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AHA urges action against racial inequities in stroke care
Stroke is a “disease of disparities,” with racial and ethnic inequities in incidence, prevalence, treatment, and outcomes, and research is needed to identify structural or “upstream” interventions to address the problem, the American Heart Association says in a new scientific statement.
including Black, Hispanic, and Indigenous peoples,” writing group chair Amytis Towfighi, MD, professor of neurology, University of Southern California, Los Angeles, says in a news release.
“While research has historically focused on describing these inequities, it is critical to develop and test interventions to address them,” Dr. Towfighi adds.
The scientific statement was published online in the journal Stroke.
It follows a 2020 AHA presidential advisory that declared structural racism a fundamental driver of poor health and early death from heart disease and stroke.
Dr. Towfighi and colleagues reviewed the literature on interventions to address racial and ethnic inequities to identify gaps and areas for future research.
They note that various interventions have shown promise in reducing inequities across the stroke continuum of care.
For example, data suggest that careful attention to stroke preparedness among patients, caregivers, and emergency medical services can reduce inequities in getting people suspected of having a stroke to the emergency department quickly, with delivery of prompt treatment.
However, insufficient research attention has been paid to reducing inequities in rehabilitation, recovery, and social reintegration, the writing group says.
In addition, most studies have addressed patient-level factors, such as medication adherence, health literacy, and health behaviors, but not upstream social factors such as structural racism, housing, income, food security, and access to care, which also affect stroke incidence, care, and outcomes.
“Combating the effects of systemic racism will involve upstream interventions, including policy changes, place-based interventions, and engaging with the health care systems that serve predominantly historically disenfranchised populations and the communities they serve, understanding the barriers, and collaboratively developing solutions to address barriers,” the writing group says.
Further research is needed across the stroke continuum of care to tackle racial and ethnic inequities in stroke care and improve outcomes, they say.
“It’s critical for historically disenfranchised communities to participate in research so that researchers may collaborate in addressing the communities’ needs and concerns,” Bernadette Boden-Albala, DrPH, MPH, vice chair of the writing group, says in the news release.
“Opportunities include working with community stakeholder groups and community organizations to advocate for partnerships with hospitals, academic medical centers, local colleges and universities; or joining community advisory boards and volunteering with the American Heart Association,” Dr. Boden-Albala adds.
Dr. Towfighi encourages health care professionals to “think outside the ‘stroke box.’ Sustainable, effective interventions to address inequities will likely require collaboration with patients, their communities, policymakers, and other sectors.”
The scientific statement was prepared by the volunteer writing group on behalf of the AHA Stroke Council, the Council on Cardiovascular and Stroke Nursing, the Council on Cardiovascular Radiology and Intervention, the Council on Clinical Cardiology, the Council on Hypertension, the Council on the Kidney in Cardiovascular Disease, and the Council on Peripheral Vascular Disease.
The research had no commercial funding.
A version of this article first appeared on Medscape.com.
Stroke is a “disease of disparities,” with racial and ethnic inequities in incidence, prevalence, treatment, and outcomes, and research is needed to identify structural or “upstream” interventions to address the problem, the American Heart Association says in a new scientific statement.
including Black, Hispanic, and Indigenous peoples,” writing group chair Amytis Towfighi, MD, professor of neurology, University of Southern California, Los Angeles, says in a news release.
“While research has historically focused on describing these inequities, it is critical to develop and test interventions to address them,” Dr. Towfighi adds.
The scientific statement was published online in the journal Stroke.
It follows a 2020 AHA presidential advisory that declared structural racism a fundamental driver of poor health and early death from heart disease and stroke.
Dr. Towfighi and colleagues reviewed the literature on interventions to address racial and ethnic inequities to identify gaps and areas for future research.
They note that various interventions have shown promise in reducing inequities across the stroke continuum of care.
For example, data suggest that careful attention to stroke preparedness among patients, caregivers, and emergency medical services can reduce inequities in getting people suspected of having a stroke to the emergency department quickly, with delivery of prompt treatment.
However, insufficient research attention has been paid to reducing inequities in rehabilitation, recovery, and social reintegration, the writing group says.
In addition, most studies have addressed patient-level factors, such as medication adherence, health literacy, and health behaviors, but not upstream social factors such as structural racism, housing, income, food security, and access to care, which also affect stroke incidence, care, and outcomes.
“Combating the effects of systemic racism will involve upstream interventions, including policy changes, place-based interventions, and engaging with the health care systems that serve predominantly historically disenfranchised populations and the communities they serve, understanding the barriers, and collaboratively developing solutions to address barriers,” the writing group says.
Further research is needed across the stroke continuum of care to tackle racial and ethnic inequities in stroke care and improve outcomes, they say.
“It’s critical for historically disenfranchised communities to participate in research so that researchers may collaborate in addressing the communities’ needs and concerns,” Bernadette Boden-Albala, DrPH, MPH, vice chair of the writing group, says in the news release.
“Opportunities include working with community stakeholder groups and community organizations to advocate for partnerships with hospitals, academic medical centers, local colleges and universities; or joining community advisory boards and volunteering with the American Heart Association,” Dr. Boden-Albala adds.
Dr. Towfighi encourages health care professionals to “think outside the ‘stroke box.’ Sustainable, effective interventions to address inequities will likely require collaboration with patients, their communities, policymakers, and other sectors.”
The scientific statement was prepared by the volunteer writing group on behalf of the AHA Stroke Council, the Council on Cardiovascular and Stroke Nursing, the Council on Cardiovascular Radiology and Intervention, the Council on Clinical Cardiology, the Council on Hypertension, the Council on the Kidney in Cardiovascular Disease, and the Council on Peripheral Vascular Disease.
The research had no commercial funding.
A version of this article first appeared on Medscape.com.
Stroke is a “disease of disparities,” with racial and ethnic inequities in incidence, prevalence, treatment, and outcomes, and research is needed to identify structural or “upstream” interventions to address the problem, the American Heart Association says in a new scientific statement.
including Black, Hispanic, and Indigenous peoples,” writing group chair Amytis Towfighi, MD, professor of neurology, University of Southern California, Los Angeles, says in a news release.
“While research has historically focused on describing these inequities, it is critical to develop and test interventions to address them,” Dr. Towfighi adds.
The scientific statement was published online in the journal Stroke.
It follows a 2020 AHA presidential advisory that declared structural racism a fundamental driver of poor health and early death from heart disease and stroke.
Dr. Towfighi and colleagues reviewed the literature on interventions to address racial and ethnic inequities to identify gaps and areas for future research.
They note that various interventions have shown promise in reducing inequities across the stroke continuum of care.
For example, data suggest that careful attention to stroke preparedness among patients, caregivers, and emergency medical services can reduce inequities in getting people suspected of having a stroke to the emergency department quickly, with delivery of prompt treatment.
However, insufficient research attention has been paid to reducing inequities in rehabilitation, recovery, and social reintegration, the writing group says.
In addition, most studies have addressed patient-level factors, such as medication adherence, health literacy, and health behaviors, but not upstream social factors such as structural racism, housing, income, food security, and access to care, which also affect stroke incidence, care, and outcomes.
“Combating the effects of systemic racism will involve upstream interventions, including policy changes, place-based interventions, and engaging with the health care systems that serve predominantly historically disenfranchised populations and the communities they serve, understanding the barriers, and collaboratively developing solutions to address barriers,” the writing group says.
Further research is needed across the stroke continuum of care to tackle racial and ethnic inequities in stroke care and improve outcomes, they say.
“It’s critical for historically disenfranchised communities to participate in research so that researchers may collaborate in addressing the communities’ needs and concerns,” Bernadette Boden-Albala, DrPH, MPH, vice chair of the writing group, says in the news release.
“Opportunities include working with community stakeholder groups and community organizations to advocate for partnerships with hospitals, academic medical centers, local colleges and universities; or joining community advisory boards and volunteering with the American Heart Association,” Dr. Boden-Albala adds.
Dr. Towfighi encourages health care professionals to “think outside the ‘stroke box.’ Sustainable, effective interventions to address inequities will likely require collaboration with patients, their communities, policymakers, and other sectors.”
The scientific statement was prepared by the volunteer writing group on behalf of the AHA Stroke Council, the Council on Cardiovascular and Stroke Nursing, the Council on Cardiovascular Radiology and Intervention, the Council on Clinical Cardiology, the Council on Hypertension, the Council on the Kidney in Cardiovascular Disease, and the Council on Peripheral Vascular Disease.
The research had no commercial funding.
A version of this article first appeared on Medscape.com.
FROM STROKE
Deep sleep may mitigate the impact of Alzheimer’s pathology
Investigators found that deep sleep, also known as non-REM (NREM) slow-wave sleep, can protect memory function in cognitively normal adults with a high beta-amyloid burden.
“Think of deep sleep almost like a life raft that keeps memory afloat, rather than memory getting dragged down by the weight of Alzheimer’s disease pathology,” senior investigator Matthew Walker, PhD, professor of neuroscience and psychology, University of California, Berkeley, said in a news release.
The study was published online in BMC Medicine.
Resilience factor
Studying resilience to existing brain pathology is “an exciting new research direction,” lead author Zsófia Zavecz, PhD, with the Center for Human Sleep Science at the University of California, Berkeley, said in an interview.
“That is, what factors explain the individual differences in cognitive function despite the same level of brain pathology, and how do some people with significant pathology have largely preserved memory?” she added.
The study included 62 cognitively normal older adults from the Berkeley Aging Cohort Study.
Sleep EEG recordings were obtained over 2 nights in a sleep lab and PET scans were used to quantify beta-amyloid. Half of the participants had high beta-amyloid burden and half were beta-amyloid negative.
After the sleep studies, all participants completed a memory task involving matching names to faces.
The results suggest that deep NREM slow-wave sleep significantly moderates the effect of beta-amyloid status on memory function.
Specifically, NREM slow-wave activity selectively supported superior memory function in adults with high beta-amyloid burden, who are most in need of cognitive reserve (B = 2.694, P = .019), the researchers report.
In contrast, adults without significant beta-amyloid pathological burden – and thus without the same need for cognitive reserve – did not similarly benefit from NREM slow-wave activity (B = –0.115, P = .876).
The findings remained significant after adjusting for age, sex, body mass index, gray matter atrophy, and previously identified cognitive reserve factors, such as education and physical activity.
Dr. Zavecz said there are several potential reasons why deep sleep may support cognitive reserve.
One is that during deep sleep specifically, memories are replayed in the brain, and this results in a “neural reorganization” that helps stabilize the memory and make it more permanent.
“Other explanations include deep sleep’s role in maintaining homeostasis in the brain’s capacity to form new neural connections and providing an optimal brain state for the clearance of toxins interfering with healthy brain functioning,” she noted.
“The extent to which sleep could offer a protective buffer against severe cognitive impairment remains to be tested. However, this study is the first step in hopefully a series of new research that will investigate sleep as a cognitive reserve factor,” said Dr. Zavecz.
Encouraging data
Reached for comment, Percy Griffin, PhD, Alzheimer’s Association director of scientific engagement, said although the study sample is small, the results are “encouraging because sleep is a modifiable factor and can therefore be targeted.”
“More work is needed in a larger population before we can fully leverage this stage of sleep to reduce the risk of developing cognitive decline,” Dr. Griffin said.
Also weighing in on this research, Shaheen Lakhan, MD, PhD, a neurologist and researcher in Boston, said the study is “exciting on two fronts – we may have an additional marker for the development of Alzheimer’s disease to predict risk and track disease, but also targets for early intervention with sleep architecture–enhancing therapies, be they drug, device, or digital.”
“For the sake of our brain health, we all must get very familiar with the concept of cognitive or brain reserve,” said Dr. Lakhan, who was not involved in the study.
“Brain reserve refers to our ability to buttress against the threat of dementia and classically it’s been associated with ongoing brain stimulation (i.e., higher education, cognitively demanding job),” he noted.
“This line of research now opens the door that optimal sleep health – especially deep NREM slow wave sleep – correlates with greater brain reserve against Alzheimer’s disease,” Dr. Lakhan said.
The study was supported by the National Institutes of Health and the University of California, Berkeley. Dr. Walker serves as an advisor to and has equity interest in Bryte, Shuni, Oura, and StimScience. Dr. Zavecz and Dr. Lakhan report no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Investigators found that deep sleep, also known as non-REM (NREM) slow-wave sleep, can protect memory function in cognitively normal adults with a high beta-amyloid burden.
“Think of deep sleep almost like a life raft that keeps memory afloat, rather than memory getting dragged down by the weight of Alzheimer’s disease pathology,” senior investigator Matthew Walker, PhD, professor of neuroscience and psychology, University of California, Berkeley, said in a news release.
The study was published online in BMC Medicine.
Resilience factor
Studying resilience to existing brain pathology is “an exciting new research direction,” lead author Zsófia Zavecz, PhD, with the Center for Human Sleep Science at the University of California, Berkeley, said in an interview.
“That is, what factors explain the individual differences in cognitive function despite the same level of brain pathology, and how do some people with significant pathology have largely preserved memory?” she added.
The study included 62 cognitively normal older adults from the Berkeley Aging Cohort Study.
Sleep EEG recordings were obtained over 2 nights in a sleep lab and PET scans were used to quantify beta-amyloid. Half of the participants had high beta-amyloid burden and half were beta-amyloid negative.
After the sleep studies, all participants completed a memory task involving matching names to faces.
The results suggest that deep NREM slow-wave sleep significantly moderates the effect of beta-amyloid status on memory function.
Specifically, NREM slow-wave activity selectively supported superior memory function in adults with high beta-amyloid burden, who are most in need of cognitive reserve (B = 2.694, P = .019), the researchers report.
In contrast, adults without significant beta-amyloid pathological burden – and thus without the same need for cognitive reserve – did not similarly benefit from NREM slow-wave activity (B = –0.115, P = .876).
The findings remained significant after adjusting for age, sex, body mass index, gray matter atrophy, and previously identified cognitive reserve factors, such as education and physical activity.
Dr. Zavecz said there are several potential reasons why deep sleep may support cognitive reserve.
One is that during deep sleep specifically, memories are replayed in the brain, and this results in a “neural reorganization” that helps stabilize the memory and make it more permanent.
“Other explanations include deep sleep’s role in maintaining homeostasis in the brain’s capacity to form new neural connections and providing an optimal brain state for the clearance of toxins interfering with healthy brain functioning,” she noted.
“The extent to which sleep could offer a protective buffer against severe cognitive impairment remains to be tested. However, this study is the first step in hopefully a series of new research that will investigate sleep as a cognitive reserve factor,” said Dr. Zavecz.
Encouraging data
Reached for comment, Percy Griffin, PhD, Alzheimer’s Association director of scientific engagement, said although the study sample is small, the results are “encouraging because sleep is a modifiable factor and can therefore be targeted.”
“More work is needed in a larger population before we can fully leverage this stage of sleep to reduce the risk of developing cognitive decline,” Dr. Griffin said.
Also weighing in on this research, Shaheen Lakhan, MD, PhD, a neurologist and researcher in Boston, said the study is “exciting on two fronts – we may have an additional marker for the development of Alzheimer’s disease to predict risk and track disease, but also targets for early intervention with sleep architecture–enhancing therapies, be they drug, device, or digital.”
“For the sake of our brain health, we all must get very familiar with the concept of cognitive or brain reserve,” said Dr. Lakhan, who was not involved in the study.
“Brain reserve refers to our ability to buttress against the threat of dementia and classically it’s been associated with ongoing brain stimulation (i.e., higher education, cognitively demanding job),” he noted.
“This line of research now opens the door that optimal sleep health – especially deep NREM slow wave sleep – correlates with greater brain reserve against Alzheimer’s disease,” Dr. Lakhan said.
The study was supported by the National Institutes of Health and the University of California, Berkeley. Dr. Walker serves as an advisor to and has equity interest in Bryte, Shuni, Oura, and StimScience. Dr. Zavecz and Dr. Lakhan report no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Investigators found that deep sleep, also known as non-REM (NREM) slow-wave sleep, can protect memory function in cognitively normal adults with a high beta-amyloid burden.
“Think of deep sleep almost like a life raft that keeps memory afloat, rather than memory getting dragged down by the weight of Alzheimer’s disease pathology,” senior investigator Matthew Walker, PhD, professor of neuroscience and psychology, University of California, Berkeley, said in a news release.
The study was published online in BMC Medicine.
Resilience factor
Studying resilience to existing brain pathology is “an exciting new research direction,” lead author Zsófia Zavecz, PhD, with the Center for Human Sleep Science at the University of California, Berkeley, said in an interview.
“That is, what factors explain the individual differences in cognitive function despite the same level of brain pathology, and how do some people with significant pathology have largely preserved memory?” she added.
The study included 62 cognitively normal older adults from the Berkeley Aging Cohort Study.
Sleep EEG recordings were obtained over 2 nights in a sleep lab and PET scans were used to quantify beta-amyloid. Half of the participants had high beta-amyloid burden and half were beta-amyloid negative.
After the sleep studies, all participants completed a memory task involving matching names to faces.
The results suggest that deep NREM slow-wave sleep significantly moderates the effect of beta-amyloid status on memory function.
Specifically, NREM slow-wave activity selectively supported superior memory function in adults with high beta-amyloid burden, who are most in need of cognitive reserve (B = 2.694, P = .019), the researchers report.
In contrast, adults without significant beta-amyloid pathological burden – and thus without the same need for cognitive reserve – did not similarly benefit from NREM slow-wave activity (B = –0.115, P = .876).
The findings remained significant after adjusting for age, sex, body mass index, gray matter atrophy, and previously identified cognitive reserve factors, such as education and physical activity.
Dr. Zavecz said there are several potential reasons why deep sleep may support cognitive reserve.
One is that during deep sleep specifically, memories are replayed in the brain, and this results in a “neural reorganization” that helps stabilize the memory and make it more permanent.
“Other explanations include deep sleep’s role in maintaining homeostasis in the brain’s capacity to form new neural connections and providing an optimal brain state for the clearance of toxins interfering with healthy brain functioning,” she noted.
“The extent to which sleep could offer a protective buffer against severe cognitive impairment remains to be tested. However, this study is the first step in hopefully a series of new research that will investigate sleep as a cognitive reserve factor,” said Dr. Zavecz.
Encouraging data
Reached for comment, Percy Griffin, PhD, Alzheimer’s Association director of scientific engagement, said although the study sample is small, the results are “encouraging because sleep is a modifiable factor and can therefore be targeted.”
“More work is needed in a larger population before we can fully leverage this stage of sleep to reduce the risk of developing cognitive decline,” Dr. Griffin said.
Also weighing in on this research, Shaheen Lakhan, MD, PhD, a neurologist and researcher in Boston, said the study is “exciting on two fronts – we may have an additional marker for the development of Alzheimer’s disease to predict risk and track disease, but also targets for early intervention with sleep architecture–enhancing therapies, be they drug, device, or digital.”
“For the sake of our brain health, we all must get very familiar with the concept of cognitive or brain reserve,” said Dr. Lakhan, who was not involved in the study.
“Brain reserve refers to our ability to buttress against the threat of dementia and classically it’s been associated with ongoing brain stimulation (i.e., higher education, cognitively demanding job),” he noted.
“This line of research now opens the door that optimal sleep health – especially deep NREM slow wave sleep – correlates with greater brain reserve against Alzheimer’s disease,” Dr. Lakhan said.
The study was supported by the National Institutes of Health and the University of California, Berkeley. Dr. Walker serves as an advisor to and has equity interest in Bryte, Shuni, Oura, and StimScience. Dr. Zavecz and Dr. Lakhan report no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
FROM BMC MEDICINE
Parkinson’s in Marines linked to toxic drinking water at Camp Lejeune
in Jacksonville, N.C.
In one of the best-documented, large-scale contaminations in U.S. history, the drinking water at the Marine Corps base was contaminated with TCE and other volatile organic compounds from about 1953 to 1987.
The new study of more than 340,000 service members found the risk of PD was 70% higher in Marines stationed at Camp Lejeune in North Carolina during the years 1975-1985, compared with Marines stationed at Camp Pendleton in Oceanside, Calif.
“This is by far the largest study to look at the association of TCE and PD and the evidence is pretty strong,” lead investigator Samuel M. Goldman, MD, MPH, with University of California, San Francisco, said in an interview.
The link is supported by animal models that show that TCE can induce a neurodegenerative syndrome that is “very similar pathologically to what we see in PD,” Dr. Goldman said.
The study was published online in JAMA Neurology.
‘Hundreds of thousands’ at risk
At Camp Lejeune during the years 1975-1985, the period of maximal contamination, the estimated monthly median TCE level was more than 70-fold the Environmental Protection Agency maximum contaminant level. Maximum contaminant levels were also exceeded for perchloroethylene (PCE) and vinyl chloride.
Dr. Goldman and colleagues had health data on 158,122 veterans – 84,824 from Camp Lejeune and 73,298 from Camp Pendleton – who served for at least 3 months between 1975 and 1985, with follow up from Jan. 1, 1997, to Feb. 17, 2021.
Demographic characteristics were similar between the two groups; most were White men with an average age of 59 years.
A total of 430 veterans had PD: 279 from Camp Lejeune (prevalence, 0.33%) and 151 from Camp Pendleton (prevalence, 0.21%).
In multivariable models, Camp Lejeune veterans had a 70% higher risk for PD (odds ratio, 1.70; 95% confidence interval, 1.39-2.07; P < .001).
“Remarkably,” the researchers noted, among veterans without PD, residence at Camp Lejeune was also associated with a significantly higher risk of having several well-established prodromal features of PD, including tremor, suggesting they may be in a prediagnostic phase of evolving PD pathology.
Importantly, they added, in addition to the exposed service members, “hundreds of thousands of family members and civilian workers exposed to contaminated water at Camp Lejeune may also be at increased risk of PD, cancers, and other health consequences. Continued prospective follow-up of this population is essential.”
‘An unreasonable risk’
The new study supports a prior, and much smaller, study by Dr. Goldman and colleagues showing TCE exposure was associated with a sixfold increased risk for PD.
TCE is a ubiquitous environmental contaminant. The EPA Toxics Release Inventory estimates 2.05 million pounds of TCE was released into the environment from industrial sites in 2017.
In an accompanying editorial, E. Ray Dorsey, MD, with the University of Rochester (N.Y.) and coauthors noted the work of Dr. Goldman and colleagues “increases the certainty” that environmental exposure to TCE and the similar compound PCE “contribute importantly to the cause of the world’s fastest-growing brain disease.”
In December, the EPA found that PCE posed “an unreasonable risk” to human health, and 1 month later, it reached the same conclusion for TCE.
“These actions could lay the foundation for increased regulation and possibly a ban of these two chemicals that have contributed to immeasurable death and disability for generations,” Dr. Dorsey and colleagues noted.
“A U.S. ban would be a step forward but would not address the tens of thousands of TCE/PCE-contaminated sites in the U.S. and around the world or the rising global use of the toxic solvents,” they added.
This research was supported by Department of Veterans Affairs. Dr. Goldman reported no relevant financial relationships. Dr. Dorsey has received personal fees from organizations including the American Neurological Association, Elsevier, International Parkinson and Movement Disorder Society, Massachusetts Medical Society, Michael J. Fox Foundation, National Institutes of Health, and WebMD, as well as numerous pharmaceutical companies.
A version of this article originally appeared on Medscape.com.
in Jacksonville, N.C.
In one of the best-documented, large-scale contaminations in U.S. history, the drinking water at the Marine Corps base was contaminated with TCE and other volatile organic compounds from about 1953 to 1987.
The new study of more than 340,000 service members found the risk of PD was 70% higher in Marines stationed at Camp Lejeune in North Carolina during the years 1975-1985, compared with Marines stationed at Camp Pendleton in Oceanside, Calif.
“This is by far the largest study to look at the association of TCE and PD and the evidence is pretty strong,” lead investigator Samuel M. Goldman, MD, MPH, with University of California, San Francisco, said in an interview.
The link is supported by animal models that show that TCE can induce a neurodegenerative syndrome that is “very similar pathologically to what we see in PD,” Dr. Goldman said.
The study was published online in JAMA Neurology.
‘Hundreds of thousands’ at risk
At Camp Lejeune during the years 1975-1985, the period of maximal contamination, the estimated monthly median TCE level was more than 70-fold the Environmental Protection Agency maximum contaminant level. Maximum contaminant levels were also exceeded for perchloroethylene (PCE) and vinyl chloride.
Dr. Goldman and colleagues had health data on 158,122 veterans – 84,824 from Camp Lejeune and 73,298 from Camp Pendleton – who served for at least 3 months between 1975 and 1985, with follow up from Jan. 1, 1997, to Feb. 17, 2021.
Demographic characteristics were similar between the two groups; most were White men with an average age of 59 years.
A total of 430 veterans had PD: 279 from Camp Lejeune (prevalence, 0.33%) and 151 from Camp Pendleton (prevalence, 0.21%).
In multivariable models, Camp Lejeune veterans had a 70% higher risk for PD (odds ratio, 1.70; 95% confidence interval, 1.39-2.07; P < .001).
“Remarkably,” the researchers noted, among veterans without PD, residence at Camp Lejeune was also associated with a significantly higher risk of having several well-established prodromal features of PD, including tremor, suggesting they may be in a prediagnostic phase of evolving PD pathology.
Importantly, they added, in addition to the exposed service members, “hundreds of thousands of family members and civilian workers exposed to contaminated water at Camp Lejeune may also be at increased risk of PD, cancers, and other health consequences. Continued prospective follow-up of this population is essential.”
‘An unreasonable risk’
The new study supports a prior, and much smaller, study by Dr. Goldman and colleagues showing TCE exposure was associated with a sixfold increased risk for PD.
TCE is a ubiquitous environmental contaminant. The EPA Toxics Release Inventory estimates 2.05 million pounds of TCE was released into the environment from industrial sites in 2017.
In an accompanying editorial, E. Ray Dorsey, MD, with the University of Rochester (N.Y.) and coauthors noted the work of Dr. Goldman and colleagues “increases the certainty” that environmental exposure to TCE and the similar compound PCE “contribute importantly to the cause of the world’s fastest-growing brain disease.”
In December, the EPA found that PCE posed “an unreasonable risk” to human health, and 1 month later, it reached the same conclusion for TCE.
“These actions could lay the foundation for increased regulation and possibly a ban of these two chemicals that have contributed to immeasurable death and disability for generations,” Dr. Dorsey and colleagues noted.
“A U.S. ban would be a step forward but would not address the tens of thousands of TCE/PCE-contaminated sites in the U.S. and around the world or the rising global use of the toxic solvents,” they added.
This research was supported by Department of Veterans Affairs. Dr. Goldman reported no relevant financial relationships. Dr. Dorsey has received personal fees from organizations including the American Neurological Association, Elsevier, International Parkinson and Movement Disorder Society, Massachusetts Medical Society, Michael J. Fox Foundation, National Institutes of Health, and WebMD, as well as numerous pharmaceutical companies.
A version of this article originally appeared on Medscape.com.
in Jacksonville, N.C.
In one of the best-documented, large-scale contaminations in U.S. history, the drinking water at the Marine Corps base was contaminated with TCE and other volatile organic compounds from about 1953 to 1987.
The new study of more than 340,000 service members found the risk of PD was 70% higher in Marines stationed at Camp Lejeune in North Carolina during the years 1975-1985, compared with Marines stationed at Camp Pendleton in Oceanside, Calif.
“This is by far the largest study to look at the association of TCE and PD and the evidence is pretty strong,” lead investigator Samuel M. Goldman, MD, MPH, with University of California, San Francisco, said in an interview.
The link is supported by animal models that show that TCE can induce a neurodegenerative syndrome that is “very similar pathologically to what we see in PD,” Dr. Goldman said.
The study was published online in JAMA Neurology.
‘Hundreds of thousands’ at risk
At Camp Lejeune during the years 1975-1985, the period of maximal contamination, the estimated monthly median TCE level was more than 70-fold the Environmental Protection Agency maximum contaminant level. Maximum contaminant levels were also exceeded for perchloroethylene (PCE) and vinyl chloride.
Dr. Goldman and colleagues had health data on 158,122 veterans – 84,824 from Camp Lejeune and 73,298 from Camp Pendleton – who served for at least 3 months between 1975 and 1985, with follow up from Jan. 1, 1997, to Feb. 17, 2021.
Demographic characteristics were similar between the two groups; most were White men with an average age of 59 years.
A total of 430 veterans had PD: 279 from Camp Lejeune (prevalence, 0.33%) and 151 from Camp Pendleton (prevalence, 0.21%).
In multivariable models, Camp Lejeune veterans had a 70% higher risk for PD (odds ratio, 1.70; 95% confidence interval, 1.39-2.07; P < .001).
“Remarkably,” the researchers noted, among veterans without PD, residence at Camp Lejeune was also associated with a significantly higher risk of having several well-established prodromal features of PD, including tremor, suggesting they may be in a prediagnostic phase of evolving PD pathology.
Importantly, they added, in addition to the exposed service members, “hundreds of thousands of family members and civilian workers exposed to contaminated water at Camp Lejeune may also be at increased risk of PD, cancers, and other health consequences. Continued prospective follow-up of this population is essential.”
‘An unreasonable risk’
The new study supports a prior, and much smaller, study by Dr. Goldman and colleagues showing TCE exposure was associated with a sixfold increased risk for PD.
TCE is a ubiquitous environmental contaminant. The EPA Toxics Release Inventory estimates 2.05 million pounds of TCE was released into the environment from industrial sites in 2017.
In an accompanying editorial, E. Ray Dorsey, MD, with the University of Rochester (N.Y.) and coauthors noted the work of Dr. Goldman and colleagues “increases the certainty” that environmental exposure to TCE and the similar compound PCE “contribute importantly to the cause of the world’s fastest-growing brain disease.”
In December, the EPA found that PCE posed “an unreasonable risk” to human health, and 1 month later, it reached the same conclusion for TCE.
“These actions could lay the foundation for increased regulation and possibly a ban of these two chemicals that have contributed to immeasurable death and disability for generations,” Dr. Dorsey and colleagues noted.
“A U.S. ban would be a step forward but would not address the tens of thousands of TCE/PCE-contaminated sites in the U.S. and around the world or the rising global use of the toxic solvents,” they added.
This research was supported by Department of Veterans Affairs. Dr. Goldman reported no relevant financial relationships. Dr. Dorsey has received personal fees from organizations including the American Neurological Association, Elsevier, International Parkinson and Movement Disorder Society, Massachusetts Medical Society, Michael J. Fox Foundation, National Institutes of Health, and WebMD, as well as numerous pharmaceutical companies.
A version of this article originally appeared on Medscape.com.
FROM JAMA NEUROLOGY
One in five brain injury trials shows errors, signs of spin
LOS ANGELES –
“This is concerning result,” said general physician Lucas Piason F. Martins, MD, of the Bahiana School of Medicine and Public Health, Salvador, Brazil. “Many of these trials have been included in clinical guidelines and cited extensively in systematic reviews and meta-analyses, especially those related to hypothermia therapy.”
Dr. Martins presented the findings at the annual meeting of the American Association of Neurological Surgeons.
Defining spin
In recent years, medical researchers have sought to define and identify spin in medical literature. According to a 2017 report in PLOS Biology, “spin refers to reporting practices that distort the interpretation of results and mislead readers so that results are viewed in a more favorable light.”
Any spin can be dangerous, Dr. Martins said, because it “can potentially mislead readers and affect the interpretation of study results, which in turn can impact clinical decision-making.”
For the new report, a systematic review, Dr. Martins and colleagues examined 150 studies published in 18 top-ranked journals including the Journal of Neurotrauma (26%), the Journal of Neurosurgery (15%), Critical Care Medicine (9%), and the New England Journal of Medicine (8%).
Studies were published between 1960 and 2020. The review protocol was previously published in BMJ Open.
According to the report, most of the 32 studies with spin (75%) had a “focus on statistically significant results not based on primary outcome.”
For example, Dr. Martins said in an interview that the abstract for a study about drug treatment of brain contusions highlighted a secondary result instead of the main finding that the medication had no effect. Another study of treatment for severe closed head injuries focused on a subgroup outcome.
As Dr. Martins noted, it’s potentially problematic for studies to have several outcomes, measure outcomes in different ways, and have multiple time points without a predefined primary outcome. “A positive finding based on such strategies could potentially be explained by chance alone,” he said.
The researchers also reported that 65% of the studies with spin highlighted “the beneficial effect of the treatment despite statistically nonsignificant results” and that 9% had incorrect statistical analysis.
The findings are especially noteworthy because “the trials we analyzed were deemed to have the highest quality of methodology,” Dr. Martins said.
The researchers didn’t identify specific studies that they deemed to have spin, and they won’t do so, Dr. Martins said. The authors do plan to reveal which journals were most spin-heavy but only when these findings are published.
Were the study authors trying to mislead readers? Not necessarily. Researchers “may search for positive results to confirm their beliefs, although with good intentions,” Dr. Martins said, adding that the researchers found that “positive research tends to be more cited.”
They also reported that studies with smaller sample sizes were more likely to have spin (P = .04).
At 21%, the percentage of studies with spin was lower than that found in some previous reports that analyzed medical literature in other specialties.
A 2019 study of 93 randomized clinical studies in cardiology, for example, found spin in 57% of abstracts and 67% of full texts. The lower number in the new study may be due to its especially conservative definition of spin, Dr. Martins said.
Appropriate methodology
Cardiologist Richard Krasuski, MD, of Duke University Medical Center, Durham, N.C., who coauthored the 2019 study into spin in cardiology studies, told this news organization that the new analysis follows appropriate methodology and appears to be valid.
It makes sense, he said, that smaller studies had more spin: “It is much harder to show statistical significance in small studies and softer endpoints can be harder to predict. Small neutral trials are also much harder to publish in high-level journals. This all increases the tendency to spin the results so the reviewer and eventually the reader is more captivated.”
Why is there so much spin in medical research? “As an investigator, you always hope to positively impact patient health and outcomes, so there is a tendency to look at secondary analyses to have something good to emphasize,” he said. “This is an inherent trait in most of us, to find something good we can focus on. I do believe that much of this is subconscious and perhaps with noble intent.”
Dr. Krasuski said that he advises trainees to look at the methodology of studies, not just the abstract or discussion sections. “You don’t have to be a trained statistician to identify how well the findings match the author’s interpretation.
“Always try to identify what the primary outcome of the study was at the time of the design and whether the investigators achieved their objective. As a reviewer, my own personal experience in research into spin makes me more cognizant of its existence, and I generally require authors to reword and tone down their message if it is not supported by the data.”
What’s next? The investigators want to look for spin in the wider neurosurgery literature, Dr. Martins said, with an eye toward developing “practical strategies to assess spin and give pragmatic recommendations for good practice in clinical research.”
No study funding is reported. Dr. Martins has no disclosures, and several study authors reported funding from the UK National Institute for Health Research. Dr. Krasuski has no disclosures.
A version of this article first appeared on Medscape.com.
LOS ANGELES –
“This is concerning result,” said general physician Lucas Piason F. Martins, MD, of the Bahiana School of Medicine and Public Health, Salvador, Brazil. “Many of these trials have been included in clinical guidelines and cited extensively in systematic reviews and meta-analyses, especially those related to hypothermia therapy.”
Dr. Martins presented the findings at the annual meeting of the American Association of Neurological Surgeons.
Defining spin
In recent years, medical researchers have sought to define and identify spin in medical literature. According to a 2017 report in PLOS Biology, “spin refers to reporting practices that distort the interpretation of results and mislead readers so that results are viewed in a more favorable light.”
Any spin can be dangerous, Dr. Martins said, because it “can potentially mislead readers and affect the interpretation of study results, which in turn can impact clinical decision-making.”
For the new report, a systematic review, Dr. Martins and colleagues examined 150 studies published in 18 top-ranked journals including the Journal of Neurotrauma (26%), the Journal of Neurosurgery (15%), Critical Care Medicine (9%), and the New England Journal of Medicine (8%).
Studies were published between 1960 and 2020. The review protocol was previously published in BMJ Open.
According to the report, most of the 32 studies with spin (75%) had a “focus on statistically significant results not based on primary outcome.”
For example, Dr. Martins said in an interview that the abstract for a study about drug treatment of brain contusions highlighted a secondary result instead of the main finding that the medication had no effect. Another study of treatment for severe closed head injuries focused on a subgroup outcome.
As Dr. Martins noted, it’s potentially problematic for studies to have several outcomes, measure outcomes in different ways, and have multiple time points without a predefined primary outcome. “A positive finding based on such strategies could potentially be explained by chance alone,” he said.
The researchers also reported that 65% of the studies with spin highlighted “the beneficial effect of the treatment despite statistically nonsignificant results” and that 9% had incorrect statistical analysis.
The findings are especially noteworthy because “the trials we analyzed were deemed to have the highest quality of methodology,” Dr. Martins said.
The researchers didn’t identify specific studies that they deemed to have spin, and they won’t do so, Dr. Martins said. The authors do plan to reveal which journals were most spin-heavy but only when these findings are published.
Were the study authors trying to mislead readers? Not necessarily. Researchers “may search for positive results to confirm their beliefs, although with good intentions,” Dr. Martins said, adding that the researchers found that “positive research tends to be more cited.”
They also reported that studies with smaller sample sizes were more likely to have spin (P = .04).
At 21%, the percentage of studies with spin was lower than that found in some previous reports that analyzed medical literature in other specialties.
A 2019 study of 93 randomized clinical studies in cardiology, for example, found spin in 57% of abstracts and 67% of full texts. The lower number in the new study may be due to its especially conservative definition of spin, Dr. Martins said.
Appropriate methodology
Cardiologist Richard Krasuski, MD, of Duke University Medical Center, Durham, N.C., who coauthored the 2019 study into spin in cardiology studies, told this news organization that the new analysis follows appropriate methodology and appears to be valid.
It makes sense, he said, that smaller studies had more spin: “It is much harder to show statistical significance in small studies and softer endpoints can be harder to predict. Small neutral trials are also much harder to publish in high-level journals. This all increases the tendency to spin the results so the reviewer and eventually the reader is more captivated.”
Why is there so much spin in medical research? “As an investigator, you always hope to positively impact patient health and outcomes, so there is a tendency to look at secondary analyses to have something good to emphasize,” he said. “This is an inherent trait in most of us, to find something good we can focus on. I do believe that much of this is subconscious and perhaps with noble intent.”
Dr. Krasuski said that he advises trainees to look at the methodology of studies, not just the abstract or discussion sections. “You don’t have to be a trained statistician to identify how well the findings match the author’s interpretation.
“Always try to identify what the primary outcome of the study was at the time of the design and whether the investigators achieved their objective. As a reviewer, my own personal experience in research into spin makes me more cognizant of its existence, and I generally require authors to reword and tone down their message if it is not supported by the data.”
What’s next? The investigators want to look for spin in the wider neurosurgery literature, Dr. Martins said, with an eye toward developing “practical strategies to assess spin and give pragmatic recommendations for good practice in clinical research.”
No study funding is reported. Dr. Martins has no disclosures, and several study authors reported funding from the UK National Institute for Health Research. Dr. Krasuski has no disclosures.
A version of this article first appeared on Medscape.com.
LOS ANGELES –
“This is concerning result,” said general physician Lucas Piason F. Martins, MD, of the Bahiana School of Medicine and Public Health, Salvador, Brazil. “Many of these trials have been included in clinical guidelines and cited extensively in systematic reviews and meta-analyses, especially those related to hypothermia therapy.”
Dr. Martins presented the findings at the annual meeting of the American Association of Neurological Surgeons.
Defining spin
In recent years, medical researchers have sought to define and identify spin in medical literature. According to a 2017 report in PLOS Biology, “spin refers to reporting practices that distort the interpretation of results and mislead readers so that results are viewed in a more favorable light.”
Any spin can be dangerous, Dr. Martins said, because it “can potentially mislead readers and affect the interpretation of study results, which in turn can impact clinical decision-making.”
For the new report, a systematic review, Dr. Martins and colleagues examined 150 studies published in 18 top-ranked journals including the Journal of Neurotrauma (26%), the Journal of Neurosurgery (15%), Critical Care Medicine (9%), and the New England Journal of Medicine (8%).
Studies were published between 1960 and 2020. The review protocol was previously published in BMJ Open.
According to the report, most of the 32 studies with spin (75%) had a “focus on statistically significant results not based on primary outcome.”
For example, Dr. Martins said in an interview that the abstract for a study about drug treatment of brain contusions highlighted a secondary result instead of the main finding that the medication had no effect. Another study of treatment for severe closed head injuries focused on a subgroup outcome.
As Dr. Martins noted, it’s potentially problematic for studies to have several outcomes, measure outcomes in different ways, and have multiple time points without a predefined primary outcome. “A positive finding based on such strategies could potentially be explained by chance alone,” he said.
The researchers also reported that 65% of the studies with spin highlighted “the beneficial effect of the treatment despite statistically nonsignificant results” and that 9% had incorrect statistical analysis.
The findings are especially noteworthy because “the trials we analyzed were deemed to have the highest quality of methodology,” Dr. Martins said.
The researchers didn’t identify specific studies that they deemed to have spin, and they won’t do so, Dr. Martins said. The authors do plan to reveal which journals were most spin-heavy but only when these findings are published.
Were the study authors trying to mislead readers? Not necessarily. Researchers “may search for positive results to confirm their beliefs, although with good intentions,” Dr. Martins said, adding that the researchers found that “positive research tends to be more cited.”
They also reported that studies with smaller sample sizes were more likely to have spin (P = .04).
At 21%, the percentage of studies with spin was lower than that found in some previous reports that analyzed medical literature in other specialties.
A 2019 study of 93 randomized clinical studies in cardiology, for example, found spin in 57% of abstracts and 67% of full texts. The lower number in the new study may be due to its especially conservative definition of spin, Dr. Martins said.
Appropriate methodology
Cardiologist Richard Krasuski, MD, of Duke University Medical Center, Durham, N.C., who coauthored the 2019 study into spin in cardiology studies, told this news organization that the new analysis follows appropriate methodology and appears to be valid.
It makes sense, he said, that smaller studies had more spin: “It is much harder to show statistical significance in small studies and softer endpoints can be harder to predict. Small neutral trials are also much harder to publish in high-level journals. This all increases the tendency to spin the results so the reviewer and eventually the reader is more captivated.”
Why is there so much spin in medical research? “As an investigator, you always hope to positively impact patient health and outcomes, so there is a tendency to look at secondary analyses to have something good to emphasize,” he said. “This is an inherent trait in most of us, to find something good we can focus on. I do believe that much of this is subconscious and perhaps with noble intent.”
Dr. Krasuski said that he advises trainees to look at the methodology of studies, not just the abstract or discussion sections. “You don’t have to be a trained statistician to identify how well the findings match the author’s interpretation.
“Always try to identify what the primary outcome of the study was at the time of the design and whether the investigators achieved their objective. As a reviewer, my own personal experience in research into spin makes me more cognizant of its existence, and I generally require authors to reword and tone down their message if it is not supported by the data.”
What’s next? The investigators want to look for spin in the wider neurosurgery literature, Dr. Martins said, with an eye toward developing “practical strategies to assess spin and give pragmatic recommendations for good practice in clinical research.”
No study funding is reported. Dr. Martins has no disclosures, and several study authors reported funding from the UK National Institute for Health Research. Dr. Krasuski has no disclosures.
A version of this article first appeared on Medscape.com.
FROM AANS 2023
Rheumatoid arthritis linked to increased Parkinson’s risk
Claims data in 55,000 patients with RA and 273,000 age- and sex-matched controls show that those with RA were 1.74 times more likely than controls to be diagnosed with PD.
“If patients with rheumatoid arthritis begin exhibiting motor symptoms such as muscle rigidity, tremors, or slowed movement, it is imperative that they be evaluated by a qualified neurologist to rule out the possibility of developing Parkinson’s disease,” study investigator Hyungjin Kim, MD, PhD, told this news organization.
Dr. Kim is an associate professor in the department of medical humanities at Sungkyunkwan University School of Medicine in Seoul, South Korea.
The findings were published online in JAMA Neurology.
Conflicting findings
The investigators note that a number of studies have examined the link between RA and PD, with conflicting results – one even showing a 35% reduced risk for PD for individuals with RA. A more recent population-based study in Taiwan showed a 37% higher rate of PD in patients with rheumatic disease.
However, previous studies did not control for important variables such as body mass index or diabetes.
For the current study, the investigators analyzed claims on about 55,000 patients diagnosed with RA between 2010 and 2017, with follow-up until 2019, and compared the outcomes of this group vs. those of 273,000 controls.
The mean age of claimants was 58 years, and 75% were female.
Results showed that those diagnosed with seropositive RA were about twice as likely as controls to be diagnosed with PD. Those with seronegative RA were 1.2 times as likely as controls to be diagnosed with PD.
Dr. Kim noted that although the pathogenic link between RA and PD remains elusive, inflammation probably plays an important role. “Inflammatory cytokines such as tumor necrosis factor alpha and interleukin-6, which are increased in RA patients, can induce microglial activation, leading to neuroinflammation,” he stated.
“These inflammatory cytokines are known to be associated with the dysfunction and degeneration of nigral dopaminergic neurons, which are important in the pathogenesis of PD,” he added.
The investigators noted that patients with RA may have been subject to more frequent health care services than controls and so were more likely to obtain a PD diagnosis.
Another possibility was that because patients with health check-ups were included in the analysis, the findings may have been biased toward those who were older and who had a higher income.
Dr. Kim noted that additional research is required to clarify the pathogenic connection between RA and PD.
“Moreover, additional studies are necessary to explore the potential influence of novel therapeutic treatments for RA on Parkinson’s disease susceptibility in patients with RA,” he said.
Commenting on the findings for this news organization, David Sulzer, PhD, professor of psychiatry, neurology, and pharmacology at Columbia University in New York, said that the study adds to the growing body of evidence showing there is an autoimmune component to PD.
Dr. Sulzer pointed to data in several papers he published with others to this effect, including one showing higher rates of PD in people with inflammatory bowel disease.
The study had no specific funding. The study investigators and Dr. Sulzer report no relevant disclosures.
A version of this article first appeared on Medscape.com.
Claims data in 55,000 patients with RA and 273,000 age- and sex-matched controls show that those with RA were 1.74 times more likely than controls to be diagnosed with PD.
“If patients with rheumatoid arthritis begin exhibiting motor symptoms such as muscle rigidity, tremors, or slowed movement, it is imperative that they be evaluated by a qualified neurologist to rule out the possibility of developing Parkinson’s disease,” study investigator Hyungjin Kim, MD, PhD, told this news organization.
Dr. Kim is an associate professor in the department of medical humanities at Sungkyunkwan University School of Medicine in Seoul, South Korea.
The findings were published online in JAMA Neurology.
Conflicting findings
The investigators note that a number of studies have examined the link between RA and PD, with conflicting results – one even showing a 35% reduced risk for PD for individuals with RA. A more recent population-based study in Taiwan showed a 37% higher rate of PD in patients with rheumatic disease.
However, previous studies did not control for important variables such as body mass index or diabetes.
For the current study, the investigators analyzed claims on about 55,000 patients diagnosed with RA between 2010 and 2017, with follow-up until 2019, and compared the outcomes of this group vs. those of 273,000 controls.
The mean age of claimants was 58 years, and 75% were female.
Results showed that those diagnosed with seropositive RA were about twice as likely as controls to be diagnosed with PD. Those with seronegative RA were 1.2 times as likely as controls to be diagnosed with PD.
Dr. Kim noted that although the pathogenic link between RA and PD remains elusive, inflammation probably plays an important role. “Inflammatory cytokines such as tumor necrosis factor alpha and interleukin-6, which are increased in RA patients, can induce microglial activation, leading to neuroinflammation,” he stated.
“These inflammatory cytokines are known to be associated with the dysfunction and degeneration of nigral dopaminergic neurons, which are important in the pathogenesis of PD,” he added.
The investigators noted that patients with RA may have been subject to more frequent health care services than controls and so were more likely to obtain a PD diagnosis.
Another possibility was that because patients with health check-ups were included in the analysis, the findings may have been biased toward those who were older and who had a higher income.
Dr. Kim noted that additional research is required to clarify the pathogenic connection between RA and PD.
“Moreover, additional studies are necessary to explore the potential influence of novel therapeutic treatments for RA on Parkinson’s disease susceptibility in patients with RA,” he said.
Commenting on the findings for this news organization, David Sulzer, PhD, professor of psychiatry, neurology, and pharmacology at Columbia University in New York, said that the study adds to the growing body of evidence showing there is an autoimmune component to PD.
Dr. Sulzer pointed to data in several papers he published with others to this effect, including one showing higher rates of PD in people with inflammatory bowel disease.
The study had no specific funding. The study investigators and Dr. Sulzer report no relevant disclosures.
A version of this article first appeared on Medscape.com.
Claims data in 55,000 patients with RA and 273,000 age- and sex-matched controls show that those with RA were 1.74 times more likely than controls to be diagnosed with PD.
“If patients with rheumatoid arthritis begin exhibiting motor symptoms such as muscle rigidity, tremors, or slowed movement, it is imperative that they be evaluated by a qualified neurologist to rule out the possibility of developing Parkinson’s disease,” study investigator Hyungjin Kim, MD, PhD, told this news organization.
Dr. Kim is an associate professor in the department of medical humanities at Sungkyunkwan University School of Medicine in Seoul, South Korea.
The findings were published online in JAMA Neurology.
Conflicting findings
The investigators note that a number of studies have examined the link between RA and PD, with conflicting results – one even showing a 35% reduced risk for PD for individuals with RA. A more recent population-based study in Taiwan showed a 37% higher rate of PD in patients with rheumatic disease.
However, previous studies did not control for important variables such as body mass index or diabetes.
For the current study, the investigators analyzed claims on about 55,000 patients diagnosed with RA between 2010 and 2017, with follow-up until 2019, and compared the outcomes of this group vs. those of 273,000 controls.
The mean age of claimants was 58 years, and 75% were female.
Results showed that those diagnosed with seropositive RA were about twice as likely as controls to be diagnosed with PD. Those with seronegative RA were 1.2 times as likely as controls to be diagnosed with PD.
Dr. Kim noted that although the pathogenic link between RA and PD remains elusive, inflammation probably plays an important role. “Inflammatory cytokines such as tumor necrosis factor alpha and interleukin-6, which are increased in RA patients, can induce microglial activation, leading to neuroinflammation,” he stated.
“These inflammatory cytokines are known to be associated with the dysfunction and degeneration of nigral dopaminergic neurons, which are important in the pathogenesis of PD,” he added.
The investigators noted that patients with RA may have been subject to more frequent health care services than controls and so were more likely to obtain a PD diagnosis.
Another possibility was that because patients with health check-ups were included in the analysis, the findings may have been biased toward those who were older and who had a higher income.
Dr. Kim noted that additional research is required to clarify the pathogenic connection between RA and PD.
“Moreover, additional studies are necessary to explore the potential influence of novel therapeutic treatments for RA on Parkinson’s disease susceptibility in patients with RA,” he said.
Commenting on the findings for this news organization, David Sulzer, PhD, professor of psychiatry, neurology, and pharmacology at Columbia University in New York, said that the study adds to the growing body of evidence showing there is an autoimmune component to PD.
Dr. Sulzer pointed to data in several papers he published with others to this effect, including one showing higher rates of PD in people with inflammatory bowel disease.
The study had no specific funding. The study investigators and Dr. Sulzer report no relevant disclosures.
A version of this article first appeared on Medscape.com.
FROM JAMA NEUROLOGY
FDA approves first drug to treat Alzheimer’s agitation
(AD), making it the first FDA-approved drug for this indication.
“Agitation is one of the most common and challenging aspects of care among patients with dementia due to Alzheimer’s disease,” Tiffany Farchione, MD, director of the division of psychiatry in the FDA’s Center for Drug Evaluation and Research, said in a news release.
Agitation can include symptoms that range from pacing or restlessness to verbal and physical aggression. “These symptoms are leading causes of assisted living or nursing home placement and have been associated with accelerated disease progression,” Dr. Farchione said.
Brexpiprazole was approved by the FDA in 2015 as an adjunctive therapy to antidepressants for adults with major depressive disorder and for adults with schizophrenia.
Approval of the supplemental application for brexpiprazole for agitation associated with AD dementia was based on results of two randomized, double-blind, placebo-controlled studies.
In both studies, patients who received 2 mg or 3 mg of brexpiprazole showed statistically significant and clinically meaningful improvements in agitation symptoms, as shown by total Cohen-Mansfield Agitation Inventory (CMAI) score, compared with patients who received placebo.
The recommended starting dosage for the treatment of agitation associated with AD dementia is 0.5 mg once daily on days 1-7; it was increased to 1 mg once daily on days 8-14 and then to the recommended target dose of 2 mg once daily.
The dosage can be increased to the maximum recommended daily dosage of 3 mg once daily after at least 14 days, depending on clinical response and tolerability.
The most common side effects of brexpiprazole in patients with agitation associated with AD dementia include headache, dizziness, urinary tract infection, nasopharyngitis, and sleep disturbances.
The drug includes a boxed warning for medications in this class that elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death.
The supplemental application for brexpiprazole for agitation had fast-track designation.
A version of this article first appeared on Medscape.com.
(AD), making it the first FDA-approved drug for this indication.
“Agitation is one of the most common and challenging aspects of care among patients with dementia due to Alzheimer’s disease,” Tiffany Farchione, MD, director of the division of psychiatry in the FDA’s Center for Drug Evaluation and Research, said in a news release.
Agitation can include symptoms that range from pacing or restlessness to verbal and physical aggression. “These symptoms are leading causes of assisted living or nursing home placement and have been associated with accelerated disease progression,” Dr. Farchione said.
Brexpiprazole was approved by the FDA in 2015 as an adjunctive therapy to antidepressants for adults with major depressive disorder and for adults with schizophrenia.
Approval of the supplemental application for brexpiprazole for agitation associated with AD dementia was based on results of two randomized, double-blind, placebo-controlled studies.
In both studies, patients who received 2 mg or 3 mg of brexpiprazole showed statistically significant and clinically meaningful improvements in agitation symptoms, as shown by total Cohen-Mansfield Agitation Inventory (CMAI) score, compared with patients who received placebo.
The recommended starting dosage for the treatment of agitation associated with AD dementia is 0.5 mg once daily on days 1-7; it was increased to 1 mg once daily on days 8-14 and then to the recommended target dose of 2 mg once daily.
The dosage can be increased to the maximum recommended daily dosage of 3 mg once daily after at least 14 days, depending on clinical response and tolerability.
The most common side effects of brexpiprazole in patients with agitation associated with AD dementia include headache, dizziness, urinary tract infection, nasopharyngitis, and sleep disturbances.
The drug includes a boxed warning for medications in this class that elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death.
The supplemental application for brexpiprazole for agitation had fast-track designation.
A version of this article first appeared on Medscape.com.
(AD), making it the first FDA-approved drug for this indication.
“Agitation is one of the most common and challenging aspects of care among patients with dementia due to Alzheimer’s disease,” Tiffany Farchione, MD, director of the division of psychiatry in the FDA’s Center for Drug Evaluation and Research, said in a news release.
Agitation can include symptoms that range from pacing or restlessness to verbal and physical aggression. “These symptoms are leading causes of assisted living or nursing home placement and have been associated with accelerated disease progression,” Dr. Farchione said.
Brexpiprazole was approved by the FDA in 2015 as an adjunctive therapy to antidepressants for adults with major depressive disorder and for adults with schizophrenia.
Approval of the supplemental application for brexpiprazole for agitation associated with AD dementia was based on results of two randomized, double-blind, placebo-controlled studies.
In both studies, patients who received 2 mg or 3 mg of brexpiprazole showed statistically significant and clinically meaningful improvements in agitation symptoms, as shown by total Cohen-Mansfield Agitation Inventory (CMAI) score, compared with patients who received placebo.
The recommended starting dosage for the treatment of agitation associated with AD dementia is 0.5 mg once daily on days 1-7; it was increased to 1 mg once daily on days 8-14 and then to the recommended target dose of 2 mg once daily.
The dosage can be increased to the maximum recommended daily dosage of 3 mg once daily after at least 14 days, depending on clinical response and tolerability.
The most common side effects of brexpiprazole in patients with agitation associated with AD dementia include headache, dizziness, urinary tract infection, nasopharyngitis, and sleep disturbances.
The drug includes a boxed warning for medications in this class that elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death.
The supplemental application for brexpiprazole for agitation had fast-track designation.
A version of this article first appeared on Medscape.com.
Hearing aids are a ‘powerful’ tool for reducing dementia risk
, new research confirms. A large observational study from the United Kingdom showed a 42% increased risk for dementia in people with hearing loss compared with their peers with no hearing trouble. In addition, there was no increased risk in those with hearing loss who used hearing aids.
“The evidence is building that hearing loss may be the most impactful modifiable risk factor for dementia in mid-life, but the effectiveness of hearing aid use on reducing the risk of dementia in the real world has remained unclear,” Dongshan Zhu, PhD, with Shandong University, Jinan, China, said in a news release.
“Our study provides the best evidence to date to suggest that hearing aids could be a minimally invasive, cost-effective treatment to mitigate the potential impact of hearing loss on dementia,” Dr. Zhu said.
The study, which was published online in Lancet Public Health, comes on the heels of the 2020 Lancet Commission report on dementia, which suggested hearing loss may be linked to approximately 8% of worldwide dementia cases.
‘Compelling’ evidence
For the study, investigators analyzed longitudinal data on 437,704 individuals, most of whom were White, from the UK Biobank (54% female; mean age at baseline, 56 years). Roughly three quarters of the cohort had no hearing loss and one quarter had some level of hearing loss, with 12% of these individuals using hearing aids.
After the researchers controlled for relevant cofactors, compared with people without hearing loss, those with hearing loss who were not using hearing aids had an increased risk for all-cause dementia (hazard ratio [HR], 1.42; 95% confidence interval [CI], 1.29-1.56).
No increased risk was seen in people with hearing loss who were using hearing aids (HR, 1.04; 95% CI, 0.98-1.10).
The positive association of hearing aid use was observed in all-cause dementia and cause-specific dementia subtypes, including Alzheimer’s disease, vascular dementia, and non–Alzheimer’s disease nonvascular dementia.
The data also suggest that the protection against dementia conferred by hearing aid use most likely stems from direct effects from hearing aids rather than indirect mediators, such as social isolation, loneliness, and low mood.
Dr. Zhu said the findings highlight the “urgent need” for the early use of hearing aids when an individual starts having trouble hearing.
“A group effort from across society is necessary, including raising awareness of hearing loss and the potential links with dementia; increasing accessibility to hearing aids by reducing cost; and more support for primary care workers to screen for hearing impairment, raise awareness, and deliver treatment such as fitting hearing aids,” Dr. Zhu said.
Writing in a linked comment, Gill Livingston, MD, and Sergi Costafreda, MD, PhD, with University College London, noted that with addition of this study, “the evidence that hearing aids are a powerful tool to reduce the risk of dementia in people with hearing loss, is as good as possible without randomized controlled trials, which might not be practically possible or ethical because people with hearing loss should not be stopped from using effective treatments.”
“The evidence is compelling that treating hearing loss is a promising way of reducing dementia risk. This is the time to increase awareness of and detection of hearing loss, as well as the acceptability and usability of hearing aids,” Dr. Livingston and Dr. Costafreda added.
High-quality evidence – with caveats
Several experts offered perspective on the analysis in a statement from the U.K.-based nonprofit Science Media Centre, which was not involved with the conduct of this study. Charles Marshall, MRCP, PhD, with Queen Mary University of London, said that the study provides “high-quality evidence” that those with hearing loss who use hearing aids are at lower risk for dementia than are those with hearing loss who do not use hearing aids.
“This raises the possibility that a proportion of dementia cases could be prevented by using hearing aids to correct hearing loss. However, the observational nature of this study makes it difficult to be sure that hearing aids are actually causing the reduced risk of dementia,” Dr. Marshall added.
“Hearing aids produce slightly distorted sound, and the brain has to adapt to this in order for hearing aids to be helpful,” he said. “People who are at risk of developing dementia in the future may have early changes in their brain that impair this adaptation, and this may lead to them choosing to not use hearing aids. This would confound the association, creating the appearance that hearing aids were reducing dementia risk, when actually their use was just identifying people with relatively healthy brains,” Dr. Marshall added.
Tara Spires-Jones, PhD, with the University of Edinburgh, said this “well-conducted” study confirms previous similar studies showing an association between hearing loss and dementia risk.
Echoing Dr. Marshall, Dr. Spires-Jones noted that this type of study cannot prove conclusively that hearing loss causes dementia.
“For example,” she said, “it is possible that people who are already in the very early stages of disease are less likely to seek help for hearing loss. However, on balance, this study and the rest of the data in the field indicate that keeping your brain healthy and engaged reduces dementia risk.”
Dr. Spires-Jones said that she agrees with the investigators that it’s “important to help people with hearing loss to get effective hearing aids to help keep their brains engaged through allowing richer social interactions.”
This study was funded by the National Natural Science Foundation of China and Shandong Province, Taishan Scholars Project, China Medical Board, and China Postdoctoral Science Foundation. Dr. Zhu, Dr. Livingston, Dr. Costafreda, Dr. Marshall, and Dr. Spires-Jones have no relevant disclosures.
A version of this article originally appeared on Medscape.com.
, new research confirms. A large observational study from the United Kingdom showed a 42% increased risk for dementia in people with hearing loss compared with their peers with no hearing trouble. In addition, there was no increased risk in those with hearing loss who used hearing aids.
“The evidence is building that hearing loss may be the most impactful modifiable risk factor for dementia in mid-life, but the effectiveness of hearing aid use on reducing the risk of dementia in the real world has remained unclear,” Dongshan Zhu, PhD, with Shandong University, Jinan, China, said in a news release.
“Our study provides the best evidence to date to suggest that hearing aids could be a minimally invasive, cost-effective treatment to mitigate the potential impact of hearing loss on dementia,” Dr. Zhu said.
The study, which was published online in Lancet Public Health, comes on the heels of the 2020 Lancet Commission report on dementia, which suggested hearing loss may be linked to approximately 8% of worldwide dementia cases.
‘Compelling’ evidence
For the study, investigators analyzed longitudinal data on 437,704 individuals, most of whom were White, from the UK Biobank (54% female; mean age at baseline, 56 years). Roughly three quarters of the cohort had no hearing loss and one quarter had some level of hearing loss, with 12% of these individuals using hearing aids.
After the researchers controlled for relevant cofactors, compared with people without hearing loss, those with hearing loss who were not using hearing aids had an increased risk for all-cause dementia (hazard ratio [HR], 1.42; 95% confidence interval [CI], 1.29-1.56).
No increased risk was seen in people with hearing loss who were using hearing aids (HR, 1.04; 95% CI, 0.98-1.10).
The positive association of hearing aid use was observed in all-cause dementia and cause-specific dementia subtypes, including Alzheimer’s disease, vascular dementia, and non–Alzheimer’s disease nonvascular dementia.
The data also suggest that the protection against dementia conferred by hearing aid use most likely stems from direct effects from hearing aids rather than indirect mediators, such as social isolation, loneliness, and low mood.
Dr. Zhu said the findings highlight the “urgent need” for the early use of hearing aids when an individual starts having trouble hearing.
“A group effort from across society is necessary, including raising awareness of hearing loss and the potential links with dementia; increasing accessibility to hearing aids by reducing cost; and more support for primary care workers to screen for hearing impairment, raise awareness, and deliver treatment such as fitting hearing aids,” Dr. Zhu said.
Writing in a linked comment, Gill Livingston, MD, and Sergi Costafreda, MD, PhD, with University College London, noted that with addition of this study, “the evidence that hearing aids are a powerful tool to reduce the risk of dementia in people with hearing loss, is as good as possible without randomized controlled trials, which might not be practically possible or ethical because people with hearing loss should not be stopped from using effective treatments.”
“The evidence is compelling that treating hearing loss is a promising way of reducing dementia risk. This is the time to increase awareness of and detection of hearing loss, as well as the acceptability and usability of hearing aids,” Dr. Livingston and Dr. Costafreda added.
High-quality evidence – with caveats
Several experts offered perspective on the analysis in a statement from the U.K.-based nonprofit Science Media Centre, which was not involved with the conduct of this study. Charles Marshall, MRCP, PhD, with Queen Mary University of London, said that the study provides “high-quality evidence” that those with hearing loss who use hearing aids are at lower risk for dementia than are those with hearing loss who do not use hearing aids.
“This raises the possibility that a proportion of dementia cases could be prevented by using hearing aids to correct hearing loss. However, the observational nature of this study makes it difficult to be sure that hearing aids are actually causing the reduced risk of dementia,” Dr. Marshall added.
“Hearing aids produce slightly distorted sound, and the brain has to adapt to this in order for hearing aids to be helpful,” he said. “People who are at risk of developing dementia in the future may have early changes in their brain that impair this adaptation, and this may lead to them choosing to not use hearing aids. This would confound the association, creating the appearance that hearing aids were reducing dementia risk, when actually their use was just identifying people with relatively healthy brains,” Dr. Marshall added.
Tara Spires-Jones, PhD, with the University of Edinburgh, said this “well-conducted” study confirms previous similar studies showing an association between hearing loss and dementia risk.
Echoing Dr. Marshall, Dr. Spires-Jones noted that this type of study cannot prove conclusively that hearing loss causes dementia.
“For example,” she said, “it is possible that people who are already in the very early stages of disease are less likely to seek help for hearing loss. However, on balance, this study and the rest of the data in the field indicate that keeping your brain healthy and engaged reduces dementia risk.”
Dr. Spires-Jones said that she agrees with the investigators that it’s “important to help people with hearing loss to get effective hearing aids to help keep their brains engaged through allowing richer social interactions.”
This study was funded by the National Natural Science Foundation of China and Shandong Province, Taishan Scholars Project, China Medical Board, and China Postdoctoral Science Foundation. Dr. Zhu, Dr. Livingston, Dr. Costafreda, Dr. Marshall, and Dr. Spires-Jones have no relevant disclosures.
A version of this article originally appeared on Medscape.com.
, new research confirms. A large observational study from the United Kingdom showed a 42% increased risk for dementia in people with hearing loss compared with their peers with no hearing trouble. In addition, there was no increased risk in those with hearing loss who used hearing aids.
“The evidence is building that hearing loss may be the most impactful modifiable risk factor for dementia in mid-life, but the effectiveness of hearing aid use on reducing the risk of dementia in the real world has remained unclear,” Dongshan Zhu, PhD, with Shandong University, Jinan, China, said in a news release.
“Our study provides the best evidence to date to suggest that hearing aids could be a minimally invasive, cost-effective treatment to mitigate the potential impact of hearing loss on dementia,” Dr. Zhu said.
The study, which was published online in Lancet Public Health, comes on the heels of the 2020 Lancet Commission report on dementia, which suggested hearing loss may be linked to approximately 8% of worldwide dementia cases.
‘Compelling’ evidence
For the study, investigators analyzed longitudinal data on 437,704 individuals, most of whom were White, from the UK Biobank (54% female; mean age at baseline, 56 years). Roughly three quarters of the cohort had no hearing loss and one quarter had some level of hearing loss, with 12% of these individuals using hearing aids.
After the researchers controlled for relevant cofactors, compared with people without hearing loss, those with hearing loss who were not using hearing aids had an increased risk for all-cause dementia (hazard ratio [HR], 1.42; 95% confidence interval [CI], 1.29-1.56).
No increased risk was seen in people with hearing loss who were using hearing aids (HR, 1.04; 95% CI, 0.98-1.10).
The positive association of hearing aid use was observed in all-cause dementia and cause-specific dementia subtypes, including Alzheimer’s disease, vascular dementia, and non–Alzheimer’s disease nonvascular dementia.
The data also suggest that the protection against dementia conferred by hearing aid use most likely stems from direct effects from hearing aids rather than indirect mediators, such as social isolation, loneliness, and low mood.
Dr. Zhu said the findings highlight the “urgent need” for the early use of hearing aids when an individual starts having trouble hearing.
“A group effort from across society is necessary, including raising awareness of hearing loss and the potential links with dementia; increasing accessibility to hearing aids by reducing cost; and more support for primary care workers to screen for hearing impairment, raise awareness, and deliver treatment such as fitting hearing aids,” Dr. Zhu said.
Writing in a linked comment, Gill Livingston, MD, and Sergi Costafreda, MD, PhD, with University College London, noted that with addition of this study, “the evidence that hearing aids are a powerful tool to reduce the risk of dementia in people with hearing loss, is as good as possible without randomized controlled trials, which might not be practically possible or ethical because people with hearing loss should not be stopped from using effective treatments.”
“The evidence is compelling that treating hearing loss is a promising way of reducing dementia risk. This is the time to increase awareness of and detection of hearing loss, as well as the acceptability and usability of hearing aids,” Dr. Livingston and Dr. Costafreda added.
High-quality evidence – with caveats
Several experts offered perspective on the analysis in a statement from the U.K.-based nonprofit Science Media Centre, which was not involved with the conduct of this study. Charles Marshall, MRCP, PhD, with Queen Mary University of London, said that the study provides “high-quality evidence” that those with hearing loss who use hearing aids are at lower risk for dementia than are those with hearing loss who do not use hearing aids.
“This raises the possibility that a proportion of dementia cases could be prevented by using hearing aids to correct hearing loss. However, the observational nature of this study makes it difficult to be sure that hearing aids are actually causing the reduced risk of dementia,” Dr. Marshall added.
“Hearing aids produce slightly distorted sound, and the brain has to adapt to this in order for hearing aids to be helpful,” he said. “People who are at risk of developing dementia in the future may have early changes in their brain that impair this adaptation, and this may lead to them choosing to not use hearing aids. This would confound the association, creating the appearance that hearing aids were reducing dementia risk, when actually their use was just identifying people with relatively healthy brains,” Dr. Marshall added.
Tara Spires-Jones, PhD, with the University of Edinburgh, said this “well-conducted” study confirms previous similar studies showing an association between hearing loss and dementia risk.
Echoing Dr. Marshall, Dr. Spires-Jones noted that this type of study cannot prove conclusively that hearing loss causes dementia.
“For example,” she said, “it is possible that people who are already in the very early stages of disease are less likely to seek help for hearing loss. However, on balance, this study and the rest of the data in the field indicate that keeping your brain healthy and engaged reduces dementia risk.”
Dr. Spires-Jones said that she agrees with the investigators that it’s “important to help people with hearing loss to get effective hearing aids to help keep their brains engaged through allowing richer social interactions.”
This study was funded by the National Natural Science Foundation of China and Shandong Province, Taishan Scholars Project, China Medical Board, and China Postdoctoral Science Foundation. Dr. Zhu, Dr. Livingston, Dr. Costafreda, Dr. Marshall, and Dr. Spires-Jones have no relevant disclosures.
A version of this article originally appeared on Medscape.com.
AHA backs screening for cognitive impairment after stroke
Screening for cognitive impairment should be part of multidisciplinary care for stroke survivors, the American Heart Association says in a new scientific statement.
“Cognitive impairment after stroke is very common, is associated with other post-stroke outcomes, and often has significant impact on the quality of life,” Nada El Husseini, MD, MHSc, chair of the scientific statement writing group, told this news organization.
“It is important to screen stroke survivors for cognitive impairment as well as for associated comorbidities such as mood and sleep disorders,” said Dr. El Husseini, associate professor of neurology at Duke University Medical Center in Durham, N.C.
The scientific statement was published online in Stroke. It’s the first to specifically focus on the cognitive impairment resulting from an overt stroke (ischemic or hemorrhagic).
‘Actionable’ considerations for care
The writing group performed a “scoping” review of the literature on the prevalence, diagnosis, and management of poststroke cognitive impairment (PSCI) to provide a framework for “actionable considerations” for clinical practice as well as to highlight gaps needing additional studies, Dr. El Husseini explained.
PSCI, ranging from mild to severe, occurs in up to 60% of stroke survivors in the first year after stroke; yet, it is often underreported and underdiagnosed, the writing group notes.
Up to 20% of stroke survivors who experience mild cognitive impairment fully recover cognitive function, and cognitive recovery is most likely within the first 6 months after a stroke.
However, improvement in cognitive impairment without return to prestroke levels is more frequent than is complete recovery. As many as one in three stroke survivors may develop dementia within 5 years of stroke.
The writing group also notes that PSCI is often associated with other conditions, including physical disability, sleep disorders, behavioral and personality changes, depression, and other neuropsychological changes – each of which may contribute to lower quality of life.
Currently, there is no “gold standard” for cognitive screening following stroke, but several brief cognitive screening tests, including the Mini–Mental State Examination and the Montreal Cognitive Assessment, are widely used to identify cognitive impairment after stroke.
The statement also highlights the importance of assessing cognitive changes over time after stroke. Stroke survivors who experience unexplained difficulties with cognitive-related activities of daily living, following care instructions, or providing a reliable health history may be candidates for additional cognitive screening.
Manage risk factors to prevent repeat stroke
“Anticipatory guidance regarding home and driving safety and, return to work (if applicable) along with interdisciplinary collaboration among different medical and ancillary specialists in the diagnosis and management of cognitive impairment is key for the holistic care of stroke survivors,” Dr. El Husseini told this news organization.
The multidisciplinary poststroke health care team could include neurologists, occupational therapists, speech therapists, nurses, neuropsychologists, gerontologists, and primary care providers.
“Because recurrent stroke is strongly associated with the development of cognitive impairment and dementia, prevention of recurrent strokes should be sought to decrease that risk,” Dr. El Husseini said. This includes addressing stroke risk factors, including high blood pressure, high cholesterol, type 2 diabetes, and atrial fibrillation.
The writing group says research is needed in the future to determine how cognitive impairment develops after stroke and the impact of nonbrain factors, including infection, frailty, and social factors.
Further research is also needed to determine best practices for cognitive screening after stroke, including the development and use of screening instruments that consider demographic, cultural, and linguistic factors in determining “normal” function.
“Perhaps the most pressing need, however, is the development of effective and culturally relevant treatments for poststroke cognitive impairment,” Dr. El Husseini said in a news release.
“We hope to see big enough clinical trials that assess various techniques, medications, and lifestyle changes in diverse groups of patients that may help improve cognitive function,” she added.
This scientific statement was prepared by the volunteer writing group on behalf of the AHA Stroke Council, the Council on Cardiovascular Radiology and Intervention, the Council on Hypertension, and the Council on Lifestyle and Cardiometabolic Health.
Screening for cognitive impairment should be part of multidisciplinary care for stroke survivors, the American Heart Association says in a new scientific statement.
“Cognitive impairment after stroke is very common, is associated with other post-stroke outcomes, and often has significant impact on the quality of life,” Nada El Husseini, MD, MHSc, chair of the scientific statement writing group, told this news organization.
“It is important to screen stroke survivors for cognitive impairment as well as for associated comorbidities such as mood and sleep disorders,” said Dr. El Husseini, associate professor of neurology at Duke University Medical Center in Durham, N.C.
The scientific statement was published online in Stroke. It’s the first to specifically focus on the cognitive impairment resulting from an overt stroke (ischemic or hemorrhagic).
‘Actionable’ considerations for care
The writing group performed a “scoping” review of the literature on the prevalence, diagnosis, and management of poststroke cognitive impairment (PSCI) to provide a framework for “actionable considerations” for clinical practice as well as to highlight gaps needing additional studies, Dr. El Husseini explained.
PSCI, ranging from mild to severe, occurs in up to 60% of stroke survivors in the first year after stroke; yet, it is often underreported and underdiagnosed, the writing group notes.
Up to 20% of stroke survivors who experience mild cognitive impairment fully recover cognitive function, and cognitive recovery is most likely within the first 6 months after a stroke.
However, improvement in cognitive impairment without return to prestroke levels is more frequent than is complete recovery. As many as one in three stroke survivors may develop dementia within 5 years of stroke.
The writing group also notes that PSCI is often associated with other conditions, including physical disability, sleep disorders, behavioral and personality changes, depression, and other neuropsychological changes – each of which may contribute to lower quality of life.
Currently, there is no “gold standard” for cognitive screening following stroke, but several brief cognitive screening tests, including the Mini–Mental State Examination and the Montreal Cognitive Assessment, are widely used to identify cognitive impairment after stroke.
The statement also highlights the importance of assessing cognitive changes over time after stroke. Stroke survivors who experience unexplained difficulties with cognitive-related activities of daily living, following care instructions, or providing a reliable health history may be candidates for additional cognitive screening.
Manage risk factors to prevent repeat stroke
“Anticipatory guidance regarding home and driving safety and, return to work (if applicable) along with interdisciplinary collaboration among different medical and ancillary specialists in the diagnosis and management of cognitive impairment is key for the holistic care of stroke survivors,” Dr. El Husseini told this news organization.
The multidisciplinary poststroke health care team could include neurologists, occupational therapists, speech therapists, nurses, neuropsychologists, gerontologists, and primary care providers.
“Because recurrent stroke is strongly associated with the development of cognitive impairment and dementia, prevention of recurrent strokes should be sought to decrease that risk,” Dr. El Husseini said. This includes addressing stroke risk factors, including high blood pressure, high cholesterol, type 2 diabetes, and atrial fibrillation.
The writing group says research is needed in the future to determine how cognitive impairment develops after stroke and the impact of nonbrain factors, including infection, frailty, and social factors.
Further research is also needed to determine best practices for cognitive screening after stroke, including the development and use of screening instruments that consider demographic, cultural, and linguistic factors in determining “normal” function.
“Perhaps the most pressing need, however, is the development of effective and culturally relevant treatments for poststroke cognitive impairment,” Dr. El Husseini said in a news release.
“We hope to see big enough clinical trials that assess various techniques, medications, and lifestyle changes in diverse groups of patients that may help improve cognitive function,” she added.
This scientific statement was prepared by the volunteer writing group on behalf of the AHA Stroke Council, the Council on Cardiovascular Radiology and Intervention, the Council on Hypertension, and the Council on Lifestyle and Cardiometabolic Health.
Screening for cognitive impairment should be part of multidisciplinary care for stroke survivors, the American Heart Association says in a new scientific statement.
“Cognitive impairment after stroke is very common, is associated with other post-stroke outcomes, and often has significant impact on the quality of life,” Nada El Husseini, MD, MHSc, chair of the scientific statement writing group, told this news organization.
“It is important to screen stroke survivors for cognitive impairment as well as for associated comorbidities such as mood and sleep disorders,” said Dr. El Husseini, associate professor of neurology at Duke University Medical Center in Durham, N.C.
The scientific statement was published online in Stroke. It’s the first to specifically focus on the cognitive impairment resulting from an overt stroke (ischemic or hemorrhagic).
‘Actionable’ considerations for care
The writing group performed a “scoping” review of the literature on the prevalence, diagnosis, and management of poststroke cognitive impairment (PSCI) to provide a framework for “actionable considerations” for clinical practice as well as to highlight gaps needing additional studies, Dr. El Husseini explained.
PSCI, ranging from mild to severe, occurs in up to 60% of stroke survivors in the first year after stroke; yet, it is often underreported and underdiagnosed, the writing group notes.
Up to 20% of stroke survivors who experience mild cognitive impairment fully recover cognitive function, and cognitive recovery is most likely within the first 6 months after a stroke.
However, improvement in cognitive impairment without return to prestroke levels is more frequent than is complete recovery. As many as one in three stroke survivors may develop dementia within 5 years of stroke.
The writing group also notes that PSCI is often associated with other conditions, including physical disability, sleep disorders, behavioral and personality changes, depression, and other neuropsychological changes – each of which may contribute to lower quality of life.
Currently, there is no “gold standard” for cognitive screening following stroke, but several brief cognitive screening tests, including the Mini–Mental State Examination and the Montreal Cognitive Assessment, are widely used to identify cognitive impairment after stroke.
The statement also highlights the importance of assessing cognitive changes over time after stroke. Stroke survivors who experience unexplained difficulties with cognitive-related activities of daily living, following care instructions, or providing a reliable health history may be candidates for additional cognitive screening.
Manage risk factors to prevent repeat stroke
“Anticipatory guidance regarding home and driving safety and, return to work (if applicable) along with interdisciplinary collaboration among different medical and ancillary specialists in the diagnosis and management of cognitive impairment is key for the holistic care of stroke survivors,” Dr. El Husseini told this news organization.
The multidisciplinary poststroke health care team could include neurologists, occupational therapists, speech therapists, nurses, neuropsychologists, gerontologists, and primary care providers.
“Because recurrent stroke is strongly associated with the development of cognitive impairment and dementia, prevention of recurrent strokes should be sought to decrease that risk,” Dr. El Husseini said. This includes addressing stroke risk factors, including high blood pressure, high cholesterol, type 2 diabetes, and atrial fibrillation.
The writing group says research is needed in the future to determine how cognitive impairment develops after stroke and the impact of nonbrain factors, including infection, frailty, and social factors.
Further research is also needed to determine best practices for cognitive screening after stroke, including the development and use of screening instruments that consider demographic, cultural, and linguistic factors in determining “normal” function.
“Perhaps the most pressing need, however, is the development of effective and culturally relevant treatments for poststroke cognitive impairment,” Dr. El Husseini said in a news release.
“We hope to see big enough clinical trials that assess various techniques, medications, and lifestyle changes in diverse groups of patients that may help improve cognitive function,” she added.
This scientific statement was prepared by the volunteer writing group on behalf of the AHA Stroke Council, the Council on Cardiovascular Radiology and Intervention, the Council on Hypertension, and the Council on Lifestyle and Cardiometabolic Health.
Head-to-head comparison of migraine meds reveals top options
BOSTON – , a new real-world analysis of data on more than 3 million migraine attacks shows.
The findings “align with results of clinical trials and recommendations from clinical treatment guidelines” and provide insights to complement clinical practice, said study investigator Chia-Chun Chiang, MD, a neurologist with Mayo Clinic, Rochester, Minn.
The findings were presented at the 2023 annual meeting of the American Academy of Neurology.
The power of big data
Despite a wide variety of acute migraine medications that are available, large-scale, head-to-head comparisons of treatment effectiveness from real-world patient experience reports are lacking, Dr. Chiang explained.
“To the best of our knowledge, this is the first study that simultaneously compared multiple acute migraine medications using a Big Data analysis approach based on real-world patient-provided data,” she said.
The researchers extracted more than 10 million self-reported migraine attack records from a migraine smartphone app called Migraine Buddy, where users can document whether a treatment was helpful, somewhat helpful, unsure, or unhelpful.
They analyzed 25 acute medications among seven classes: acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), triptans, combination analgesics (acetaminophen/aspirin/caffeine), ergots, antiemetics, and opioids. The newer gepants and ditan medication classes of medications were not included because of the relatively lower numbers of usage when data was extracted (2014-2020).
The researchers employed a two-level nested logistic regression model to analyze the odds of treatment effectiveness of each medication by adjusting concurrent medications and the covariance within the same user.
The final analysis included more than 3.1 million migraine attacks among 278,000 users globally.
Using ibuprofen as the reference, triptans, ergots, and antiemetics had the highest efficacy with mean odds ratios of 4.8, 3.02, and 2.67, respectively, followed by opioids (OR, 2.49), NSAIDs (OR, 1.94), combination analgesics (OR, 1.69), others (OR, 1.49), and acetaminophen (OR, 0.83).
Individual medications with the highest patient-reported effectiveness were eletriptan (Relpax; OR, 6.1), zolmitriptan (Zomig; OR, 5.7) and sumatriptan (Zecuity; OR, 5.2).
This migraine medication comparative effectiveness analysis, based on patient-reported outcomes, “supports and complements the treatment recommendations from national headache societies based on randomized controlled trials and meta-analyses and strongly supports the use of triptans,” Dr. Chiang said.
End of trial-and-error?
Commenting on this research, Shaheen Lakhan, MD, PhD, a neurologist and researcher in Boston, said “This is a great study of Big Data in that it shows the power of the smartphone to collect real-world data and smart researchers like at Mayo Clinic to analyze them.”
“The study sheds light on how different therapeutics compare with each other. The next iteration of this line of research, I would hope, would be to determine if particular medications are effective for a particular migraine population, and even down to individuals with migraine,” said Dr. Lakhan, who wasn’t involved in the study.
“Once those models are appropriately built, long gone will be the era of trial-and-error medicine,” Dr. Lakhan added.
The study had no specific funding. Dr. Chiang has served as a consultant for Satsuma. Dr. Lakhan reports no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
BOSTON – , a new real-world analysis of data on more than 3 million migraine attacks shows.
The findings “align with results of clinical trials and recommendations from clinical treatment guidelines” and provide insights to complement clinical practice, said study investigator Chia-Chun Chiang, MD, a neurologist with Mayo Clinic, Rochester, Minn.
The findings were presented at the 2023 annual meeting of the American Academy of Neurology.
The power of big data
Despite a wide variety of acute migraine medications that are available, large-scale, head-to-head comparisons of treatment effectiveness from real-world patient experience reports are lacking, Dr. Chiang explained.
“To the best of our knowledge, this is the first study that simultaneously compared multiple acute migraine medications using a Big Data analysis approach based on real-world patient-provided data,” she said.
The researchers extracted more than 10 million self-reported migraine attack records from a migraine smartphone app called Migraine Buddy, where users can document whether a treatment was helpful, somewhat helpful, unsure, or unhelpful.
They analyzed 25 acute medications among seven classes: acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), triptans, combination analgesics (acetaminophen/aspirin/caffeine), ergots, antiemetics, and opioids. The newer gepants and ditan medication classes of medications were not included because of the relatively lower numbers of usage when data was extracted (2014-2020).
The researchers employed a two-level nested logistic regression model to analyze the odds of treatment effectiveness of each medication by adjusting concurrent medications and the covariance within the same user.
The final analysis included more than 3.1 million migraine attacks among 278,000 users globally.
Using ibuprofen as the reference, triptans, ergots, and antiemetics had the highest efficacy with mean odds ratios of 4.8, 3.02, and 2.67, respectively, followed by opioids (OR, 2.49), NSAIDs (OR, 1.94), combination analgesics (OR, 1.69), others (OR, 1.49), and acetaminophen (OR, 0.83).
Individual medications with the highest patient-reported effectiveness were eletriptan (Relpax; OR, 6.1), zolmitriptan (Zomig; OR, 5.7) and sumatriptan (Zecuity; OR, 5.2).
This migraine medication comparative effectiveness analysis, based on patient-reported outcomes, “supports and complements the treatment recommendations from national headache societies based on randomized controlled trials and meta-analyses and strongly supports the use of triptans,” Dr. Chiang said.
End of trial-and-error?
Commenting on this research, Shaheen Lakhan, MD, PhD, a neurologist and researcher in Boston, said “This is a great study of Big Data in that it shows the power of the smartphone to collect real-world data and smart researchers like at Mayo Clinic to analyze them.”
“The study sheds light on how different therapeutics compare with each other. The next iteration of this line of research, I would hope, would be to determine if particular medications are effective for a particular migraine population, and even down to individuals with migraine,” said Dr. Lakhan, who wasn’t involved in the study.
“Once those models are appropriately built, long gone will be the era of trial-and-error medicine,” Dr. Lakhan added.
The study had no specific funding. Dr. Chiang has served as a consultant for Satsuma. Dr. Lakhan reports no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
BOSTON – , a new real-world analysis of data on more than 3 million migraine attacks shows.
The findings “align with results of clinical trials and recommendations from clinical treatment guidelines” and provide insights to complement clinical practice, said study investigator Chia-Chun Chiang, MD, a neurologist with Mayo Clinic, Rochester, Minn.
The findings were presented at the 2023 annual meeting of the American Academy of Neurology.
The power of big data
Despite a wide variety of acute migraine medications that are available, large-scale, head-to-head comparisons of treatment effectiveness from real-world patient experience reports are lacking, Dr. Chiang explained.
“To the best of our knowledge, this is the first study that simultaneously compared multiple acute migraine medications using a Big Data analysis approach based on real-world patient-provided data,” she said.
The researchers extracted more than 10 million self-reported migraine attack records from a migraine smartphone app called Migraine Buddy, where users can document whether a treatment was helpful, somewhat helpful, unsure, or unhelpful.
They analyzed 25 acute medications among seven classes: acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), triptans, combination analgesics (acetaminophen/aspirin/caffeine), ergots, antiemetics, and opioids. The newer gepants and ditan medication classes of medications were not included because of the relatively lower numbers of usage when data was extracted (2014-2020).
The researchers employed a two-level nested logistic regression model to analyze the odds of treatment effectiveness of each medication by adjusting concurrent medications and the covariance within the same user.
The final analysis included more than 3.1 million migraine attacks among 278,000 users globally.
Using ibuprofen as the reference, triptans, ergots, and antiemetics had the highest efficacy with mean odds ratios of 4.8, 3.02, and 2.67, respectively, followed by opioids (OR, 2.49), NSAIDs (OR, 1.94), combination analgesics (OR, 1.69), others (OR, 1.49), and acetaminophen (OR, 0.83).
Individual medications with the highest patient-reported effectiveness were eletriptan (Relpax; OR, 6.1), zolmitriptan (Zomig; OR, 5.7) and sumatriptan (Zecuity; OR, 5.2).
This migraine medication comparative effectiveness analysis, based on patient-reported outcomes, “supports and complements the treatment recommendations from national headache societies based on randomized controlled trials and meta-analyses and strongly supports the use of triptans,” Dr. Chiang said.
End of trial-and-error?
Commenting on this research, Shaheen Lakhan, MD, PhD, a neurologist and researcher in Boston, said “This is a great study of Big Data in that it shows the power of the smartphone to collect real-world data and smart researchers like at Mayo Clinic to analyze them.”
“The study sheds light on how different therapeutics compare with each other. The next iteration of this line of research, I would hope, would be to determine if particular medications are effective for a particular migraine population, and even down to individuals with migraine,” said Dr. Lakhan, who wasn’t involved in the study.
“Once those models are appropriately built, long gone will be the era of trial-and-error medicine,” Dr. Lakhan added.
The study had no specific funding. Dr. Chiang has served as a consultant for Satsuma. Dr. Lakhan reports no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
AT AAN 2023
Oral antiamyloid shows disease-modifying potential Phase 3 trial underway
BOSTON – , represented by positive changes in plasma and imaging biomarkers of Alzheimer’s disease pathology.
Use of the drug, ALZ-801 (Alzheon), led to a significant reduction of plasma phosphorylated–tau 181 (p-tau181) , a marker of amyloid-induced neuronal injury in Alzheimer’s disease, as well as slowing of hippocampal atrophy and stabilization of cognition.
“The 12-month results of our phase 2 trial support the finding that ALZ-801 blocks misfolding of amyloid monomers and subsequent formation of neurotoxic amyloid oligomers, the key initial step in the amyloid aggregation cascade, which leads to a rapid and sustained reduction of brain neurodegeneration as measured by plasma p-tau181,” John Hey, PhD, Alzheon’s chief scientific officer, said in a statement.
“The severalfold greater reduction on the p-tau181 biomarker in plasma compared to plaque-clearing antiamyloid antibodies, combined with preservation of brain hippocampal volume and their positive correlations with cognitive benefits, further validate the disease-modifying effects of ALZ-801 in Alzheimer’s patients,” Dr. Hey added.
The results were presented at the 2023 annual meeting of the American Academy of Neurology.
ALZ-801 is an optimized prodrug of tramiprosate that has been shown to inhibit amyloid-beta 42 aggregation into toxic oligomers.
The ongoing phase 2 study is evaluating the effects of oral ALZ-801 (265 mg twice daily) on biomarkers of Alzheimer’s disease pathology for 84 adults with early Alzheimer’s disease who have either the APOE4/4 or APOE3/4 genotype. These genotypes represent the majority of patients with Alzheimer’s disease.
The mean age of the cohort was 69 years, and 51% are women; 70% had mild cognitive impairment, and 30% had mild Alzheimer’s disease. The mean Mini-Mental State Examination score for the cohort was 26.0. Roughly half were taking a cholinesterase inhibitor.
Significant plasma p-tau181 reduction was observed at 13 weeks. Levels were reduced by 41% by 52 weeks (P = .016). There was also a significant 5% reduction in plasma amyloid-beta 42 and 40 at 52 weeks (P = .002 and P = .005, respectively), Dr. Hey reported.
After 12 months of treatment, hippocampal atrophy was reduced by about 23%, and expansion of ventricular volume was reduced by about 15%, both in comparison with matched controls from the Alzheimer’s Disease Neuroimaging Initiative.
Composite cognitive z-score improved significantly at 13 and 26 weeks and remained above baseline at 52 weeks in comparison with matched ADNI controls. “These are very promising data,” Dr. Hey told conference attendees.
He noted that the safety profile of ALZ-801 remains favorable and consistent with prior safety data. Common adverse events were mild nausea and SARS-CoV-2 infection. There were no drug-related serious events or amyloid-related imaging abnormalities–edema (ARIA-E).
The phase 3 APOLLOE4 study of ALZ-801 is underway. This double-blind, randomized study is comparing oral ALZ-801 with placebo over 78 weeks for roughly 300 adults with early Alzheimer’s disease who have the APOE4/4 genotype. APOLLOE4 is expected to be completed in mid 2024.
The APOLLOE4 study is supported by a $47 million grant from the National Institute on Aging. The U.S. Food and Drug Administration has granted ALZ-801 fast-track designation.
More accessible option?
Reached for comment, Percy Griffin, PhD, Alzheimer’s Association director of scientific engagement, noted that the “biggest difference between this drug and others is that it is taken orally, rather than delivered through an infusion. This is important and valuable for reducing patient and caregiver burden and increasing ease of use and access.”
It’s also noteworthy that ALZ-801 was not associated with ARIA-E, “which has been reported in other antiamyloid trials and can occasionally be serious,” Dr. Griffin said.
Overall, he said the results are “encouraging, but more work is needed. If studies results continue to be positive, this treatment may provide a more accessible option for people who are at higher risk of ARIA,” Dr. Griffin said.
The study was funded by Alzheon. Dr. Hey is an employee of Alzheon and holds stock in the company. Dr. Griffin has disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
BOSTON – , represented by positive changes in plasma and imaging biomarkers of Alzheimer’s disease pathology.
Use of the drug, ALZ-801 (Alzheon), led to a significant reduction of plasma phosphorylated–tau 181 (p-tau181) , a marker of amyloid-induced neuronal injury in Alzheimer’s disease, as well as slowing of hippocampal atrophy and stabilization of cognition.
“The 12-month results of our phase 2 trial support the finding that ALZ-801 blocks misfolding of amyloid monomers and subsequent formation of neurotoxic amyloid oligomers, the key initial step in the amyloid aggregation cascade, which leads to a rapid and sustained reduction of brain neurodegeneration as measured by plasma p-tau181,” John Hey, PhD, Alzheon’s chief scientific officer, said in a statement.
“The severalfold greater reduction on the p-tau181 biomarker in plasma compared to plaque-clearing antiamyloid antibodies, combined with preservation of brain hippocampal volume and their positive correlations with cognitive benefits, further validate the disease-modifying effects of ALZ-801 in Alzheimer’s patients,” Dr. Hey added.
The results were presented at the 2023 annual meeting of the American Academy of Neurology.
ALZ-801 is an optimized prodrug of tramiprosate that has been shown to inhibit amyloid-beta 42 aggregation into toxic oligomers.
The ongoing phase 2 study is evaluating the effects of oral ALZ-801 (265 mg twice daily) on biomarkers of Alzheimer’s disease pathology for 84 adults with early Alzheimer’s disease who have either the APOE4/4 or APOE3/4 genotype. These genotypes represent the majority of patients with Alzheimer’s disease.
The mean age of the cohort was 69 years, and 51% are women; 70% had mild cognitive impairment, and 30% had mild Alzheimer’s disease. The mean Mini-Mental State Examination score for the cohort was 26.0. Roughly half were taking a cholinesterase inhibitor.
Significant plasma p-tau181 reduction was observed at 13 weeks. Levels were reduced by 41% by 52 weeks (P = .016). There was also a significant 5% reduction in plasma amyloid-beta 42 and 40 at 52 weeks (P = .002 and P = .005, respectively), Dr. Hey reported.
After 12 months of treatment, hippocampal atrophy was reduced by about 23%, and expansion of ventricular volume was reduced by about 15%, both in comparison with matched controls from the Alzheimer’s Disease Neuroimaging Initiative.
Composite cognitive z-score improved significantly at 13 and 26 weeks and remained above baseline at 52 weeks in comparison with matched ADNI controls. “These are very promising data,” Dr. Hey told conference attendees.
He noted that the safety profile of ALZ-801 remains favorable and consistent with prior safety data. Common adverse events were mild nausea and SARS-CoV-2 infection. There were no drug-related serious events or amyloid-related imaging abnormalities–edema (ARIA-E).
The phase 3 APOLLOE4 study of ALZ-801 is underway. This double-blind, randomized study is comparing oral ALZ-801 with placebo over 78 weeks for roughly 300 adults with early Alzheimer’s disease who have the APOE4/4 genotype. APOLLOE4 is expected to be completed in mid 2024.
The APOLLOE4 study is supported by a $47 million grant from the National Institute on Aging. The U.S. Food and Drug Administration has granted ALZ-801 fast-track designation.
More accessible option?
Reached for comment, Percy Griffin, PhD, Alzheimer’s Association director of scientific engagement, noted that the “biggest difference between this drug and others is that it is taken orally, rather than delivered through an infusion. This is important and valuable for reducing patient and caregiver burden and increasing ease of use and access.”
It’s also noteworthy that ALZ-801 was not associated with ARIA-E, “which has been reported in other antiamyloid trials and can occasionally be serious,” Dr. Griffin said.
Overall, he said the results are “encouraging, but more work is needed. If studies results continue to be positive, this treatment may provide a more accessible option for people who are at higher risk of ARIA,” Dr. Griffin said.
The study was funded by Alzheon. Dr. Hey is an employee of Alzheon and holds stock in the company. Dr. Griffin has disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
BOSTON – , represented by positive changes in plasma and imaging biomarkers of Alzheimer’s disease pathology.
Use of the drug, ALZ-801 (Alzheon), led to a significant reduction of plasma phosphorylated–tau 181 (p-tau181) , a marker of amyloid-induced neuronal injury in Alzheimer’s disease, as well as slowing of hippocampal atrophy and stabilization of cognition.
“The 12-month results of our phase 2 trial support the finding that ALZ-801 blocks misfolding of amyloid monomers and subsequent formation of neurotoxic amyloid oligomers, the key initial step in the amyloid aggregation cascade, which leads to a rapid and sustained reduction of brain neurodegeneration as measured by plasma p-tau181,” John Hey, PhD, Alzheon’s chief scientific officer, said in a statement.
“The severalfold greater reduction on the p-tau181 biomarker in plasma compared to plaque-clearing antiamyloid antibodies, combined with preservation of brain hippocampal volume and their positive correlations with cognitive benefits, further validate the disease-modifying effects of ALZ-801 in Alzheimer’s patients,” Dr. Hey added.
The results were presented at the 2023 annual meeting of the American Academy of Neurology.
ALZ-801 is an optimized prodrug of tramiprosate that has been shown to inhibit amyloid-beta 42 aggregation into toxic oligomers.
The ongoing phase 2 study is evaluating the effects of oral ALZ-801 (265 mg twice daily) on biomarkers of Alzheimer’s disease pathology for 84 adults with early Alzheimer’s disease who have either the APOE4/4 or APOE3/4 genotype. These genotypes represent the majority of patients with Alzheimer’s disease.
The mean age of the cohort was 69 years, and 51% are women; 70% had mild cognitive impairment, and 30% had mild Alzheimer’s disease. The mean Mini-Mental State Examination score for the cohort was 26.0. Roughly half were taking a cholinesterase inhibitor.
Significant plasma p-tau181 reduction was observed at 13 weeks. Levels were reduced by 41% by 52 weeks (P = .016). There was also a significant 5% reduction in plasma amyloid-beta 42 and 40 at 52 weeks (P = .002 and P = .005, respectively), Dr. Hey reported.
After 12 months of treatment, hippocampal atrophy was reduced by about 23%, and expansion of ventricular volume was reduced by about 15%, both in comparison with matched controls from the Alzheimer’s Disease Neuroimaging Initiative.
Composite cognitive z-score improved significantly at 13 and 26 weeks and remained above baseline at 52 weeks in comparison with matched ADNI controls. “These are very promising data,” Dr. Hey told conference attendees.
He noted that the safety profile of ALZ-801 remains favorable and consistent with prior safety data. Common adverse events were mild nausea and SARS-CoV-2 infection. There were no drug-related serious events or amyloid-related imaging abnormalities–edema (ARIA-E).
The phase 3 APOLLOE4 study of ALZ-801 is underway. This double-blind, randomized study is comparing oral ALZ-801 with placebo over 78 weeks for roughly 300 adults with early Alzheimer’s disease who have the APOE4/4 genotype. APOLLOE4 is expected to be completed in mid 2024.
The APOLLOE4 study is supported by a $47 million grant from the National Institute on Aging. The U.S. Food and Drug Administration has granted ALZ-801 fast-track designation.
More accessible option?
Reached for comment, Percy Griffin, PhD, Alzheimer’s Association director of scientific engagement, noted that the “biggest difference between this drug and others is that it is taken orally, rather than delivered through an infusion. This is important and valuable for reducing patient and caregiver burden and increasing ease of use and access.”
It’s also noteworthy that ALZ-801 was not associated with ARIA-E, “which has been reported in other antiamyloid trials and can occasionally be serious,” Dr. Griffin said.
Overall, he said the results are “encouraging, but more work is needed. If studies results continue to be positive, this treatment may provide a more accessible option for people who are at higher risk of ARIA,” Dr. Griffin said.
The study was funded by Alzheon. Dr. Hey is an employee of Alzheon and holds stock in the company. Dr. Griffin has disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
FROM AAN 2023