of Philadelphia and assistant professor of psychiatry and pediatrics at University of Pennsylvania, also in Philadelphia.
The researchers used rigorous propensity score matching, longitudinal data, and brain imaging, which are “innovative methods that provide more evidence on potential mechanisms linking insufficient sleep and child outcomes,” said Dr. Williamson, who was not involved in the study.
While the investigators focused on sleep duration, child sleep health is multidimensional and includes other elements like timing and perception of sleep quality, Dr. Williamson noted. “For example, some research shows that having a sleep schedule that varies night to night is linked to poor child outcomes.”
Dr. Williamson tells families and clinicians that “sleep is a pillar of health,” equal to diet and exercise. That said, sleep recommendations need to fit within a family’s life – taking into account after school activities and late-night homework sessions. But extending sleep by just “20-30 minutes can make a meaningful difference for daytime functioning,” Dr. Williamson said.
Start school later?
Researchers have only relatively recently begun to understand how insufficient sleep affects adolescent neurocognitive development long term, and this study provides “crucial evidence” about the consequences, Lydia Gabriela Speyer, PhD, said in an editorial published with the study. Dr. Speyer is affiliated with the department of psychology at the University of Cambridge (England).
“Given the novel finding that insufficient sleep is associated with changes in brain structure and connectivity that are long-lasting, early intervention is crucial because such neural changes are probably not reversible and might consequently affect adolescents’ development into adulthood,” Dr. Speyer wrote.
Delaying school start times could be one way to help kids get more sleep. The American Academy of Pediatrics and the American Academy of Sleep Medicine recommend that middle schools and high schools start no earlier than 8:30 a.m. to better align with students’ circadian rhythm, Dr. Speyer noted.
As it is in the United States, most schools start closer to 8 a.m. In California, though, a law that went into effect on July 1 prohibits high schools from starting before 8:30 a.m. Other states are weighing similar legislation.
The research was supported by the National Institutes of Health. Dr. Wang and his coauthors and Dr. Speyer had no conflict of interest disclosures. Dr. Williamson is a sleep expert for the Pediatric Sleep Council (www.babysleep.com), which provides free information about early childhood sleep, but she does not receive compensation for this role.
Children who do not get enough sleep for one night can be cranky, groggy, or meltdown prone the next day.
Over time, though, insufficient sleep may impair neurodevelopment in ways that can be measured on brain scans and tests long term, a new study shows.
Research published in The Lancet Child & Adolescent Health found that 9- and 10-year-olds who do not get at least 9 hours of sleep most nights tend to have less gray matter and smaller areas of the brain responsible for attention, memory, and inhibition control, relative to children who do get enough sleep.
The researchers also found a relationship between insufficient sleep and disrupted connections between the basal ganglia and cortical regions of the brain. These disruptions appeared to be linked to depression, thought problems, and impairments in crystallized intelligence, a type of intelligence that depends on memory.
The overall patterns persisted 2 years later, even as those who got enough sleep at baseline gradually slept less over time, while those who were not getting enough sleep to begin with continued to sleep about the same amount, the researchers reported.
The results bolster the case for delaying school start times, as California recently did, according one researcher who was not involved in the study.
The ABCD Study
To examine how insufficient sleep affects children’s mental health, cognition, brain function, and brain structure over 2 years, Ze Wang, PhD, professor of diagnostic radiology and nuclear medicine at the University of Maryland, Baltimore, and colleagues analyzed data from the ongoing Adolescent Brain Cognitive Development (ABCD) Study. The ABCD Study is tracking the biologic and behavioral development of more than 11,000 children in the United States who were recruited for the study when they were 9 or 10 years old.
For their new analysis, Dr. Wang’s group focused on 6,042 participants: 3,021 children with insufficient sleep who were matched with an equal number of participants who were similar in many respects, including sex, socioeconomic status, and puberty status, except they got at least 9 hours of sleep. They also looked at outcomes 2 years later from 749 of the matched pairs who had results available.
The investigators determined sleep duration based on how parents answered the question: “How many hours of sleep does your child get on most nights in the past 6 months?” Possible answers included at least 9 hours, 8-9 hours, 7-8 hours, 5-7 hours, or less than 5 hours. They also looked at functional and structural MRI scans, test results, and responses to questionnaires.
Negative effects of inadequate sleep were spread over “several different domains including brain structure, function, cognition, behavior, and mental health,” Dr. Wang said.
The strength of the relationship between sleep duration and the various outcomes was “modest” and based on group averages, he said. So, a given child who does not sleep for 9 hours most nights won’t necessarily perform worse than a child who gets enough sleep.
Still, modest effects may accumulate and have lasting consequences, Dr. Wang said.
Crystallized intelligence
The researchers looked at 42 behavioral outcomes, 32 of which were significantly different between the groups. Four outcomes in particular – depression, thought problems, performance on a picture-vocabulary test, and crystallized intelligence – were areas where insufficient sleep seemed to have a larger negative effect.
Sleep duration’s relationship with crystallized intelligence was twice that for fluid intelligence, which does not depend on memory.
“Sleep affects memory,” Dr. Wang said. “Crystallized intelligence depends on learned skills and knowledge, which are memory. In this sense, sleep is related to crystallized intelligence.”
One limitation of the study is that some parents may not accurately report how much sleep their child gets, Dr. Wang acknowledged. Children may be awake when parents think they are asleep, for example.
And although the results show getting 9 hours of sleep may help neurocognitive development, it’s also possible that excessive amounts of sleep could be problematic, the study authors wrote.
Further experiments are needed to prove that insufficient sleep – and not some other, unaccounted for factor – causes the observed impairments in neurodevelopment.
To promote healthy sleep, parents should keep a strict routine for their children, such as a regular bedtime and no electronic devices in the bedroom, Dr. Wang suggested. More physical activity during the day also should help.
If children have high levels of stress and depression, “finding the source is critical,” he said. Likewise, clinicians should consider how mental health can affect their patients’ sleep.
More to healthy sleep than duration
“This study both aligns with and advances existing research on the importance of sufficient sleep for child well-being,” said Ariel A. Williamson, PhD, DBSM, a psychologist and pediatric sleep expert in the department of child and adolescent psychiatry and behavioral sciences at Children’s Hospital of Philadelphia and assistant professor of psychiatry and pediatrics at University of Pennsylvania, also in Philadelphia.
The researchers used rigorous propensity score matching, longitudinal data, and brain imaging, which are “innovative methods that provide more evidence on potential mechanisms linking insufficient sleep and child outcomes,” said Dr. Williamson, who was not involved in the study.
While the investigators focused on sleep duration, child sleep health is multidimensional and includes other elements like timing and perception of sleep quality, Dr. Williamson noted. “For example, some research shows that having a sleep schedule that varies night to night is linked to poor child outcomes.”
Dr. Williamson tells families and clinicians that “sleep is a pillar of health,” equal to diet and exercise. That said, sleep recommendations need to fit within a family’s life – taking into account after school activities and late-night homework sessions. But extending sleep by just “20-30 minutes can make a meaningful difference for daytime functioning,” Dr. Williamson said.
Start school later?
Researchers have only relatively recently begun to understand how insufficient sleep affects adolescent neurocognitive development long term, and this study provides “crucial evidence” about the consequences, Lydia Gabriela Speyer, PhD, said in an editorial published with the study. Dr. Speyer is affiliated with the department of psychology at the University of Cambridge (England).
“Given the novel finding that insufficient sleep is associated with changes in brain structure and connectivity that are long-lasting, early intervention is crucial because such neural changes are probably not reversible and might consequently affect adolescents’ development into adulthood,” Dr. Speyer wrote.
Delaying school start times could be one way to help kids get more sleep. The American Academy of Pediatrics and the American Academy of Sleep Medicine recommend that middle schools and high schools start no earlier than 8:30 a.m. to better align with students’ circadian rhythm, Dr. Speyer noted.
As it is in the United States, most schools start closer to 8 a.m. In California, though, a law that went into effect on July 1 prohibits high schools from starting before 8:30 a.m. Other states are weighing similar legislation.
The research was supported by the National Institutes of Health. Dr. Wang and his coauthors and Dr. Speyer had no conflict of interest disclosures. Dr. Williamson is a sleep expert for the Pediatric Sleep Council (www.babysleep.com), which provides free information about early childhood sleep, but she does not receive compensation for this role.
Children who do not get enough sleep for one night can be cranky, groggy, or meltdown prone the next day.
Over time, though, insufficient sleep may impair neurodevelopment in ways that can be measured on brain scans and tests long term, a new study shows.
Research published in The Lancet Child & Adolescent Health found that 9- and 10-year-olds who do not get at least 9 hours of sleep most nights tend to have less gray matter and smaller areas of the brain responsible for attention, memory, and inhibition control, relative to children who do get enough sleep.
The researchers also found a relationship between insufficient sleep and disrupted connections between the basal ganglia and cortical regions of the brain. These disruptions appeared to be linked to depression, thought problems, and impairments in crystallized intelligence, a type of intelligence that depends on memory.
The overall patterns persisted 2 years later, even as those who got enough sleep at baseline gradually slept less over time, while those who were not getting enough sleep to begin with continued to sleep about the same amount, the researchers reported.
The results bolster the case for delaying school start times, as California recently did, according one researcher who was not involved in the study.
The ABCD Study
To examine how insufficient sleep affects children’s mental health, cognition, brain function, and brain structure over 2 years, Ze Wang, PhD, professor of diagnostic radiology and nuclear medicine at the University of Maryland, Baltimore, and colleagues analyzed data from the ongoing Adolescent Brain Cognitive Development (ABCD) Study. The ABCD Study is tracking the biologic and behavioral development of more than 11,000 children in the United States who were recruited for the study when they were 9 or 10 years old.
For their new analysis, Dr. Wang’s group focused on 6,042 participants: 3,021 children with insufficient sleep who were matched with an equal number of participants who were similar in many respects, including sex, socioeconomic status, and puberty status, except they got at least 9 hours of sleep. They also looked at outcomes 2 years later from 749 of the matched pairs who had results available.
The investigators determined sleep duration based on how parents answered the question: “How many hours of sleep does your child get on most nights in the past 6 months?” Possible answers included at least 9 hours, 8-9 hours, 7-8 hours, 5-7 hours, or less than 5 hours. They also looked at functional and structural MRI scans, test results, and responses to questionnaires.
Negative effects of inadequate sleep were spread over “several different domains including brain structure, function, cognition, behavior, and mental health,” Dr. Wang said.
The strength of the relationship between sleep duration and the various outcomes was “modest” and based on group averages, he said. So, a given child who does not sleep for 9 hours most nights won’t necessarily perform worse than a child who gets enough sleep.
Still, modest effects may accumulate and have lasting consequences, Dr. Wang said.
Crystallized intelligence
The researchers looked at 42 behavioral outcomes, 32 of which were significantly different between the groups. Four outcomes in particular – depression, thought problems, performance on a picture-vocabulary test, and crystallized intelligence – were areas where insufficient sleep seemed to have a larger negative effect.
Sleep duration’s relationship with crystallized intelligence was twice that for fluid intelligence, which does not depend on memory.
“Sleep affects memory,” Dr. Wang said. “Crystallized intelligence depends on learned skills and knowledge, which are memory. In this sense, sleep is related to crystallized intelligence.”
One limitation of the study is that some parents may not accurately report how much sleep their child gets, Dr. Wang acknowledged. Children may be awake when parents think they are asleep, for example.
And although the results show getting 9 hours of sleep may help neurocognitive development, it’s also possible that excessive amounts of sleep could be problematic, the study authors wrote.
Further experiments are needed to prove that insufficient sleep – and not some other, unaccounted for factor – causes the observed impairments in neurodevelopment.
To promote healthy sleep, parents should keep a strict routine for their children, such as a regular bedtime and no electronic devices in the bedroom, Dr. Wang suggested. More physical activity during the day also should help.
If children have high levels of stress and depression, “finding the source is critical,” he said. Likewise, clinicians should consider how mental health can affect their patients’ sleep.
More to healthy sleep than duration
“This study both aligns with and advances existing research on the importance of sufficient sleep for child well-being,” said Ariel A. Williamson, PhD, DBSM, a psychologist and pediatric sleep expert in the department of child and adolescent psychiatry and behavioral sciences at Children’s Hospital of Philadelphia and assistant professor of psychiatry and pediatrics at University of Pennsylvania, also in Philadelphia.
The researchers used rigorous propensity score matching, longitudinal data, and brain imaging, which are “innovative methods that provide more evidence on potential mechanisms linking insufficient sleep and child outcomes,” said Dr. Williamson, who was not involved in the study.
While the investigators focused on sleep duration, child sleep health is multidimensional and includes other elements like timing and perception of sleep quality, Dr. Williamson noted. “For example, some research shows that having a sleep schedule that varies night to night is linked to poor child outcomes.”
Dr. Williamson tells families and clinicians that “sleep is a pillar of health,” equal to diet and exercise. That said, sleep recommendations need to fit within a family’s life – taking into account after school activities and late-night homework sessions. But extending sleep by just “20-30 minutes can make a meaningful difference for daytime functioning,” Dr. Williamson said.
Start school later?
Researchers have only relatively recently begun to understand how insufficient sleep affects adolescent neurocognitive development long term, and this study provides “crucial evidence” about the consequences, Lydia Gabriela Speyer, PhD, said in an editorial published with the study. Dr. Speyer is affiliated with the department of psychology at the University of Cambridge (England).
“Given the novel finding that insufficient sleep is associated with changes in brain structure and connectivity that are long-lasting, early intervention is crucial because such neural changes are probably not reversible and might consequently affect adolescents’ development into adulthood,” Dr. Speyer wrote.
Delaying school start times could be one way to help kids get more sleep. The American Academy of Pediatrics and the American Academy of Sleep Medicine recommend that middle schools and high schools start no earlier than 8:30 a.m. to better align with students’ circadian rhythm, Dr. Speyer noted.
As it is in the United States, most schools start closer to 8 a.m. In California, though, a law that went into effect on July 1 prohibits high schools from starting before 8:30 a.m. Other states are weighing similar legislation.
The research was supported by the National Institutes of Health. Dr. Wang and his coauthors and Dr. Speyer had no conflict of interest disclosures. Dr. Williamson is a sleep expert for the Pediatric Sleep Council (www.babysleep.com), which provides free information about early childhood sleep, but she does not receive compensation for this role.
FROM THE LANCET CHILD & ADOLESCENT HEALTH
FDA clears new neurostimulation system for chronic pain
The “next generation” of its proprietary BurstDR stimulation, FlexBurst360 therapy, provides pain coverage across up to six areas of the trunk and limbs, with programming that can be adjusted as a patient’s individual therapeutic needs evolve, the manufacturer noted.
“Using FlexBurst360 therapy on the Proclaim Plus system, physicians can identify the lowest effective dose of stimulation for each patient and adapt it based on evolving pain needs,” the company said in a news release.
The system also has therapy settings accessed with a mobile device.
Through their mobile devices, patients can access the manufacturer’s NeuroSphere Virtual Clinic, which allows them to communicate with their providers and receive remote adjustments to their therapeutic settings as needed.
Game changer?
The newly approved system has a battery life of up to 10 years, akin to the company’s Proclaim XR neurostimulation system for chronic pain. As reported at the time by this news organization, that system was approved by the FDA in 2019.
More than 50 million people in the United States experience chronic pain and most have pain in more than one area of the body. Steven Falowski, MD, with Argires Marotti Neurosurgical Associates of Lancaster, Pa., noted in the release that spinal cord stimulation has provided “tremendous relief” for patients with chronic pain.
Dr. Falowski added that “with its ability to mimic natural patterns found in the brain, the Abbott BurstDR platform has been a game changer” for these patients.
“However, despite the many benefits of BurstDR, such as being effective as a low-energy stimulation therapy, some patients continue to be burdened ... because of multiple painful areas and evolving pain,” he said.
“Now, with Proclaim Plus and FlexBurst360, an already established platform has been improved to treat more patients who suffer from pain across different body parts and changing pain over time,” said Dr. Falowski.
A version of this article first appeared on Medscape.com.
The “next generation” of its proprietary BurstDR stimulation, FlexBurst360 therapy, provides pain coverage across up to six areas of the trunk and limbs, with programming that can be adjusted as a patient’s individual therapeutic needs evolve, the manufacturer noted.
“Using FlexBurst360 therapy on the Proclaim Plus system, physicians can identify the lowest effective dose of stimulation for each patient and adapt it based on evolving pain needs,” the company said in a news release.
The system also has therapy settings accessed with a mobile device.
Through their mobile devices, patients can access the manufacturer’s NeuroSphere Virtual Clinic, which allows them to communicate with their providers and receive remote adjustments to their therapeutic settings as needed.
Game changer?
The newly approved system has a battery life of up to 10 years, akin to the company’s Proclaim XR neurostimulation system for chronic pain. As reported at the time by this news organization, that system was approved by the FDA in 2019.
More than 50 million people in the United States experience chronic pain and most have pain in more than one area of the body. Steven Falowski, MD, with Argires Marotti Neurosurgical Associates of Lancaster, Pa., noted in the release that spinal cord stimulation has provided “tremendous relief” for patients with chronic pain.
Dr. Falowski added that “with its ability to mimic natural patterns found in the brain, the Abbott BurstDR platform has been a game changer” for these patients.
“However, despite the many benefits of BurstDR, such as being effective as a low-energy stimulation therapy, some patients continue to be burdened ... because of multiple painful areas and evolving pain,” he said.
“Now, with Proclaim Plus and FlexBurst360, an already established platform has been improved to treat more patients who suffer from pain across different body parts and changing pain over time,” said Dr. Falowski.
A version of this article first appeared on Medscape.com.
The “next generation” of its proprietary BurstDR stimulation, FlexBurst360 therapy, provides pain coverage across up to six areas of the trunk and limbs, with programming that can be adjusted as a patient’s individual therapeutic needs evolve, the manufacturer noted.
“Using FlexBurst360 therapy on the Proclaim Plus system, physicians can identify the lowest effective dose of stimulation for each patient and adapt it based on evolving pain needs,” the company said in a news release.
The system also has therapy settings accessed with a mobile device.
Through their mobile devices, patients can access the manufacturer’s NeuroSphere Virtual Clinic, which allows them to communicate with their providers and receive remote adjustments to their therapeutic settings as needed.
Game changer?
The newly approved system has a battery life of up to 10 years, akin to the company’s Proclaim XR neurostimulation system for chronic pain. As reported at the time by this news organization, that system was approved by the FDA in 2019.
More than 50 million people in the United States experience chronic pain and most have pain in more than one area of the body. Steven Falowski, MD, with Argires Marotti Neurosurgical Associates of Lancaster, Pa., noted in the release that spinal cord stimulation has provided “tremendous relief” for patients with chronic pain.
Dr. Falowski added that “with its ability to mimic natural patterns found in the brain, the Abbott BurstDR platform has been a game changer” for these patients.
“However, despite the many benefits of BurstDR, such as being effective as a low-energy stimulation therapy, some patients continue to be burdened ... because of multiple painful areas and evolving pain,” he said.
“Now, with Proclaim Plus and FlexBurst360, an already established platform has been improved to treat more patients who suffer from pain across different body parts and changing pain over time,” said Dr. Falowski.
A version of this article first appeared on Medscape.com.
Watching TV, using computer have opposite ties to dementia risk
The relationship to dementia with these activities remained strong no matter how much physical activity a person did, the authors wrote in Proceedings of the National Academy of Sciences.
Both watching TV and using a computer have been linked to increased risk of chronic disease and mortality, while exercise and physical activity (PA) have shown benefit in reducing cognitive decline, structural brain atrophy, and dementia risk in older adults, the authors wrote.
The authors said they wanted to try to understand the effects of watching TV and using computers on dementia risk, because people in the United States and Europe have been engaging in both of these activities more often.
They concluded that it’s not the sitting part of sedentary behavior (SB) that potentially has the effect on dementia but what people are doing while sitting.
Some of the results were surprising, lead author David Raichlen, PhD, professor of Human and Evolutionary Biology at University of Southern California, Los Angeles, said in an interview.
Previous literature on sedentary behaviors have documented their negative effects on a wide range of health outcomes, rather than finding positive associations, he explained.
More than 140,000 included in study
The researchers conducted their prospective cohort study using data from the United Kingdom Biobank. After excluding people younger than 60, those with prevalent dementia at the start of follow-up, and those without complete data, 146,651 participants were included.
The participants were followed from their baseline visit until they received a dementia diagnosis, died, were lost to follow-up, or were last admitted to the hospital.
TV-watching time was linked with an increased risk of incident dementia (HR [95% confidence interval] = 1.31 [1.23-1.40]), and computer use was linked with a reduced risk of incident dementia HR [95% CI] = 0.80 [0.76-0.85]).
TV’s link with higher dementia risk increased in those who had the highest use, compared with those who had the lowest use (HR [95% CI] = 1.28 [1.18-1.39].
Similarly, the link with risk reduction for dementia with computer use increased with more use.
Both medium and high computer time were associated with reduced risk of incident dementia (HR [95% CI] = 0.70 [0.64-0.76] and HR [95% CI] = 0.76 [0.70-0.83] respectively).
Dr. Raichlen pointed out that the high use of TV in this study was 4 or more hours a day and computer use – which included leisure use, not work use – had benefits on dementia risk after just half an hour.
These results remained significant after researchers adjusted for demographic, health, and lifestyle variables, including time spent on physical activity, sleeping, obesity, alcohol consumption, smoking status, diet scores, education level, body mass index, and employment type.
Physical is still better than sedentary activity
One potential reason for the different effects on dementia risk in the two activities studied, the authors write, is that sitting down to watch TV is associated with “uniquely low levels of muscle activity and energy expenditure, compared with sitting to use a computer.”
Andrew Budson, MD, chief of Cognitive & Behavioral Neurology and Associate Chief of Staff for Education for the VA Boston Healthcare System, Mass., who was not part of the study, said he thinks a more likely explanation for the study findings lies in the active versus passive tasks required in the two kinds of viewing that the authors reference.
“When we’re doing cognitive activity involving using the computer, we’re using large parts of our cortex to carry out that activity, whereas when we’re watching TV, there are probably relatively small amounts of our brain that are actually active,” Dr. Budson, author of Seven Steps to Managing Your Memory, explained in an interview.
“This is one of the first times I’ve been convinced that even when the computer activity isn’t completely new and novel, it may be beneficial,” Dr. Budson said.
It would be much better to do physical activity, but if the choice is sedentary activity, active cognitive activities, such as computer use, are better than TV watching, he continued.
The results of the current study are consistent with previous work showing that the type of sedentary behavior matters, according to the authors.
“Several studies have shown that TV time is associated with mortality and poor cardiometabolic biomarkers, whereas computer time is not,” they wrote.
A limitation of the study is that sedentary behaviors were self-reported via questionnaires, and there may be errors in recall.
“The use of objective methods for measuring both SB and PA are needed in future studies,” they write.
The authors receive support from the National Institutes of Health, the State of Arizona, the Arizona Department of Health Services, and the McKnight Brain Research Foundation. Neither the authors nor Dr. Budson declared relevant financial relationships.
The relationship to dementia with these activities remained strong no matter how much physical activity a person did, the authors wrote in Proceedings of the National Academy of Sciences.
Both watching TV and using a computer have been linked to increased risk of chronic disease and mortality, while exercise and physical activity (PA) have shown benefit in reducing cognitive decline, structural brain atrophy, and dementia risk in older adults, the authors wrote.
The authors said they wanted to try to understand the effects of watching TV and using computers on dementia risk, because people in the United States and Europe have been engaging in both of these activities more often.
They concluded that it’s not the sitting part of sedentary behavior (SB) that potentially has the effect on dementia but what people are doing while sitting.
Some of the results were surprising, lead author David Raichlen, PhD, professor of Human and Evolutionary Biology at University of Southern California, Los Angeles, said in an interview.
Previous literature on sedentary behaviors have documented their negative effects on a wide range of health outcomes, rather than finding positive associations, he explained.
More than 140,000 included in study
The researchers conducted their prospective cohort study using data from the United Kingdom Biobank. After excluding people younger than 60, those with prevalent dementia at the start of follow-up, and those without complete data, 146,651 participants were included.
The participants were followed from their baseline visit until they received a dementia diagnosis, died, were lost to follow-up, or were last admitted to the hospital.
TV-watching time was linked with an increased risk of incident dementia (HR [95% confidence interval] = 1.31 [1.23-1.40]), and computer use was linked with a reduced risk of incident dementia HR [95% CI] = 0.80 [0.76-0.85]).
TV’s link with higher dementia risk increased in those who had the highest use, compared with those who had the lowest use (HR [95% CI] = 1.28 [1.18-1.39].
Similarly, the link with risk reduction for dementia with computer use increased with more use.
Both medium and high computer time were associated with reduced risk of incident dementia (HR [95% CI] = 0.70 [0.64-0.76] and HR [95% CI] = 0.76 [0.70-0.83] respectively).
Dr. Raichlen pointed out that the high use of TV in this study was 4 or more hours a day and computer use – which included leisure use, not work use – had benefits on dementia risk after just half an hour.
These results remained significant after researchers adjusted for demographic, health, and lifestyle variables, including time spent on physical activity, sleeping, obesity, alcohol consumption, smoking status, diet scores, education level, body mass index, and employment type.
Physical is still better than sedentary activity
One potential reason for the different effects on dementia risk in the two activities studied, the authors write, is that sitting down to watch TV is associated with “uniquely low levels of muscle activity and energy expenditure, compared with sitting to use a computer.”
Andrew Budson, MD, chief of Cognitive & Behavioral Neurology and Associate Chief of Staff for Education for the VA Boston Healthcare System, Mass., who was not part of the study, said he thinks a more likely explanation for the study findings lies in the active versus passive tasks required in the two kinds of viewing that the authors reference.
“When we’re doing cognitive activity involving using the computer, we’re using large parts of our cortex to carry out that activity, whereas when we’re watching TV, there are probably relatively small amounts of our brain that are actually active,” Dr. Budson, author of Seven Steps to Managing Your Memory, explained in an interview.
“This is one of the first times I’ve been convinced that even when the computer activity isn’t completely new and novel, it may be beneficial,” Dr. Budson said.
It would be much better to do physical activity, but if the choice is sedentary activity, active cognitive activities, such as computer use, are better than TV watching, he continued.
The results of the current study are consistent with previous work showing that the type of sedentary behavior matters, according to the authors.
“Several studies have shown that TV time is associated with mortality and poor cardiometabolic biomarkers, whereas computer time is not,” they wrote.
A limitation of the study is that sedentary behaviors were self-reported via questionnaires, and there may be errors in recall.
“The use of objective methods for measuring both SB and PA are needed in future studies,” they write.
The authors receive support from the National Institutes of Health, the State of Arizona, the Arizona Department of Health Services, and the McKnight Brain Research Foundation. Neither the authors nor Dr. Budson declared relevant financial relationships.
The relationship to dementia with these activities remained strong no matter how much physical activity a person did, the authors wrote in Proceedings of the National Academy of Sciences.
Both watching TV and using a computer have been linked to increased risk of chronic disease and mortality, while exercise and physical activity (PA) have shown benefit in reducing cognitive decline, structural brain atrophy, and dementia risk in older adults, the authors wrote.
The authors said they wanted to try to understand the effects of watching TV and using computers on dementia risk, because people in the United States and Europe have been engaging in both of these activities more often.
They concluded that it’s not the sitting part of sedentary behavior (SB) that potentially has the effect on dementia but what people are doing while sitting.
Some of the results were surprising, lead author David Raichlen, PhD, professor of Human and Evolutionary Biology at University of Southern California, Los Angeles, said in an interview.
Previous literature on sedentary behaviors have documented their negative effects on a wide range of health outcomes, rather than finding positive associations, he explained.
More than 140,000 included in study
The researchers conducted their prospective cohort study using data from the United Kingdom Biobank. After excluding people younger than 60, those with prevalent dementia at the start of follow-up, and those without complete data, 146,651 participants were included.
The participants were followed from their baseline visit until they received a dementia diagnosis, died, were lost to follow-up, or were last admitted to the hospital.
TV-watching time was linked with an increased risk of incident dementia (HR [95% confidence interval] = 1.31 [1.23-1.40]), and computer use was linked with a reduced risk of incident dementia HR [95% CI] = 0.80 [0.76-0.85]).
TV’s link with higher dementia risk increased in those who had the highest use, compared with those who had the lowest use (HR [95% CI] = 1.28 [1.18-1.39].
Similarly, the link with risk reduction for dementia with computer use increased with more use.
Both medium and high computer time were associated with reduced risk of incident dementia (HR [95% CI] = 0.70 [0.64-0.76] and HR [95% CI] = 0.76 [0.70-0.83] respectively).
Dr. Raichlen pointed out that the high use of TV in this study was 4 or more hours a day and computer use – which included leisure use, not work use – had benefits on dementia risk after just half an hour.
These results remained significant after researchers adjusted for demographic, health, and lifestyle variables, including time spent on physical activity, sleeping, obesity, alcohol consumption, smoking status, diet scores, education level, body mass index, and employment type.
Physical is still better than sedentary activity
One potential reason for the different effects on dementia risk in the two activities studied, the authors write, is that sitting down to watch TV is associated with “uniquely low levels of muscle activity and energy expenditure, compared with sitting to use a computer.”
Andrew Budson, MD, chief of Cognitive & Behavioral Neurology and Associate Chief of Staff for Education for the VA Boston Healthcare System, Mass., who was not part of the study, said he thinks a more likely explanation for the study findings lies in the active versus passive tasks required in the two kinds of viewing that the authors reference.
“When we’re doing cognitive activity involving using the computer, we’re using large parts of our cortex to carry out that activity, whereas when we’re watching TV, there are probably relatively small amounts of our brain that are actually active,” Dr. Budson, author of Seven Steps to Managing Your Memory, explained in an interview.
“This is one of the first times I’ve been convinced that even when the computer activity isn’t completely new and novel, it may be beneficial,” Dr. Budson said.
It would be much better to do physical activity, but if the choice is sedentary activity, active cognitive activities, such as computer use, are better than TV watching, he continued.
The results of the current study are consistent with previous work showing that the type of sedentary behavior matters, according to the authors.
“Several studies have shown that TV time is associated with mortality and poor cardiometabolic biomarkers, whereas computer time is not,” they wrote.
A limitation of the study is that sedentary behaviors were self-reported via questionnaires, and there may be errors in recall.
“The use of objective methods for measuring both SB and PA are needed in future studies,” they write.
The authors receive support from the National Institutes of Health, the State of Arizona, the Arizona Department of Health Services, and the McKnight Brain Research Foundation. Neither the authors nor Dr. Budson declared relevant financial relationships.
FROM PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES
Atrial cardiopathy linked to 35% higher dementia risk
“We cautiously suggest that an understanding of this relationship might provide a basis for new interventional strategies to help thwart the development of dementia,” the authors write.
The research, led by Michelle C. Johansen, MD, department of neurology, Johns Hopkins University, Baltimore, was published online in the Journal of the American Heart Association.
Atrial cardiopathy, characterized by abnormal size and function of the left atrium, has been associated with an increased risk of stroke and atrial fibrillation (AFib), and because both stroke and AFib are associated with an increased dementia risk, the authors write, it was important to investigate whether atrial cardiopathy is linked to dementia.
If that’s the case, they reasoned, the next question was whether that link is independent of AFib and stroke, and their new research suggests that it is.
For this analysis, the researchers conducted a prospective cohort analysis of participants in the Atherosclerosis Risk in Communities (ARIC) study who were attending visit 5 (2011-2013). During their fifth, sixth, and seventh clinical visits, the ARIC participants were evaluated for cognitive decline indicating dementia.
They studied a diverse population of 5,078 older adults living in four U.S. communities: Washington County, Md.; Forsyth County, N.C.; the northwestern suburbs of Minneapolis; and Jackson, Miss.
Just more than a third (34%) had atrial cardiopathy (average age, 75 years; 59% female; 21% Black) and 763 participants developed dementia.
Investigators found that atrial cardiopathy was significantly associated with dementia (adjusted hazard ratio, 1.35 [95% confidence interval, 1.16-1.58]).
They considered ARIC participants to have atrial cardiopathy if they had at least one of the following: P-wave terminal force greater than 5,000 mV·ms in ECG lead V1; NTproBNP greater than 250 pg/mL; or left atrial volume index greater than or equal to 34 mL/m2 by transthoracic echocardiography.
The risk of dementia was even stronger when the researchers defined cardiopathy by at least two biomarkers instead of one (aHR, 1.54 [95% CI, 1.25-1.89]).
The authors point out, however, that this study is observational and cannot make a causal link.
Clifford Kavinsky, MD, PhD, head of the Comprehensive Stroke and Cardiology Clinic at Rush University Medical Center, Chicago, told this news organization that much more research would need to be done to show convincingly that atrial cardiopathy causes dementia.
He called the findings “provocative in trying to understand in a general sense how cardiac dysfunction leads to dementia.”
“We all know heart failure leads to dementia, but now we see there may be a relationship with just dysfunction of the upper chambers,” he said.
Unresolved questions
But it still not clear is what is mediating the connection, who is at risk, and how the increased risk can be prevented, he said.
He said he also wonders whether the results eliminated all patients with atrial fibrillation, a point the authors acknowledge as well.
Researchers list in the limitations that “asymptomatic AFib or silent cerebral infarction may have been missed by the ARIC adjudication process.”
There is broad understanding that preventing heart disease is important for a wide array of reasons, Dr. Kavinsky noted, and one of the reasons is cognitive deterioration.
He said this study helps identify that “even dysfunction of the upper chambers of the heart contributes to the evolution of dementia.”
The study amplifies the need to shift to prevention with heart disease in general, and more specifically in atrial dysfunction, Dr. Kavinsky said, noting a lot of atrial dysfunction is mediated by underlying hypertension and coronary disease.
Researchers evaluated cognitive decline in all participants with a comprehensive array of neuropsychological tests and interviewed some of the patients.
“A diagnosis of dementia was generated based on testing results by a computer diagnostic algorithm and then decided upon by an expert based on the Diagnostic and Statistical Manual of Mental Disorders and the criteria outlined by the National Institutes of Health and the National Institutes of Health,” they write.
Dr. Johansen reported funding from National Institute of Neurological Disorders and Stroke. Study coauthor disclosures are listed in the paper. Dr. Kavinsky has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
“We cautiously suggest that an understanding of this relationship might provide a basis for new interventional strategies to help thwart the development of dementia,” the authors write.
The research, led by Michelle C. Johansen, MD, department of neurology, Johns Hopkins University, Baltimore, was published online in the Journal of the American Heart Association.
Atrial cardiopathy, characterized by abnormal size and function of the left atrium, has been associated with an increased risk of stroke and atrial fibrillation (AFib), and because both stroke and AFib are associated with an increased dementia risk, the authors write, it was important to investigate whether atrial cardiopathy is linked to dementia.
If that’s the case, they reasoned, the next question was whether that link is independent of AFib and stroke, and their new research suggests that it is.
For this analysis, the researchers conducted a prospective cohort analysis of participants in the Atherosclerosis Risk in Communities (ARIC) study who were attending visit 5 (2011-2013). During their fifth, sixth, and seventh clinical visits, the ARIC participants were evaluated for cognitive decline indicating dementia.
They studied a diverse population of 5,078 older adults living in four U.S. communities: Washington County, Md.; Forsyth County, N.C.; the northwestern suburbs of Minneapolis; and Jackson, Miss.
Just more than a third (34%) had atrial cardiopathy (average age, 75 years; 59% female; 21% Black) and 763 participants developed dementia.
Investigators found that atrial cardiopathy was significantly associated with dementia (adjusted hazard ratio, 1.35 [95% confidence interval, 1.16-1.58]).
They considered ARIC participants to have atrial cardiopathy if they had at least one of the following: P-wave terminal force greater than 5,000 mV·ms in ECG lead V1; NTproBNP greater than 250 pg/mL; or left atrial volume index greater than or equal to 34 mL/m2 by transthoracic echocardiography.
The risk of dementia was even stronger when the researchers defined cardiopathy by at least two biomarkers instead of one (aHR, 1.54 [95% CI, 1.25-1.89]).
The authors point out, however, that this study is observational and cannot make a causal link.
Clifford Kavinsky, MD, PhD, head of the Comprehensive Stroke and Cardiology Clinic at Rush University Medical Center, Chicago, told this news organization that much more research would need to be done to show convincingly that atrial cardiopathy causes dementia.
He called the findings “provocative in trying to understand in a general sense how cardiac dysfunction leads to dementia.”
“We all know heart failure leads to dementia, but now we see there may be a relationship with just dysfunction of the upper chambers,” he said.
Unresolved questions
But it still not clear is what is mediating the connection, who is at risk, and how the increased risk can be prevented, he said.
He said he also wonders whether the results eliminated all patients with atrial fibrillation, a point the authors acknowledge as well.
Researchers list in the limitations that “asymptomatic AFib or silent cerebral infarction may have been missed by the ARIC adjudication process.”
There is broad understanding that preventing heart disease is important for a wide array of reasons, Dr. Kavinsky noted, and one of the reasons is cognitive deterioration.
He said this study helps identify that “even dysfunction of the upper chambers of the heart contributes to the evolution of dementia.”
The study amplifies the need to shift to prevention with heart disease in general, and more specifically in atrial dysfunction, Dr. Kavinsky said, noting a lot of atrial dysfunction is mediated by underlying hypertension and coronary disease.
Researchers evaluated cognitive decline in all participants with a comprehensive array of neuropsychological tests and interviewed some of the patients.
“A diagnosis of dementia was generated based on testing results by a computer diagnostic algorithm and then decided upon by an expert based on the Diagnostic and Statistical Manual of Mental Disorders and the criteria outlined by the National Institutes of Health and the National Institutes of Health,” they write.
Dr. Johansen reported funding from National Institute of Neurological Disorders and Stroke. Study coauthor disclosures are listed in the paper. Dr. Kavinsky has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
“We cautiously suggest that an understanding of this relationship might provide a basis for new interventional strategies to help thwart the development of dementia,” the authors write.
The research, led by Michelle C. Johansen, MD, department of neurology, Johns Hopkins University, Baltimore, was published online in the Journal of the American Heart Association.
Atrial cardiopathy, characterized by abnormal size and function of the left atrium, has been associated with an increased risk of stroke and atrial fibrillation (AFib), and because both stroke and AFib are associated with an increased dementia risk, the authors write, it was important to investigate whether atrial cardiopathy is linked to dementia.
If that’s the case, they reasoned, the next question was whether that link is independent of AFib and stroke, and their new research suggests that it is.
For this analysis, the researchers conducted a prospective cohort analysis of participants in the Atherosclerosis Risk in Communities (ARIC) study who were attending visit 5 (2011-2013). During their fifth, sixth, and seventh clinical visits, the ARIC participants were evaluated for cognitive decline indicating dementia.
They studied a diverse population of 5,078 older adults living in four U.S. communities: Washington County, Md.; Forsyth County, N.C.; the northwestern suburbs of Minneapolis; and Jackson, Miss.
Just more than a third (34%) had atrial cardiopathy (average age, 75 years; 59% female; 21% Black) and 763 participants developed dementia.
Investigators found that atrial cardiopathy was significantly associated with dementia (adjusted hazard ratio, 1.35 [95% confidence interval, 1.16-1.58]).
They considered ARIC participants to have atrial cardiopathy if they had at least one of the following: P-wave terminal force greater than 5,000 mV·ms in ECG lead V1; NTproBNP greater than 250 pg/mL; or left atrial volume index greater than or equal to 34 mL/m2 by transthoracic echocardiography.
The risk of dementia was even stronger when the researchers defined cardiopathy by at least two biomarkers instead of one (aHR, 1.54 [95% CI, 1.25-1.89]).
The authors point out, however, that this study is observational and cannot make a causal link.
Clifford Kavinsky, MD, PhD, head of the Comprehensive Stroke and Cardiology Clinic at Rush University Medical Center, Chicago, told this news organization that much more research would need to be done to show convincingly that atrial cardiopathy causes dementia.
He called the findings “provocative in trying to understand in a general sense how cardiac dysfunction leads to dementia.”
“We all know heart failure leads to dementia, but now we see there may be a relationship with just dysfunction of the upper chambers,” he said.
Unresolved questions
But it still not clear is what is mediating the connection, who is at risk, and how the increased risk can be prevented, he said.
He said he also wonders whether the results eliminated all patients with atrial fibrillation, a point the authors acknowledge as well.
Researchers list in the limitations that “asymptomatic AFib or silent cerebral infarction may have been missed by the ARIC adjudication process.”
There is broad understanding that preventing heart disease is important for a wide array of reasons, Dr. Kavinsky noted, and one of the reasons is cognitive deterioration.
He said this study helps identify that “even dysfunction of the upper chambers of the heart contributes to the evolution of dementia.”
The study amplifies the need to shift to prevention with heart disease in general, and more specifically in atrial dysfunction, Dr. Kavinsky said, noting a lot of atrial dysfunction is mediated by underlying hypertension and coronary disease.
Researchers evaluated cognitive decline in all participants with a comprehensive array of neuropsychological tests and interviewed some of the patients.
“A diagnosis of dementia was generated based on testing results by a computer diagnostic algorithm and then decided upon by an expert based on the Diagnostic and Statistical Manual of Mental Disorders and the criteria outlined by the National Institutes of Health and the National Institutes of Health,” they write.
Dr. Johansen reported funding from National Institute of Neurological Disorders and Stroke. Study coauthor disclosures are listed in the paper. Dr. Kavinsky has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.