Literature Review

Extraverts and individuals who are disciplined are less likely to experience cognitive decline later in life, whereas those with neuroticism have an increased risk for cognitive dysfunction, new research shows.

Investigators analyzed data from almost 2,000 individuals enrolled in the Rush Memory and Aging Project (MAP) – a longitudinal study of older adults living in the greater Chicago metropolitan region and northeastern Illinois – with recruitment that began in 1997 and continues through today. Participants received a personality assessment as well as annual assessments of their cognitive abilities.

Those with high scores on measures of conscientiousness were significantly less likely to progress from normal cognition to mild cognitive impairment (MCI) during the study. In fact, scoring an extra 1 standard deviation on the conscientiousness scale was associated with a 22% lower risk of transitioning from no cognitive impairment (NCI) to MCI. On the other hand, scoring an additional 1 SD on a neuroticism scale was associated with a 12% increased risk of transitioning to MCI.

Participants who scored high on extraversion, as well as those who scored high on conscientiousness or low on neuroticism, tended to maintain normal cognitive functioning longer than other participants.

“Personality traits reflect relatively enduring patterns of thinking and behaving, which may cumulatively affect engagement in healthy and unhealthy behaviors and thought patterns across the lifespan,” lead author Tomiko Yoneda, PhD, a postdoctoral researcher in the department of medical social sciences, Northwestern University, Chicago, said in an interview.

“The accumulation of lifelong experiences may then contribute to susceptibility of particular diseases or disorders, such as mild cognitive impairment, or contribute to individual differences in the ability to withstand age-related neurological changes,” she added.

The study was published online in the Journal of Personality and Social Psychology.
 

Competing risk factors

Personality traits “reflect an individual’s persistent patterns of thinking, feeling, and behaving,” Dr. Yoneda said.

“For example, conscientiousness is characterized by competence, dutifulness, and self-discipline, while neuroticism is characterized by anxiety, depressive symptoms, and emotional instability. Likewise, individuals high in extraversion tend to be enthusiastic, gregarious, talkative, and assertive,” she added.

Previous research “suggests that low conscientiousness and high neuroticism are associated with an increased risk of cognitive impairment,” she continued. However, “there is also an increased risk of death in older adulthood – in other words, these outcomes are ‘competing risk factors.’”

Dr. Yoneda said her team wanted to “examine the impact of personality traits on the simultaneous risk of transitioning to mild cognitive impairment, dementia, and death.”  

For the study, the researchers analyzed data from 1,954 participants in MAP (mean age at baseline 80 years, 73.7% female, 86.8% White), who received a personality assessment and annual assessments of their cognitive abilities.

To assess personality traits – in particular, conscientiousness, neuroticism, and extraversion – the researchers used the NEO Five Factor Inventory (NEO-FFI). They also used multistate survival modeling to examine the potential association between these traits and transitions from one cognitive status category to another (NCI, MCI, and dementia) and to death.
 

Cognitive healthspan

By the end of the study, over half of the sample (54%) had died.

Most transitions showed “relative stability in cognitive status across measurement occasions.”

• NCI to NCI (n = 7,368)
• MCI to MCI (n = 1,244)
• Dementia to dementia (n = 876)

There were 725 “backward transitions” from MCI to NCI, “which may reflect improvement or within-person variability in cognitive functioning, or learning effects,” the authors note.

There were only 114 “backward transitions” from dementia to MCI and only 12 from dementia to NCI, “suggesting that improvement in cognitive status was relatively rare, particularly once an individual progresses to dementia.”

After adjusting for demographics, depressive symptoms, and apolipoprotein (APOE) ε4 allele, the researchers found that personality traits were the most important factors in the transition from NCI to MCI.

Higher conscientiousness was associated with a decreased risk of transitioning from NCI to MCI (hazard ratio, 0.78; 95% confidence interval, 0.72-0.85). Conversely, higher neuroticism was associated with an increased risk of transitioning from NCI to MCI (HR, 1.12; 95% CI, 1.04-1.21) and a significantly decreased likelihood of transition back from MCI to NCI (HR, 0.90; 95% CI, 0.81-1.00).

Scoring ~6 points on a conscientiousness scale ranging from 0-48 (that is, 1 SD on the scale) was significantly associated with ~22% lower risk of transitioning forward from NCI to MCI, while scoring ~7 more points on a neuroticism scale (1 SD) was significantly associated with ~12% higher risk of transitioning from NCI to MCI.

Higher extraversion was associated with an increased likelihood of transitioning from MCI back to NCI (HR, 1.12; 95% CI, 1.03-1.22), and although extraversion was not associated with a longer total lifespan, participants who scored high on extraversion, as well as those who scored low on conscientiousness or low on neuroticism, maintained normal cognitive function longer than other participants.

“Our results suggest that high conscientiousness and low neuroticism may protect individuals against mild cognitive impairment,” said Dr. Yoneda.

Importantly, individuals who were either higher in conscientiousness, higher in extraversion, or lower in neuroticism had more years of “cognitive healthspan,” meaning more years without cognitive impairment,” she added.

In addition, “individuals lower in neuroticism and higher in extraversion were more likely to recover after receiving an MCI diagnosis, suggesting that these traits may be protective even after an individual starts to progress to dementia,” she said.

The authors note that the study focused on only three of the Big Five personality traits, while the other 2 – openness to experience and agreeableness – may also be associated with cognitive aging processes and mortality.

Nevertheless, given the current results, alongside extensive research in the personality field, aiming to increase conscientiousness through persistent behavioral change is one potential strategy for promoting healthy cognitive aging, Dr. Yoneda said.
 

‘Invaluable window’

In a comment, Brent Roberts, PhD, professor of psychology, University of Illinois Urbana-Champaign, said the study provides an “invaluable window into how personality affects the process of decline and either accelerates it, as in the role of neuroticism, or decelerates it, as in the role of conscientiousness.”

“I think the most fascinating finding was the fact that extraversion was related to transitioning from MCI back to NCI. These types of transitions have simply not been part of prior research, and it provides utterly unique insights and opportunities for interventions that may actually help people recover from a decline,” said Dr. Roberts, who was not involved in the research.

Claire Sexton, DPhil, Alzheimer’s Association director of scientific programs and outreach, called the paper “novel” because it investigated the transitions between normal cognition and mild impairment and between mild impairment and dementia.

Dr. Sexton, who was associated with this research team, cautioned that is it observational, “so it can illuminate associations or correlations, but not causes. As a result, we can’t say for sure what the mechanisms are behind these potential connections between personality and cognition, and more research is needed.”

The research was supported by the Alzheimer Society Research Program, Social Sciences and Humanities Research Council, and the National Institute on Aging of the National Institutes of Health. Dr. Yoneda and co-authors, Dr. Roberts, and Dr. Sexton have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Extraverts and individuals who are disciplined are less likely to experience cognitive decline later in life, whereas those with neuroticism have an increased risk for cognitive dysfunction, new research shows.

Investigators analyzed data from almost 2,000 individuals enrolled in the Rush Memory and Aging Project (MAP) – a longitudinal study of older adults living in the greater Chicago metropolitan region and northeastern Illinois – with recruitment that began in 1997 and continues through today. Participants received a personality assessment as well as annual assessments of their cognitive abilities.

Those with high scores on measures of conscientiousness were significantly less likely to progress from normal cognition to mild cognitive impairment (MCI) during the study. In fact, scoring an extra 1 standard deviation on the conscientiousness scale was associated with a 22% lower risk of transitioning from no cognitive impairment (NCI) to MCI. On the other hand, scoring an additional 1 SD on a neuroticism scale was associated with a 12% increased risk of transitioning to MCI.

Participants who scored high on extraversion, as well as those who scored high on conscientiousness or low on neuroticism, tended to maintain normal cognitive functioning longer than other participants.

“Personality traits reflect relatively enduring patterns of thinking and behaving, which may cumulatively affect engagement in healthy and unhealthy behaviors and thought patterns across the lifespan,” lead author Tomiko Yoneda, PhD, a postdoctoral researcher in the department of medical social sciences, Northwestern University, Chicago, said in an interview.

“The accumulation of lifelong experiences may then contribute to susceptibility of particular diseases or disorders, such as mild cognitive impairment, or contribute to individual differences in the ability to withstand age-related neurological changes,” she added.

The study was published online in the Journal of Personality and Social Psychology.
 

Competing risk factors

Personality traits “reflect an individual’s persistent patterns of thinking, feeling, and behaving,” Dr. Yoneda said.

“For example, conscientiousness is characterized by competence, dutifulness, and self-discipline, while neuroticism is characterized by anxiety, depressive symptoms, and emotional instability. Likewise, individuals high in extraversion tend to be enthusiastic, gregarious, talkative, and assertive,” she added.

Previous research “suggests that low conscientiousness and high neuroticism are associated with an increased risk of cognitive impairment,” she continued. However, “there is also an increased risk of death in older adulthood – in other words, these outcomes are ‘competing risk factors.’”

Dr. Yoneda said her team wanted to “examine the impact of personality traits on the simultaneous risk of transitioning to mild cognitive impairment, dementia, and death.”  

For the study, the researchers analyzed data from 1,954 participants in MAP (mean age at baseline 80 years, 73.7% female, 86.8% White), who received a personality assessment and annual assessments of their cognitive abilities.

To assess personality traits – in particular, conscientiousness, neuroticism, and extraversion – the researchers used the NEO Five Factor Inventory (NEO-FFI). They also used multistate survival modeling to examine the potential association between these traits and transitions from one cognitive status category to another (NCI, MCI, and dementia) and to death.
 

Cognitive healthspan

By the end of the study, over half of the sample (54%) had died.

Most transitions showed “relative stability in cognitive status across measurement occasions.”

• NCI to NCI (n = 7,368)
• MCI to MCI (n = 1,244)
• Dementia to dementia (n = 876)

There were 725 “backward transitions” from MCI to NCI, “which may reflect improvement or within-person variability in cognitive functioning, or learning effects,” the authors note.

There were only 114 “backward transitions” from dementia to MCI and only 12 from dementia to NCI, “suggesting that improvement in cognitive status was relatively rare, particularly once an individual progresses to dementia.”

After adjusting for demographics, depressive symptoms, and apolipoprotein (APOE) ε4 allele, the researchers found that personality traits were the most important factors in the transition from NCI to MCI.

Higher conscientiousness was associated with a decreased risk of transitioning from NCI to MCI (hazard ratio, 0.78; 95% confidence interval, 0.72-0.85). Conversely, higher neuroticism was associated with an increased risk of transitioning from NCI to MCI (HR, 1.12; 95% CI, 1.04-1.21) and a significantly decreased likelihood of transition back from MCI to NCI (HR, 0.90; 95% CI, 0.81-1.00).

Scoring ~6 points on a conscientiousness scale ranging from 0-48 (that is, 1 SD on the scale) was significantly associated with ~22% lower risk of transitioning forward from NCI to MCI, while scoring ~7 more points on a neuroticism scale (1 SD) was significantly associated with ~12% higher risk of transitioning from NCI to MCI.

Higher extraversion was associated with an increased likelihood of transitioning from MCI back to NCI (HR, 1.12; 95% CI, 1.03-1.22), and although extraversion was not associated with a longer total lifespan, participants who scored high on extraversion, as well as those who scored low on conscientiousness or low on neuroticism, maintained normal cognitive function longer than other participants.

“Our results suggest that high conscientiousness and low neuroticism may protect individuals against mild cognitive impairment,” said Dr. Yoneda.

Importantly, individuals who were either higher in conscientiousness, higher in extraversion, or lower in neuroticism had more years of “cognitive healthspan,” meaning more years without cognitive impairment,” she added.

In addition, “individuals lower in neuroticism and higher in extraversion were more likely to recover after receiving an MCI diagnosis, suggesting that these traits may be protective even after an individual starts to progress to dementia,” she said.

The authors note that the study focused on only three of the Big Five personality traits, while the other 2 – openness to experience and agreeableness – may also be associated with cognitive aging processes and mortality.

Nevertheless, given the current results, alongside extensive research in the personality field, aiming to increase conscientiousness through persistent behavioral change is one potential strategy for promoting healthy cognitive aging, Dr. Yoneda said.
 

‘Invaluable window’

In a comment, Brent Roberts, PhD, professor of psychology, University of Illinois Urbana-Champaign, said the study provides an “invaluable window into how personality affects the process of decline and either accelerates it, as in the role of neuroticism, or decelerates it, as in the role of conscientiousness.”

“I think the most fascinating finding was the fact that extraversion was related to transitioning from MCI back to NCI. These types of transitions have simply not been part of prior research, and it provides utterly unique insights and opportunities for interventions that may actually help people recover from a decline,” said Dr. Roberts, who was not involved in the research.

Claire Sexton, DPhil, Alzheimer’s Association director of scientific programs and outreach, called the paper “novel” because it investigated the transitions between normal cognition and mild impairment and between mild impairment and dementia.

Dr. Sexton, who was associated with this research team, cautioned that is it observational, “so it can illuminate associations or correlations, but not causes. As a result, we can’t say for sure what the mechanisms are behind these potential connections between personality and cognition, and more research is needed.”

The research was supported by the Alzheimer Society Research Program, Social Sciences and Humanities Research Council, and the National Institute on Aging of the National Institutes of Health. Dr. Yoneda and co-authors, Dr. Roberts, and Dr. Sexton have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Extraverts and individuals who are disciplined are less likely to experience cognitive decline later in life, whereas those with neuroticism have an increased risk for cognitive dysfunction, new research shows.

Investigators analyzed data from almost 2,000 individuals enrolled in the Rush Memory and Aging Project (MAP) – a longitudinal study of older adults living in the greater Chicago metropolitan region and northeastern Illinois – with recruitment that began in 1997 and continues through today. Participants received a personality assessment as well as annual assessments of their cognitive abilities.

Those with high scores on measures of conscientiousness were significantly less likely to progress from normal cognition to mild cognitive impairment (MCI) during the study. In fact, scoring an extra 1 standard deviation on the conscientiousness scale was associated with a 22% lower risk of transitioning from no cognitive impairment (NCI) to MCI. On the other hand, scoring an additional 1 SD on a neuroticism scale was associated with a 12% increased risk of transitioning to MCI.

Participants who scored high on extraversion, as well as those who scored high on conscientiousness or low on neuroticism, tended to maintain normal cognitive functioning longer than other participants.

“Personality traits reflect relatively enduring patterns of thinking and behaving, which may cumulatively affect engagement in healthy and unhealthy behaviors and thought patterns across the lifespan,” lead author Tomiko Yoneda, PhD, a postdoctoral researcher in the department of medical social sciences, Northwestern University, Chicago, said in an interview.

“The accumulation of lifelong experiences may then contribute to susceptibility of particular diseases or disorders, such as mild cognitive impairment, or contribute to individual differences in the ability to withstand age-related neurological changes,” she added.

The study was published online in the Journal of Personality and Social Psychology.
 

Competing risk factors

Personality traits “reflect an individual’s persistent patterns of thinking, feeling, and behaving,” Dr. Yoneda said.

“For example, conscientiousness is characterized by competence, dutifulness, and self-discipline, while neuroticism is characterized by anxiety, depressive symptoms, and emotional instability. Likewise, individuals high in extraversion tend to be enthusiastic, gregarious, talkative, and assertive,” she added.

Previous research “suggests that low conscientiousness and high neuroticism are associated with an increased risk of cognitive impairment,” she continued. However, “there is also an increased risk of death in older adulthood – in other words, these outcomes are ‘competing risk factors.’”

Dr. Yoneda said her team wanted to “examine the impact of personality traits on the simultaneous risk of transitioning to mild cognitive impairment, dementia, and death.”  

For the study, the researchers analyzed data from 1,954 participants in MAP (mean age at baseline 80 years, 73.7% female, 86.8% White), who received a personality assessment and annual assessments of their cognitive abilities.

To assess personality traits – in particular, conscientiousness, neuroticism, and extraversion – the researchers used the NEO Five Factor Inventory (NEO-FFI). They also used multistate survival modeling to examine the potential association between these traits and transitions from one cognitive status category to another (NCI, MCI, and dementia) and to death.
 

Cognitive healthspan

By the end of the study, over half of the sample (54%) had died.

Most transitions showed “relative stability in cognitive status across measurement occasions.”

• NCI to NCI (n = 7,368)
• MCI to MCI (n = 1,244)
• Dementia to dementia (n = 876)

There were 725 “backward transitions” from MCI to NCI, “which may reflect improvement or within-person variability in cognitive functioning, or learning effects,” the authors note.

There were only 114 “backward transitions” from dementia to MCI and only 12 from dementia to NCI, “suggesting that improvement in cognitive status was relatively rare, particularly once an individual progresses to dementia.”

After adjusting for demographics, depressive symptoms, and apolipoprotein (APOE) ε4 allele, the researchers found that personality traits were the most important factors in the transition from NCI to MCI.

Higher conscientiousness was associated with a decreased risk of transitioning from NCI to MCI (hazard ratio, 0.78; 95% confidence interval, 0.72-0.85). Conversely, higher neuroticism was associated with an increased risk of transitioning from NCI to MCI (HR, 1.12; 95% CI, 1.04-1.21) and a significantly decreased likelihood of transition back from MCI to NCI (HR, 0.90; 95% CI, 0.81-1.00).

Scoring ~6 points on a conscientiousness scale ranging from 0-48 (that is, 1 SD on the scale) was significantly associated with ~22% lower risk of transitioning forward from NCI to MCI, while scoring ~7 more points on a neuroticism scale (1 SD) was significantly associated with ~12% higher risk of transitioning from NCI to MCI.

Higher extraversion was associated with an increased likelihood of transitioning from MCI back to NCI (HR, 1.12; 95% CI, 1.03-1.22), and although extraversion was not associated with a longer total lifespan, participants who scored high on extraversion, as well as those who scored low on conscientiousness or low on neuroticism, maintained normal cognitive function longer than other participants.

“Our results suggest that high conscientiousness and low neuroticism may protect individuals against mild cognitive impairment,” said Dr. Yoneda.

Importantly, individuals who were either higher in conscientiousness, higher in extraversion, or lower in neuroticism had more years of “cognitive healthspan,” meaning more years without cognitive impairment,” she added.

In addition, “individuals lower in neuroticism and higher in extraversion were more likely to recover after receiving an MCI diagnosis, suggesting that these traits may be protective even after an individual starts to progress to dementia,” she said.

The authors note that the study focused on only three of the Big Five personality traits, while the other 2 – openness to experience and agreeableness – may also be associated with cognitive aging processes and mortality.

Nevertheless, given the current results, alongside extensive research in the personality field, aiming to increase conscientiousness through persistent behavioral change is one potential strategy for promoting healthy cognitive aging, Dr. Yoneda said.
 

‘Invaluable window’

In a comment, Brent Roberts, PhD, professor of psychology, University of Illinois Urbana-Champaign, said the study provides an “invaluable window into how personality affects the process of decline and either accelerates it, as in the role of neuroticism, or decelerates it, as in the role of conscientiousness.”

“I think the most fascinating finding was the fact that extraversion was related to transitioning from MCI back to NCI. These types of transitions have simply not been part of prior research, and it provides utterly unique insights and opportunities for interventions that may actually help people recover from a decline,” said Dr. Roberts, who was not involved in the research.

Claire Sexton, DPhil, Alzheimer’s Association director of scientific programs and outreach, called the paper “novel” because it investigated the transitions between normal cognition and mild impairment and between mild impairment and dementia.

Dr. Sexton, who was associated with this research team, cautioned that is it observational, “so it can illuminate associations or correlations, but not causes. As a result, we can’t say for sure what the mechanisms are behind these potential connections between personality and cognition, and more research is needed.”

The research was supported by the Alzheimer Society Research Program, Social Sciences and Humanities Research Council, and the National Institute on Aging of the National Institutes of Health. Dr. Yoneda and co-authors, Dr. Roberts, and Dr. Sexton have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Emotional or sexual abuse in childhood may increase risk of multiple sclerosis (MS) in women, and risk may increase further with exposure to multiple kinds of abuse, according to the first prospective cohort study of its kind.

More research is needed to uncover underlying mechanisms of action, according to lead author Karine Eid, MD, a PhD candidate at Haukeland University Hospital, Bergen, Norway, and colleagues.

“Trauma and stressful life events have been associated with an increased risk of autoimmune disorders,” the investigators wrote in the Journal Of Neurology, Neurosurgery, & Psychiatry. “Whether adverse events in childhood can have an impact on MS susceptibility is not known.”

The present study recruited participants from the Norwegian Mother, Father and Child cohort, a population consisting of Norwegian women who were pregnant from 1999 to 2008. Of the 77,997 participating women, 14,477 reported emotional, sexual, and/or physical abuse in childhood, while the remaining 63,520 women reported no abuse. After a mean follow-up of 13 years, 300 women were diagnosed with MS, among whom 24% reported a history of childhood abuse, compared with 19% among women who did not develop MS.

To look for associations between childhood abuse and risk of MS, the investigators used a Cox model adjusted for confounders and mediators, including smoking, obesity, adult socioeconomic factors, and childhood social status. The model revealed that emotional abuse increased the risk of MS by 40% (hazard ratio [HR] 1.40; 95% confidence interval [CI], 1.03-1.90), and sexual abuse increased the risk of MS by 65% (HR 1.65; 95% CI, 1.13-2.39).

Although physical abuse alone did not significantly increase risk of MS (HR 1.31; 95% CI, 0.83-2.06), it did contribute to a dose-response relationship when women were exposed to more than one type of childhood abuse. Women exposed to two out of three abuse categories had a 66% increased risk of MS (HR 1.66; 95% CI, 1.04-2.67), whereas women exposed to all three types of abuse had the highest risk of MS, at 93% (HR 1.93; 95% CI, 1.02-3.67).

Dr. Eid and colleagues noted that their findings are supported by previous retrospective research, and discussed possible mechanisms of action.

“The increased risk of MS after exposure to childhood sexual and emotional abuse may have a biological explanation,” they wrote. “Childhood abuse can cause dysregulation of the hypothalamic-pituitary-adrenal axis, lead to oxidative stress, and induce a proinflammatory state decades into adulthood. Psychological stress has been shown to disrupt the blood-brain barrier and cause epigenetic changes that may increase the risk of neurodegenerative disorders, including MS.

“The underlying mechanisms behind this association should be investigated further,” they concluded.
 

Study findings should guide interventions

Commenting on the research, Ruth Ann Marrie, MD, PhD, professor of medicine and community health sciences and director of the multiple sclerosis clinic at Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, said that the present study “has several strengths compared to prior studies – including that it is prospective and the sample size.”

Dr. Marrie, who was not involved in the study, advised clinicians in the field to take note of the findings, as patients with a history of abuse may need unique interventions.

“Providers need to recognize the higher prevalence of childhood maltreatment in people with MS,” Dr. Marrie said in an interview. “These findings dovetail with others that suggest that adverse childhood experiences are associated with increased mental health concerns and pain catastrophizing in people with MS. Affected individuals may benefit from additional psychological supports and trauma-informed care.”

Tiffany Joy Braley, MD, associate professor of neurology, and Carri Polick, RN and PhD candidate at the school of nursing, University of Michigan, Ann Arbor, who published a case report last year highlighting the importance of evaluating stress exposure in MS, suggested that the findings should guide interventions at both a system and patient level.

“Although a cause-and-effect relationship cannot be established by the current study, these and related findings should be considered in the context of system level and policy interventions that address links between environment and health care disparities,” they said in a joint, written comment. “Given recent impetus to provide trauma-informed health care, these data could be particularly informative in neurological conditions which are associated with high mental health comorbidity. Traumatic stress screening practices could lead to referrals for appropriate support services and more personalized health care.”

While several mechanisms have been proposed to explain the link between traumatic stress and MS, more work is needed in this area, they added.

This knowledge gap was acknowledged by Dr. Marrie.

“Our understanding of the etiology of MS remains incomplete,” Dr. Marrie said. “We still need a better understanding of mechanisms by which adverse childhood experiences lead to MS, how they interact with other risk factors for MS (beyond smoking and obesity), and whether there are any interventions that can mitigate the risk of developing MS that is associated with adverse childhood experiences.”

The investigators disclosed relationships with Novartis, Biogen, Merck, and others. Dr. Marrie receives research support from the Canadian Institutes of Health Research, the National Multiple Sclerosis Society, MS Society of Canada, the Consortium of Multiple Sclerosis Centers, Crohn’s and Colitis Canada, Research Manitoba, and the Arthritis Society; she has no pharmaceutical support. Dr. Braley and Ms. Polick reported no conflicts of interest.

Emotional or sexual abuse in childhood may increase risk of multiple sclerosis (MS) in women, and risk may increase further with exposure to multiple kinds of abuse, according to the first prospective cohort study of its kind.

More research is needed to uncover underlying mechanisms of action, according to lead author Karine Eid, MD, a PhD candidate at Haukeland University Hospital, Bergen, Norway, and colleagues.

“Trauma and stressful life events have been associated with an increased risk of autoimmune disorders,” the investigators wrote in the Journal Of Neurology, Neurosurgery, & Psychiatry. “Whether adverse events in childhood can have an impact on MS susceptibility is not known.”

The present study recruited participants from the Norwegian Mother, Father and Child cohort, a population consisting of Norwegian women who were pregnant from 1999 to 2008. Of the 77,997 participating women, 14,477 reported emotional, sexual, and/or physical abuse in childhood, while the remaining 63,520 women reported no abuse. After a mean follow-up of 13 years, 300 women were diagnosed with MS, among whom 24% reported a history of childhood abuse, compared with 19% among women who did not develop MS.

To look for associations between childhood abuse and risk of MS, the investigators used a Cox model adjusted for confounders and mediators, including smoking, obesity, adult socioeconomic factors, and childhood social status. The model revealed that emotional abuse increased the risk of MS by 40% (hazard ratio [HR] 1.40; 95% confidence interval [CI], 1.03-1.90), and sexual abuse increased the risk of MS by 65% (HR 1.65; 95% CI, 1.13-2.39).

Although physical abuse alone did not significantly increase risk of MS (HR 1.31; 95% CI, 0.83-2.06), it did contribute to a dose-response relationship when women were exposed to more than one type of childhood abuse. Women exposed to two out of three abuse categories had a 66% increased risk of MS (HR 1.66; 95% CI, 1.04-2.67), whereas women exposed to all three types of abuse had the highest risk of MS, at 93% (HR 1.93; 95% CI, 1.02-3.67).

Dr. Eid and colleagues noted that their findings are supported by previous retrospective research, and discussed possible mechanisms of action.

“The increased risk of MS after exposure to childhood sexual and emotional abuse may have a biological explanation,” they wrote. “Childhood abuse can cause dysregulation of the hypothalamic-pituitary-adrenal axis, lead to oxidative stress, and induce a proinflammatory state decades into adulthood. Psychological stress has been shown to disrupt the blood-brain barrier and cause epigenetic changes that may increase the risk of neurodegenerative disorders, including MS.

“The underlying mechanisms behind this association should be investigated further,” they concluded.
 

Study findings should guide interventions

Commenting on the research, Ruth Ann Marrie, MD, PhD, professor of medicine and community health sciences and director of the multiple sclerosis clinic at Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, said that the present study “has several strengths compared to prior studies – including that it is prospective and the sample size.”

Dr. Marrie, who was not involved in the study, advised clinicians in the field to take note of the findings, as patients with a history of abuse may need unique interventions.

“Providers need to recognize the higher prevalence of childhood maltreatment in people with MS,” Dr. Marrie said in an interview. “These findings dovetail with others that suggest that adverse childhood experiences are associated with increased mental health concerns and pain catastrophizing in people with MS. Affected individuals may benefit from additional psychological supports and trauma-informed care.”

Tiffany Joy Braley, MD, associate professor of neurology, and Carri Polick, RN and PhD candidate at the school of nursing, University of Michigan, Ann Arbor, who published a case report last year highlighting the importance of evaluating stress exposure in MS, suggested that the findings should guide interventions at both a system and patient level.

“Although a cause-and-effect relationship cannot be established by the current study, these and related findings should be considered in the context of system level and policy interventions that address links between environment and health care disparities,” they said in a joint, written comment. “Given recent impetus to provide trauma-informed health care, these data could be particularly informative in neurological conditions which are associated with high mental health comorbidity. Traumatic stress screening practices could lead to referrals for appropriate support services and more personalized health care.”

While several mechanisms have been proposed to explain the link between traumatic stress and MS, more work is needed in this area, they added.

This knowledge gap was acknowledged by Dr. Marrie.

“Our understanding of the etiology of MS remains incomplete,” Dr. Marrie said. “We still need a better understanding of mechanisms by which adverse childhood experiences lead to MS, how they interact with other risk factors for MS (beyond smoking and obesity), and whether there are any interventions that can mitigate the risk of developing MS that is associated with adverse childhood experiences.”

The investigators disclosed relationships with Novartis, Biogen, Merck, and others. Dr. Marrie receives research support from the Canadian Institutes of Health Research, the National Multiple Sclerosis Society, MS Society of Canada, the Consortium of Multiple Sclerosis Centers, Crohn’s and Colitis Canada, Research Manitoba, and the Arthritis Society; she has no pharmaceutical support. Dr. Braley and Ms. Polick reported no conflicts of interest.

Emotional or sexual abuse in childhood may increase risk of multiple sclerosis (MS) in women, and risk may increase further with exposure to multiple kinds of abuse, according to the first prospective cohort study of its kind.

More research is needed to uncover underlying mechanisms of action, according to lead author Karine Eid, MD, a PhD candidate at Haukeland University Hospital, Bergen, Norway, and colleagues.

“Trauma and stressful life events have been associated with an increased risk of autoimmune disorders,” the investigators wrote in the Journal Of Neurology, Neurosurgery, & Psychiatry. “Whether adverse events in childhood can have an impact on MS susceptibility is not known.”

The present study recruited participants from the Norwegian Mother, Father and Child cohort, a population consisting of Norwegian women who were pregnant from 1999 to 2008. Of the 77,997 participating women, 14,477 reported emotional, sexual, and/or physical abuse in childhood, while the remaining 63,520 women reported no abuse. After a mean follow-up of 13 years, 300 women were diagnosed with MS, among whom 24% reported a history of childhood abuse, compared with 19% among women who did not develop MS.

To look for associations between childhood abuse and risk of MS, the investigators used a Cox model adjusted for confounders and mediators, including smoking, obesity, adult socioeconomic factors, and childhood social status. The model revealed that emotional abuse increased the risk of MS by 40% (hazard ratio [HR] 1.40; 95% confidence interval [CI], 1.03-1.90), and sexual abuse increased the risk of MS by 65% (HR 1.65; 95% CI, 1.13-2.39).

Although physical abuse alone did not significantly increase risk of MS (HR 1.31; 95% CI, 0.83-2.06), it did contribute to a dose-response relationship when women were exposed to more than one type of childhood abuse. Women exposed to two out of three abuse categories had a 66% increased risk of MS (HR 1.66; 95% CI, 1.04-2.67), whereas women exposed to all three types of abuse had the highest risk of MS, at 93% (HR 1.93; 95% CI, 1.02-3.67).

Dr. Eid and colleagues noted that their findings are supported by previous retrospective research, and discussed possible mechanisms of action.

“The increased risk of MS after exposure to childhood sexual and emotional abuse may have a biological explanation,” they wrote. “Childhood abuse can cause dysregulation of the hypothalamic-pituitary-adrenal axis, lead to oxidative stress, and induce a proinflammatory state decades into adulthood. Psychological stress has been shown to disrupt the blood-brain barrier and cause epigenetic changes that may increase the risk of neurodegenerative disorders, including MS.

“The underlying mechanisms behind this association should be investigated further,” they concluded.
 

Study findings should guide interventions

Commenting on the research, Ruth Ann Marrie, MD, PhD, professor of medicine and community health sciences and director of the multiple sclerosis clinic at Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, said that the present study “has several strengths compared to prior studies – including that it is prospective and the sample size.”

Dr. Marrie, who was not involved in the study, advised clinicians in the field to take note of the findings, as patients with a history of abuse may need unique interventions.

“Providers need to recognize the higher prevalence of childhood maltreatment in people with MS,” Dr. Marrie said in an interview. “These findings dovetail with others that suggest that adverse childhood experiences are associated with increased mental health concerns and pain catastrophizing in people with MS. Affected individuals may benefit from additional psychological supports and trauma-informed care.”

Tiffany Joy Braley, MD, associate professor of neurology, and Carri Polick, RN and PhD candidate at the school of nursing, University of Michigan, Ann Arbor, who published a case report last year highlighting the importance of evaluating stress exposure in MS, suggested that the findings should guide interventions at both a system and patient level.

“Although a cause-and-effect relationship cannot be established by the current study, these and related findings should be considered in the context of system level and policy interventions that address links between environment and health care disparities,” they said in a joint, written comment. “Given recent impetus to provide trauma-informed health care, these data could be particularly informative in neurological conditions which are associated with high mental health comorbidity. Traumatic stress screening practices could lead to referrals for appropriate support services and more personalized health care.”

While several mechanisms have been proposed to explain the link between traumatic stress and MS, more work is needed in this area, they added.

This knowledge gap was acknowledged by Dr. Marrie.

“Our understanding of the etiology of MS remains incomplete,” Dr. Marrie said. “We still need a better understanding of mechanisms by which adverse childhood experiences lead to MS, how they interact with other risk factors for MS (beyond smoking and obesity), and whether there are any interventions that can mitigate the risk of developing MS that is associated with adverse childhood experiences.”

The investigators disclosed relationships with Novartis, Biogen, Merck, and others. Dr. Marrie receives research support from the Canadian Institutes of Health Research, the National Multiple Sclerosis Society, MS Society of Canada, the Consortium of Multiple Sclerosis Centers, Crohn’s and Colitis Canada, Research Manitoba, and the Arthritis Society; she has no pharmaceutical support. Dr. Braley and Ms. Polick reported no conflicts of interest.

Long-term cannabis use is linked to hippocampal atrophy and poorer cognitive function in midlife – known risk factors for dementia.

A large prospective, longitudinal study showed long-term cannabis users had an intelligence quotient (IQ) decline from age 18 to midlife (mean, 5.5 IQ points), poorer learning and processing speed, compared with childhood, and self-reported memory and attention problems. Long-term cannabis users also showed hippocampal atrophy at midlife (age 45), which combined with mild midlife cognitive deficits, all known risk factors for dementia.

“Long-term cannabis users – people who have used cannabis from 18 or 19 years old and continued using through midlife – showed cognitive deficits, compared with nonusers. They also showed more severe cognitive deficits, compared with long-term alcohol users and long-term tobacco users. But people who used infrequently or recreationally in midlife did not show as severe cognitive deficits. Cognitive deficits were confined to cannabis users,” lead investigator Madeline Meier, PhD, associate professor of psychology, Arizona State University, Tempe, said in an interview.

“Long-term cannabis users had smaller hippocampal volume, but we also found that smaller hippocampal volume did not explain the cognitive deficits among the long-term cannabis users,” she added.

The study was recently published online in the American Journal of Psychiatry.
 

Growing use in Boomers

Long-term cannabis use has been associated with memory problems. Studies examining the impact of cannabis use on the brain have shown conflicting results. Some suggest regular use in adolescence is associated with altered connectivity and reduced volume of brain regions involved in executive functions such as memory, learning, and impulse control compared with those who do not use cannabis.

Others found no significant structural differences between the brains of cannabis users and nonusers.

An earlier, large longitudinal study in New Zealand found that persistent cannabis use (with frequent use starting in adolescence) was associated with a loss of an average of six (or up to eight) IQ points measured in mid-adulthood.

Cannabis use is increasing among Baby Boomers – a group born between 1946 and 1964 – who used cannabis at historically high rates as young adults, and who now use it at historically high rates in midlife and as older adults.

To date, case-control studies, which are predominantly in adolescents and young adults, have found that cannabis users show subtle cognitive deficits and structural brain differences, but it is unclear whether these differences in young cannabis users might be larger in midlife and in older adults who have longer histories of use.

The study included a representative cohort of 1,037 individuals in Dunedin, New Zealand, born between April 1972 and March 1973, and followed from age 3 to 45.

Cannabis use and dependence were assessed at ages 18, 21, 26, 32, 38, and 45. IQ was assessed at ages 7, 9, 11, and 45. Specific neuropsychological functions and hippocampal volume were assessed at age 45. 

“Most of the previous research has focused on adolescent and young-adult cannabis users. What we’re looking at here is long-term cannabis users in midlife, and we’re finding that long-term users show cognitive deficits. But we’re not just looking at a snapshot of people in midlife, we’re also doing a longitudinal comparison – comparing them to themselves in childhood. We saw that long-term cannabis users showed a decline in IQ from childhood to adulthood,” said Dr. Meier. 

Participants in the study are members of the Dunedin Longitudinal Study, a representative birth cohort (n = 1,037; 91% of eligible births; 52% male) born between April 1972 and March 1973 in Dunedin, New Zealand, who participated in the first assessment at age 3.

This cohort matched socioeconomic status (SES), key health indicators, and demographics. Assessments were carried out at birth and ages 3, 5, 7, 9, 11, 13, 15, 18, 21, 26, 32, 38, and 45. IQ was assessed at ages 7, 9, 11, and 45. Specific neuropsychological functions and hippocampal volume were assessed at age 45. 
 

Shrinking hippocampal volume

Cannabis use, cognitive function, and hippocampal volume were assessed comparing long-term cannabis users (n = 84) against five distinct groups:

• Lifelong cannabis nonusers (n = 196) – to replicate the control group most often reported in the case-control literature
• Midlife recreational cannabis users (n = 65) – to determine if cognitive deficits and structural brain differences are apparent in nonproblem users – the majority of cannabis users
• Long-term tobacco users (n = 75)
• Long-term alcohol users (n = 57) – benchmark comparisons for any cannabis findings and to disentangle potential cannabis effects from tobacco and alcohol effects
• Cannabis quitters (n = 58) – to determine whether differences are apparent after cessation

Tests were conducted on dose-response associations using continuously measured persistence of cannabis use, rigorously adjusting for numerous confounders derived from multiple longitudinal waves and data sources.

The investigators also tested whether associations between continuously measured persistence of cannabis use and cognitive deficits were mediated by hippocampal volume differences.

The hippocampus was the area of focus because it has a high density of cannabinoid receptors and is also instrumental for learning and memory, which is one of the most consistently impaired cognitive domains in cannabis users, and has been the brain region that most consistently emerges as smaller in cannabis users relative to controls. Structural MRI was done at age 45 for 875 participants (93% of age 45 participants).

Of 997 cohort members still alive at age 45, 938 (94.1%) were assessed at age 45. Age 45 participants did not differ significantly from other participants on childhood SES, childhood self-control, or childhood IQ. Cognitive functioning among midlife recreational cannabis users was similar to representative cohort norms, suggesting that infrequent recreational cannabis use in midlife is unlikely to compromise cognitive functioning.

However, long-term cannabis users did not perform significantly worse on any test than cannabis quitters. Cannabis quitters showed subtle cognitive deficits that may explain inconsistent findings on the benefits of cessation.

Smaller hippocampal volume is thought to be a possible mediator of cannabis-related cognitive deficits because the hippocampus is rich in CB1 receptors and is involved in learning and memory.

Long-term cannabis users had smaller bilateral volume in total hippocampus and 5 of 12 structurally and functionally distinct subregions (tail, hippocampal amygdala transition area, CA1, molecular layer, and dentate gyrus), and significantly smaller volumes than midlife recreational cannabis users in the left and right hippocampus, and 3 of 12 subfields (tail, CA1, and molecular layer), compared with non-users, consistent with case-control studies.
 

More potent

“If you’ve been using cannabis very long term and now are in midlife, you might want to consider quitting. Quitting is associated with slightly better cognitive performance in midlife. We also need to watch for risk of dementia. We know that people who show cognitive deficits at midlife are at elevated risk for later life dementia. And the deficits we saw among long-term cannabis users (although fairly mild), they were in the range in terms of effect size of what we see among people in other studies who have gone on to develop dementia in later life,” said Dr. Meier.

The study findings conflict with those of other studies, including one by the same research group, which compared the cognitive functioning of twins who were discordant for cannabis use and found little evidence of cannabis-related cognitive deficits. Because long-term cannabis users also use tobacco, alcohol, and other illicit drugs, disentangling cannabis effects from other substances is challenging.

“Long-term cannabis users tend to be long-term polysubstance users, so it’s hard to isolate,” said Dr. Meier.

Additionally, some group sizes were small, raising concerns about low statistical power.

“Group sizes were small but we didn’t rely only on those group comparisons; however, we did find statistical differences. We also tested highly statistically powered dose-response associations between persistence of cannabis use over ages 18-45 and each of our outcomes (IQ, learning, and processing speed in midlife) while adjusting possible alternate explanations such as low childhood IQ, other substance use, [and] socioeconomic backgrounds.

“These dose-response associations used large sample sizes, were highly powered, and took into account a number of alternative explanations. These two different approaches showed very similar findings and one bolstered the other,” said Dr. Meier.

The study’s results were based on individuals who began using cannabis in the 1980s or ‘90s, but the concentration of tetrahydrocannabinol (THC) has risen in recent years.

“When the study began, THC concentration was approximately 4%. Over the last decade we have seen it go up to 12% or even higher. A recent study surveying U.S. dispensaries found 20% THC. If THC accounts for impairment, then the effects can be larger [with higher concentrations]. One of the challenges in the U.S. is that there are laws prohibiting researchers from testing cannabis, so we have to rely on product labels, which we know are unreliable,” said Dr. Meier.

A separate report is forthcoming with results of exploratory analyses of associations between long-term cannabis use and comprehensive MRI measures of global and regional gray and white matter.

The data will also be used to answer a number of different questions about cognitive deficits, brain structure, aging preparedness, social preparedness (strength of social networks), financial and health preparedness, and biological aging (the pace of aging relative to chronological age) in long-term cannabis users, Dr. Meier noted.
 

‘Fantastic’ research

Commenting on the research for this news organization , Andrew J. Saxon, MD, professor, department of psychiatry & behavioral sciences at University of Washington, Seattle, and a member of the American Psychiatric Association’s Council on Addiction Psychiatry, said the study “provides more evidence that heavy and regular cannabis use is not benign behavior.”

“It’s a fantastic piece of research in which they enrolled participants at birth and have followed them up to age 45. In most of the other research that has been done, we have no idea what their baseline was. What’s so remarkable here is that they can clearly demonstrate the loss of IQ points from childhood to age 45,” said Dr. Saxon.

“It is clear that, in people using cannabis long term, cognition is impaired. It would be good to have a better handle on how much cognitive function can be regained if you quit, because that could be a motivator for quitting in people where cannabis is having an adverse effect on their lives,” he added.

On the issue of THC potency, Dr. Saxon said that, while it’s true the potency of cannabis is increasing in terms of THC concentrations, the question is: “Do people who use cannabis use a set amount or do they imbibe until they achieve the state of altered consciousness that they’re seeking? Although there has been some research in the area of self-regulation and cannabis potency, we do not yet have the answers to determine if there is any causation,” said Dr. Saxon.

Dr. Meier and Dr. Saxon reported no relevant financial conflicts of interest.

A version of this article first appeared on Medscape.com.

Long-term cannabis use is linked to hippocampal atrophy and poorer cognitive function in midlife – known risk factors for dementia.

A large prospective, longitudinal study showed long-term cannabis users had an intelligence quotient (IQ) decline from age 18 to midlife (mean, 5.5 IQ points), poorer learning and processing speed, compared with childhood, and self-reported memory and attention problems. Long-term cannabis users also showed hippocampal atrophy at midlife (age 45), which combined with mild midlife cognitive deficits, all known risk factors for dementia.

“Long-term cannabis users – people who have used cannabis from 18 or 19 years old and continued using through midlife – showed cognitive deficits, compared with nonusers. They also showed more severe cognitive deficits, compared with long-term alcohol users and long-term tobacco users. But people who used infrequently or recreationally in midlife did not show as severe cognitive deficits. Cognitive deficits were confined to cannabis users,” lead investigator Madeline Meier, PhD, associate professor of psychology, Arizona State University, Tempe, said in an interview.

“Long-term cannabis users had smaller hippocampal volume, but we also found that smaller hippocampal volume did not explain the cognitive deficits among the long-term cannabis users,” she added.

The study was recently published online in the American Journal of Psychiatry.
 

Growing use in Boomers

Long-term cannabis use has been associated with memory problems. Studies examining the impact of cannabis use on the brain have shown conflicting results. Some suggest regular use in adolescence is associated with altered connectivity and reduced volume of brain regions involved in executive functions such as memory, learning, and impulse control compared with those who do not use cannabis.

Others found no significant structural differences between the brains of cannabis users and nonusers.

An earlier, large longitudinal study in New Zealand found that persistent cannabis use (with frequent use starting in adolescence) was associated with a loss of an average of six (or up to eight) IQ points measured in mid-adulthood.

Cannabis use is increasing among Baby Boomers – a group born between 1946 and 1964 – who used cannabis at historically high rates as young adults, and who now use it at historically high rates in midlife and as older adults.

To date, case-control studies, which are predominantly in adolescents and young adults, have found that cannabis users show subtle cognitive deficits and structural brain differences, but it is unclear whether these differences in young cannabis users might be larger in midlife and in older adults who have longer histories of use.

The study included a representative cohort of 1,037 individuals in Dunedin, New Zealand, born between April 1972 and March 1973, and followed from age 3 to 45.

Cannabis use and dependence were assessed at ages 18, 21, 26, 32, 38, and 45. IQ was assessed at ages 7, 9, 11, and 45. Specific neuropsychological functions and hippocampal volume were assessed at age 45. 

“Most of the previous research has focused on adolescent and young-adult cannabis users. What we’re looking at here is long-term cannabis users in midlife, and we’re finding that long-term users show cognitive deficits. But we’re not just looking at a snapshot of people in midlife, we’re also doing a longitudinal comparison – comparing them to themselves in childhood. We saw that long-term cannabis users showed a decline in IQ from childhood to adulthood,” said Dr. Meier. 

Participants in the study are members of the Dunedin Longitudinal Study, a representative birth cohort (n = 1,037; 91% of eligible births; 52% male) born between April 1972 and March 1973 in Dunedin, New Zealand, who participated in the first assessment at age 3.

This cohort matched socioeconomic status (SES), key health indicators, and demographics. Assessments were carried out at birth and ages 3, 5, 7, 9, 11, 13, 15, 18, 21, 26, 32, 38, and 45. IQ was assessed at ages 7, 9, 11, and 45. Specific neuropsychological functions and hippocampal volume were assessed at age 45. 
 

Shrinking hippocampal volume

Cannabis use, cognitive function, and hippocampal volume were assessed comparing long-term cannabis users (n = 84) against five distinct groups:

• Lifelong cannabis nonusers (n = 196) – to replicate the control group most often reported in the case-control literature
• Midlife recreational cannabis users (n = 65) – to determine if cognitive deficits and structural brain differences are apparent in nonproblem users – the majority of cannabis users
• Long-term tobacco users (n = 75)
• Long-term alcohol users (n = 57) – benchmark comparisons for any cannabis findings and to disentangle potential cannabis effects from tobacco and alcohol effects
• Cannabis quitters (n = 58) – to determine whether differences are apparent after cessation

Tests were conducted on dose-response associations using continuously measured persistence of cannabis use, rigorously adjusting for numerous confounders derived from multiple longitudinal waves and data sources.

The investigators also tested whether associations between continuously measured persistence of cannabis use and cognitive deficits were mediated by hippocampal volume differences.

The hippocampus was the area of focus because it has a high density of cannabinoid receptors and is also instrumental for learning and memory, which is one of the most consistently impaired cognitive domains in cannabis users, and has been the brain region that most consistently emerges as smaller in cannabis users relative to controls. Structural MRI was done at age 45 for 875 participants (93% of age 45 participants).

Of 997 cohort members still alive at age 45, 938 (94.1%) were assessed at age 45. Age 45 participants did not differ significantly from other participants on childhood SES, childhood self-control, or childhood IQ. Cognitive functioning among midlife recreational cannabis users was similar to representative cohort norms, suggesting that infrequent recreational cannabis use in midlife is unlikely to compromise cognitive functioning.

However, long-term cannabis users did not perform significantly worse on any test than cannabis quitters. Cannabis quitters showed subtle cognitive deficits that may explain inconsistent findings on the benefits of cessation.

Smaller hippocampal volume is thought to be a possible mediator of cannabis-related cognitive deficits because the hippocampus is rich in CB1 receptors and is involved in learning and memory.

Long-term cannabis users had smaller bilateral volume in total hippocampus and 5 of 12 structurally and functionally distinct subregions (tail, hippocampal amygdala transition area, CA1, molecular layer, and dentate gyrus), and significantly smaller volumes than midlife recreational cannabis users in the left and right hippocampus, and 3 of 12 subfields (tail, CA1, and molecular layer), compared with non-users, consistent with case-control studies.
 

More potent

“If you’ve been using cannabis very long term and now are in midlife, you might want to consider quitting. Quitting is associated with slightly better cognitive performance in midlife. We also need to watch for risk of dementia. We know that people who show cognitive deficits at midlife are at elevated risk for later life dementia. And the deficits we saw among long-term cannabis users (although fairly mild), they were in the range in terms of effect size of what we see among people in other studies who have gone on to develop dementia in later life,” said Dr. Meier.

The study findings conflict with those of other studies, including one by the same research group, which compared the cognitive functioning of twins who were discordant for cannabis use and found little evidence of cannabis-related cognitive deficits. Because long-term cannabis users also use tobacco, alcohol, and other illicit drugs, disentangling cannabis effects from other substances is challenging.

“Long-term cannabis users tend to be long-term polysubstance users, so it’s hard to isolate,” said Dr. Meier.

Additionally, some group sizes were small, raising concerns about low statistical power.

“Group sizes were small but we didn’t rely only on those group comparisons; however, we did find statistical differences. We also tested highly statistically powered dose-response associations between persistence of cannabis use over ages 18-45 and each of our outcomes (IQ, learning, and processing speed in midlife) while adjusting possible alternate explanations such as low childhood IQ, other substance use, [and] socioeconomic backgrounds.

“These dose-response associations used large sample sizes, were highly powered, and took into account a number of alternative explanations. These two different approaches showed very similar findings and one bolstered the other,” said Dr. Meier.

The study’s results were based on individuals who began using cannabis in the 1980s or ‘90s, but the concentration of tetrahydrocannabinol (THC) has risen in recent years.

“When the study began, THC concentration was approximately 4%. Over the last decade we have seen it go up to 12% or even higher. A recent study surveying U.S. dispensaries found 20% THC. If THC accounts for impairment, then the effects can be larger [with higher concentrations]. One of the challenges in the U.S. is that there are laws prohibiting researchers from testing cannabis, so we have to rely on product labels, which we know are unreliable,” said Dr. Meier.

A separate report is forthcoming with results of exploratory analyses of associations between long-term cannabis use and comprehensive MRI measures of global and regional gray and white matter.

The data will also be used to answer a number of different questions about cognitive deficits, brain structure, aging preparedness, social preparedness (strength of social networks), financial and health preparedness, and biological aging (the pace of aging relative to chronological age) in long-term cannabis users, Dr. Meier noted.
 

‘Fantastic’ research

Commenting on the research for this news organization , Andrew J. Saxon, MD, professor, department of psychiatry & behavioral sciences at University of Washington, Seattle, and a member of the American Psychiatric Association’s Council on Addiction Psychiatry, said the study “provides more evidence that heavy and regular cannabis use is not benign behavior.”

“It’s a fantastic piece of research in which they enrolled participants at birth and have followed them up to age 45. In most of the other research that has been done, we have no idea what their baseline was. What’s so remarkable here is that they can clearly demonstrate the loss of IQ points from childhood to age 45,” said Dr. Saxon.

“It is clear that, in people using cannabis long term, cognition is impaired. It would be good to have a better handle on how much cognitive function can be regained if you quit, because that could be a motivator for quitting in people where cannabis is having an adverse effect on their lives,” he added.

On the issue of THC potency, Dr. Saxon said that, while it’s true the potency of cannabis is increasing in terms of THC concentrations, the question is: “Do people who use cannabis use a set amount or do they imbibe until they achieve the state of altered consciousness that they’re seeking? Although there has been some research in the area of self-regulation and cannabis potency, we do not yet have the answers to determine if there is any causation,” said Dr. Saxon.

Dr. Meier and Dr. Saxon reported no relevant financial conflicts of interest.

A version of this article first appeared on Medscape.com.

Long-term cannabis use is linked to hippocampal atrophy and poorer cognitive function in midlife – known risk factors for dementia.

A large prospective, longitudinal study showed long-term cannabis users had an intelligence quotient (IQ) decline from age 18 to midlife (mean, 5.5 IQ points), poorer learning and processing speed, compared with childhood, and self-reported memory and attention problems. Long-term cannabis users also showed hippocampal atrophy at midlife (age 45), which combined with mild midlife cognitive deficits, all known risk factors for dementia.

“Long-term cannabis users – people who have used cannabis from 18 or 19 years old and continued using through midlife – showed cognitive deficits, compared with nonusers. They also showed more severe cognitive deficits, compared with long-term alcohol users and long-term tobacco users. But people who used infrequently or recreationally in midlife did not show as severe cognitive deficits. Cognitive deficits were confined to cannabis users,” lead investigator Madeline Meier, PhD, associate professor of psychology, Arizona State University, Tempe, said in an interview.

“Long-term cannabis users had smaller hippocampal volume, but we also found that smaller hippocampal volume did not explain the cognitive deficits among the long-term cannabis users,” she added.

The study was recently published online in the American Journal of Psychiatry.
 

Growing use in Boomers

Long-term cannabis use has been associated with memory problems. Studies examining the impact of cannabis use on the brain have shown conflicting results. Some suggest regular use in adolescence is associated with altered connectivity and reduced volume of brain regions involved in executive functions such as memory, learning, and impulse control compared with those who do not use cannabis.

Others found no significant structural differences between the brains of cannabis users and nonusers.

An earlier, large longitudinal study in New Zealand found that persistent cannabis use (with frequent use starting in adolescence) was associated with a loss of an average of six (or up to eight) IQ points measured in mid-adulthood.

Cannabis use is increasing among Baby Boomers – a group born between 1946 and 1964 – who used cannabis at historically high rates as young adults, and who now use it at historically high rates in midlife and as older adults.

To date, case-control studies, which are predominantly in adolescents and young adults, have found that cannabis users show subtle cognitive deficits and structural brain differences, but it is unclear whether these differences in young cannabis users might be larger in midlife and in older adults who have longer histories of use.

The study included a representative cohort of 1,037 individuals in Dunedin, New Zealand, born between April 1972 and March 1973, and followed from age 3 to 45.

Cannabis use and dependence were assessed at ages 18, 21, 26, 32, 38, and 45. IQ was assessed at ages 7, 9, 11, and 45. Specific neuropsychological functions and hippocampal volume were assessed at age 45. 

“Most of the previous research has focused on adolescent and young-adult cannabis users. What we’re looking at here is long-term cannabis users in midlife, and we’re finding that long-term users show cognitive deficits. But we’re not just looking at a snapshot of people in midlife, we’re also doing a longitudinal comparison – comparing them to themselves in childhood. We saw that long-term cannabis users showed a decline in IQ from childhood to adulthood,” said Dr. Meier. 

Participants in the study are members of the Dunedin Longitudinal Study, a representative birth cohort (n = 1,037; 91% of eligible births; 52% male) born between April 1972 and March 1973 in Dunedin, New Zealand, who participated in the first assessment at age 3.

This cohort matched socioeconomic status (SES), key health indicators, and demographics. Assessments were carried out at birth and ages 3, 5, 7, 9, 11, 13, 15, 18, 21, 26, 32, 38, and 45. IQ was assessed at ages 7, 9, 11, and 45. Specific neuropsychological functions and hippocampal volume were assessed at age 45. 
 

Shrinking hippocampal volume

Cannabis use, cognitive function, and hippocampal volume were assessed comparing long-term cannabis users (n = 84) against five distinct groups:

• Lifelong cannabis nonusers (n = 196) – to replicate the control group most often reported in the case-control literature
• Midlife recreational cannabis users (n = 65) – to determine if cognitive deficits and structural brain differences are apparent in nonproblem users – the majority of cannabis users
• Long-term tobacco users (n = 75)
• Long-term alcohol users (n = 57) – benchmark comparisons for any cannabis findings and to disentangle potential cannabis effects from tobacco and alcohol effects
• Cannabis quitters (n = 58) – to determine whether differences are apparent after cessation

Tests were conducted on dose-response associations using continuously measured persistence of cannabis use, rigorously adjusting for numerous confounders derived from multiple longitudinal waves and data sources.

The investigators also tested whether associations between continuously measured persistence of cannabis use and cognitive deficits were mediated by hippocampal volume differences.

The hippocampus was the area of focus because it has a high density of cannabinoid receptors and is also instrumental for learning and memory, which is one of the most consistently impaired cognitive domains in cannabis users, and has been the brain region that most consistently emerges as smaller in cannabis users relative to controls. Structural MRI was done at age 45 for 875 participants (93% of age 45 participants).

Of 997 cohort members still alive at age 45, 938 (94.1%) were assessed at age 45. Age 45 participants did not differ significantly from other participants on childhood SES, childhood self-control, or childhood IQ. Cognitive functioning among midlife recreational cannabis users was similar to representative cohort norms, suggesting that infrequent recreational cannabis use in midlife is unlikely to compromise cognitive functioning.

However, long-term cannabis users did not perform significantly worse on any test than cannabis quitters. Cannabis quitters showed subtle cognitive deficits that may explain inconsistent findings on the benefits of cessation.

Smaller hippocampal volume is thought to be a possible mediator of cannabis-related cognitive deficits because the hippocampus is rich in CB1 receptors and is involved in learning and memory.

Long-term cannabis users had smaller bilateral volume in total hippocampus and 5 of 12 structurally and functionally distinct subregions (tail, hippocampal amygdala transition area, CA1, molecular layer, and dentate gyrus), and significantly smaller volumes than midlife recreational cannabis users in the left and right hippocampus, and 3 of 12 subfields (tail, CA1, and molecular layer), compared with non-users, consistent with case-control studies.
 

More potent

“If you’ve been using cannabis very long term and now are in midlife, you might want to consider quitting. Quitting is associated with slightly better cognitive performance in midlife. We also need to watch for risk of dementia. We know that people who show cognitive deficits at midlife are at elevated risk for later life dementia. And the deficits we saw among long-term cannabis users (although fairly mild), they were in the range in terms of effect size of what we see among people in other studies who have gone on to develop dementia in later life,” said Dr. Meier.

The study findings conflict with those of other studies, including one by the same research group, which compared the cognitive functioning of twins who were discordant for cannabis use and found little evidence of cannabis-related cognitive deficits. Because long-term cannabis users also use tobacco, alcohol, and other illicit drugs, disentangling cannabis effects from other substances is challenging.

“Long-term cannabis users tend to be long-term polysubstance users, so it’s hard to isolate,” said Dr. Meier.

Additionally, some group sizes were small, raising concerns about low statistical power.

“Group sizes were small but we didn’t rely only on those group comparisons; however, we did find statistical differences. We also tested highly statistically powered dose-response associations between persistence of cannabis use over ages 18-45 and each of our outcomes (IQ, learning, and processing speed in midlife) while adjusting possible alternate explanations such as low childhood IQ, other substance use, [and] socioeconomic backgrounds.

“These dose-response associations used large sample sizes, were highly powered, and took into account a number of alternative explanations. These two different approaches showed very similar findings and one bolstered the other,” said Dr. Meier.

The study’s results were based on individuals who began using cannabis in the 1980s or ‘90s, but the concentration of tetrahydrocannabinol (THC) has risen in recent years.

“When the study began, THC concentration was approximately 4%. Over the last decade we have seen it go up to 12% or even higher. A recent study surveying U.S. dispensaries found 20% THC. If THC accounts for impairment, then the effects can be larger [with higher concentrations]. One of the challenges in the U.S. is that there are laws prohibiting researchers from testing cannabis, so we have to rely on product labels, which we know are unreliable,” said Dr. Meier.

A separate report is forthcoming with results of exploratory analyses of associations between long-term cannabis use and comprehensive MRI measures of global and regional gray and white matter.

The data will also be used to answer a number of different questions about cognitive deficits, brain structure, aging preparedness, social preparedness (strength of social networks), financial and health preparedness, and biological aging (the pace of aging relative to chronological age) in long-term cannabis users, Dr. Meier noted.
 

‘Fantastic’ research

Commenting on the research for this news organization , Andrew J. Saxon, MD, professor, department of psychiatry & behavioral sciences at University of Washington, Seattle, and a member of the American Psychiatric Association’s Council on Addiction Psychiatry, said the study “provides more evidence that heavy and regular cannabis use is not benign behavior.”

“It’s a fantastic piece of research in which they enrolled participants at birth and have followed them up to age 45. In most of the other research that has been done, we have no idea what their baseline was. What’s so remarkable here is that they can clearly demonstrate the loss of IQ points from childhood to age 45,” said Dr. Saxon.

“It is clear that, in people using cannabis long term, cognition is impaired. It would be good to have a better handle on how much cognitive function can be regained if you quit, because that could be a motivator for quitting in people where cannabis is having an adverse effect on their lives,” he added.

On the issue of THC potency, Dr. Saxon said that, while it’s true the potency of cannabis is increasing in terms of THC concentrations, the question is: “Do people who use cannabis use a set amount or do they imbibe until they achieve the state of altered consciousness that they’re seeking? Although there has been some research in the area of self-regulation and cannabis potency, we do not yet have the answers to determine if there is any causation,” said Dr. Saxon.

Dr. Meier and Dr. Saxon reported no relevant financial conflicts of interest.

A version of this article first appeared on Medscape.com.

Statins may protect against age-related parkinsonism, new research suggests. An observational study showed older adults taking statins had a lower risk for parkinsonism than their counterparts not taking statins – an effect that may be partially mediated by less severe intracranial atherosclerosis in statin users.

“These findings further support the idea that cerebrovascular disease pathologies accumulating in older brains may be an unrecognized contributor to the common occurrence of parkinsonism in old age,” the investigators wrote. “More importantly, these findings suggest that statins may have a potential therapeutic role in decreasing the magnitude of parkinsonism in older adults,” they added.

The study was published online in Neurology.
 

No clinical recommendations ... yet

The findings are based on 2,841 older adults enrolled in one of three ongoing clinical pathological studies at Rush Alzheimer’s Disease Center, Chicago.

Participants’ average age at baseline was 76 years, and 75% were women. None had parkinsonism at the start of the study. One-third of participants (n = 936) were taking statins. During an average follow-up of 6 years, 1,432 (50%) participants developed parkinsonism.

After controlling for demographics, vascular risk factors, and diseases, use of a statin at baseline was associated with a 16% lower risk for parkinsonism (hazard ratio, 0.84; 95% confidence interval, 0.74-0.96; P = .008). Compared with low-intensity statin therapy, moderate- or high-intensity statin therapy was associated with a 7% lower risk for parkinsonism (HR, 0.93; 95% CI, 0.87-1.00; P = .043).

The researchers also examined the brains of 1,044 people who died during the study at a mean age of 89 years. They found statin use prior to death was associated with a 37% lower odds of cerebral atherosclerosis, compared with no statin use prior to death (odds ratio, 0.63; 95% CI, 0.50-0.79; P < .001).

In a mediation analysis, both a direct (OR, 0.73; 95% CI, 0.54-0.93; P = .008) and an indirect (OR, 0.92; 95% CI, 0.88-0.97; P = .002) pathway via less severe cerebrovascular disease linked statins to parkinsonism, indicating that cerebral atherosclerosis mediated 17% of the association between statins and parkinsonism.

In line with other studies, there was no association between statins and other neurodegenerative pathologies, including Parkinson’s disease pathology. However, even older adults with a clinical diagnosis of Parkinson’s disease often show mixed brain pathologies, including cerebrovascular disease pathologies.

“Therefore, we think that statins may be beneficial against parkinsonism in patients with Parkinson’s disease, dependent on how much cerebrovascular disease pathologies they have, including atherosclerosis,” said study investigator Shahram Oveisgharan, MD, with Rush Alzheimer’s Disease Center, Rush University Medical Center, Chicago.

However, since the results stem from an observational study, “we do not yet recommend using statins in large scale for older adults at risk for parkinsonism,” Dr. Oveisgharan said.
 

A mixed picture

Reached for comment, Shaheen Lakhan, MD, neurologist in Newton, Massachusetts, noted that since statins were first discovered in the fermented broth of a common soil fungus in the late 1970s, they have proven to reduce cholesterol, heart disease, and stroke.

“The jury is out, however, on [their] effects on diseases such as dementia, autoimmune/inflammatory conditions, bacterial/viral infections, cancer, and parkinsonism,” he said.

“Also, the question often remains whether any benefit gained from statins is from cholesterol-lowering or through another mechanism. When there is such a mixed picture, it generally means that the drug has an effect, but not for everyone,” Dr. Lakhan said. “Much work must now be done to stratify for which patients are statins effective, ineffective, or even harmful in these conditions,” he added.

The study was supported by the National Institutes of Health. Dr. Oveisgharan and Dr. Lakhan have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Statins may protect against age-related parkinsonism, new research suggests. An observational study showed older adults taking statins had a lower risk for parkinsonism than their counterparts not taking statins – an effect that may be partially mediated by less severe intracranial atherosclerosis in statin users.

“These findings further support the idea that cerebrovascular disease pathologies accumulating in older brains may be an unrecognized contributor to the common occurrence of parkinsonism in old age,” the investigators wrote. “More importantly, these findings suggest that statins may have a potential therapeutic role in decreasing the magnitude of parkinsonism in older adults,” they added.

The study was published online in Neurology.
 

No clinical recommendations ... yet

The findings are based on 2,841 older adults enrolled in one of three ongoing clinical pathological studies at Rush Alzheimer’s Disease Center, Chicago.

Participants’ average age at baseline was 76 years, and 75% were women. None had parkinsonism at the start of the study. One-third of participants (n = 936) were taking statins. During an average follow-up of 6 years, 1,432 (50%) participants developed parkinsonism.

After controlling for demographics, vascular risk factors, and diseases, use of a statin at baseline was associated with a 16% lower risk for parkinsonism (hazard ratio, 0.84; 95% confidence interval, 0.74-0.96; P = .008). Compared with low-intensity statin therapy, moderate- or high-intensity statin therapy was associated with a 7% lower risk for parkinsonism (HR, 0.93; 95% CI, 0.87-1.00; P = .043).

The researchers also examined the brains of 1,044 people who died during the study at a mean age of 89 years. They found statin use prior to death was associated with a 37% lower odds of cerebral atherosclerosis, compared with no statin use prior to death (odds ratio, 0.63; 95% CI, 0.50-0.79; P < .001).

In a mediation analysis, both a direct (OR, 0.73; 95% CI, 0.54-0.93; P = .008) and an indirect (OR, 0.92; 95% CI, 0.88-0.97; P = .002) pathway via less severe cerebrovascular disease linked statins to parkinsonism, indicating that cerebral atherosclerosis mediated 17% of the association between statins and parkinsonism.

In line with other studies, there was no association between statins and other neurodegenerative pathologies, including Parkinson’s disease pathology. However, even older adults with a clinical diagnosis of Parkinson’s disease often show mixed brain pathologies, including cerebrovascular disease pathologies.

“Therefore, we think that statins may be beneficial against parkinsonism in patients with Parkinson’s disease, dependent on how much cerebrovascular disease pathologies they have, including atherosclerosis,” said study investigator Shahram Oveisgharan, MD, with Rush Alzheimer’s Disease Center, Rush University Medical Center, Chicago.

However, since the results stem from an observational study, “we do not yet recommend using statins in large scale for older adults at risk for parkinsonism,” Dr. Oveisgharan said.
 

A mixed picture

Reached for comment, Shaheen Lakhan, MD, neurologist in Newton, Massachusetts, noted that since statins were first discovered in the fermented broth of a common soil fungus in the late 1970s, they have proven to reduce cholesterol, heart disease, and stroke.

“The jury is out, however, on [their] effects on diseases such as dementia, autoimmune/inflammatory conditions, bacterial/viral infections, cancer, and parkinsonism,” he said.

“Also, the question often remains whether any benefit gained from statins is from cholesterol-lowering or through another mechanism. When there is such a mixed picture, it generally means that the drug has an effect, but not for everyone,” Dr. Lakhan said. “Much work must now be done to stratify for which patients are statins effective, ineffective, or even harmful in these conditions,” he added.

The study was supported by the National Institutes of Health. Dr. Oveisgharan and Dr. Lakhan have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Statins may protect against age-related parkinsonism, new research suggests. An observational study showed older adults taking statins had a lower risk for parkinsonism than their counterparts not taking statins – an effect that may be partially mediated by less severe intracranial atherosclerosis in statin users.

“These findings further support the idea that cerebrovascular disease pathologies accumulating in older brains may be an unrecognized contributor to the common occurrence of parkinsonism in old age,” the investigators wrote. “More importantly, these findings suggest that statins may have a potential therapeutic role in decreasing the magnitude of parkinsonism in older adults,” they added.

The study was published online in Neurology.
 

No clinical recommendations ... yet

The findings are based on 2,841 older adults enrolled in one of three ongoing clinical pathological studies at Rush Alzheimer’s Disease Center, Chicago.

Participants’ average age at baseline was 76 years, and 75% were women. None had parkinsonism at the start of the study. One-third of participants (n = 936) were taking statins. During an average follow-up of 6 years, 1,432 (50%) participants developed parkinsonism.

After controlling for demographics, vascular risk factors, and diseases, use of a statin at baseline was associated with a 16% lower risk for parkinsonism (hazard ratio, 0.84; 95% confidence interval, 0.74-0.96; P = .008). Compared with low-intensity statin therapy, moderate- or high-intensity statin therapy was associated with a 7% lower risk for parkinsonism (HR, 0.93; 95% CI, 0.87-1.00; P = .043).

The researchers also examined the brains of 1,044 people who died during the study at a mean age of 89 years. They found statin use prior to death was associated with a 37% lower odds of cerebral atherosclerosis, compared with no statin use prior to death (odds ratio, 0.63; 95% CI, 0.50-0.79; P < .001).

In a mediation analysis, both a direct (OR, 0.73; 95% CI, 0.54-0.93; P = .008) and an indirect (OR, 0.92; 95% CI, 0.88-0.97; P = .002) pathway via less severe cerebrovascular disease linked statins to parkinsonism, indicating that cerebral atherosclerosis mediated 17% of the association between statins and parkinsonism.

In line with other studies, there was no association between statins and other neurodegenerative pathologies, including Parkinson’s disease pathology. However, even older adults with a clinical diagnosis of Parkinson’s disease often show mixed brain pathologies, including cerebrovascular disease pathologies.

“Therefore, we think that statins may be beneficial against parkinsonism in patients with Parkinson’s disease, dependent on how much cerebrovascular disease pathologies they have, including atherosclerosis,” said study investigator Shahram Oveisgharan, MD, with Rush Alzheimer’s Disease Center, Rush University Medical Center, Chicago.

However, since the results stem from an observational study, “we do not yet recommend using statins in large scale for older adults at risk for parkinsonism,” Dr. Oveisgharan said.
 

A mixed picture

Reached for comment, Shaheen Lakhan, MD, neurologist in Newton, Massachusetts, noted that since statins were first discovered in the fermented broth of a common soil fungus in the late 1970s, they have proven to reduce cholesterol, heart disease, and stroke.

“The jury is out, however, on [their] effects on diseases such as dementia, autoimmune/inflammatory conditions, bacterial/viral infections, cancer, and parkinsonism,” he said.

“Also, the question often remains whether any benefit gained from statins is from cholesterol-lowering or through another mechanism. When there is such a mixed picture, it generally means that the drug has an effect, but not for everyone,” Dr. Lakhan said. “Much work must now be done to stratify for which patients are statins effective, ineffective, or even harmful in these conditions,” he added.

The study was supported by the National Institutes of Health. Dr. Oveisgharan and Dr. Lakhan have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

An experimental brain-computer interface has allowed a man with amyotrophic lateral sclerosis (ALS) who was unable to speak or move to communicate.

Using a commercially available implant and newly designed software, the patient, who was in the advanced stages of Lou Gehrig’s disease and unable to move his eyes, was able to interact with researchers and caregivers, requesting goulash, beer, and music from the band Tool, thanking the researchers who developed the technology and inviting his 4-year-old son to watch a Disney film.

The investigators note the study shows for the first time that communication is possible in patients in a completely locked-in state (CLIS) and offers hope for a better quality of life in this population.

“It should encourage them to live after artificial respiration and to ask for brain-computer interfaces before they become CLIS,” study investigator Niels Birbaumer, PhD, a professor emeritus of the University of Tübingen, Germany, said in an interview. The study was published online March 22 in Nature Communications.

Although the findings appear promising, they build on previous research that was the subject of a 2019 investigation by the largest grant-funding agency in Germany. This controversy prompted the institute that led the current research to appoint an independent expert to audit and monitor the new study.
 

Mechanism a ‘mystery’

Use of brain-computer interface (BCI) technology to allow ALS patients to communicate has increased in recent years. BCIs capture brain signals, transmit them to a computer, and convert them into a command that the computer carries out.

Previous research shows patients with ALS who retain eye movement and control have been able to use BCIs to communicate. However, until now, the technology has not worked as well in CLIS patients, who have full-body paralysis.

In 2019, German and Swiss researchers implanted two 64-microde arrays in the brain of a 34-year-old patient who was diagnosed with ALS in 2015.

The electrodes measure neuronal activity while an amplifier located on the outside of the patient’s skull amplifies the signals to a computer. Software created by the research team decodes the signals and translates them into commands.

Using an auditory feedback system, the patient was able to use his mind to modulate the pitch of a tone to either high (meaning “yes”) or low (meaning “no.”) Just how the brain does this is a mystery, Dr. Birbaumer said.

A speller program reads letters aloud, first in groups and then individually. When a group contained letters the patient needed to spell a word, he used auditory feedback to select the high-pitch tone.

Initially, the patient was able to correctly spell his name. Ultimately, he was able to form complete sentences. The patient correctly spelled words on 44 of the 107 days in that phase of the experiment, spelling an average of just one character per minute.

Still, the researchers note he was able to interact with his caretakers, family, and researchers, even offering input on changes to make the device more effective.
 

Controversial history

In 2017, Dr. Birbaumer and Ujwal Chaudhary, PhD, who is the lead author on this current study, published a study in PLOS Biology. That research analyzed a brain-monitoring technique that the scientists claimed enabled patients with ALS who were completely locked in to answer yes or no questions correctly.

Allegations from a whistleblower at the University of Tübingen, where Dr. Birbaumer was a senior professor and Dr. Chaudhary was a postdoctoral researcher, prompted an investigation by the Deutsche Forschungsgemeinschaft, or German Research Foundation (DFG).

The whistleblower claimed that the 2017 paper and a second study published in 2019 contained incomplete data and misrepresented the findings. The DFG investigation found evidence of scientific misconduct and required that Dr. Birbaumer return the grant he had received for the research. The agency also banned Dr. Birbaumer from applying for grants or serving as a grant reviewer for 5 years. Dr. Chaudhary was banned for 3 years. PLOS Biology later retracted the papers.

Both researchers have refuted the allegations and have reportedly sued the German Research Foundation.

“We have no information about the status of our lawsuit against the DFG; it’s still pending,” Dr. Birbaumer told this news organization. “I hope they investigate our present study because the study of 2017 they did not investigate carefully enough.”
 

Results ‘not stunningly good’

The controversial history prompted the Wyss Center, Geneva, which led this new study, to seek out at an independent BCI expert to audit and monitor the study.

Nick Ramsey, PhD, a professor of cognitive neuroscience at the Brain Center of the University Medical Center Utrecht, the Netherlands, agreed to take on the assignment in March 2020.

Dr. Ramsey has also conducted research on BCI in patients with ALS, but his work has not included patients in CLIS.

“I judged the study to be compliant with universal standards of scientific integrity,” Dr. Ramsey told this news organization. “I am confident that the data and results presented in the paper are valid and will withstand academic and medical scrutiny.”

Commenting on the new findings, Dr. Ramsey noted that the results of the study are “not stunningly good, as the user could only communicate during a limited number of days, and even then with considerable slowness,” Dr. Ramsey said. However, he added that the study does provide proof of principle that communication is possible in CLIS patients.

“The question remains whether a BCI implant continues to work well in these patients, as there are some indications that people in such a state may lose their mental capabilities within months or a few years as a result of the disease and can thus no longer generate a wish to communicate,” Dr. Ramsey said.

Responding to a query from this news organization, a spokesperson for Nature Communications declined to comment on the new study but said that journal editors are “are alert to controversies within each field and take care when considering submissions during the peer-review process.”

“We have rigorous policies to safeguard the integrity of the research we publish,” the spokesperson continued, “including to ensure that research has been conducted to a high ethical standard and is reported transparently.”

The research was funded by Wyss Center for Bio and Neuroengineering, Geneva and Deutsche Forschungsgemeinschaft. The authors have disclosed no relevant financial relationships. Dr. Ramsey received payment from the Wyss Center for his advisory role in this project.

A version of this article first appeared on Medscape.com.

An experimental brain-computer interface has allowed a man with amyotrophic lateral sclerosis (ALS) who was unable to speak or move to communicate.

Using a commercially available implant and newly designed software, the patient, who was in the advanced stages of Lou Gehrig’s disease and unable to move his eyes, was able to interact with researchers and caregivers, requesting goulash, beer, and music from the band Tool, thanking the researchers who developed the technology and inviting his 4-year-old son to watch a Disney film.

The investigators note the study shows for the first time that communication is possible in patients in a completely locked-in state (CLIS) and offers hope for a better quality of life in this population.

“It should encourage them to live after artificial respiration and to ask for brain-computer interfaces before they become CLIS,” study investigator Niels Birbaumer, PhD, a professor emeritus of the University of Tübingen, Germany, said in an interview. The study was published online March 22 in Nature Communications.

Although the findings appear promising, they build on previous research that was the subject of a 2019 investigation by the largest grant-funding agency in Germany. This controversy prompted the institute that led the current research to appoint an independent expert to audit and monitor the new study.
 

Mechanism a ‘mystery’

Use of brain-computer interface (BCI) technology to allow ALS patients to communicate has increased in recent years. BCIs capture brain signals, transmit them to a computer, and convert them into a command that the computer carries out.

Previous research shows patients with ALS who retain eye movement and control have been able to use BCIs to communicate. However, until now, the technology has not worked as well in CLIS patients, who have full-body paralysis.

In 2019, German and Swiss researchers implanted two 64-microde arrays in the brain of a 34-year-old patient who was diagnosed with ALS in 2015.

The electrodes measure neuronal activity while an amplifier located on the outside of the patient’s skull amplifies the signals to a computer. Software created by the research team decodes the signals and translates them into commands.

Using an auditory feedback system, the patient was able to use his mind to modulate the pitch of a tone to either high (meaning “yes”) or low (meaning “no.”) Just how the brain does this is a mystery, Dr. Birbaumer said.

A speller program reads letters aloud, first in groups and then individually. When a group contained letters the patient needed to spell a word, he used auditory feedback to select the high-pitch tone.

Initially, the patient was able to correctly spell his name. Ultimately, he was able to form complete sentences. The patient correctly spelled words on 44 of the 107 days in that phase of the experiment, spelling an average of just one character per minute.

Still, the researchers note he was able to interact with his caretakers, family, and researchers, even offering input on changes to make the device more effective.
 

Controversial history

In 2017, Dr. Birbaumer and Ujwal Chaudhary, PhD, who is the lead author on this current study, published a study in PLOS Biology. That research analyzed a brain-monitoring technique that the scientists claimed enabled patients with ALS who were completely locked in to answer yes or no questions correctly.

Allegations from a whistleblower at the University of Tübingen, where Dr. Birbaumer was a senior professor and Dr. Chaudhary was a postdoctoral researcher, prompted an investigation by the Deutsche Forschungsgemeinschaft, or German Research Foundation (DFG).

The whistleblower claimed that the 2017 paper and a second study published in 2019 contained incomplete data and misrepresented the findings. The DFG investigation found evidence of scientific misconduct and required that Dr. Birbaumer return the grant he had received for the research. The agency also banned Dr. Birbaumer from applying for grants or serving as a grant reviewer for 5 years. Dr. Chaudhary was banned for 3 years. PLOS Biology later retracted the papers.

Both researchers have refuted the allegations and have reportedly sued the German Research Foundation.

“We have no information about the status of our lawsuit against the DFG; it’s still pending,” Dr. Birbaumer told this news organization. “I hope they investigate our present study because the study of 2017 they did not investigate carefully enough.”
 

Results ‘not stunningly good’

The controversial history prompted the Wyss Center, Geneva, which led this new study, to seek out at an independent BCI expert to audit and monitor the study.

Nick Ramsey, PhD, a professor of cognitive neuroscience at the Brain Center of the University Medical Center Utrecht, the Netherlands, agreed to take on the assignment in March 2020.

Dr. Ramsey has also conducted research on BCI in patients with ALS, but his work has not included patients in CLIS.

“I judged the study to be compliant with universal standards of scientific integrity,” Dr. Ramsey told this news organization. “I am confident that the data and results presented in the paper are valid and will withstand academic and medical scrutiny.”

Commenting on the new findings, Dr. Ramsey noted that the results of the study are “not stunningly good, as the user could only communicate during a limited number of days, and even then with considerable slowness,” Dr. Ramsey said. However, he added that the study does provide proof of principle that communication is possible in CLIS patients.

“The question remains whether a BCI implant continues to work well in these patients, as there are some indications that people in such a state may lose their mental capabilities within months or a few years as a result of the disease and can thus no longer generate a wish to communicate,” Dr. Ramsey said.

Responding to a query from this news organization, a spokesperson for Nature Communications declined to comment on the new study but said that journal editors are “are alert to controversies within each field and take care when considering submissions during the peer-review process.”

“We have rigorous policies to safeguard the integrity of the research we publish,” the spokesperson continued, “including to ensure that research has been conducted to a high ethical standard and is reported transparently.”

The research was funded by Wyss Center for Bio and Neuroengineering, Geneva and Deutsche Forschungsgemeinschaft. The authors have disclosed no relevant financial relationships. Dr. Ramsey received payment from the Wyss Center for his advisory role in this project.

A version of this article first appeared on Medscape.com.

An experimental brain-computer interface has allowed a man with amyotrophic lateral sclerosis (ALS) who was unable to speak or move to communicate.

Using a commercially available implant and newly designed software, the patient, who was in the advanced stages of Lou Gehrig’s disease and unable to move his eyes, was able to interact with researchers and caregivers, requesting goulash, beer, and music from the band Tool, thanking the researchers who developed the technology and inviting his 4-year-old son to watch a Disney film.

The investigators note the study shows for the first time that communication is possible in patients in a completely locked-in state (CLIS) and offers hope for a better quality of life in this population.

“It should encourage them to live after artificial respiration and to ask for brain-computer interfaces before they become CLIS,” study investigator Niels Birbaumer, PhD, a professor emeritus of the University of Tübingen, Germany, said in an interview. The study was published online March 22 in Nature Communications.

Although the findings appear promising, they build on previous research that was the subject of a 2019 investigation by the largest grant-funding agency in Germany. This controversy prompted the institute that led the current research to appoint an independent expert to audit and monitor the new study.
 

Mechanism a ‘mystery’

Use of brain-computer interface (BCI) technology to allow ALS patients to communicate has increased in recent years. BCIs capture brain signals, transmit them to a computer, and convert them into a command that the computer carries out.

Previous research shows patients with ALS who retain eye movement and control have been able to use BCIs to communicate. However, until now, the technology has not worked as well in CLIS patients, who have full-body paralysis.

In 2019, German and Swiss researchers implanted two 64-microde arrays in the brain of a 34-year-old patient who was diagnosed with ALS in 2015.

The electrodes measure neuronal activity while an amplifier located on the outside of the patient’s skull amplifies the signals to a computer. Software created by the research team decodes the signals and translates them into commands.

Using an auditory feedback system, the patient was able to use his mind to modulate the pitch of a tone to either high (meaning “yes”) or low (meaning “no.”) Just how the brain does this is a mystery, Dr. Birbaumer said.

A speller program reads letters aloud, first in groups and then individually. When a group contained letters the patient needed to spell a word, he used auditory feedback to select the high-pitch tone.

Initially, the patient was able to correctly spell his name. Ultimately, he was able to form complete sentences. The patient correctly spelled words on 44 of the 107 days in that phase of the experiment, spelling an average of just one character per minute.

Still, the researchers note he was able to interact with his caretakers, family, and researchers, even offering input on changes to make the device more effective.
 

Controversial history

In 2017, Dr. Birbaumer and Ujwal Chaudhary, PhD, who is the lead author on this current study, published a study in PLOS Biology. That research analyzed a brain-monitoring technique that the scientists claimed enabled patients with ALS who were completely locked in to answer yes or no questions correctly.

Allegations from a whistleblower at the University of Tübingen, where Dr. Birbaumer was a senior professor and Dr. Chaudhary was a postdoctoral researcher, prompted an investigation by the Deutsche Forschungsgemeinschaft, or German Research Foundation (DFG).

The whistleblower claimed that the 2017 paper and a second study published in 2019 contained incomplete data and misrepresented the findings. The DFG investigation found evidence of scientific misconduct and required that Dr. Birbaumer return the grant he had received for the research. The agency also banned Dr. Birbaumer from applying for grants or serving as a grant reviewer for 5 years. Dr. Chaudhary was banned for 3 years. PLOS Biology later retracted the papers.

Both researchers have refuted the allegations and have reportedly sued the German Research Foundation.

“We have no information about the status of our lawsuit against the DFG; it’s still pending,” Dr. Birbaumer told this news organization. “I hope they investigate our present study because the study of 2017 they did not investigate carefully enough.”
 

Results ‘not stunningly good’

The controversial history prompted the Wyss Center, Geneva, which led this new study, to seek out at an independent BCI expert to audit and monitor the study.

Nick Ramsey, PhD, a professor of cognitive neuroscience at the Brain Center of the University Medical Center Utrecht, the Netherlands, agreed to take on the assignment in March 2020.

Dr. Ramsey has also conducted research on BCI in patients with ALS, but his work has not included patients in CLIS.

“I judged the study to be compliant with universal standards of scientific integrity,” Dr. Ramsey told this news organization. “I am confident that the data and results presented in the paper are valid and will withstand academic and medical scrutiny.”

Commenting on the new findings, Dr. Ramsey noted that the results of the study are “not stunningly good, as the user could only communicate during a limited number of days, and even then with considerable slowness,” Dr. Ramsey said. However, he added that the study does provide proof of principle that communication is possible in CLIS patients.

“The question remains whether a BCI implant continues to work well in these patients, as there are some indications that people in such a state may lose their mental capabilities within months or a few years as a result of the disease and can thus no longer generate a wish to communicate,” Dr. Ramsey said.

Responding to a query from this news organization, a spokesperson for Nature Communications declined to comment on the new study but said that journal editors are “are alert to controversies within each field and take care when considering submissions during the peer-review process.”

“We have rigorous policies to safeguard the integrity of the research we publish,” the spokesperson continued, “including to ensure that research has been conducted to a high ethical standard and is reported transparently.”

The research was funded by Wyss Center for Bio and Neuroengineering, Geneva and Deutsche Forschungsgemeinschaft. The authors have disclosed no relevant financial relationships. Dr. Ramsey received payment from the Wyss Center for his advisory role in this project.

A version of this article first appeared on Medscape.com.

Differing state regulations and a paucity of research has made it difficult to develop consensus guidelines for the use of cannabinoids in treating drug-resistant epilepsy. A recent review article draws from existing clinical trials and clinical experience in New South Wales, Australia, to fill this gap with interim guidance for both pediatric and adult patients. The article was published in the British Journal of Clinical Pharmacology.

The only current U.S. guidelines are from the American Academy of Neurology’s position statement on the use of medical cannabis for neurologic disorders and the American Epilepsy Society’s position statement on cannabis as a treatment for epileptic seizures. The AAN statement “highlights the current evidence, which currently only supports [Food and Drug Administration]–approved CBD [cannabidiol] (Epidiolex) for specific epilepsy syndromes,” said Daniel Freedman, DO, an assistant professor of neurology at the University of Texas at Austin and coauthor of the AAN’s position statement.

“Rescheduling marijuana will enable researchers to study CBD, THC [tetrahydrocannabinol], and other cannabinoids in high-quality studies so that we can better understand what works and for which conditions,” said Dr. Freedman, who was not involved in the Australian guidance document. He noted that little consensus exists because little evidence exists outside the handful of trials for Epidiolex.

“There are some patients with epilepsy that can benefit from high-quality, pharmaceutical-grade CBD products,” Dr. Freedman said. “These patients need to be carefully identified by a neurologist or epileptologist and prescribed a legal, safe, quality-controlled, and FDA-regulated product.”
 

Appropriate patient populations

Drug-resistant epilepsy, defined as failure of two appropriate antiseizure medications, affects an estimated one third of people with epilepsy, the new guideline notes. Though many over-the-counter products are available at dispensaries in the 33 U.S. states that allow use of cannabis for medical purposes, Epidiolex (cannabidiol) is the only FDA-approved drug for epilepsy that contains a substance derived from cannabis and the only one for which evidence from randomized, controlled trials exists.

Dr. Freedman notes that hemp-derived CBD oils are classified differently in the United States than marijuana-derived CBD oil, including Epidiolex, and are loosely regulated supplements or food additives commonly seen, for example at gas station.

“The point I drive home to patients is that you wouldn’t get your antibiotics from a gas station, so please don’t get your seizure medication from there,” Dr. Freedman said. “Studies have been done on ‘over-the-counter’ CBD oils and shown that they have variable quality, sometimes no detectable CBD, and sometimes other chemicals added like THC.”

Studies of Epidiolex showed that cannabidiol more effectively reduced seizure frequency than placebo for pediatric patients with Dravet syndrome (42% reduction) and for pediatric and adult patients with Lennox-Gastaut syndrome (39% reduction) or tuberous sclerosis complex (49% reduction). Efficacy was similar across dosing from 10-50 mg/kg per day, but higher doses involved higher rates of serious adverse events.

No reliable evidence in humans exists for THC or other cannabinoids in treating epilepsy.

The Australian guidance recommends limiting cannabis treatment to patients with severe drug-resistant epilepsy; a diagnosis of Dravet syndrome, Lennox-Gastaut syndrome, or tuberous sclerosis complex; and previous treatment with four approved antiseizure medications and/or the ketogenic diet, epilepsy surgery, or neurostimulator. The authors provide specific criteria for each of these conditions and then address exceptional cases that may be considered outside that criteria, such as patients under 2 years old, severe epilepsy with extended or repeated hospitalization or ICU admission, or a dangerous seizure type. The review also includes a detailed list of exclusion criteria for CBD medicine use.

The authors advised a thorough consent process before prescribing any cannabinoids, including therapeutic goals and stopping criteria; the lack of evidence available on dosing, efficacy, and side effects; and the potential for dependence or withdrawal. Consent discussions should also note whether the products are unregistered and not covered by external payers (anything other than Epidiolex currently), any activity restrictions, and any implications for occupational drug screening.
 

Considerations for unapproved cannabinoids

The authors note several factors to consider if prescribing or recommending a nonapproved, nonregulated cannabis medicine, including the ”differences between registered plant-derived cannabis medicines, synthetic cannabis medicines, and unregistered hemp-derived products.” Epidiolex is plant derived while other cannabis-derived medications (Marinol, Syndos, and Cesamet) that have been approved for nonepilepsy conditions, such as nausea associated with chemotherapy, are synthetic.

The guidance document notes several reasons to use a regulated medication instead of an unregulated product:

• Manufacturing processes can differ for unregulated products, including inconsistency in batches and unknown shelf life.
• Quality control processes, including risk of impurities, are much better with regulated products, which also have a system in place for safety recalls.
• More scientific evidence is available for regulated products.
• Safety surveillance reporting is more robust and standardized for regulated products whereas adverse event reporting is less reliable for unregulated products.
• Nonregulated products are rarely covered by insurance or other reimbursement.

Legal considerations will also vary by jurisdiction. ”Right now in the U.S. we have a confused legality where state level programs are still technically illegal at the federal level and I imagine there are some quality differences amongst dispensaries and states,” Dr. Freedman said. “Whenever there is disagreement between state and federal laws, this creates tension for our patients.” He noted, for example, that a patient using a CBD product that contains THC may, even if legal in their state, be confiscated by the Transportation Security Administration at an airport since it is not FDA approved and is not legal, according to the Drug Enforcement Agency.

The authors noted that inadequate data on long-term CBD use and data on neurodevelopmental effects of THC in children, teens, and young adults means THC products should be contraindicated for these age groups. (Epidiolex has less than 2% THC.) Drug interactions should also be considered, particularly for clobazam, CYP3A4 inhibitors or inducers (including St. John’s wort), digoxin, or a mechanistic target of rapamycin inhibitor.

Dr. Freedman said that most neurologists are comfortable prescribing Epidiolex since it has FDA approval while prescribing unapproved products varies more in the field. “Now that many states have compassionate use programs for medical marijuana, some neurologists do this as well,” Dr. Freedman said. Patients often ask about unregulated CBD or CBD+THC products because they’re seen as “natural and therefore better than manufactured pharmaceuticals.”

“I think this is the naturalistic fallacy at work and try to educate my patients on that since our only high-level data to show marijuana products work for epilepsy comes from a pharmaceutical company,” Dr. Freedman said. “My reasons for hesitating on compassionate use are that there is often THC, with variable amounts of concentration, and we know that THC can harm the developing pediatric brain.”
 

Dosing and adverse effects

Pediatric and adult dosing differences need to be considered, and “patient response (efficacy and toxicity) to these medications varies widely,” the authors noted. They advised getting serum transaminases (ALT and AST) and total bilirubin levels before beginning treatment. All patients should begin Epidiolex at a low dose, such as 2-5 mg/kg per day of CBD in two divided doses, the authors advise, and titrate slowly while monitoring for side effects (no more than 5 mg/kg per day per week). The current dosing range for CBD is 5-20 mg/kg per day in two divided doses, with higher rates involving more risk of adverse events.

“Note that some cannabinoids auto-inhibit their own metabolism and some have active metabolites with longer half-lives,” the authors wrote. “Therefore, dose or frequency may need to be reduced over time, unless tolerance occurs.” These doses, specific to Epidiolex, “cannot necessarily be applied to other oral CBD formulations or other types of epilepsy.” This guidance also does not apply to inhaled or transdermal routes of administration.

The most common adverse events were sleepiness – which occurred in up to 60% of trial participants – as well as diarrhea, decreases in appetite and weight, and drug interactions. Risk of hepatotoxicity means there’s a need to monitor liver function and adjust dosing for patients with moderate or severe hepatic impairment. “Other short-term side effects reported only with THC-containing cannabinoid compounds include increased risk of cardiac and cerebrovascular events, anxiety and psychosis risk, dependency, and withdrawal,” the authors wrote.

Though no withdrawal syndrome has been linked to stopping CBD, the authors suggested decreasing the dose by 10% every 2 days if stopping is not urgent.

“The key points to this issue are that CBD and all marijuana products need to be safe and regulated,” Dr. Freedman said. “Any claims about them need to be backed by high-quality evidence looking at that specific product for that specific condition.”

Dr. Freedman noted the need for children to receive treatment from clinicians with expertise in their specific condition since many other evidence-based treatments exist even for patients with epilepsy syndromes that are difficult to treat, such as other medications, surgery, and specialized diets.

“We need to fix the inconsistent regulation between over-the-counter CBD products, state dispensaries, and federal laws,” Dr. Freedman added. “Any medicine being used to treat children should be held to the same FDA standard of safety and efficacy.”

Dr. Freedman and the authors had no conflicts of interest. No external funding was noted.

Differing state regulations and a paucity of research has made it difficult to develop consensus guidelines for the use of cannabinoids in treating drug-resistant epilepsy. A recent review article draws from existing clinical trials and clinical experience in New South Wales, Australia, to fill this gap with interim guidance for both pediatric and adult patients. The article was published in the British Journal of Clinical Pharmacology.

The only current U.S. guidelines are from the American Academy of Neurology’s position statement on the use of medical cannabis for neurologic disorders and the American Epilepsy Society’s position statement on cannabis as a treatment for epileptic seizures. The AAN statement “highlights the current evidence, which currently only supports [Food and Drug Administration]–approved CBD [cannabidiol] (Epidiolex) for specific epilepsy syndromes,” said Daniel Freedman, DO, an assistant professor of neurology at the University of Texas at Austin and coauthor of the AAN’s position statement.

“Rescheduling marijuana will enable researchers to study CBD, THC [tetrahydrocannabinol], and other cannabinoids in high-quality studies so that we can better understand what works and for which conditions,” said Dr. Freedman, who was not involved in the Australian guidance document. He noted that little consensus exists because little evidence exists outside the handful of trials for Epidiolex.

“There are some patients with epilepsy that can benefit from high-quality, pharmaceutical-grade CBD products,” Dr. Freedman said. “These patients need to be carefully identified by a neurologist or epileptologist and prescribed a legal, safe, quality-controlled, and FDA-regulated product.”
 

Appropriate patient populations

Drug-resistant epilepsy, defined as failure of two appropriate antiseizure medications, affects an estimated one third of people with epilepsy, the new guideline notes. Though many over-the-counter products are available at dispensaries in the 33 U.S. states that allow use of cannabis for medical purposes, Epidiolex (cannabidiol) is the only FDA-approved drug for epilepsy that contains a substance derived from cannabis and the only one for which evidence from randomized, controlled trials exists.

Dr. Freedman notes that hemp-derived CBD oils are classified differently in the United States than marijuana-derived CBD oil, including Epidiolex, and are loosely regulated supplements or food additives commonly seen, for example at gas station.

“The point I drive home to patients is that you wouldn’t get your antibiotics from a gas station, so please don’t get your seizure medication from there,” Dr. Freedman said. “Studies have been done on ‘over-the-counter’ CBD oils and shown that they have variable quality, sometimes no detectable CBD, and sometimes other chemicals added like THC.”

Studies of Epidiolex showed that cannabidiol more effectively reduced seizure frequency than placebo for pediatric patients with Dravet syndrome (42% reduction) and for pediatric and adult patients with Lennox-Gastaut syndrome (39% reduction) or tuberous sclerosis complex (49% reduction). Efficacy was similar across dosing from 10-50 mg/kg per day, but higher doses involved higher rates of serious adverse events.

No reliable evidence in humans exists for THC or other cannabinoids in treating epilepsy.

The Australian guidance recommends limiting cannabis treatment to patients with severe drug-resistant epilepsy; a diagnosis of Dravet syndrome, Lennox-Gastaut syndrome, or tuberous sclerosis complex; and previous treatment with four approved antiseizure medications and/or the ketogenic diet, epilepsy surgery, or neurostimulator. The authors provide specific criteria for each of these conditions and then address exceptional cases that may be considered outside that criteria, such as patients under 2 years old, severe epilepsy with extended or repeated hospitalization or ICU admission, or a dangerous seizure type. The review also includes a detailed list of exclusion criteria for CBD medicine use.

The authors advised a thorough consent process before prescribing any cannabinoids, including therapeutic goals and stopping criteria; the lack of evidence available on dosing, efficacy, and side effects; and the potential for dependence or withdrawal. Consent discussions should also note whether the products are unregistered and not covered by external payers (anything other than Epidiolex currently), any activity restrictions, and any implications for occupational drug screening.
 

Considerations for unapproved cannabinoids

The authors note several factors to consider if prescribing or recommending a nonapproved, nonregulated cannabis medicine, including the ”differences between registered plant-derived cannabis medicines, synthetic cannabis medicines, and unregistered hemp-derived products.” Epidiolex is plant derived while other cannabis-derived medications (Marinol, Syndos, and Cesamet) that have been approved for nonepilepsy conditions, such as nausea associated with chemotherapy, are synthetic.

The guidance document notes several reasons to use a regulated medication instead of an unregulated product:

• Manufacturing processes can differ for unregulated products, including inconsistency in batches and unknown shelf life.
• Quality control processes, including risk of impurities, are much better with regulated products, which also have a system in place for safety recalls.
• More scientific evidence is available for regulated products.
• Safety surveillance reporting is more robust and standardized for regulated products whereas adverse event reporting is less reliable for unregulated products.
• Nonregulated products are rarely covered by insurance or other reimbursement.

Legal considerations will also vary by jurisdiction. ”Right now in the U.S. we have a confused legality where state level programs are still technically illegal at the federal level and I imagine there are some quality differences amongst dispensaries and states,” Dr. Freedman said. “Whenever there is disagreement between state and federal laws, this creates tension for our patients.” He noted, for example, that a patient using a CBD product that contains THC may, even if legal in their state, be confiscated by the Transportation Security Administration at an airport since it is not FDA approved and is not legal, according to the Drug Enforcement Agency.

The authors noted that inadequate data on long-term CBD use and data on neurodevelopmental effects of THC in children, teens, and young adults means THC products should be contraindicated for these age groups. (Epidiolex has less than 2% THC.) Drug interactions should also be considered, particularly for clobazam, CYP3A4 inhibitors or inducers (including St. John’s wort), digoxin, or a mechanistic target of rapamycin inhibitor.

Dr. Freedman said that most neurologists are comfortable prescribing Epidiolex since it has FDA approval while prescribing unapproved products varies more in the field. “Now that many states have compassionate use programs for medical marijuana, some neurologists do this as well,” Dr. Freedman said. Patients often ask about unregulated CBD or CBD+THC products because they’re seen as “natural and therefore better than manufactured pharmaceuticals.”

“I think this is the naturalistic fallacy at work and try to educate my patients on that since our only high-level data to show marijuana products work for epilepsy comes from a pharmaceutical company,” Dr. Freedman said. “My reasons for hesitating on compassionate use are that there is often THC, with variable amounts of concentration, and we know that THC can harm the developing pediatric brain.”
 

Dosing and adverse effects

Pediatric and adult dosing differences need to be considered, and “patient response (efficacy and toxicity) to these medications varies widely,” the authors noted. They advised getting serum transaminases (ALT and AST) and total bilirubin levels before beginning treatment. All patients should begin Epidiolex at a low dose, such as 2-5 mg/kg per day of CBD in two divided doses, the authors advise, and titrate slowly while monitoring for side effects (no more than 5 mg/kg per day per week). The current dosing range for CBD is 5-20 mg/kg per day in two divided doses, with higher rates involving more risk of adverse events.

“Note that some cannabinoids auto-inhibit their own metabolism and some have active metabolites with longer half-lives,” the authors wrote. “Therefore, dose or frequency may need to be reduced over time, unless tolerance occurs.” These doses, specific to Epidiolex, “cannot necessarily be applied to other oral CBD formulations or other types of epilepsy.” This guidance also does not apply to inhaled or transdermal routes of administration.

The most common adverse events were sleepiness – which occurred in up to 60% of trial participants – as well as diarrhea, decreases in appetite and weight, and drug interactions. Risk of hepatotoxicity means there’s a need to monitor liver function and adjust dosing for patients with moderate or severe hepatic impairment. “Other short-term side effects reported only with THC-containing cannabinoid compounds include increased risk of cardiac and cerebrovascular events, anxiety and psychosis risk, dependency, and withdrawal,” the authors wrote.

Though no withdrawal syndrome has been linked to stopping CBD, the authors suggested decreasing the dose by 10% every 2 days if stopping is not urgent.

“The key points to this issue are that CBD and all marijuana products need to be safe and regulated,” Dr. Freedman said. “Any claims about them need to be backed by high-quality evidence looking at that specific product for that specific condition.”

Dr. Freedman noted the need for children to receive treatment from clinicians with expertise in their specific condition since many other evidence-based treatments exist even for patients with epilepsy syndromes that are difficult to treat, such as other medications, surgery, and specialized diets.

“We need to fix the inconsistent regulation between over-the-counter CBD products, state dispensaries, and federal laws,” Dr. Freedman added. “Any medicine being used to treat children should be held to the same FDA standard of safety and efficacy.”

Dr. Freedman and the authors had no conflicts of interest. No external funding was noted.

Differing state regulations and a paucity of research has made it difficult to develop consensus guidelines for the use of cannabinoids in treating drug-resistant epilepsy. A recent review article draws from existing clinical trials and clinical experience in New South Wales, Australia, to fill this gap with interim guidance for both pediatric and adult patients. The article was published in the British Journal of Clinical Pharmacology.

The only current U.S. guidelines are from the American Academy of Neurology’s position statement on the use of medical cannabis for neurologic disorders and the American Epilepsy Society’s position statement on cannabis as a treatment for epileptic seizures. The AAN statement “highlights the current evidence, which currently only supports [Food and Drug Administration]–approved CBD [cannabidiol] (Epidiolex) for specific epilepsy syndromes,” said Daniel Freedman, DO, an assistant professor of neurology at the University of Texas at Austin and coauthor of the AAN’s position statement.

“Rescheduling marijuana will enable researchers to study CBD, THC [tetrahydrocannabinol], and other cannabinoids in high-quality studies so that we can better understand what works and for which conditions,” said Dr. Freedman, who was not involved in the Australian guidance document. He noted that little consensus exists because little evidence exists outside the handful of trials for Epidiolex.

“There are some patients with epilepsy that can benefit from high-quality, pharmaceutical-grade CBD products,” Dr. Freedman said. “These patients need to be carefully identified by a neurologist or epileptologist and prescribed a legal, safe, quality-controlled, and FDA-regulated product.”
 

Appropriate patient populations

Drug-resistant epilepsy, defined as failure of two appropriate antiseizure medications, affects an estimated one third of people with epilepsy, the new guideline notes. Though many over-the-counter products are available at dispensaries in the 33 U.S. states that allow use of cannabis for medical purposes, Epidiolex (cannabidiol) is the only FDA-approved drug for epilepsy that contains a substance derived from cannabis and the only one for which evidence from randomized, controlled trials exists.

Dr. Freedman notes that hemp-derived CBD oils are classified differently in the United States than marijuana-derived CBD oil, including Epidiolex, and are loosely regulated supplements or food additives commonly seen, for example at gas station.

“The point I drive home to patients is that you wouldn’t get your antibiotics from a gas station, so please don’t get your seizure medication from there,” Dr. Freedman said. “Studies have been done on ‘over-the-counter’ CBD oils and shown that they have variable quality, sometimes no detectable CBD, and sometimes other chemicals added like THC.”

Studies of Epidiolex showed that cannabidiol more effectively reduced seizure frequency than placebo for pediatric patients with Dravet syndrome (42% reduction) and for pediatric and adult patients with Lennox-Gastaut syndrome (39% reduction) or tuberous sclerosis complex (49% reduction). Efficacy was similar across dosing from 10-50 mg/kg per day, but higher doses involved higher rates of serious adverse events.

No reliable evidence in humans exists for THC or other cannabinoids in treating epilepsy.

The Australian guidance recommends limiting cannabis treatment to patients with severe drug-resistant epilepsy; a diagnosis of Dravet syndrome, Lennox-Gastaut syndrome, or tuberous sclerosis complex; and previous treatment with four approved antiseizure medications and/or the ketogenic diet, epilepsy surgery, or neurostimulator. The authors provide specific criteria for each of these conditions and then address exceptional cases that may be considered outside that criteria, such as patients under 2 years old, severe epilepsy with extended or repeated hospitalization or ICU admission, or a dangerous seizure type. The review also includes a detailed list of exclusion criteria for CBD medicine use.

The authors advised a thorough consent process before prescribing any cannabinoids, including therapeutic goals and stopping criteria; the lack of evidence available on dosing, efficacy, and side effects; and the potential for dependence or withdrawal. Consent discussions should also note whether the products are unregistered and not covered by external payers (anything other than Epidiolex currently), any activity restrictions, and any implications for occupational drug screening.
 

Considerations for unapproved cannabinoids

The authors note several factors to consider if prescribing or recommending a nonapproved, nonregulated cannabis medicine, including the ”differences between registered plant-derived cannabis medicines, synthetic cannabis medicines, and unregistered hemp-derived products.” Epidiolex is plant derived while other cannabis-derived medications (Marinol, Syndos, and Cesamet) that have been approved for nonepilepsy conditions, such as nausea associated with chemotherapy, are synthetic.

The guidance document notes several reasons to use a regulated medication instead of an unregulated product:

• Manufacturing processes can differ for unregulated products, including inconsistency in batches and unknown shelf life.
• Quality control processes, including risk of impurities, are much better with regulated products, which also have a system in place for safety recalls.
• More scientific evidence is available for regulated products.
• Safety surveillance reporting is more robust and standardized for regulated products whereas adverse event reporting is less reliable for unregulated products.
• Nonregulated products are rarely covered by insurance or other reimbursement.

Legal considerations will also vary by jurisdiction. ”Right now in the U.S. we have a confused legality where state level programs are still technically illegal at the federal level and I imagine there are some quality differences amongst dispensaries and states,” Dr. Freedman said. “Whenever there is disagreement between state and federal laws, this creates tension for our patients.” He noted, for example, that a patient using a CBD product that contains THC may, even if legal in their state, be confiscated by the Transportation Security Administration at an airport since it is not FDA approved and is not legal, according to the Drug Enforcement Agency.

The authors noted that inadequate data on long-term CBD use and data on neurodevelopmental effects of THC in children, teens, and young adults means THC products should be contraindicated for these age groups. (Epidiolex has less than 2% THC.) Drug interactions should also be considered, particularly for clobazam, CYP3A4 inhibitors or inducers (including St. John’s wort), digoxin, or a mechanistic target of rapamycin inhibitor.

Dr. Freedman said that most neurologists are comfortable prescribing Epidiolex since it has FDA approval while prescribing unapproved products varies more in the field. “Now that many states have compassionate use programs for medical marijuana, some neurologists do this as well,” Dr. Freedman said. Patients often ask about unregulated CBD or CBD+THC products because they’re seen as “natural and therefore better than manufactured pharmaceuticals.”

“I think this is the naturalistic fallacy at work and try to educate my patients on that since our only high-level data to show marijuana products work for epilepsy comes from a pharmaceutical company,” Dr. Freedman said. “My reasons for hesitating on compassionate use are that there is often THC, with variable amounts of concentration, and we know that THC can harm the developing pediatric brain.”
 

Dosing and adverse effects

Pediatric and adult dosing differences need to be considered, and “patient response (efficacy and toxicity) to these medications varies widely,” the authors noted. They advised getting serum transaminases (ALT and AST) and total bilirubin levels before beginning treatment. All patients should begin Epidiolex at a low dose, such as 2-5 mg/kg per day of CBD in two divided doses, the authors advise, and titrate slowly while monitoring for side effects (no more than 5 mg/kg per day per week). The current dosing range for CBD is 5-20 mg/kg per day in two divided doses, with higher rates involving more risk of adverse events.

“Note that some cannabinoids auto-inhibit their own metabolism and some have active metabolites with longer half-lives,” the authors wrote. “Therefore, dose or frequency may need to be reduced over time, unless tolerance occurs.” These doses, specific to Epidiolex, “cannot necessarily be applied to other oral CBD formulations or other types of epilepsy.” This guidance also does not apply to inhaled or transdermal routes of administration.

The most common adverse events were sleepiness – which occurred in up to 60% of trial participants – as well as diarrhea, decreases in appetite and weight, and drug interactions. Risk of hepatotoxicity means there’s a need to monitor liver function and adjust dosing for patients with moderate or severe hepatic impairment. “Other short-term side effects reported only with THC-containing cannabinoid compounds include increased risk of cardiac and cerebrovascular events, anxiety and psychosis risk, dependency, and withdrawal,” the authors wrote.

Though no withdrawal syndrome has been linked to stopping CBD, the authors suggested decreasing the dose by 10% every 2 days if stopping is not urgent.

“The key points to this issue are that CBD and all marijuana products need to be safe and regulated,” Dr. Freedman said. “Any claims about them need to be backed by high-quality evidence looking at that specific product for that specific condition.”

Dr. Freedman noted the need for children to receive treatment from clinicians with expertise in their specific condition since many other evidence-based treatments exist even for patients with epilepsy syndromes that are difficult to treat, such as other medications, surgery, and specialized diets.

“We need to fix the inconsistent regulation between over-the-counter CBD products, state dispensaries, and federal laws,” Dr. Freedman added. “Any medicine being used to treat children should be held to the same FDA standard of safety and efficacy.”

Dr. Freedman and the authors had no conflicts of interest. No external funding was noted.

Loss of vestibular function is a key contributor to a well-documented increased risk for falls in patients with Alzheimer’s disease (AD), new research confirms.

Falls are twice as common in patients with AD versu older individuals without the disorder and significantly increase the likelihood of institutionalization.

However, researchers recorded fewer falls in patients with a better functioning vestibular system, which detects head movements and plays a critical role in spatial orientation, posture, gait, and balance.

The results suggest that improving vestibular function with currently available therapies may prevent falls, something the researchers will investigate in a new clinical trial launching next month.

“One of the most dangerous and impactful symptoms in terms of function in patients with Alzheimer’s disease is their increased predisposition to falls,” study investigator Yuri Agrawal, MD, department of otolaryngology–head and neck surgery, Johns Hopkins University School of Medicine, Baltimore, said in an interview. “Alzheimer’s is the sixth leading cause of death in the U.S., and some people actually say that that high mortality rate is because of their predisposition to falls and the injuries that occur.”

The study was published online Feb. 14 in the Journal of Alzheimer’s Disease.
 

The ‘sixth hidden sense’

The vestibular system consists of three semicircular canals, which detect rotational head movement, and two otolith organs called the utricle and the saccule, which sense linear head movements and the orientation of the head with respect to gravity.

“We call the vestibular system the sixth hidden sense because it’s not a conscious perception like taste or smell,” Dr. Agrawal said. “It’s constantly providing input to our brain about where we are in space.”

Dr. Agrawal and colleagues previously reported that vestibular loss is twice as common in Alzheimer’s patients as in cognitively unimpaired age-matched controls. Now, they wanted to know if this sensory loss was associated with an increased risk for falls in this population.

The study included 48 patients age greater than or equal to 60 years with mild-to-moderate AD between 2018 and 2020. They also included an age-matched control group of healthy controls with no cognitive impairment.

Researchers assessed vestibular function at baseline by measuring semicircular canal and saccular function. One test required participants to wear goggles and complete a series of tests with their eyes open and closed while researchers recorded their eye movement with video-oculography. They also measured participants’ balance using the Berg Balance Scale.

Relative to matched controls, AD patients exhibited increased lateral instability when their eyes were open (P = .033) and closed (P = .042). Studies suggest that lateral stability declines more quickly with age and that instability with eyes closed is the single biggest predictor of incident falls in community-dwelling adults.

To determine if poor vestibular function increased fall risk in patients with AD, researchers followed the cohort for up to 2 years.

“We found that patients with vestibular loss at baseline were 50% more likely to fall, adjusting for other factors that could contribute to that,” Dr. Agrawal said.

Specifically, better semicircular canal function was significantly associated with lower likelihood of falls, even after adjusting for confounders (adjusted hazard ratio, 0.65; P = .009).
 

Can therapy help?

Commenting on the findings, James Burke, MD, PhD, professor of neurology at Duke University Medical Center, Durham, N.C., said that the finding that impaired vestibular function is associated with increased falls “significantly advances our understanding of the topic” and suggests that treating vestibular dysfunction could reduce falls in Alzheimer’s patients.

“Screening patients with Alzheimer’s disease for impaired vestibular function could lead to identification of individuals at high risk of falls and target those who would benefit from vestibular therapy,” he said.

Vestibular rehabilitation therapy is often used to treat a number of disorders related to vestibular function loss. There are also studies underway to measure the efficacy of a vestibular implant that works much like a cochlear implant.

While evaluation of vestibular function is currently not routinely included in AD care, studies such as these suggest it may be time to consider adding it to the standard of care, Jennifer Coto, PhD, assistant professor of otolaryngology at the University of Miami Miller School of Medicine, said in an interview.

“Best practice guidelines for management of Alzheimer’s patients should be revised to include routine vestibular evaluation and support from a multidisciplinary team that may address other crucial areas of functioning, particularly psychological functioning, sleep, and independence,” she said.

“Future research also needs to evaluate the effectiveness of vestibular therapy in patients with Alzheimer’s and the benefits of early identification and intervention for preventing recurrent falls.”

Dr. Agrawal is leading a 5-year, $3.5 million National Institute on Aging study that seeks to do just that. Enrollment in the study begins next month. Patients will complete an initial in-person screening, but the remainder of the study will be conducted virtually.

Therapies will be noninvasive, nonpharmaceutical, and performed in participants’ homes. If the therapy is successful at reducing falls, Dr. Agrawal said the virtual design would significantly broaden its potential patient reach.

The study was funded by the National Institute on Aging. Study authors’ disclosures are reported in the original article. Dr. Coto and Dr. Burke report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Loss of vestibular function is a key contributor to a well-documented increased risk for falls in patients with Alzheimer’s disease (AD), new research confirms.

Falls are twice as common in patients with AD versu older individuals without the disorder and significantly increase the likelihood of institutionalization.

However, researchers recorded fewer falls in patients with a better functioning vestibular system, which detects head movements and plays a critical role in spatial orientation, posture, gait, and balance.

The results suggest that improving vestibular function with currently available therapies may prevent falls, something the researchers will investigate in a new clinical trial launching next month.

“One of the most dangerous and impactful symptoms in terms of function in patients with Alzheimer’s disease is their increased predisposition to falls,” study investigator Yuri Agrawal, MD, department of otolaryngology–head and neck surgery, Johns Hopkins University School of Medicine, Baltimore, said in an interview. “Alzheimer’s is the sixth leading cause of death in the U.S., and some people actually say that that high mortality rate is because of their predisposition to falls and the injuries that occur.”

The study was published online Feb. 14 in the Journal of Alzheimer’s Disease.
 

The ‘sixth hidden sense’

The vestibular system consists of three semicircular canals, which detect rotational head movement, and two otolith organs called the utricle and the saccule, which sense linear head movements and the orientation of the head with respect to gravity.

“We call the vestibular system the sixth hidden sense because it’s not a conscious perception like taste or smell,” Dr. Agrawal said. “It’s constantly providing input to our brain about where we are in space.”

Dr. Agrawal and colleagues previously reported that vestibular loss is twice as common in Alzheimer’s patients as in cognitively unimpaired age-matched controls. Now, they wanted to know if this sensory loss was associated with an increased risk for falls in this population.

The study included 48 patients age greater than or equal to 60 years with mild-to-moderate AD between 2018 and 2020. They also included an age-matched control group of healthy controls with no cognitive impairment.

Researchers assessed vestibular function at baseline by measuring semicircular canal and saccular function. One test required participants to wear goggles and complete a series of tests with their eyes open and closed while researchers recorded their eye movement with video-oculography. They also measured participants’ balance using the Berg Balance Scale.

Relative to matched controls, AD patients exhibited increased lateral instability when their eyes were open (P = .033) and closed (P = .042). Studies suggest that lateral stability declines more quickly with age and that instability with eyes closed is the single biggest predictor of incident falls in community-dwelling adults.

To determine if poor vestibular function increased fall risk in patients with AD, researchers followed the cohort for up to 2 years.

“We found that patients with vestibular loss at baseline were 50% more likely to fall, adjusting for other factors that could contribute to that,” Dr. Agrawal said.

Specifically, better semicircular canal function was significantly associated with lower likelihood of falls, even after adjusting for confounders (adjusted hazard ratio, 0.65; P = .009).
 

Can therapy help?

Commenting on the findings, James Burke, MD, PhD, professor of neurology at Duke University Medical Center, Durham, N.C., said that the finding that impaired vestibular function is associated with increased falls “significantly advances our understanding of the topic” and suggests that treating vestibular dysfunction could reduce falls in Alzheimer’s patients.

“Screening patients with Alzheimer’s disease for impaired vestibular function could lead to identification of individuals at high risk of falls and target those who would benefit from vestibular therapy,” he said.

Vestibular rehabilitation therapy is often used to treat a number of disorders related to vestibular function loss. There are also studies underway to measure the efficacy of a vestibular implant that works much like a cochlear implant.

While evaluation of vestibular function is currently not routinely included in AD care, studies such as these suggest it may be time to consider adding it to the standard of care, Jennifer Coto, PhD, assistant professor of otolaryngology at the University of Miami Miller School of Medicine, said in an interview.

“Best practice guidelines for management of Alzheimer’s patients should be revised to include routine vestibular evaluation and support from a multidisciplinary team that may address other crucial areas of functioning, particularly psychological functioning, sleep, and independence,” she said.

“Future research also needs to evaluate the effectiveness of vestibular therapy in patients with Alzheimer’s and the benefits of early identification and intervention for preventing recurrent falls.”

Dr. Agrawal is leading a 5-year, $3.5 million National Institute on Aging study that seeks to do just that. Enrollment in the study begins next month. Patients will complete an initial in-person screening, but the remainder of the study will be conducted virtually.

Therapies will be noninvasive, nonpharmaceutical, and performed in participants’ homes. If the therapy is successful at reducing falls, Dr. Agrawal said the virtual design would significantly broaden its potential patient reach.

The study was funded by the National Institute on Aging. Study authors’ disclosures are reported in the original article. Dr. Coto and Dr. Burke report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Loss of vestibular function is a key contributor to a well-documented increased risk for falls in patients with Alzheimer’s disease (AD), new research confirms.

Falls are twice as common in patients with AD versu older individuals without the disorder and significantly increase the likelihood of institutionalization.

However, researchers recorded fewer falls in patients with a better functioning vestibular system, which detects head movements and plays a critical role in spatial orientation, posture, gait, and balance.

The results suggest that improving vestibular function with currently available therapies may prevent falls, something the researchers will investigate in a new clinical trial launching next month.

“One of the most dangerous and impactful symptoms in terms of function in patients with Alzheimer’s disease is their increased predisposition to falls,” study investigator Yuri Agrawal, MD, department of otolaryngology–head and neck surgery, Johns Hopkins University School of Medicine, Baltimore, said in an interview. “Alzheimer’s is the sixth leading cause of death in the U.S., and some people actually say that that high mortality rate is because of their predisposition to falls and the injuries that occur.”

The study was published online Feb. 14 in the Journal of Alzheimer’s Disease.
 

The ‘sixth hidden sense’

The vestibular system consists of three semicircular canals, which detect rotational head movement, and two otolith organs called the utricle and the saccule, which sense linear head movements and the orientation of the head with respect to gravity.

“We call the vestibular system the sixth hidden sense because it’s not a conscious perception like taste or smell,” Dr. Agrawal said. “It’s constantly providing input to our brain about where we are in space.”

Dr. Agrawal and colleagues previously reported that vestibular loss is twice as common in Alzheimer’s patients as in cognitively unimpaired age-matched controls. Now, they wanted to know if this sensory loss was associated with an increased risk for falls in this population.

The study included 48 patients age greater than or equal to 60 years with mild-to-moderate AD between 2018 and 2020. They also included an age-matched control group of healthy controls with no cognitive impairment.

Researchers assessed vestibular function at baseline by measuring semicircular canal and saccular function. One test required participants to wear goggles and complete a series of tests with their eyes open and closed while researchers recorded their eye movement with video-oculography. They also measured participants’ balance using the Berg Balance Scale.

Relative to matched controls, AD patients exhibited increased lateral instability when their eyes were open (P = .033) and closed (P = .042). Studies suggest that lateral stability declines more quickly with age and that instability with eyes closed is the single biggest predictor of incident falls in community-dwelling adults.

To determine if poor vestibular function increased fall risk in patients with AD, researchers followed the cohort for up to 2 years.

“We found that patients with vestibular loss at baseline were 50% more likely to fall, adjusting for other factors that could contribute to that,” Dr. Agrawal said.

Specifically, better semicircular canal function was significantly associated with lower likelihood of falls, even after adjusting for confounders (adjusted hazard ratio, 0.65; P = .009).
 

Can therapy help?

Commenting on the findings, James Burke, MD, PhD, professor of neurology at Duke University Medical Center, Durham, N.C., said that the finding that impaired vestibular function is associated with increased falls “significantly advances our understanding of the topic” and suggests that treating vestibular dysfunction could reduce falls in Alzheimer’s patients.

“Screening patients with Alzheimer’s disease for impaired vestibular function could lead to identification of individuals at high risk of falls and target those who would benefit from vestibular therapy,” he said.

Vestibular rehabilitation therapy is often used to treat a number of disorders related to vestibular function loss. There are also studies underway to measure the efficacy of a vestibular implant that works much like a cochlear implant.

While evaluation of vestibular function is currently not routinely included in AD care, studies such as these suggest it may be time to consider adding it to the standard of care, Jennifer Coto, PhD, assistant professor of otolaryngology at the University of Miami Miller School of Medicine, said in an interview.

“Best practice guidelines for management of Alzheimer’s patients should be revised to include routine vestibular evaluation and support from a multidisciplinary team that may address other crucial areas of functioning, particularly psychological functioning, sleep, and independence,” she said.

“Future research also needs to evaluate the effectiveness of vestibular therapy in patients with Alzheimer’s and the benefits of early identification and intervention for preventing recurrent falls.”

Dr. Agrawal is leading a 5-year, $3.5 million National Institute on Aging study that seeks to do just that. Enrollment in the study begins next month. Patients will complete an initial in-person screening, but the remainder of the study will be conducted virtually.

Therapies will be noninvasive, nonpharmaceutical, and performed in participants’ homes. If the therapy is successful at reducing falls, Dr. Agrawal said the virtual design would significantly broaden its potential patient reach.

The study was funded by the National Institute on Aging. Study authors’ disclosures are reported in the original article. Dr. Coto and Dr. Burke report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

It’s no secret that heavy drinking is linked to potential health problems, from liver damage to a higher risk of cancer. But most people probably wouldn’t think a nightcap every evening is much of a health threat.

Now, new evidence published in Nature Communications suggests even one drink a day is linked to detectable changes in the brain, though it’s not clear whether the alcohol is causing the differences.

Previous research has found that people with alcohol use disorder have structural changes in their brains, compared with healthy people’s brains, such as reduced gray-matter and white-matter volume.

But those findings were in people with a history of heavy drinking, defined by the National Institute on Alcohol Abuse and Alcoholism as more than four drinks a day for men and more than three drinks a day for women.

The national dietary guidelines from the U.S. Department of Health & Human Services advise drinking no more than two standard drinks for men and one drink for women each day. A standard drink in the United States is 12 ounces of beer, 5 ounces of wine, or 1½ ounce of liquor.

But could even this modest amount of alcohol make a difference to our brains?

Researchers examined functional MRI brain scans from 36,678 healthy adults, aged 40-69 years, in the United Kingdom and compared those findings with their weekly alcohol consumption, adjusting for differences in age, sex, height, social and economic status, and country of residence, among other things.

In line with past studies, the researchers found that, as a person drank more alcohol, their gray-matter and white-matter volume decreased, getting worse the more drinks they had in a week.

But the researchers also noted that they could tell the difference between brain images of people who never drank alcohol and those who had just one or two drinks a day.

Going from 1 unit of alcohol to 2 – which in the United Kingdom means a full pint of beer or standard glass of wine – was linked to changes similar to 2 years of aging in the brain.

Other than comparing the changes with aging, it’s not yet clear what the findings mean until the scientists do more research, including looking at the genes of the people who took part in the study.

The study also has several drawbacks. The people who were studied are all middle-aged Europeans, so findings might be different in younger people or those with different ancestries. People also self-reported how much alcohol they drank for the past year, which they might not remember correctly or which might be different from previous years, including past years of heavy drinking.

And since the researchers compared drinking habits with brain imaging at one point in time, it’s not possible to say whether alcohol is actually causing the brain differences they saw.

Still, the findings raise the question of whether national guidelines should be revisited, and whether it’s better to cut that evening drink to a half-glass of wine instead.

A version of this article first appeared on WebMD.com.

It’s no secret that heavy drinking is linked to potential health problems, from liver damage to a higher risk of cancer. But most people probably wouldn’t think a nightcap every evening is much of a health threat.

Now, new evidence published in Nature Communications suggests even one drink a day is linked to detectable changes in the brain, though it’s not clear whether the alcohol is causing the differences.

Previous research has found that people with alcohol use disorder have structural changes in their brains, compared with healthy people’s brains, such as reduced gray-matter and white-matter volume.

But those findings were in people with a history of heavy drinking, defined by the National Institute on Alcohol Abuse and Alcoholism as more than four drinks a day for men and more than three drinks a day for women.

The national dietary guidelines from the U.S. Department of Health & Human Services advise drinking no more than two standard drinks for men and one drink for women each day. A standard drink in the United States is 12 ounces of beer, 5 ounces of wine, or 1½ ounce of liquor.

But could even this modest amount of alcohol make a difference to our brains?

Researchers examined functional MRI brain scans from 36,678 healthy adults, aged 40-69 years, in the United Kingdom and compared those findings with their weekly alcohol consumption, adjusting for differences in age, sex, height, social and economic status, and country of residence, among other things.

In line with past studies, the researchers found that, as a person drank more alcohol, their gray-matter and white-matter volume decreased, getting worse the more drinks they had in a week.

But the researchers also noted that they could tell the difference between brain images of people who never drank alcohol and those who had just one or two drinks a day.

Going from 1 unit of alcohol to 2 – which in the United Kingdom means a full pint of beer or standard glass of wine – was linked to changes similar to 2 years of aging in the brain.

Other than comparing the changes with aging, it’s not yet clear what the findings mean until the scientists do more research, including looking at the genes of the people who took part in the study.

The study also has several drawbacks. The people who were studied are all middle-aged Europeans, so findings might be different in younger people or those with different ancestries. People also self-reported how much alcohol they drank for the past year, which they might not remember correctly or which might be different from previous years, including past years of heavy drinking.

And since the researchers compared drinking habits with brain imaging at one point in time, it’s not possible to say whether alcohol is actually causing the brain differences they saw.

Still, the findings raise the question of whether national guidelines should be revisited, and whether it’s better to cut that evening drink to a half-glass of wine instead.

A version of this article first appeared on WebMD.com.

It’s no secret that heavy drinking is linked to potential health problems, from liver damage to a higher risk of cancer. But most people probably wouldn’t think a nightcap every evening is much of a health threat.

Now, new evidence published in Nature Communications suggests even one drink a day is linked to detectable changes in the brain, though it’s not clear whether the alcohol is causing the differences.

Previous research has found that people with alcohol use disorder have structural changes in their brains, compared with healthy people’s brains, such as reduced gray-matter and white-matter volume.

But those findings were in people with a history of heavy drinking, defined by the National Institute on Alcohol Abuse and Alcoholism as more than four drinks a day for men and more than three drinks a day for women.

The national dietary guidelines from the U.S. Department of Health & Human Services advise drinking no more than two standard drinks for men and one drink for women each day. A standard drink in the United States is 12 ounces of beer, 5 ounces of wine, or 1½ ounce of liquor.

But could even this modest amount of alcohol make a difference to our brains?

Researchers examined functional MRI brain scans from 36,678 healthy adults, aged 40-69 years, in the United Kingdom and compared those findings with their weekly alcohol consumption, adjusting for differences in age, sex, height, social and economic status, and country of residence, among other things.

In line with past studies, the researchers found that, as a person drank more alcohol, their gray-matter and white-matter volume decreased, getting worse the more drinks they had in a week.

But the researchers also noted that they could tell the difference between brain images of people who never drank alcohol and those who had just one or two drinks a day.

Going from 1 unit of alcohol to 2 – which in the United Kingdom means a full pint of beer or standard glass of wine – was linked to changes similar to 2 years of aging in the brain.

Other than comparing the changes with aging, it’s not yet clear what the findings mean until the scientists do more research, including looking at the genes of the people who took part in the study.

The study also has several drawbacks. The people who were studied are all middle-aged Europeans, so findings might be different in younger people or those with different ancestries. People also self-reported how much alcohol they drank for the past year, which they might not remember correctly or which might be different from previous years, including past years of heavy drinking.

And since the researchers compared drinking habits with brain imaging at one point in time, it’s not possible to say whether alcohol is actually causing the brain differences they saw.

Still, the findings raise the question of whether national guidelines should be revisited, and whether it’s better to cut that evening drink to a half-glass of wine instead.

A version of this article first appeared on WebMD.com.

The endocannabinoid system is a promising therapeutic target for the treatment of migraine, according to Italian researchers at the University of Pavia, and the C. Mondino National Institute of Neurology Foundation. “The complexity of the endocannabinoid system calls for accurate biochemical and pharmacological characterization of any new compounds undergoing testing and development,” noted Rosaria Greco, PhD. She and her colleagues authored a review on the topic that was published online Feb. 18, 2022, in Headache.

Although cannabis has been investigated for both the treatment and prevention of migraine, evidence for its benefit is weak because of lack of controlled studies, they explained. Archival data from a large database “showed greater improvements in men than in women and suggested that concentrated preparations were more effective than flower consumption.” In addition, a small single-center study linked nabilone, a synthetic cannabinoid, to reductions in pain duration, intensity, and daily intake of analgesics among patients with medication overuse headache. Finally, a pilot study reported a reduction in pain intensity among patients with chronic migraine treated with a combination of tested a combination of delta-9-tetrahydrocannabinol and cannabidiol. “Methodologically sound studies are now needed to investigate the possible effects of cannabis in migraine treatment and to define strains, formulations, and dosage,” they noted.
 

Not just cannabis

In addition to exogenous cannabis, there are now preclinical studies suggesting other compounds that interact with the endocannabinoid system “are also able to modulate the pathways involved in migraine-related pain,” the study authors wrote. “But the road ahead is still long. Multiple molecules linked to the endocannabinoid system have emerged as potential therapeutic targets.

The complexity of the system demands caution and precise biochemical and pharmacological characterization of the new compounds to be tested and developed.”

Among these compounds are endogenous ligands such as N-arachidonoylethanolamine (anandamide) and 2-arachidonoylglycerol that specifically target CB1 and CB2 receptors. Additionally, there are endocannabinoid-based drugs that also target the CB1/CB2 receptors, as well as other substances, such as lipids (palmitoylethanolamide [PEA]) and enzymes, that do not bind to the CB1/CB2 receptors but are responsible for endocannabinoid biosynthesis.

There is some evidence that the endocannabinoid system may be dysfunctional in patients with migraine, and the authors noted their work has shown that PEA plasma levels are increased during experimentally triggered migraine-like attacks. Thus, some preclinical and preliminary evidence suggests that administration of PEA or anandamide may have analgesic and anti-inflammatory effects in migraine.

Another approach is the inhibition of endocannabinoid catabolic enzymes, which could circumvent the adverse effects associated with direct activation of CB receptors. “Endocannabinoid tone enhancement has been proposed as an alternative modality of activation of CB receptors and is possibly devoid of the psychotropic effects reported with CB receptor agonists,” noted the authors, who have shown in animal and preclinical studies that inhibition of fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase can modulate migraine pain.

Yet another way of indirectly impacting CB receptors is through their allosteric ligands, an approach that “deserves further investigation”, and “might provide interesting leads for clinical development, given that it may have a favorable side-effect profile with limited psychomimetic and depressant effects,” wrote the authors. And finally, inhibition of N-acylethanolamine acid amide hydrolase, the enzyme that preferentially hydrolyzes PEA, might be a promising approach.

“The multiplicity of options and the wealth of data already obtained in animal models underscore the importance of further advancing research in this area,” the authors concluded.
 

Patients are taking cannabinoids; physicians should learn about them

Commenting on the paper, Alan Rapaport, MD, clinical professor of neurology at the University of California, Los Angeles, said “this well-done paper points out the complexity of the endocannabinoid system and the multiple ways of getting it to work for certain patients. It details some of the studies that show beneficial results in migraine, medication overuse headache, chronic migraine, and pain. Patients with headache, other types of pain, anxiety, nausea, sleep issues, and other symptoms are already taking cannabinoids, usually derived from the marijuana plant, that are not well regulated. A few are prescribed drugs which target CB1 and CB2 receptors. Patients often get relief of some of their symptoms, sometimes getting high and many times not.

“The paper makes the point that previous studies are often small, not carefully controlled, or well documented. We do need to start doing larger, properly designed studies and getting them into the literature. Doctors need to learn more about these treatments. The next step will be to get [Food and Drug Administration]–approved treatments, so physicians and nurses will know exactly what we are giving, the beneficial effects to expect in a certain percentage of patients, and the adverse events to warn our patients about. Cannabinoids have been tried by a large percentage of patients with headache and pain. Now we need to standardize the various treatments that are sure to be suggested in the future.”

The study was funded by the Migraine Research Foundation, and the Italian Ministry of Health. The study authors declared no conflicts of interest.

The endocannabinoid system is a promising therapeutic target for the treatment of migraine, according to Italian researchers at the University of Pavia, and the C. Mondino National Institute of Neurology Foundation. “The complexity of the endocannabinoid system calls for accurate biochemical and pharmacological characterization of any new compounds undergoing testing and development,” noted Rosaria Greco, PhD. She and her colleagues authored a review on the topic that was published online Feb. 18, 2022, in Headache.

Although cannabis has been investigated for both the treatment and prevention of migraine, evidence for its benefit is weak because of lack of controlled studies, they explained. Archival data from a large database “showed greater improvements in men than in women and suggested that concentrated preparations were more effective than flower consumption.” In addition, a small single-center study linked nabilone, a synthetic cannabinoid, to reductions in pain duration, intensity, and daily intake of analgesics among patients with medication overuse headache. Finally, a pilot study reported a reduction in pain intensity among patients with chronic migraine treated with a combination of tested a combination of delta-9-tetrahydrocannabinol and cannabidiol. “Methodologically sound studies are now needed to investigate the possible effects of cannabis in migraine treatment and to define strains, formulations, and dosage,” they noted.
 

Not just cannabis

In addition to exogenous cannabis, there are now preclinical studies suggesting other compounds that interact with the endocannabinoid system “are also able to modulate the pathways involved in migraine-related pain,” the study authors wrote. “But the road ahead is still long. Multiple molecules linked to the endocannabinoid system have emerged as potential therapeutic targets.

The complexity of the system demands caution and precise biochemical and pharmacological characterization of the new compounds to be tested and developed.”

Among these compounds are endogenous ligands such as N-arachidonoylethanolamine (anandamide) and 2-arachidonoylglycerol that specifically target CB1 and CB2 receptors. Additionally, there are endocannabinoid-based drugs that also target the CB1/CB2 receptors, as well as other substances, such as lipids (palmitoylethanolamide [PEA]) and enzymes, that do not bind to the CB1/CB2 receptors but are responsible for endocannabinoid biosynthesis.

There is some evidence that the endocannabinoid system may be dysfunctional in patients with migraine, and the authors noted their work has shown that PEA plasma levels are increased during experimentally triggered migraine-like attacks. Thus, some preclinical and preliminary evidence suggests that administration of PEA or anandamide may have analgesic and anti-inflammatory effects in migraine.

Another approach is the inhibition of endocannabinoid catabolic enzymes, which could circumvent the adverse effects associated with direct activation of CB receptors. “Endocannabinoid tone enhancement has been proposed as an alternative modality of activation of CB receptors and is possibly devoid of the psychotropic effects reported with CB receptor agonists,” noted the authors, who have shown in animal and preclinical studies that inhibition of fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase can modulate migraine pain.

Yet another way of indirectly impacting CB receptors is through their allosteric ligands, an approach that “deserves further investigation”, and “might provide interesting leads for clinical development, given that it may have a favorable side-effect profile with limited psychomimetic and depressant effects,” wrote the authors. And finally, inhibition of N-acylethanolamine acid amide hydrolase, the enzyme that preferentially hydrolyzes PEA, might be a promising approach.

“The multiplicity of options and the wealth of data already obtained in animal models underscore the importance of further advancing research in this area,” the authors concluded.
 

Patients are taking cannabinoids; physicians should learn about them

Commenting on the paper, Alan Rapaport, MD, clinical professor of neurology at the University of California, Los Angeles, said “this well-done paper points out the complexity of the endocannabinoid system and the multiple ways of getting it to work for certain patients. It details some of the studies that show beneficial results in migraine, medication overuse headache, chronic migraine, and pain. Patients with headache, other types of pain, anxiety, nausea, sleep issues, and other symptoms are already taking cannabinoids, usually derived from the marijuana plant, that are not well regulated. A few are prescribed drugs which target CB1 and CB2 receptors. Patients often get relief of some of their symptoms, sometimes getting high and many times not.

“The paper makes the point that previous studies are often small, not carefully controlled, or well documented. We do need to start doing larger, properly designed studies and getting them into the literature. Doctors need to learn more about these treatments. The next step will be to get [Food and Drug Administration]–approved treatments, so physicians and nurses will know exactly what we are giving, the beneficial effects to expect in a certain percentage of patients, and the adverse events to warn our patients about. Cannabinoids have been tried by a large percentage of patients with headache and pain. Now we need to standardize the various treatments that are sure to be suggested in the future.”

The study was funded by the Migraine Research Foundation, and the Italian Ministry of Health. The study authors declared no conflicts of interest.

The endocannabinoid system is a promising therapeutic target for the treatment of migraine, according to Italian researchers at the University of Pavia, and the C. Mondino National Institute of Neurology Foundation. “The complexity of the endocannabinoid system calls for accurate biochemical and pharmacological characterization of any new compounds undergoing testing and development,” noted Rosaria Greco, PhD. She and her colleagues authored a review on the topic that was published online Feb. 18, 2022, in Headache.

Although cannabis has been investigated for both the treatment and prevention of migraine, evidence for its benefit is weak because of lack of controlled studies, they explained. Archival data from a large database “showed greater improvements in men than in women and suggested that concentrated preparations were more effective than flower consumption.” In addition, a small single-center study linked nabilone, a synthetic cannabinoid, to reductions in pain duration, intensity, and daily intake of analgesics among patients with medication overuse headache. Finally, a pilot study reported a reduction in pain intensity among patients with chronic migraine treated with a combination of tested a combination of delta-9-tetrahydrocannabinol and cannabidiol. “Methodologically sound studies are now needed to investigate the possible effects of cannabis in migraine treatment and to define strains, formulations, and dosage,” they noted.
 

Not just cannabis

In addition to exogenous cannabis, there are now preclinical studies suggesting other compounds that interact with the endocannabinoid system “are also able to modulate the pathways involved in migraine-related pain,” the study authors wrote. “But the road ahead is still long. Multiple molecules linked to the endocannabinoid system have emerged as potential therapeutic targets.

The complexity of the system demands caution and precise biochemical and pharmacological characterization of the new compounds to be tested and developed.”

Among these compounds are endogenous ligands such as N-arachidonoylethanolamine (anandamide) and 2-arachidonoylglycerol that specifically target CB1 and CB2 receptors. Additionally, there are endocannabinoid-based drugs that also target the CB1/CB2 receptors, as well as other substances, such as lipids (palmitoylethanolamide [PEA]) and enzymes, that do not bind to the CB1/CB2 receptors but are responsible for endocannabinoid biosynthesis.

There is some evidence that the endocannabinoid system may be dysfunctional in patients with migraine, and the authors noted their work has shown that PEA plasma levels are increased during experimentally triggered migraine-like attacks. Thus, some preclinical and preliminary evidence suggests that administration of PEA or anandamide may have analgesic and anti-inflammatory effects in migraine.

Another approach is the inhibition of endocannabinoid catabolic enzymes, which could circumvent the adverse effects associated with direct activation of CB receptors. “Endocannabinoid tone enhancement has been proposed as an alternative modality of activation of CB receptors and is possibly devoid of the psychotropic effects reported with CB receptor agonists,” noted the authors, who have shown in animal and preclinical studies that inhibition of fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase can modulate migraine pain.

Yet another way of indirectly impacting CB receptors is through their allosteric ligands, an approach that “deserves further investigation”, and “might provide interesting leads for clinical development, given that it may have a favorable side-effect profile with limited psychomimetic and depressant effects,” wrote the authors. And finally, inhibition of N-acylethanolamine acid amide hydrolase, the enzyme that preferentially hydrolyzes PEA, might be a promising approach.

“The multiplicity of options and the wealth of data already obtained in animal models underscore the importance of further advancing research in this area,” the authors concluded.
 

Patients are taking cannabinoids; physicians should learn about them

Commenting on the paper, Alan Rapaport, MD, clinical professor of neurology at the University of California, Los Angeles, said “this well-done paper points out the complexity of the endocannabinoid system and the multiple ways of getting it to work for certain patients. It details some of the studies that show beneficial results in migraine, medication overuse headache, chronic migraine, and pain. Patients with headache, other types of pain, anxiety, nausea, sleep issues, and other symptoms are already taking cannabinoids, usually derived from the marijuana plant, that are not well regulated. A few are prescribed drugs which target CB1 and CB2 receptors. Patients often get relief of some of their symptoms, sometimes getting high and many times not.

“The paper makes the point that previous studies are often small, not carefully controlled, or well documented. We do need to start doing larger, properly designed studies and getting them into the literature. Doctors need to learn more about these treatments. The next step will be to get [Food and Drug Administration]–approved treatments, so physicians and nurses will know exactly what we are giving, the beneficial effects to expect in a certain percentage of patients, and the adverse events to warn our patients about. Cannabinoids have been tried by a large percentage of patients with headache and pain. Now we need to standardize the various treatments that are sure to be suggested in the future.”

The study was funded by the Migraine Research Foundation, and the Italian Ministry of Health. The study authors declared no conflicts of interest.

Lack of contact with the outside world and an active lifestyle could play a role in why indigenous groups in the remote Amazon of Bolivia have some of the lowest rates of dementia in the world.   

What to know

• Only about 1% of members of the Tsimane and Moseten peoples of the Bolivian Amazon suffer from dementia, compared with 11% of people aged 65 and older in the United States.
• Underscoring the profound relationship between lifestyle and cognitive health, something about the preindustrial subsistence lifestyle of the groups appears to protect older tribe members from dementia.
• The rate of  generally accepted as typical in aging is comparable between the tribes and rates in developed countries such as the United States.
• The Tsimane and Moseten people remain very physically active throughout their lives by fishing, hunting, and farming and experience less brain atrophy than their American and European peers.
• Indigenous populations elsewhere in the world have been found to have high rates of dementia, which are attributed to more contact with their nonindigenous neighbors and adoption of their lifestyles.

--From staff reports

This is a summary of the article, “Study: Some of the world’s lowest rates of dementia found in Amazonian indigenous groups,” published by Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association, on March 9, 2022. The full article can be found on news.ucsb.edu.



A version of this article first appeared on Medscape.com.

Lack of contact with the outside world and an active lifestyle could play a role in why indigenous groups in the remote Amazon of Bolivia have some of the lowest rates of dementia in the world.   

What to know

• Only about 1% of members of the Tsimane and Moseten peoples of the Bolivian Amazon suffer from dementia, compared with 11% of people aged 65 and older in the United States.
• Underscoring the profound relationship between lifestyle and cognitive health, something about the preindustrial subsistence lifestyle of the groups appears to protect older tribe members from dementia.
• The rate of  generally accepted as typical in aging is comparable between the tribes and rates in developed countries such as the United States.
• The Tsimane and Moseten people remain very physically active throughout their lives by fishing, hunting, and farming and experience less brain atrophy than their American and European peers.
• Indigenous populations elsewhere in the world have been found to have high rates of dementia, which are attributed to more contact with their nonindigenous neighbors and adoption of their lifestyles.

--From staff reports

This is a summary of the article, “Study: Some of the world’s lowest rates of dementia found in Amazonian indigenous groups,” published by Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association, on March 9, 2022. The full article can be found on news.ucsb.edu.



A version of this article first appeared on Medscape.com.

Lack of contact with the outside world and an active lifestyle could play a role in why indigenous groups in the remote Amazon of Bolivia have some of the lowest rates of dementia in the world.   

What to know

• Only about 1% of members of the Tsimane and Moseten peoples of the Bolivian Amazon suffer from dementia, compared with 11% of people aged 65 and older in the United States.
• Underscoring the profound relationship between lifestyle and cognitive health, something about the preindustrial subsistence lifestyle of the groups appears to protect older tribe members from dementia.
• The rate of  generally accepted as typical in aging is comparable between the tribes and rates in developed countries such as the United States.
• The Tsimane and Moseten people remain very physically active throughout their lives by fishing, hunting, and farming and experience less brain atrophy than their American and European peers.
• Indigenous populations elsewhere in the world have been found to have high rates of dementia, which are attributed to more contact with their nonindigenous neighbors and adoption of their lifestyles.

--From staff reports

This is a summary of the article, “Study: Some of the world’s lowest rates of dementia found in Amazonian indigenous groups,” published by Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association, on March 9, 2022. The full article can be found on news.ucsb.edu.



A version of this article first appeared on Medscape.com.