Alzheimer's & Cognition

Older adults taking psychotropic medication before contracting COVID-19 are at increased risk of dementia in the year following the illness, new research suggests.

Results from a large study of more than 1,700 patients who had been hospitalized with COVID showed a greater than twofold increased risk for post-COVID dementia in those taking antipsychotics and mood stabilizers/anticonvulsants – medications often used to treat schizophrenia, psychosis, bipolar disorder, and seizures.

“We know that pre-existing psychiatric illness is associated with poor COVID-19 outcomes, but our study is the first to show an association with certain psychiatric medications and dementia,” co-investigator Liron Sinvani, MD, the Feinstein Institutes for Medical Research, Manhasset, New York, said in an interview.

Feinstein Institutes for Medical Research

‘Striking’ dementia rate

Using electronic health records, the researchers evaluated pre-COVID psychotropic medication use and post-COVID dementia onset in 1,755 adults aged 65 and older. All were hospitalized with COVID-19 at Northwell Health between March 1 and April 20, 2020.

A “striking” 13% of the participants (n = 223) developed dementia within 1-year of follow-up, the investigators report.

Among the 438 patients (25%) exposed to at least one psychotropic medication before COVID-19, 105 (24%) developed dementia in the year following COVID versus 118 of 1,317 (9%) patients with no pre-COVID exposure to psychotropic medication (odds ratio, 3.2; 95% confidence interval, 2.37-4.32).

Both pre-COVID psychotropic medication use (OR, 2.7; 95% CI, 1.8-4.0, P < .001) and delirium (OR, 3.0; 95% CI, 1.9-4.6, P < .001) were significantly associated with post-COVID dementia at 1 year.

In a sensitivity analysis in the subset of 423 patients with at least one documented neurologic or psychiatric diagnosis at the time of COVID admission, and after adjusting for confounding factors, pre-COVID psychotropic medication use remained significantly linked to post-COVID dementia onset (OR, 3.09; 95% CI, 1.5-6.6, P = .002).

Drug classes most strongly associated with 1-year post-COVID dementia onset were antipsychotics (OR, 2.8, 95% CI, 1.7-4.4, P < .001) and mood stabilizers/anticonvulsants (OR, 2.4, 95% CI, 1.39-4.02, P = .001).

In a further exploratory analysis, the psychotropics valproic acid (multiple brands) and haloperidol (Haldol) had the largest association with post-COVID dementia.

Antidepressants as a class were not associated with post-COVID dementia, but the potential effects of two commonly prescribed antidepressants in older adults, mirtazapine (Remeron) and escitalopram (Lexapro), “warrant further investigation,” the researchers note.
 

Predictive risk marker?

“This research shows that psychotropic medications can be considered a predictive risk marker for post-COVID dementia. In patients taking psychotropic medications, COVID-19 could have accelerated progression of dementia after hospitalization,” lead author Yun Freudenberg-Hua, MD, the Feinstein Institutes, said in a news release.

It is unclear why psychotropic medications may raise the risk for dementia onset after COVID, the investigators note.

“It is intuitive that psychotropic medications indicate pre-existing neuropsychiatric conditions in which COVID-19 occurs. It is possible that psychotropic medications may potentiate the neurostructural changes that have been found in the brain of those who have recovered from COVID-19,” they write.

The sensitivity analysis in patients with documented neurologic and psychiatric diagnoses supports this interpretation. 

COVID-19 may also accelerate the underlying brain disorders for which psychotropic medications were prescribed, leading to the greater incidence of post-COVID dementia, the researchers write.

“It is important to note that this study is in no way recommending people should stop taking antipsychotics but simply that clinicians need to factor in a patient’s medication history while considering post-COVID aftereffects,” Dr. Freudenberg-Hua said.

“Given that the number of patients with dementia is projected to triple in the next 30 years, these findings have significant public health implications,” Dr. Sinvani added.

She noted that “care partners and health care professionals” should look for early signs of dementia, such as forgetfulness and depressive symptoms, in their patients.

“Future studies must continue to evaluate these associations, which are key for potential future interventions to prevent dementia,” Dr. Sinvani said.

The study was funded by the National Institutes of Health. Dr. Freudenberg-Hua co-owns stock and stock options from Regeneron Pharmaceuticals. Dr. Sinvani has disclosed no relevant financial relationships.

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

Older adults taking psychotropic medication before contracting COVID-19 are at increased risk of dementia in the year following the illness, new research suggests.

Results from a large study of more than 1,700 patients who had been hospitalized with COVID showed a greater than twofold increased risk for post-COVID dementia in those taking antipsychotics and mood stabilizers/anticonvulsants – medications often used to treat schizophrenia, psychosis, bipolar disorder, and seizures.

“We know that pre-existing psychiatric illness is associated with poor COVID-19 outcomes, but our study is the first to show an association with certain psychiatric medications and dementia,” co-investigator Liron Sinvani, MD, the Feinstein Institutes for Medical Research, Manhasset, New York, said in an interview.

Feinstein Institutes for Medical Research

‘Striking’ dementia rate

Using electronic health records, the researchers evaluated pre-COVID psychotropic medication use and post-COVID dementia onset in 1,755 adults aged 65 and older. All were hospitalized with COVID-19 at Northwell Health between March 1 and April 20, 2020.

A “striking” 13% of the participants (n = 223) developed dementia within 1-year of follow-up, the investigators report.

Among the 438 patients (25%) exposed to at least one psychotropic medication before COVID-19, 105 (24%) developed dementia in the year following COVID versus 118 of 1,317 (9%) patients with no pre-COVID exposure to psychotropic medication (odds ratio, 3.2; 95% confidence interval, 2.37-4.32).

Both pre-COVID psychotropic medication use (OR, 2.7; 95% CI, 1.8-4.0, P < .001) and delirium (OR, 3.0; 95% CI, 1.9-4.6, P < .001) were significantly associated with post-COVID dementia at 1 year.

In a sensitivity analysis in the subset of 423 patients with at least one documented neurologic or psychiatric diagnosis at the time of COVID admission, and after adjusting for confounding factors, pre-COVID psychotropic medication use remained significantly linked to post-COVID dementia onset (OR, 3.09; 95% CI, 1.5-6.6, P = .002).

Drug classes most strongly associated with 1-year post-COVID dementia onset were antipsychotics (OR, 2.8, 95% CI, 1.7-4.4, P < .001) and mood stabilizers/anticonvulsants (OR, 2.4, 95% CI, 1.39-4.02, P = .001).

In a further exploratory analysis, the psychotropics valproic acid (multiple brands) and haloperidol (Haldol) had the largest association with post-COVID dementia.

Antidepressants as a class were not associated with post-COVID dementia, but the potential effects of two commonly prescribed antidepressants in older adults, mirtazapine (Remeron) and escitalopram (Lexapro), “warrant further investigation,” the researchers note.
 

Predictive risk marker?

“This research shows that psychotropic medications can be considered a predictive risk marker for post-COVID dementia. In patients taking psychotropic medications, COVID-19 could have accelerated progression of dementia after hospitalization,” lead author Yun Freudenberg-Hua, MD, the Feinstein Institutes, said in a news release.

It is unclear why psychotropic medications may raise the risk for dementia onset after COVID, the investigators note.

“It is intuitive that psychotropic medications indicate pre-existing neuropsychiatric conditions in which COVID-19 occurs. It is possible that psychotropic medications may potentiate the neurostructural changes that have been found in the brain of those who have recovered from COVID-19,” they write.

The sensitivity analysis in patients with documented neurologic and psychiatric diagnoses supports this interpretation. 

COVID-19 may also accelerate the underlying brain disorders for which psychotropic medications were prescribed, leading to the greater incidence of post-COVID dementia, the researchers write.

“It is important to note that this study is in no way recommending people should stop taking antipsychotics but simply that clinicians need to factor in a patient’s medication history while considering post-COVID aftereffects,” Dr. Freudenberg-Hua said.

“Given that the number of patients with dementia is projected to triple in the next 30 years, these findings have significant public health implications,” Dr. Sinvani added.

She noted that “care partners and health care professionals” should look for early signs of dementia, such as forgetfulness and depressive symptoms, in their patients.

“Future studies must continue to evaluate these associations, which are key for potential future interventions to prevent dementia,” Dr. Sinvani said.

The study was funded by the National Institutes of Health. Dr. Freudenberg-Hua co-owns stock and stock options from Regeneron Pharmaceuticals. Dr. Sinvani has disclosed no relevant financial relationships.

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

Older adults taking psychotropic medication before contracting COVID-19 are at increased risk of dementia in the year following the illness, new research suggests.

Results from a large study of more than 1,700 patients who had been hospitalized with COVID showed a greater than twofold increased risk for post-COVID dementia in those taking antipsychotics and mood stabilizers/anticonvulsants – medications often used to treat schizophrenia, psychosis, bipolar disorder, and seizures.

“We know that pre-existing psychiatric illness is associated with poor COVID-19 outcomes, but our study is the first to show an association with certain psychiatric medications and dementia,” co-investigator Liron Sinvani, MD, the Feinstein Institutes for Medical Research, Manhasset, New York, said in an interview.

Feinstein Institutes for Medical Research

‘Striking’ dementia rate

Using electronic health records, the researchers evaluated pre-COVID psychotropic medication use and post-COVID dementia onset in 1,755 adults aged 65 and older. All were hospitalized with COVID-19 at Northwell Health between March 1 and April 20, 2020.

A “striking” 13% of the participants (n = 223) developed dementia within 1-year of follow-up, the investigators report.

Among the 438 patients (25%) exposed to at least one psychotropic medication before COVID-19, 105 (24%) developed dementia in the year following COVID versus 118 of 1,317 (9%) patients with no pre-COVID exposure to psychotropic medication (odds ratio, 3.2; 95% confidence interval, 2.37-4.32).

Both pre-COVID psychotropic medication use (OR, 2.7; 95% CI, 1.8-4.0, P < .001) and delirium (OR, 3.0; 95% CI, 1.9-4.6, P < .001) were significantly associated with post-COVID dementia at 1 year.

In a sensitivity analysis in the subset of 423 patients with at least one documented neurologic or psychiatric diagnosis at the time of COVID admission, and after adjusting for confounding factors, pre-COVID psychotropic medication use remained significantly linked to post-COVID dementia onset (OR, 3.09; 95% CI, 1.5-6.6, P = .002).

Drug classes most strongly associated with 1-year post-COVID dementia onset were antipsychotics (OR, 2.8, 95% CI, 1.7-4.4, P < .001) and mood stabilizers/anticonvulsants (OR, 2.4, 95% CI, 1.39-4.02, P = .001).

In a further exploratory analysis, the psychotropics valproic acid (multiple brands) and haloperidol (Haldol) had the largest association with post-COVID dementia.

Antidepressants as a class were not associated with post-COVID dementia, but the potential effects of two commonly prescribed antidepressants in older adults, mirtazapine (Remeron) and escitalopram (Lexapro), “warrant further investigation,” the researchers note.
 

Predictive risk marker?

“This research shows that psychotropic medications can be considered a predictive risk marker for post-COVID dementia. In patients taking psychotropic medications, COVID-19 could have accelerated progression of dementia after hospitalization,” lead author Yun Freudenberg-Hua, MD, the Feinstein Institutes, said in a news release.

It is unclear why psychotropic medications may raise the risk for dementia onset after COVID, the investigators note.

“It is intuitive that psychotropic medications indicate pre-existing neuropsychiatric conditions in which COVID-19 occurs. It is possible that psychotropic medications may potentiate the neurostructural changes that have been found in the brain of those who have recovered from COVID-19,” they write.

The sensitivity analysis in patients with documented neurologic and psychiatric diagnoses supports this interpretation. 

COVID-19 may also accelerate the underlying brain disorders for which psychotropic medications were prescribed, leading to the greater incidence of post-COVID dementia, the researchers write.

“It is important to note that this study is in no way recommending people should stop taking antipsychotics but simply that clinicians need to factor in a patient’s medication history while considering post-COVID aftereffects,” Dr. Freudenberg-Hua said.

“Given that the number of patients with dementia is projected to triple in the next 30 years, these findings have significant public health implications,” Dr. Sinvani added.

She noted that “care partners and health care professionals” should look for early signs of dementia, such as forgetfulness and depressive symptoms, in their patients.

“Future studies must continue to evaluate these associations, which are key for potential future interventions to prevent dementia,” Dr. Sinvani said.

The study was funded by the National Institutes of Health. Dr. Freudenberg-Hua co-owns stock and stock options from Regeneron Pharmaceuticals. Dr. Sinvani has disclosed no relevant financial relationships.

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

Hospitalized COVID-19 survivors showed greater cognitive impairment 6 months later, compared with patients hospitalized for other causes, but the overall disease burden was similar, based on data from 85 adults with COVID-19.

Previous studies have shown that cognitive and neuropsychiatric symptoms can occur from 2-6 months after COVID-19 recovery, and such symptoms are known to be associated with hospitalization for other severe medical conditions, Vardan Nersesjan, MD, of Copenhagen University Hospital, and colleagues wrote.

However, it remains unknown if COVID-19 is associated with a unique pattern of cognitive and mental impairment compared with other similarly severe medical conditions, they said.

In a study published in JAMA Psychiatry (2022 Mar 23. doi: 10.1001/jamapsychiatry.2022.0284), the researchers identified 85 adult COVID-19 survivors and 61 controls with non-COVID medical conditions who were treated and released between July 2020 and July 2021. The COVID-19 patients and controls were matched for age, sex, and ICU status. Cognitive impairment was assessed using the Mini-International Neuropsychiatric Interview, the Montreal Cognitive Assessment (MoCA), neurologic examination, and a semistructured interview to determine subjective symptoms.

The primary outcomes were the total scores on the MoCA and any new-onset psychiatric diagnoses. Secondary outcomes included specific psychiatric diagnoses such as depression, neurologic examination findings, and self-reported neuropsychiatric and cognitive symptoms. The mean age of the COVID-19 patients was 56.8 years, and 42% were women.

At 6 months’ follow-up, cognitive status was significantly lower in COVID-19 survivors, compared with controls, based on total geometric mean MoCA scores (26.7 vs. 27.5, P = .01). However, cognitive status improved significantly from 19.2 at hospital discharge to 26.1 at 6 months in 15 of the COVID-19 patients (P = .004), the researchers noted.

New-onset psychiatric diagnoses occurred in 16 COVID-19 patients and 12 of the controls (19% vs. 20%); this difference was not significant.

Secondary outcomes were not significantly different at 6 months between the groups, with the exception of anosmia, which was significantly more common in the COVID-19 patients; however, the significance disappeared in adjusted analysis, the researchers said.

The study findings were limited by several factors including the inability to prove causality because of the case-control feature and by the inability to detect small differences in neuropsychiatric outcomes, the researchers noted.

However, the results were strengthened by the use of a prospectively matched control group with similar disease severity admitted to the same hospital in the same time frame. Although the overall burden of neuropsychiatric and neurologic symptoms and diagnoses appeared similar in COVID-19 patients and those with other medical conditions, more research in larger populations is needed to determine smaller differences in neuropsychiatric profiles, the researchers noted.

Study fills research gap

The study is important at this time because, although prolonged neuropsychiatric and cognitive symptoms have been reported after COVID-19, the field lacked prospective case-control studies with well-matched controls to investigate whether these outcomes differed from those seen in other critical illnesses that had also required hospitalization, corresponding author Michael E. Benros, MD, of the Mental Health Center, Copenhagen, said in an interview.

“I was surprised that there was a significant worse cognitive functioning among COVID-19 patients 6 months after symptom onset also when compared to this well-matched control group that had been hospitalized for non–COVID-19 illness, although the absolute difference between the groups in cognition score were small,” said Dr. Benros. “Another notable finding is the large improvement in cognitive functioning from discharge to follow-up,” he added on behalf of himself and fellow corresponding author Daniel Kondziella, MD.

The study results show that cognitive function affected by COVID-19 and critical illness as observed at discharge showed a substantial improvement at 6 months after symptom onset, said Dr. Benros. “However, the cognitive function was significantly worse among severely ill COVID-19 patients 6 months after symptom onset when compared to a matched control group of individuals hospitalized for non–COVID-19 illness, although this difference in cognitive function was rather small in absolute numbers, and smaller than what had been suggested by other studies that lacked control groups. Strikingly, neuropsychiatric disorders were similar across the two groups, which was also the case when looking at neuropsychiatric symptoms.

“Larger prospective case-control studies of neuropsychiatric and cognitive functioning after COVID-19, compared with matched controls are still needed to detect smaller differences, and more detailed cognitive domains, and with longer follow-up time, which we are currently conducting,” Dr. Benros said.  
 

Controlled studies will help planning

“Lingering neuropsychiatric complications are common after COVID-19, but only controlled studies can tell us whether these complications are specific to COVID-19, rather than a general effect of having been medically ill,” Alasdair G. Rooney, MRCPsych MD PhD, of the University of Edinburgh, said in an interview. “The answer matters ultimately because COVID-19 is a new disease; societies and health care services need to be able to plan for its specific consequences.”

The health status of the control group is important as well. “Most previous studies had compared COVID-19 survivors against healthy controls or patients from a historical database. This new study compared COVID-19 survivors against those hospitalized for other medical causes over the same period,” Dr. Rooney said. “This is a more stringent test of whether COVID-19 has specific neurocognitive and neuropsychiatric consequences.

“The study found that new-onset neuropsychiatric diagnoses and symptoms were no more likely to occur after COVID-19 than after similarly severe medical illnesses,” Dr. Rooney said. “This negative finding runs counter to some earlier studies and may surprise some.” The findings need to be replicated in larger samples, but the current study shows the importance of prospectively recruiting active controls.

“In a subgroup analysis, some patients showed good improvement in cognitive scores between discharge and follow-up. While unsurprising, this is encouraging and suggests that the early postdischarge months are an important time for neurocognitive recovery,” Dr. Rooney noted.

“The findings suggest that COVID-19 may impair attention more selectively than other medical causes of hospitalization. COVID-19 survivors may also be at higher risk of significant overall cognitive impairment than survivors of similarly severe medical illnesses, after a similar duration,” said Dr. Rooney. “If the results are replicated by other prospective studies, they would suggest that there is something about COVID-19 that causes clinically significant neurocognitive difficulties in a minority of survivors.

“Larger well-controlled studies are required, with longer follow-up and more detailed neurocognitive testing,” as the duration of impairment and scope for further recovery are not known, Dr. Rooney added. Also unknown is whether COVID-19 affects attention permanently, or whether recovery is simply slower after COVID-19 compared to other medical illnesses.

“Knowing who is at the greatest risk of severe cognitive impairment after COVID-19 is important and likely to allow tailoring of more effective shielding strategies,” said Dr. Rooney. “This study was conducted before the widespread availability of vaccines for COVID-19. Long-term neuropsychiatric outcomes in vaccinated patients remain largely unknown. Arguably, these are now more important to understand, as future COVID-19 waves will occur mainly among vaccinated individuals.”

The study was supported by the Lundbeck Foundation and the Novo Nordisk Foundation. Lead author Dr. Nersesjan had no financial conflicts to disclose. Dr. Benros reported grants from Lundbeck Foundation and Novo Nordisk Foundation during the conduct of the study. Dr. Rooney had no financial conflicts to disclose.

This article was updated 3/25/22.

Hospitalized COVID-19 survivors showed greater cognitive impairment 6 months later, compared with patients hospitalized for other causes, but the overall disease burden was similar, based on data from 85 adults with COVID-19.

Previous studies have shown that cognitive and neuropsychiatric symptoms can occur from 2-6 months after COVID-19 recovery, and such symptoms are known to be associated with hospitalization for other severe medical conditions, Vardan Nersesjan, MD, of Copenhagen University Hospital, and colleagues wrote.

However, it remains unknown if COVID-19 is associated with a unique pattern of cognitive and mental impairment compared with other similarly severe medical conditions, they said.

In a study published in JAMA Psychiatry (2022 Mar 23. doi: 10.1001/jamapsychiatry.2022.0284), the researchers identified 85 adult COVID-19 survivors and 61 controls with non-COVID medical conditions who were treated and released between July 2020 and July 2021. The COVID-19 patients and controls were matched for age, sex, and ICU status. Cognitive impairment was assessed using the Mini-International Neuropsychiatric Interview, the Montreal Cognitive Assessment (MoCA), neurologic examination, and a semistructured interview to determine subjective symptoms.

The primary outcomes were the total scores on the MoCA and any new-onset psychiatric diagnoses. Secondary outcomes included specific psychiatric diagnoses such as depression, neurologic examination findings, and self-reported neuropsychiatric and cognitive symptoms. The mean age of the COVID-19 patients was 56.8 years, and 42% were women.

At 6 months’ follow-up, cognitive status was significantly lower in COVID-19 survivors, compared with controls, based on total geometric mean MoCA scores (26.7 vs. 27.5, P = .01). However, cognitive status improved significantly from 19.2 at hospital discharge to 26.1 at 6 months in 15 of the COVID-19 patients (P = .004), the researchers noted.

New-onset psychiatric diagnoses occurred in 16 COVID-19 patients and 12 of the controls (19% vs. 20%); this difference was not significant.

Secondary outcomes were not significantly different at 6 months between the groups, with the exception of anosmia, which was significantly more common in the COVID-19 patients; however, the significance disappeared in adjusted analysis, the researchers said.

The study findings were limited by several factors including the inability to prove causality because of the case-control feature and by the inability to detect small differences in neuropsychiatric outcomes, the researchers noted.

However, the results were strengthened by the use of a prospectively matched control group with similar disease severity admitted to the same hospital in the same time frame. Although the overall burden of neuropsychiatric and neurologic symptoms and diagnoses appeared similar in COVID-19 patients and those with other medical conditions, more research in larger populations is needed to determine smaller differences in neuropsychiatric profiles, the researchers noted.

Study fills research gap

The study is important at this time because, although prolonged neuropsychiatric and cognitive symptoms have been reported after COVID-19, the field lacked prospective case-control studies with well-matched controls to investigate whether these outcomes differed from those seen in other critical illnesses that had also required hospitalization, corresponding author Michael E. Benros, MD, of the Mental Health Center, Copenhagen, said in an interview.

“I was surprised that there was a significant worse cognitive functioning among COVID-19 patients 6 months after symptom onset also when compared to this well-matched control group that had been hospitalized for non–COVID-19 illness, although the absolute difference between the groups in cognition score were small,” said Dr. Benros. “Another notable finding is the large improvement in cognitive functioning from discharge to follow-up,” he added on behalf of himself and fellow corresponding author Daniel Kondziella, MD.

The study results show that cognitive function affected by COVID-19 and critical illness as observed at discharge showed a substantial improvement at 6 months after symptom onset, said Dr. Benros. “However, the cognitive function was significantly worse among severely ill COVID-19 patients 6 months after symptom onset when compared to a matched control group of individuals hospitalized for non–COVID-19 illness, although this difference in cognitive function was rather small in absolute numbers, and smaller than what had been suggested by other studies that lacked control groups. Strikingly, neuropsychiatric disorders were similar across the two groups, which was also the case when looking at neuropsychiatric symptoms.

“Larger prospective case-control studies of neuropsychiatric and cognitive functioning after COVID-19, compared with matched controls are still needed to detect smaller differences, and more detailed cognitive domains, and with longer follow-up time, which we are currently conducting,” Dr. Benros said.  
 

Controlled studies will help planning

“Lingering neuropsychiatric complications are common after COVID-19, but only controlled studies can tell us whether these complications are specific to COVID-19, rather than a general effect of having been medically ill,” Alasdair G. Rooney, MRCPsych MD PhD, of the University of Edinburgh, said in an interview. “The answer matters ultimately because COVID-19 is a new disease; societies and health care services need to be able to plan for its specific consequences.”

The health status of the control group is important as well. “Most previous studies had compared COVID-19 survivors against healthy controls or patients from a historical database. This new study compared COVID-19 survivors against those hospitalized for other medical causes over the same period,” Dr. Rooney said. “This is a more stringent test of whether COVID-19 has specific neurocognitive and neuropsychiatric consequences.

“The study found that new-onset neuropsychiatric diagnoses and symptoms were no more likely to occur after COVID-19 than after similarly severe medical illnesses,” Dr. Rooney said. “This negative finding runs counter to some earlier studies and may surprise some.” The findings need to be replicated in larger samples, but the current study shows the importance of prospectively recruiting active controls.

“In a subgroup analysis, some patients showed good improvement in cognitive scores between discharge and follow-up. While unsurprising, this is encouraging and suggests that the early postdischarge months are an important time for neurocognitive recovery,” Dr. Rooney noted.

“The findings suggest that COVID-19 may impair attention more selectively than other medical causes of hospitalization. COVID-19 survivors may also be at higher risk of significant overall cognitive impairment than survivors of similarly severe medical illnesses, after a similar duration,” said Dr. Rooney. “If the results are replicated by other prospective studies, they would suggest that there is something about COVID-19 that causes clinically significant neurocognitive difficulties in a minority of survivors.

“Larger well-controlled studies are required, with longer follow-up and more detailed neurocognitive testing,” as the duration of impairment and scope for further recovery are not known, Dr. Rooney added. Also unknown is whether COVID-19 affects attention permanently, or whether recovery is simply slower after COVID-19 compared to other medical illnesses.

“Knowing who is at the greatest risk of severe cognitive impairment after COVID-19 is important and likely to allow tailoring of more effective shielding strategies,” said Dr. Rooney. “This study was conducted before the widespread availability of vaccines for COVID-19. Long-term neuropsychiatric outcomes in vaccinated patients remain largely unknown. Arguably, these are now more important to understand, as future COVID-19 waves will occur mainly among vaccinated individuals.”

The study was supported by the Lundbeck Foundation and the Novo Nordisk Foundation. Lead author Dr. Nersesjan had no financial conflicts to disclose. Dr. Benros reported grants from Lundbeck Foundation and Novo Nordisk Foundation during the conduct of the study. Dr. Rooney had no financial conflicts to disclose.

This article was updated 3/25/22.

Hospitalized COVID-19 survivors showed greater cognitive impairment 6 months later, compared with patients hospitalized for other causes, but the overall disease burden was similar, based on data from 85 adults with COVID-19.

Previous studies have shown that cognitive and neuropsychiatric symptoms can occur from 2-6 months after COVID-19 recovery, and such symptoms are known to be associated with hospitalization for other severe medical conditions, Vardan Nersesjan, MD, of Copenhagen University Hospital, and colleagues wrote.

However, it remains unknown if COVID-19 is associated with a unique pattern of cognitive and mental impairment compared with other similarly severe medical conditions, they said.

In a study published in JAMA Psychiatry (2022 Mar 23. doi: 10.1001/jamapsychiatry.2022.0284), the researchers identified 85 adult COVID-19 survivors and 61 controls with non-COVID medical conditions who were treated and released between July 2020 and July 2021. The COVID-19 patients and controls were matched for age, sex, and ICU status. Cognitive impairment was assessed using the Mini-International Neuropsychiatric Interview, the Montreal Cognitive Assessment (MoCA), neurologic examination, and a semistructured interview to determine subjective symptoms.

The primary outcomes were the total scores on the MoCA and any new-onset psychiatric diagnoses. Secondary outcomes included specific psychiatric diagnoses such as depression, neurologic examination findings, and self-reported neuropsychiatric and cognitive symptoms. The mean age of the COVID-19 patients was 56.8 years, and 42% were women.

At 6 months’ follow-up, cognitive status was significantly lower in COVID-19 survivors, compared with controls, based on total geometric mean MoCA scores (26.7 vs. 27.5, P = .01). However, cognitive status improved significantly from 19.2 at hospital discharge to 26.1 at 6 months in 15 of the COVID-19 patients (P = .004), the researchers noted.

New-onset psychiatric diagnoses occurred in 16 COVID-19 patients and 12 of the controls (19% vs. 20%); this difference was not significant.

Secondary outcomes were not significantly different at 6 months between the groups, with the exception of anosmia, which was significantly more common in the COVID-19 patients; however, the significance disappeared in adjusted analysis, the researchers said.

The study findings were limited by several factors including the inability to prove causality because of the case-control feature and by the inability to detect small differences in neuropsychiatric outcomes, the researchers noted.

However, the results were strengthened by the use of a prospectively matched control group with similar disease severity admitted to the same hospital in the same time frame. Although the overall burden of neuropsychiatric and neurologic symptoms and diagnoses appeared similar in COVID-19 patients and those with other medical conditions, more research in larger populations is needed to determine smaller differences in neuropsychiatric profiles, the researchers noted.

Study fills research gap

The study is important at this time because, although prolonged neuropsychiatric and cognitive symptoms have been reported after COVID-19, the field lacked prospective case-control studies with well-matched controls to investigate whether these outcomes differed from those seen in other critical illnesses that had also required hospitalization, corresponding author Michael E. Benros, MD, of the Mental Health Center, Copenhagen, said in an interview.

“I was surprised that there was a significant worse cognitive functioning among COVID-19 patients 6 months after symptom onset also when compared to this well-matched control group that had been hospitalized for non–COVID-19 illness, although the absolute difference between the groups in cognition score were small,” said Dr. Benros. “Another notable finding is the large improvement in cognitive functioning from discharge to follow-up,” he added on behalf of himself and fellow corresponding author Daniel Kondziella, MD.

The study results show that cognitive function affected by COVID-19 and critical illness as observed at discharge showed a substantial improvement at 6 months after symptom onset, said Dr. Benros. “However, the cognitive function was significantly worse among severely ill COVID-19 patients 6 months after symptom onset when compared to a matched control group of individuals hospitalized for non–COVID-19 illness, although this difference in cognitive function was rather small in absolute numbers, and smaller than what had been suggested by other studies that lacked control groups. Strikingly, neuropsychiatric disorders were similar across the two groups, which was also the case when looking at neuropsychiatric symptoms.

“Larger prospective case-control studies of neuropsychiatric and cognitive functioning after COVID-19, compared with matched controls are still needed to detect smaller differences, and more detailed cognitive domains, and with longer follow-up time, which we are currently conducting,” Dr. Benros said.  
 

Controlled studies will help planning

“Lingering neuropsychiatric complications are common after COVID-19, but only controlled studies can tell us whether these complications are specific to COVID-19, rather than a general effect of having been medically ill,” Alasdair G. Rooney, MRCPsych MD PhD, of the University of Edinburgh, said in an interview. “The answer matters ultimately because COVID-19 is a new disease; societies and health care services need to be able to plan for its specific consequences.”

The health status of the control group is important as well. “Most previous studies had compared COVID-19 survivors against healthy controls or patients from a historical database. This new study compared COVID-19 survivors against those hospitalized for other medical causes over the same period,” Dr. Rooney said. “This is a more stringent test of whether COVID-19 has specific neurocognitive and neuropsychiatric consequences.

“The study found that new-onset neuropsychiatric diagnoses and symptoms were no more likely to occur after COVID-19 than after similarly severe medical illnesses,” Dr. Rooney said. “This negative finding runs counter to some earlier studies and may surprise some.” The findings need to be replicated in larger samples, but the current study shows the importance of prospectively recruiting active controls.

“In a subgroup analysis, some patients showed good improvement in cognitive scores between discharge and follow-up. While unsurprising, this is encouraging and suggests that the early postdischarge months are an important time for neurocognitive recovery,” Dr. Rooney noted.

“The findings suggest that COVID-19 may impair attention more selectively than other medical causes of hospitalization. COVID-19 survivors may also be at higher risk of significant overall cognitive impairment than survivors of similarly severe medical illnesses, after a similar duration,” said Dr. Rooney. “If the results are replicated by other prospective studies, they would suggest that there is something about COVID-19 that causes clinically significant neurocognitive difficulties in a minority of survivors.

“Larger well-controlled studies are required, with longer follow-up and more detailed neurocognitive testing,” as the duration of impairment and scope for further recovery are not known, Dr. Rooney added. Also unknown is whether COVID-19 affects attention permanently, or whether recovery is simply slower after COVID-19 compared to other medical illnesses.

“Knowing who is at the greatest risk of severe cognitive impairment after COVID-19 is important and likely to allow tailoring of more effective shielding strategies,” said Dr. Rooney. “This study was conducted before the widespread availability of vaccines for COVID-19. Long-term neuropsychiatric outcomes in vaccinated patients remain largely unknown. Arguably, these are now more important to understand, as future COVID-19 waves will occur mainly among vaccinated individuals.”

The study was supported by the Lundbeck Foundation and the Novo Nordisk Foundation. Lead author Dr. Nersesjan had no financial conflicts to disclose. Dr. Benros reported grants from Lundbeck Foundation and Novo Nordisk Foundation during the conduct of the study. Dr. Rooney had no financial conflicts to disclose.

This article was updated 3/25/22.

As the controversial Alzheimer’s disease (AD) drug aducanumab (Aduhelm) begins its integration into clinical practice, some physicians are concerned the drug’s prescribing label does not include adequate brain imaging recommendations to detect amyloid-related imaging abnormalities (ARIA).

Specifically, the drug’s label calls for three MRI brain scans before, and during, the titration period. The problem is the trial data used for the drug’s approval by the U.S. Food and Drug Administration included five MRIs to screen for ARIA.

“We recommend proceeding as per the clinical trials,” said Meghan Riddle, MD, associate director, Memory and Aging program, Butler Hospital, and assistant professor of psychiatry and human behavior, Brown University, Providence, R.I.

Dr. Riddle shared her team’s clinical experience with aducanumab, as well as information on four ARIA cases from their clinic, during a presentation at the American Association for Geriatric Psychiatry (AAGP) 2022 Annual Meeting.
 

Significant safety risk?

As previously reported by this news organization, the FDA granted accelerated approval of aducanumab for AD last year.

ARIA is the most common risk associated with aducanumab and has two types: ARIA-E (with edema) and ARIA-H (with hemosiderin). These can co-occur, particularly in areas of high amyloid burden, Dr. Riddle noted during her presentation.

ARIA is often detected incidentally via MRI. Patients are usually asymptomatic, but when they do have symptoms, headache, dizziness, and vision changes are the most common complaints. However, these are generally mild, said Dr. Riddle.

Nevertheless, in some cases, there can be severe sequelae, including severe edema or bleeding and seizures, she added.

A major risk factor for ARIA is apolipoprotein 4 (APOE ε4) status. Carriers are twice as likely to develop ARIA as non-carriers.

“If you’re heterozygote for APOE ε4, you have about a 40% chance of developing ARIA, and if you’re homozygote, you have about a 66% chance of developing ARIA,” Dr. Riddle said.

Given the high rate of ARIA in APOE ε4 carriers, the team from Butler Hospital recommends APOE testing prior to treatment with aducanumab.

The risk for developing ARIA is highest within the year of dose titration, Dr. Riddle noted. The current FDA label recommends obtaining a recent brain MRI, within 1 year, and then scans before the 7th and 12th infusions. However, the protocol during the clinical trials of aducanumab included MRI at baseline and prior to the 5th, 7th, 9th, and 12th infusions.

Dr. Riddle’s group has opted to continue the research protocol with new patients. “There’s concern that the decreased MRI monitoring based on the current FDA label may pose a significant safety risk, particularly among those who we know are already at a higher risk of developing ARIA,” she said.

Dr. Riddle also shared how her team selects aducanumab candidates. They need to have mild cognitive impairment (MCI), a mini-mental state examination (MMSE) score of 24 to 30, and a recent MRI to review for eligibility and APOE testing.

The most common reason for treatment exclusion is advanced disease and comorbidity, such as stroke.

Once approved for treatment, patients receive monthly infusions titrated over 6 months – 1 mg/kg for 2 months, 3 mg/kg for 2 months, 6 mg/kg for 2 months, then 10 mg/kg.

Patients are monitored to ensure safety and tolerability and regular review of MRI findings. In addition, patients and their families receive ongoing education about the drug.

Dr. Riddle and her team permanently discontinue the aducanumab if patients develop microhemorrhage, more than one area of superficial siderosis, more than 10 microhemorrhages, more than two episodes of ARIA, or severe symptoms of ARIA.
 

Four cases

Of the 11 patients who were candidates for aducanumab treatment, four developed ARIA. All are APOE ε4 carriers, with two homozygotes and two heterozygotes. All had severe radiographic ARIA-E, with one developing ARIA-H.

“Importantly, they were all initially asymptomatic and the ARIA was just picked up on their regular surveillance MRI,” said Dr. Riddle. She added that the drug was discontinued in all four cases.

Three of the ARIA cases were detected prior to the 5th scan, which is “concerning,” said Dr. Riddle. “Based on the current FDA label of safety monitoring, they don’t recommend doing that MRI. So [clinicians] would have dosed through that ARIA, which could put someone at much greater risk of developing severe symptoms.”

In addition, 14 patients at the center are receiving treatment with aducanumab. However, at this point they have not yet received their first MRI screen.

Dr. Riddle noted that when patients are told they are not candidates for treatment, or when treatment is discontinued, they are upset. However, she added, there is also a substantial level of understanding.

“We have a very layered discussion that includes the simple fact that we still aren’t sure if this is going to provide any clinical benefit, that this decision [to approve the drug] was accelerated, and that data are still being gathered,” Dr. Riddle added.

Dr. Riddle noted that the risk of ARIA is highest during the dose titration period: “There’s a signal that once you get to the 10 mg/kg dose, that plateaus.”

None of the patients at her center have reached that 12-month treatment mark. “The current plan is to do the MRI at 12 months then to give serial MRIs but less frequently, and whether that’s at 6 months or annually is yet to be determined.”

“We’re kind of writing these protocols as information evolves,” Dr. Riddle said.

The Memory and Aging Program receives grants from NIH-ADNI, Alzheimer’s Association, Fain Family Foundation, Joukowsky Family Foundation, Winter Family, Rhode Island Foundation, Goodman Family Foundation, and Global Alzheimer Platform Foundation; and clinical trials include: Lilly, Biogen, Genentech, Avid, Roche, Eisai, and Novartis. Dr. Riddle has disclosed no relevant financial relationships.

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

As the controversial Alzheimer’s disease (AD) drug aducanumab (Aduhelm) begins its integration into clinical practice, some physicians are concerned the drug’s prescribing label does not include adequate brain imaging recommendations to detect amyloid-related imaging abnormalities (ARIA).

Specifically, the drug’s label calls for three MRI brain scans before, and during, the titration period. The problem is the trial data used for the drug’s approval by the U.S. Food and Drug Administration included five MRIs to screen for ARIA.

“We recommend proceeding as per the clinical trials,” said Meghan Riddle, MD, associate director, Memory and Aging program, Butler Hospital, and assistant professor of psychiatry and human behavior, Brown University, Providence, R.I.

Dr. Riddle shared her team’s clinical experience with aducanumab, as well as information on four ARIA cases from their clinic, during a presentation at the American Association for Geriatric Psychiatry (AAGP) 2022 Annual Meeting.
 

Significant safety risk?

As previously reported by this news organization, the FDA granted accelerated approval of aducanumab for AD last year.

ARIA is the most common risk associated with aducanumab and has two types: ARIA-E (with edema) and ARIA-H (with hemosiderin). These can co-occur, particularly in areas of high amyloid burden, Dr. Riddle noted during her presentation.

ARIA is often detected incidentally via MRI. Patients are usually asymptomatic, but when they do have symptoms, headache, dizziness, and vision changes are the most common complaints. However, these are generally mild, said Dr. Riddle.

Nevertheless, in some cases, there can be severe sequelae, including severe edema or bleeding and seizures, she added.

A major risk factor for ARIA is apolipoprotein 4 (APOE ε4) status. Carriers are twice as likely to develop ARIA as non-carriers.

“If you’re heterozygote for APOE ε4, you have about a 40% chance of developing ARIA, and if you’re homozygote, you have about a 66% chance of developing ARIA,” Dr. Riddle said.

Given the high rate of ARIA in APOE ε4 carriers, the team from Butler Hospital recommends APOE testing prior to treatment with aducanumab.

The risk for developing ARIA is highest within the year of dose titration, Dr. Riddle noted. The current FDA label recommends obtaining a recent brain MRI, within 1 year, and then scans before the 7th and 12th infusions. However, the protocol during the clinical trials of aducanumab included MRI at baseline and prior to the 5th, 7th, 9th, and 12th infusions.

Dr. Riddle’s group has opted to continue the research protocol with new patients. “There’s concern that the decreased MRI monitoring based on the current FDA label may pose a significant safety risk, particularly among those who we know are already at a higher risk of developing ARIA,” she said.

Dr. Riddle also shared how her team selects aducanumab candidates. They need to have mild cognitive impairment (MCI), a mini-mental state examination (MMSE) score of 24 to 30, and a recent MRI to review for eligibility and APOE testing.

The most common reason for treatment exclusion is advanced disease and comorbidity, such as stroke.

Once approved for treatment, patients receive monthly infusions titrated over 6 months – 1 mg/kg for 2 months, 3 mg/kg for 2 months, 6 mg/kg for 2 months, then 10 mg/kg.

Patients are monitored to ensure safety and tolerability and regular review of MRI findings. In addition, patients and their families receive ongoing education about the drug.

Dr. Riddle and her team permanently discontinue the aducanumab if patients develop microhemorrhage, more than one area of superficial siderosis, more than 10 microhemorrhages, more than two episodes of ARIA, or severe symptoms of ARIA.
 

Four cases

Of the 11 patients who were candidates for aducanumab treatment, four developed ARIA. All are APOE ε4 carriers, with two homozygotes and two heterozygotes. All had severe radiographic ARIA-E, with one developing ARIA-H.

“Importantly, they were all initially asymptomatic and the ARIA was just picked up on their regular surveillance MRI,” said Dr. Riddle. She added that the drug was discontinued in all four cases.

Three of the ARIA cases were detected prior to the 5th scan, which is “concerning,” said Dr. Riddle. “Based on the current FDA label of safety monitoring, they don’t recommend doing that MRI. So [clinicians] would have dosed through that ARIA, which could put someone at much greater risk of developing severe symptoms.”

In addition, 14 patients at the center are receiving treatment with aducanumab. However, at this point they have not yet received their first MRI screen.

Dr. Riddle noted that when patients are told they are not candidates for treatment, or when treatment is discontinued, they are upset. However, she added, there is also a substantial level of understanding.

“We have a very layered discussion that includes the simple fact that we still aren’t sure if this is going to provide any clinical benefit, that this decision [to approve the drug] was accelerated, and that data are still being gathered,” Dr. Riddle added.

Dr. Riddle noted that the risk of ARIA is highest during the dose titration period: “There’s a signal that once you get to the 10 mg/kg dose, that plateaus.”

None of the patients at her center have reached that 12-month treatment mark. “The current plan is to do the MRI at 12 months then to give serial MRIs but less frequently, and whether that’s at 6 months or annually is yet to be determined.”

“We’re kind of writing these protocols as information evolves,” Dr. Riddle said.

The Memory and Aging Program receives grants from NIH-ADNI, Alzheimer’s Association, Fain Family Foundation, Joukowsky Family Foundation, Winter Family, Rhode Island Foundation, Goodman Family Foundation, and Global Alzheimer Platform Foundation; and clinical trials include: Lilly, Biogen, Genentech, Avid, Roche, Eisai, and Novartis. Dr. Riddle has disclosed no relevant financial relationships.

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

As the controversial Alzheimer’s disease (AD) drug aducanumab (Aduhelm) begins its integration into clinical practice, some physicians are concerned the drug’s prescribing label does not include adequate brain imaging recommendations to detect amyloid-related imaging abnormalities (ARIA).

Specifically, the drug’s label calls for three MRI brain scans before, and during, the titration period. The problem is the trial data used for the drug’s approval by the U.S. Food and Drug Administration included five MRIs to screen for ARIA.

“We recommend proceeding as per the clinical trials,” said Meghan Riddle, MD, associate director, Memory and Aging program, Butler Hospital, and assistant professor of psychiatry and human behavior, Brown University, Providence, R.I.

Dr. Riddle shared her team’s clinical experience with aducanumab, as well as information on four ARIA cases from their clinic, during a presentation at the American Association for Geriatric Psychiatry (AAGP) 2022 Annual Meeting.
 

Significant safety risk?

As previously reported by this news organization, the FDA granted accelerated approval of aducanumab for AD last year.

ARIA is the most common risk associated with aducanumab and has two types: ARIA-E (with edema) and ARIA-H (with hemosiderin). These can co-occur, particularly in areas of high amyloid burden, Dr. Riddle noted during her presentation.

ARIA is often detected incidentally via MRI. Patients are usually asymptomatic, but when they do have symptoms, headache, dizziness, and vision changes are the most common complaints. However, these are generally mild, said Dr. Riddle.

Nevertheless, in some cases, there can be severe sequelae, including severe edema or bleeding and seizures, she added.

A major risk factor for ARIA is apolipoprotein 4 (APOE ε4) status. Carriers are twice as likely to develop ARIA as non-carriers.

“If you’re heterozygote for APOE ε4, you have about a 40% chance of developing ARIA, and if you’re homozygote, you have about a 66% chance of developing ARIA,” Dr. Riddle said.

Given the high rate of ARIA in APOE ε4 carriers, the team from Butler Hospital recommends APOE testing prior to treatment with aducanumab.

The risk for developing ARIA is highest within the year of dose titration, Dr. Riddle noted. The current FDA label recommends obtaining a recent brain MRI, within 1 year, and then scans before the 7th and 12th infusions. However, the protocol during the clinical trials of aducanumab included MRI at baseline and prior to the 5th, 7th, 9th, and 12th infusions.

Dr. Riddle’s group has opted to continue the research protocol with new patients. “There’s concern that the decreased MRI monitoring based on the current FDA label may pose a significant safety risk, particularly among those who we know are already at a higher risk of developing ARIA,” she said.

Dr. Riddle also shared how her team selects aducanumab candidates. They need to have mild cognitive impairment (MCI), a mini-mental state examination (MMSE) score of 24 to 30, and a recent MRI to review for eligibility and APOE testing.

The most common reason for treatment exclusion is advanced disease and comorbidity, such as stroke.

Once approved for treatment, patients receive monthly infusions titrated over 6 months – 1 mg/kg for 2 months, 3 mg/kg for 2 months, 6 mg/kg for 2 months, then 10 mg/kg.

Patients are monitored to ensure safety and tolerability and regular review of MRI findings. In addition, patients and their families receive ongoing education about the drug.

Dr. Riddle and her team permanently discontinue the aducanumab if patients develop microhemorrhage, more than one area of superficial siderosis, more than 10 microhemorrhages, more than two episodes of ARIA, or severe symptoms of ARIA.
 

Four cases

Of the 11 patients who were candidates for aducanumab treatment, four developed ARIA. All are APOE ε4 carriers, with two homozygotes and two heterozygotes. All had severe radiographic ARIA-E, with one developing ARIA-H.

“Importantly, they were all initially asymptomatic and the ARIA was just picked up on their regular surveillance MRI,” said Dr. Riddle. She added that the drug was discontinued in all four cases.

Three of the ARIA cases were detected prior to the 5th scan, which is “concerning,” said Dr. Riddle. “Based on the current FDA label of safety monitoring, they don’t recommend doing that MRI. So [clinicians] would have dosed through that ARIA, which could put someone at much greater risk of developing severe symptoms.”

In addition, 14 patients at the center are receiving treatment with aducanumab. However, at this point they have not yet received their first MRI screen.

Dr. Riddle noted that when patients are told they are not candidates for treatment, or when treatment is discontinued, they are upset. However, she added, there is also a substantial level of understanding.

“We have a very layered discussion that includes the simple fact that we still aren’t sure if this is going to provide any clinical benefit, that this decision [to approve the drug] was accelerated, and that data are still being gathered,” Dr. Riddle added.

Dr. Riddle noted that the risk of ARIA is highest during the dose titration period: “There’s a signal that once you get to the 10 mg/kg dose, that plateaus.”

None of the patients at her center have reached that 12-month treatment mark. “The current plan is to do the MRI at 12 months then to give serial MRIs but less frequently, and whether that’s at 6 months or annually is yet to be determined.”

“We’re kind of writing these protocols as information evolves,” Dr. Riddle said.

The Memory and Aging Program receives grants from NIH-ADNI, Alzheimer’s Association, Fain Family Foundation, Joukowsky Family Foundation, Winter Family, Rhode Island Foundation, Goodman Family Foundation, and Global Alzheimer Platform Foundation; and clinical trials include: Lilly, Biogen, Genentech, Avid, Roche, Eisai, and Novartis. Dr. Riddle has disclosed 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.

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.

The Food and Drug Administration has approved donepezil transdermal system (Adlarity) for patients with mild, moderate, or severe Alzheimer’s disease, the manufacturer has announced.

Adlarity is the first and only once-weekly patch to continuously deliver consistent doses of the acetylcholinesterase inhibitor through the skin, bypassing the digestive system and resulting in low likelihood of gastrointestinal side effects associated with oral donepezil, the company said in a press release.

Each patch delivers either 5 mg or 10 mg of donepezil daily for 7 days. After that, it is removed and a new patch is applied.

“The availability of a once-weekly patch formulation of donepezil has the potential to substantially benefit patients, caregivers, and health care providers,” Pierre Tariot, MD, director of the Banner Alzheimer’s Institute, Phoenix, said in the release.

“It offers effective, well-tolerated, and stable dosing for 7 days for patients who cannot take daily oral donepezil reliably because of impaired memory. It can also offer benefits for those patients who have diminished ability to swallow or have GI side effects associated with ingestion of oral donepezil,” Dr. Tariot added.

The FDA approved Adlarity through the 505(b)(2) regulatory pathway, which allows the agency to refer to previous findings of safety and efficacy for an already-approved product, as well as to review findings from further studies of the product.

The company expects the donepezil transdermal patch to be available in early Fall 2022.

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

The Food and Drug Administration has approved donepezil transdermal system (Adlarity) for patients with mild, moderate, or severe Alzheimer’s disease, the manufacturer has announced.

Adlarity is the first and only once-weekly patch to continuously deliver consistent doses of the acetylcholinesterase inhibitor through the skin, bypassing the digestive system and resulting in low likelihood of gastrointestinal side effects associated with oral donepezil, the company said in a press release.

Each patch delivers either 5 mg or 10 mg of donepezil daily for 7 days. After that, it is removed and a new patch is applied.

“The availability of a once-weekly patch formulation of donepezil has the potential to substantially benefit patients, caregivers, and health care providers,” Pierre Tariot, MD, director of the Banner Alzheimer’s Institute, Phoenix, said in the release.

“It offers effective, well-tolerated, and stable dosing for 7 days for patients who cannot take daily oral donepezil reliably because of impaired memory. It can also offer benefits for those patients who have diminished ability to swallow or have GI side effects associated with ingestion of oral donepezil,” Dr. Tariot added.

The FDA approved Adlarity through the 505(b)(2) regulatory pathway, which allows the agency to refer to previous findings of safety and efficacy for an already-approved product, as well as to review findings from further studies of the product.

The company expects the donepezil transdermal patch to be available in early Fall 2022.

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

The Food and Drug Administration has approved donepezil transdermal system (Adlarity) for patients with mild, moderate, or severe Alzheimer’s disease, the manufacturer has announced.

Adlarity is the first and only once-weekly patch to continuously deliver consistent doses of the acetylcholinesterase inhibitor through the skin, bypassing the digestive system and resulting in low likelihood of gastrointestinal side effects associated with oral donepezil, the company said in a press release.

Each patch delivers either 5 mg or 10 mg of donepezil daily for 7 days. After that, it is removed and a new patch is applied.

“The availability of a once-weekly patch formulation of donepezil has the potential to substantially benefit patients, caregivers, and health care providers,” Pierre Tariot, MD, director of the Banner Alzheimer’s Institute, Phoenix, said in the release.

“It offers effective, well-tolerated, and stable dosing for 7 days for patients who cannot take daily oral donepezil reliably because of impaired memory. It can also offer benefits for those patients who have diminished ability to swallow or have GI side effects associated with ingestion of oral donepezil,” Dr. Tariot added.

The FDA approved Adlarity through the 505(b)(2) regulatory pathway, which allows the agency to refer to previous findings of safety and efficacy for an already-approved product, as well as to review findings from further studies of the product.

The company expects the donepezil transdermal patch to be available in early Fall 2022.

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

The American Academy of Neurology (AAN) has released new expert guidance on palliative care for patients with stroke, dementia, Parkinson’s disease, and other neurologic disorders.

Palliative care includes much more than hospice services, lead author of the new position statement Lynne P. Taylor, MD, University of Washington, Seattle, and a fellow of the AAN, said in a press release.

“Neurologists provide palliative care to people living with life-altering neurologic illnesses not just at the end of life but throughout the course of a disease, improving their lives with symptom control,” Dr. Taylor added.

The position paper, developed by a joint committee of the AAN, American Neurological Association, and Child Neurology Society, was published online March 8 in Neurology.
 

Guidance across the lifespan

The new paper, an update of previous position statements, includes palliative care guidance for different neurologic disorders across the lifespan. For example, neuropalliative care for neonates deserves “extra consideration,” because one-third of pediatric deaths occur during the neonatal period, most often in the neonatal intensive care unit, and after withdrawal of life-sustaining interventions, the authors note.

For older children, neuropalliative care consultation benefits families trying to maximize the quality of the remainder of their child’s life. Decisionmaking must consider the child’s cognitive abilities, the diagnosis, the perceived level of suffering, parental values, and the family’s understanding of the prognosis, the authors note.

They note that discussions about prognosis are often difficult but critical. Previous research “supports that patients desire prognostic information even when prognosis is uncertain and appreciate when their physicians disclose the presence of that uncertainty,” the authors note.

Also important is engaging in shared decisionmaking with patients and families. “This approach requires the physician to elicit a patient’s goals, make recommendations based on whether medical treatments are likely to achieve those goals, and work with patients and families to finalize a treatment plan,” according to the new guidance.
 

Ethical considerations

When treatments are physiologically futile, clinicians need to explain why interventions that may cause harm and have no benefit are not offered.

The authors cite cardiopulmonary resuscitation in the setting of cardiac arrest from irreversible herniation as an example of futility in the context of neurologic disease.

When life-prolonging care is no longer an option, clinicians have an obligation to shift the focus of care to preserving quality of life and comfort as much as possible, they add.

Hospices, which provide comfort-focused medical care as well as psychosocial and spiritual support, are reserved for patients believed to be in the last 6 months of their life if their disease follows the expected course.

The investigators also broached ethical considerations for individual neurologic conditions. Concerns for disorders of consciousness include misdiagnosis or inaccurate prognostication, and serial examinations are needed to re-evaluate levels of cognition, psychological state, decisionmaking capacity, and disease trajectory.

In patients with locked-in syndrome, a state of irreversible paralysis, often with respiratory and vocal paralysis, consciousness may range from a chronic minimally conscious state to intact cognition.

Without careful examination, patients with preserved consciousness may be mistaken as having a disorder of consciousness and risk their decisional capacity being ignored, the researchers note.

These patients may need assistance from speech pathologists to identify techniques to enhance communication, such as careful “yes/no” questioning, communication boards, or advanced eye-gaze technology, they add.
 

Stroke, dementia, Parkinson’s guidance

For stroke, the guidance suggests neurologists encourage patients with retained decisionmaking capacity to complete advance care planning given the risk of recurrent stroke and loss of capacity in the future.

For dementia, a proper and timely diagnosis can help patients and their families prepare for the consequences of cognitive dysfunction and loss of autonomy while respecting their identified values, the authors write.

They note that for Parkinson’s disease, which is marked by slow functional and cognitive decline, neurologists must aim to anticipate and treat symptoms, address psychosocial and spiritual distress and caregiver burden, and engage patients and families in advance care planning before onset of cognitive impairment.

For patients with amyotrophic lateral sclerosis (ALS) and related disorders, clinicians should aim to document goals and treatment preferences prior to extreme weakness and aphonia.

It is also important to anticipate patient preferences for future disability-specific decisions, such as those related to feeding tubes and mechanical ventilation, and to identify the patient’s minimal acceptable outcome from these life-sustaining interventions.

On the topic of withdrawal of treatment, the paper notes that competent patients have the right to refuse life-prolonging therapies, including artificial nutrition, hydration, mechanical ventilation, and antibiotics. If physicians have a moral objection to removing life-support systems, they are obligated to transfer the care of the patient to another physician, the authors add.

Once a decision is made to forgo life-sustaining treatment, physicians should minimize subsequent suffering. The investigators note most symptoms at the end of life can be managed without sedation.

In broaching the “gap” in neurology training programs, the statement referred to a survey of 49 neurology residency programs. Results showed that 42% of respondents reported being dissatisfied with their palliative care education.
 

Well-timed update

Kate T. Brizzi, MD, a Boston neurologist with experience in hospice and palliative care, said the updated position statement is “well-timed” as neuropalliative care has evolved dramatically over the last decade.

“In the last several years, I’ve witnessed a significant increase in trainee interest in the field, and there is growing recognition of how a palliative care approach can improve patient care and hopefully outcomes,” said Dr. Brizzi.

She praised the authors for doing “an excellent job” in highlighting the ethical challenges facing the neurology provider, particularly as it relates to prognostication in an uncertain setting.

Dr. Brizzi noted communication tools that help facilitate discussions around shared decisionmaking “have enhanced our ability to meet the palliative care needs of our patients and can be incorporated by any provider.”

However, she added that the paper only briefly comments on the role of the neurologist in “lawful physician-hastened death.”

“I anticipate that this will be an area of further discussion in the neurology and palliative care community in the future, as requests for hastened death are frequently encountered from patients with serious neurologic illness,” she said.

Dr. Brizzi also noted the importance of understanding the reasons behind the request – and addressing patient worries related to end-of-life care, which can frequently help alleviate distress.

There was no targeted funding for this paper. Coauthor Salvador Cruz-Flores, MD, department of neurology, Texas Tech University Center, El Paso, reported participation on member adjudication committees for clinical trials for Novo Nordisk, Sunovion, and Galapagos. The remaining authors have disclosed no relevant financial relationships.

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

The American Academy of Neurology (AAN) has released new expert guidance on palliative care for patients with stroke, dementia, Parkinson’s disease, and other neurologic disorders.

Palliative care includes much more than hospice services, lead author of the new position statement Lynne P. Taylor, MD, University of Washington, Seattle, and a fellow of the AAN, said in a press release.

“Neurologists provide palliative care to people living with life-altering neurologic illnesses not just at the end of life but throughout the course of a disease, improving their lives with symptom control,” Dr. Taylor added.

The position paper, developed by a joint committee of the AAN, American Neurological Association, and Child Neurology Society, was published online March 8 in Neurology.
 

Guidance across the lifespan

The new paper, an update of previous position statements, includes palliative care guidance for different neurologic disorders across the lifespan. For example, neuropalliative care for neonates deserves “extra consideration,” because one-third of pediatric deaths occur during the neonatal period, most often in the neonatal intensive care unit, and after withdrawal of life-sustaining interventions, the authors note.

For older children, neuropalliative care consultation benefits families trying to maximize the quality of the remainder of their child’s life. Decisionmaking must consider the child’s cognitive abilities, the diagnosis, the perceived level of suffering, parental values, and the family’s understanding of the prognosis, the authors note.

They note that discussions about prognosis are often difficult but critical. Previous research “supports that patients desire prognostic information even when prognosis is uncertain and appreciate when their physicians disclose the presence of that uncertainty,” the authors note.

Also important is engaging in shared decisionmaking with patients and families. “This approach requires the physician to elicit a patient’s goals, make recommendations based on whether medical treatments are likely to achieve those goals, and work with patients and families to finalize a treatment plan,” according to the new guidance.
 

Ethical considerations

When treatments are physiologically futile, clinicians need to explain why interventions that may cause harm and have no benefit are not offered.

The authors cite cardiopulmonary resuscitation in the setting of cardiac arrest from irreversible herniation as an example of futility in the context of neurologic disease.

When life-prolonging care is no longer an option, clinicians have an obligation to shift the focus of care to preserving quality of life and comfort as much as possible, they add.

Hospices, which provide comfort-focused medical care as well as psychosocial and spiritual support, are reserved for patients believed to be in the last 6 months of their life if their disease follows the expected course.

The investigators also broached ethical considerations for individual neurologic conditions. Concerns for disorders of consciousness include misdiagnosis or inaccurate prognostication, and serial examinations are needed to re-evaluate levels of cognition, psychological state, decisionmaking capacity, and disease trajectory.

In patients with locked-in syndrome, a state of irreversible paralysis, often with respiratory and vocal paralysis, consciousness may range from a chronic minimally conscious state to intact cognition.

Without careful examination, patients with preserved consciousness may be mistaken as having a disorder of consciousness and risk their decisional capacity being ignored, the researchers note.

These patients may need assistance from speech pathologists to identify techniques to enhance communication, such as careful “yes/no” questioning, communication boards, or advanced eye-gaze technology, they add.
 

Stroke, dementia, Parkinson’s guidance

For stroke, the guidance suggests neurologists encourage patients with retained decisionmaking capacity to complete advance care planning given the risk of recurrent stroke and loss of capacity in the future.

For dementia, a proper and timely diagnosis can help patients and their families prepare for the consequences of cognitive dysfunction and loss of autonomy while respecting their identified values, the authors write.

They note that for Parkinson’s disease, which is marked by slow functional and cognitive decline, neurologists must aim to anticipate and treat symptoms, address psychosocial and spiritual distress and caregiver burden, and engage patients and families in advance care planning before onset of cognitive impairment.

For patients with amyotrophic lateral sclerosis (ALS) and related disorders, clinicians should aim to document goals and treatment preferences prior to extreme weakness and aphonia.

It is also important to anticipate patient preferences for future disability-specific decisions, such as those related to feeding tubes and mechanical ventilation, and to identify the patient’s minimal acceptable outcome from these life-sustaining interventions.

On the topic of withdrawal of treatment, the paper notes that competent patients have the right to refuse life-prolonging therapies, including artificial nutrition, hydration, mechanical ventilation, and antibiotics. If physicians have a moral objection to removing life-support systems, they are obligated to transfer the care of the patient to another physician, the authors add.

Once a decision is made to forgo life-sustaining treatment, physicians should minimize subsequent suffering. The investigators note most symptoms at the end of life can be managed without sedation.

In broaching the “gap” in neurology training programs, the statement referred to a survey of 49 neurology residency programs. Results showed that 42% of respondents reported being dissatisfied with their palliative care education.
 

Well-timed update

Kate T. Brizzi, MD, a Boston neurologist with experience in hospice and palliative care, said the updated position statement is “well-timed” as neuropalliative care has evolved dramatically over the last decade.

“In the last several years, I’ve witnessed a significant increase in trainee interest in the field, and there is growing recognition of how a palliative care approach can improve patient care and hopefully outcomes,” said Dr. Brizzi.

She praised the authors for doing “an excellent job” in highlighting the ethical challenges facing the neurology provider, particularly as it relates to prognostication in an uncertain setting.

Dr. Brizzi noted communication tools that help facilitate discussions around shared decisionmaking “have enhanced our ability to meet the palliative care needs of our patients and can be incorporated by any provider.”

However, she added that the paper only briefly comments on the role of the neurologist in “lawful physician-hastened death.”

“I anticipate that this will be an area of further discussion in the neurology and palliative care community in the future, as requests for hastened death are frequently encountered from patients with serious neurologic illness,” she said.

Dr. Brizzi also noted the importance of understanding the reasons behind the request – and addressing patient worries related to end-of-life care, which can frequently help alleviate distress.

There was no targeted funding for this paper. Coauthor Salvador Cruz-Flores, MD, department of neurology, Texas Tech University Center, El Paso, reported participation on member adjudication committees for clinical trials for Novo Nordisk, Sunovion, and Galapagos. The remaining authors have disclosed no relevant financial relationships.

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

The American Academy of Neurology (AAN) has released new expert guidance on palliative care for patients with stroke, dementia, Parkinson’s disease, and other neurologic disorders.

Palliative care includes much more than hospice services, lead author of the new position statement Lynne P. Taylor, MD, University of Washington, Seattle, and a fellow of the AAN, said in a press release.

“Neurologists provide palliative care to people living with life-altering neurologic illnesses not just at the end of life but throughout the course of a disease, improving their lives with symptom control,” Dr. Taylor added.

The position paper, developed by a joint committee of the AAN, American Neurological Association, and Child Neurology Society, was published online March 8 in Neurology.
 

Guidance across the lifespan

The new paper, an update of previous position statements, includes palliative care guidance for different neurologic disorders across the lifespan. For example, neuropalliative care for neonates deserves “extra consideration,” because one-third of pediatric deaths occur during the neonatal period, most often in the neonatal intensive care unit, and after withdrawal of life-sustaining interventions, the authors note.

For older children, neuropalliative care consultation benefits families trying to maximize the quality of the remainder of their child’s life. Decisionmaking must consider the child’s cognitive abilities, the diagnosis, the perceived level of suffering, parental values, and the family’s understanding of the prognosis, the authors note.

They note that discussions about prognosis are often difficult but critical. Previous research “supports that patients desire prognostic information even when prognosis is uncertain and appreciate when their physicians disclose the presence of that uncertainty,” the authors note.

Also important is engaging in shared decisionmaking with patients and families. “This approach requires the physician to elicit a patient’s goals, make recommendations based on whether medical treatments are likely to achieve those goals, and work with patients and families to finalize a treatment plan,” according to the new guidance.
 

Ethical considerations

When treatments are physiologically futile, clinicians need to explain why interventions that may cause harm and have no benefit are not offered.

The authors cite cardiopulmonary resuscitation in the setting of cardiac arrest from irreversible herniation as an example of futility in the context of neurologic disease.

When life-prolonging care is no longer an option, clinicians have an obligation to shift the focus of care to preserving quality of life and comfort as much as possible, they add.

Hospices, which provide comfort-focused medical care as well as psychosocial and spiritual support, are reserved for patients believed to be in the last 6 months of their life if their disease follows the expected course.

The investigators also broached ethical considerations for individual neurologic conditions. Concerns for disorders of consciousness include misdiagnosis or inaccurate prognostication, and serial examinations are needed to re-evaluate levels of cognition, psychological state, decisionmaking capacity, and disease trajectory.

In patients with locked-in syndrome, a state of irreversible paralysis, often with respiratory and vocal paralysis, consciousness may range from a chronic minimally conscious state to intact cognition.

Without careful examination, patients with preserved consciousness may be mistaken as having a disorder of consciousness and risk their decisional capacity being ignored, the researchers note.

These patients may need assistance from speech pathologists to identify techniques to enhance communication, such as careful “yes/no” questioning, communication boards, or advanced eye-gaze technology, they add.
 

Stroke, dementia, Parkinson’s guidance

For stroke, the guidance suggests neurologists encourage patients with retained decisionmaking capacity to complete advance care planning given the risk of recurrent stroke and loss of capacity in the future.

For dementia, a proper and timely diagnosis can help patients and their families prepare for the consequences of cognitive dysfunction and loss of autonomy while respecting their identified values, the authors write.

They note that for Parkinson’s disease, which is marked by slow functional and cognitive decline, neurologists must aim to anticipate and treat symptoms, address psychosocial and spiritual distress and caregiver burden, and engage patients and families in advance care planning before onset of cognitive impairment.

For patients with amyotrophic lateral sclerosis (ALS) and related disorders, clinicians should aim to document goals and treatment preferences prior to extreme weakness and aphonia.

It is also important to anticipate patient preferences for future disability-specific decisions, such as those related to feeding tubes and mechanical ventilation, and to identify the patient’s minimal acceptable outcome from these life-sustaining interventions.

On the topic of withdrawal of treatment, the paper notes that competent patients have the right to refuse life-prolonging therapies, including artificial nutrition, hydration, mechanical ventilation, and antibiotics. If physicians have a moral objection to removing life-support systems, they are obligated to transfer the care of the patient to another physician, the authors add.

Once a decision is made to forgo life-sustaining treatment, physicians should minimize subsequent suffering. The investigators note most symptoms at the end of life can be managed without sedation.

In broaching the “gap” in neurology training programs, the statement referred to a survey of 49 neurology residency programs. Results showed that 42% of respondents reported being dissatisfied with their palliative care education.
 

Well-timed update

Kate T. Brizzi, MD, a Boston neurologist with experience in hospice and palliative care, said the updated position statement is “well-timed” as neuropalliative care has evolved dramatically over the last decade.

“In the last several years, I’ve witnessed a significant increase in trainee interest in the field, and there is growing recognition of how a palliative care approach can improve patient care and hopefully outcomes,” said Dr. Brizzi.

She praised the authors for doing “an excellent job” in highlighting the ethical challenges facing the neurology provider, particularly as it relates to prognostication in an uncertain setting.

Dr. Brizzi noted communication tools that help facilitate discussions around shared decisionmaking “have enhanced our ability to meet the palliative care needs of our patients and can be incorporated by any provider.”

However, she added that the paper only briefly comments on the role of the neurologist in “lawful physician-hastened death.”

“I anticipate that this will be an area of further discussion in the neurology and palliative care community in the future, as requests for hastened death are frequently encountered from patients with serious neurologic illness,” she said.

Dr. Brizzi also noted the importance of understanding the reasons behind the request – and addressing patient worries related to end-of-life care, which can frequently help alleviate distress.

There was no targeted funding for this paper. Coauthor Salvador Cruz-Flores, MD, department of neurology, Texas Tech University Center, El Paso, reported participation on member adjudication committees for clinical trials for Novo Nordisk, Sunovion, and Galapagos. The remaining authors have disclosed no relevant financial relationships.

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.

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.

A high-fiber diet, especially one rich in soluble fiber, is linked to a lower risk of incident disabling dementia, new research shows.

Investigators administered a dietary survey to 3,700 healthy adults at midlife and then followed them for up to 20 years. They found that participants who consumed the most fiber had approximately a 25% lower risk of developing dementia in later life.

“This study showed that people with a high intake of dietary fiber, especially soluble fiber, have a lower risk of dementia,” study investigator Kazumasa Yamagishi, MD, PhD, professor, department of public health medicine, faculty of medicine and health, Services Research and Development Center, University of Tsukuba, Japan, said in an interview.

CDC/Debora Cartagena

“There are still many unknowns about the causes of dementia, and it is not appropriate to determine causality based on the results of a single cohort study. However, the results of this study can be said to be one of the findings that will lead to the prevention of dementia,” Dr. Yamagishi said.

The study was published online Feb. 6 in Nutritional Neuroscience.
 

Brain-gut interaction

Brain-gut interaction has recently received attention for its potential involvement in the development of dementia. “The concept of brain-gut interaction emerged from the idea that the central nervous system communicates bidirectionally with the gastrointestinal tract, suggesting that the gut microbiome may influence brain plasticity and cognitive function,” the authors wrote.

A diet high in soluble fiber attenuates neuroinflammation in mouse models. Other animal studies have suggested that insoluble fiber might also have a beneficial effect on the microbiome.

The researchers wanted to see whether dietary fiber intake – especially soluble fiber – is associated with a reduced risk of dementia. They also investigated whether there was any difference between dementia in patients with vs. without a history of stroke.

In a previous study, these same researchers reported an inverse association between eating beans, which are high in fiber, and risk of disabling dementia. In the current study, the researchers extended the analyses to dietary fiber intake of total, soluble, and insoluble fibers, as well as other fiber-containing foods, such potatoes, vegetables, and fruits. However, they distinguished potatoes from other vegetables because the composition of starch in potatoes differs.

“Dietary fiber is a nutrient found in grains, potatoes, vegetables, and fruits and is known to affect intestinal bacteria,” Dr. Yamagishi said. “Recently, some experimental studies have shown that intestinal bacteria may be involved in cognitive functions as well as diseases of the digestive tract. However, there have been no studies that have actually examined the relationship between dietary fiber intake and the subsequent risk of dementia in large numbers of general people.”

The researchers turned to participants in the Circulatory Risk in Communities Study (CIRCS), an ongoing dynamic community cohort study involving five communities in Japan. The current study focused on communities where disabling dementia surveillance is conducted.

Participants (n = 3,739) ranged in age from 40 to 64 years (mean age, 51 years) at the time they completed the 24-hour dietary recall survey, and they participated in annual health checkups from 1985 to 1999. Potential risk factors for disabling dementia were measured at the time the dietary surveys were conducted. Participants were then followed for a median of 19.7 years (1999-2020) to confirm incident, disabling dementia.

“Disabling dementia” was defined as dementia that required care under the National Long-Term Care Insurance System and was further categorized on the basis of having a history or not having a history of stroke.

The researchers divided participants into quartiles, based on the amount of total, soluble, and insoluble intake reported in their surveys. They found that men tended to consume less total fiber compared to women.
 

Unclear mechanism

During follow-up, 670 participants developed disabling dementia.

Total fiber intake was “inversely and linearly” associated with risk of incident dementia, the authors reported, with each successive quartile associated with a lower risk compared to the lowest quartile (P for trend = .03).

The association remained after adjustment for potential factors that might affect dementia onset, such as body mass index, systolic blood pressure, antihypertensive medication use, serum total cholesterol, cholesterol-lowering medication, and diabetes (P for trend = .05).

“The inverse association was more evident for soluble fiber intake and was confined to dementia without a history of stroke,” the authors reported. Moreover, potatoes, not vegetables or fruits, showed a similar association.

“The mechanisms are currently unknown but might involve the interactions that take place between the gut and the brain,” Dr. Yamagishi said in a release.

“One possibility is that soluble fiber regulates the composition of gut bacteria. This composition may affect neuroinflammation, which plays a role in the onset of dementia,” he suggested. “It’s also possible that dietary fiber may reduce other risk factors for dementia, such as body weight, blood pressure, lipids, and glucose levels.”

The authors noted several limitations. For example, they did not distinguish between Alzheimer’s and non-Alzheimer’s dementia. Moreover, they classified dietary habits on the basis of a single survey, and participants’ dietary patterns might have changed over the study period.

In addition, Dr. Yamagishi noted, it is “important to confirm the association in other populations.”
 

Balance is key

In an interview, Uma Naidoo, MD, director of nutritional and lifestyle psychiatry, Massachusetts General Hospital, and nutrition educator at Harvard Medical School, both in Boston, said the study “adds to the growing pool of evidence suggesting that a diet rich in colorful, plant-based foods can benefit our neurological and psychiatric health, especially as we age.”

Dr. Naidoo, a chef and the author of “This Is Your Brain on Food,” who was not involved in the study, continued, “In nutritional psychiatry, balance is key and therefore consuming a well-rounded diet including ample amounts of fiber – particularly from sources like steel-cut oats, beans, lentils, and numerous other fruits and vegetables – can be part of a healthy lifestyle and prevention against cognitive decline in later years.

“While the study authors admit to limitations within the study, in my opinion, eating healthier has so many mental and physical health benefits that it’s a nutritional psychiatry no-brainer,” she added.

The study was partly supported by Health and Labour Science Research Grants for Dementia from the Ministry of Health, Labour and Welfare of Japan; JSPS Kakenhi; FULLHAP; and the Osaka University International Joint Research Promotion Programme with University College London. The authors and Dr. Naidoo report no relevant financial relationships.

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

A high-fiber diet, especially one rich in soluble fiber, is linked to a lower risk of incident disabling dementia, new research shows.

Investigators administered a dietary survey to 3,700 healthy adults at midlife and then followed them for up to 20 years. They found that participants who consumed the most fiber had approximately a 25% lower risk of developing dementia in later life.

“This study showed that people with a high intake of dietary fiber, especially soluble fiber, have a lower risk of dementia,” study investigator Kazumasa Yamagishi, MD, PhD, professor, department of public health medicine, faculty of medicine and health, Services Research and Development Center, University of Tsukuba, Japan, said in an interview.

CDC/Debora Cartagena

“There are still many unknowns about the causes of dementia, and it is not appropriate to determine causality based on the results of a single cohort study. However, the results of this study can be said to be one of the findings that will lead to the prevention of dementia,” Dr. Yamagishi said.

The study was published online Feb. 6 in Nutritional Neuroscience.
 

Brain-gut interaction

Brain-gut interaction has recently received attention for its potential involvement in the development of dementia. “The concept of brain-gut interaction emerged from the idea that the central nervous system communicates bidirectionally with the gastrointestinal tract, suggesting that the gut microbiome may influence brain plasticity and cognitive function,” the authors wrote.

A diet high in soluble fiber attenuates neuroinflammation in mouse models. Other animal studies have suggested that insoluble fiber might also have a beneficial effect on the microbiome.

The researchers wanted to see whether dietary fiber intake – especially soluble fiber – is associated with a reduced risk of dementia. They also investigated whether there was any difference between dementia in patients with vs. without a history of stroke.

In a previous study, these same researchers reported an inverse association between eating beans, which are high in fiber, and risk of disabling dementia. In the current study, the researchers extended the analyses to dietary fiber intake of total, soluble, and insoluble fibers, as well as other fiber-containing foods, such potatoes, vegetables, and fruits. However, they distinguished potatoes from other vegetables because the composition of starch in potatoes differs.

“Dietary fiber is a nutrient found in grains, potatoes, vegetables, and fruits and is known to affect intestinal bacteria,” Dr. Yamagishi said. “Recently, some experimental studies have shown that intestinal bacteria may be involved in cognitive functions as well as diseases of the digestive tract. However, there have been no studies that have actually examined the relationship between dietary fiber intake and the subsequent risk of dementia in large numbers of general people.”

The researchers turned to participants in the Circulatory Risk in Communities Study (CIRCS), an ongoing dynamic community cohort study involving five communities in Japan. The current study focused on communities where disabling dementia surveillance is conducted.

Participants (n = 3,739) ranged in age from 40 to 64 years (mean age, 51 years) at the time they completed the 24-hour dietary recall survey, and they participated in annual health checkups from 1985 to 1999. Potential risk factors for disabling dementia were measured at the time the dietary surveys were conducted. Participants were then followed for a median of 19.7 years (1999-2020) to confirm incident, disabling dementia.

“Disabling dementia” was defined as dementia that required care under the National Long-Term Care Insurance System and was further categorized on the basis of having a history or not having a history of stroke.

The researchers divided participants into quartiles, based on the amount of total, soluble, and insoluble intake reported in their surveys. They found that men tended to consume less total fiber compared to women.
 

Unclear mechanism

During follow-up, 670 participants developed disabling dementia.

Total fiber intake was “inversely and linearly” associated with risk of incident dementia, the authors reported, with each successive quartile associated with a lower risk compared to the lowest quartile (P for trend = .03).

The association remained after adjustment for potential factors that might affect dementia onset, such as body mass index, systolic blood pressure, antihypertensive medication use, serum total cholesterol, cholesterol-lowering medication, and diabetes (P for trend = .05).

“The inverse association was more evident for soluble fiber intake and was confined to dementia without a history of stroke,” the authors reported. Moreover, potatoes, not vegetables or fruits, showed a similar association.

“The mechanisms are currently unknown but might involve the interactions that take place between the gut and the brain,” Dr. Yamagishi said in a release.

“One possibility is that soluble fiber regulates the composition of gut bacteria. This composition may affect neuroinflammation, which plays a role in the onset of dementia,” he suggested. “It’s also possible that dietary fiber may reduce other risk factors for dementia, such as body weight, blood pressure, lipids, and glucose levels.”

The authors noted several limitations. For example, they did not distinguish between Alzheimer’s and non-Alzheimer’s dementia. Moreover, they classified dietary habits on the basis of a single survey, and participants’ dietary patterns might have changed over the study period.

In addition, Dr. Yamagishi noted, it is “important to confirm the association in other populations.”
 

Balance is key

In an interview, Uma Naidoo, MD, director of nutritional and lifestyle psychiatry, Massachusetts General Hospital, and nutrition educator at Harvard Medical School, both in Boston, said the study “adds to the growing pool of evidence suggesting that a diet rich in colorful, plant-based foods can benefit our neurological and psychiatric health, especially as we age.”

Dr. Naidoo, a chef and the author of “This Is Your Brain on Food,” who was not involved in the study, continued, “In nutritional psychiatry, balance is key and therefore consuming a well-rounded diet including ample amounts of fiber – particularly from sources like steel-cut oats, beans, lentils, and numerous other fruits and vegetables – can be part of a healthy lifestyle and prevention against cognitive decline in later years.

“While the study authors admit to limitations within the study, in my opinion, eating healthier has so many mental and physical health benefits that it’s a nutritional psychiatry no-brainer,” she added.

The study was partly supported by Health and Labour Science Research Grants for Dementia from the Ministry of Health, Labour and Welfare of Japan; JSPS Kakenhi; FULLHAP; and the Osaka University International Joint Research Promotion Programme with University College London. The authors and Dr. Naidoo report no relevant financial relationships.

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

A high-fiber diet, especially one rich in soluble fiber, is linked to a lower risk of incident disabling dementia, new research shows.

Investigators administered a dietary survey to 3,700 healthy adults at midlife and then followed them for up to 20 years. They found that participants who consumed the most fiber had approximately a 25% lower risk of developing dementia in later life.

“This study showed that people with a high intake of dietary fiber, especially soluble fiber, have a lower risk of dementia,” study investigator Kazumasa Yamagishi, MD, PhD, professor, department of public health medicine, faculty of medicine and health, Services Research and Development Center, University of Tsukuba, Japan, said in an interview.

CDC/Debora Cartagena

“There are still many unknowns about the causes of dementia, and it is not appropriate to determine causality based on the results of a single cohort study. However, the results of this study can be said to be one of the findings that will lead to the prevention of dementia,” Dr. Yamagishi said.

The study was published online Feb. 6 in Nutritional Neuroscience.
 

Brain-gut interaction

Brain-gut interaction has recently received attention for its potential involvement in the development of dementia. “The concept of brain-gut interaction emerged from the idea that the central nervous system communicates bidirectionally with the gastrointestinal tract, suggesting that the gut microbiome may influence brain plasticity and cognitive function,” the authors wrote.

A diet high in soluble fiber attenuates neuroinflammation in mouse models. Other animal studies have suggested that insoluble fiber might also have a beneficial effect on the microbiome.

The researchers wanted to see whether dietary fiber intake – especially soluble fiber – is associated with a reduced risk of dementia. They also investigated whether there was any difference between dementia in patients with vs. without a history of stroke.

In a previous study, these same researchers reported an inverse association between eating beans, which are high in fiber, and risk of disabling dementia. In the current study, the researchers extended the analyses to dietary fiber intake of total, soluble, and insoluble fibers, as well as other fiber-containing foods, such potatoes, vegetables, and fruits. However, they distinguished potatoes from other vegetables because the composition of starch in potatoes differs.

“Dietary fiber is a nutrient found in grains, potatoes, vegetables, and fruits and is known to affect intestinal bacteria,” Dr. Yamagishi said. “Recently, some experimental studies have shown that intestinal bacteria may be involved in cognitive functions as well as diseases of the digestive tract. However, there have been no studies that have actually examined the relationship between dietary fiber intake and the subsequent risk of dementia in large numbers of general people.”

The researchers turned to participants in the Circulatory Risk in Communities Study (CIRCS), an ongoing dynamic community cohort study involving five communities in Japan. The current study focused on communities where disabling dementia surveillance is conducted.

Participants (n = 3,739) ranged in age from 40 to 64 years (mean age, 51 years) at the time they completed the 24-hour dietary recall survey, and they participated in annual health checkups from 1985 to 1999. Potential risk factors for disabling dementia were measured at the time the dietary surveys were conducted. Participants were then followed for a median of 19.7 years (1999-2020) to confirm incident, disabling dementia.

“Disabling dementia” was defined as dementia that required care under the National Long-Term Care Insurance System and was further categorized on the basis of having a history or not having a history of stroke.

The researchers divided participants into quartiles, based on the amount of total, soluble, and insoluble intake reported in their surveys. They found that men tended to consume less total fiber compared to women.
 

Unclear mechanism

During follow-up, 670 participants developed disabling dementia.

Total fiber intake was “inversely and linearly” associated with risk of incident dementia, the authors reported, with each successive quartile associated with a lower risk compared to the lowest quartile (P for trend = .03).

The association remained after adjustment for potential factors that might affect dementia onset, such as body mass index, systolic blood pressure, antihypertensive medication use, serum total cholesterol, cholesterol-lowering medication, and diabetes (P for trend = .05).

“The inverse association was more evident for soluble fiber intake and was confined to dementia without a history of stroke,” the authors reported. Moreover, potatoes, not vegetables or fruits, showed a similar association.

“The mechanisms are currently unknown but might involve the interactions that take place between the gut and the brain,” Dr. Yamagishi said in a release.

“One possibility is that soluble fiber regulates the composition of gut bacteria. This composition may affect neuroinflammation, which plays a role in the onset of dementia,” he suggested. “It’s also possible that dietary fiber may reduce other risk factors for dementia, such as body weight, blood pressure, lipids, and glucose levels.”

The authors noted several limitations. For example, they did not distinguish between Alzheimer’s and non-Alzheimer’s dementia. Moreover, they classified dietary habits on the basis of a single survey, and participants’ dietary patterns might have changed over the study period.

In addition, Dr. Yamagishi noted, it is “important to confirm the association in other populations.”
 

Balance is key

In an interview, Uma Naidoo, MD, director of nutritional and lifestyle psychiatry, Massachusetts General Hospital, and nutrition educator at Harvard Medical School, both in Boston, said the study “adds to the growing pool of evidence suggesting that a diet rich in colorful, plant-based foods can benefit our neurological and psychiatric health, especially as we age.”

Dr. Naidoo, a chef and the author of “This Is Your Brain on Food,” who was not involved in the study, continued, “In nutritional psychiatry, balance is key and therefore consuming a well-rounded diet including ample amounts of fiber – particularly from sources like steel-cut oats, beans, lentils, and numerous other fruits and vegetables – can be part of a healthy lifestyle and prevention against cognitive decline in later years.

“While the study authors admit to limitations within the study, in my opinion, eating healthier has so many mental and physical health benefits that it’s a nutritional psychiatry no-brainer,” she added.

The study was partly supported by Health and Labour Science Research Grants for Dementia from the Ministry of Health, Labour and Welfare of Japan; JSPS Kakenhi; FULLHAP; and the Osaka University International Joint Research Promotion Programme with University College London. The authors and Dr. Naidoo report no relevant financial relationships.

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

Earlier menopause appears to be associated with a higher risk of dementia, and earlier onset of dementia, compared with menopause at normal age or later, according to a large study.

“Being aware of this increased risk can help women practice strategies to prevent dementia and to work with their physicians to closely monitor their cognitive status as they age,” study investigator Wenting Hao, MD, with Shandong University, Jinan, China, says in a news release.

The findings were presented in an e-poster March 1 at the Epidemiology, Prevention, Lifestyle & Cardiometabolic Health (EPI|Lifestyle) 2022 conference sponsored by the American Heart Association.
 

UK Biobank data

Dr. Hao and colleagues examined health data for 153,291 women who were 60 years old on average when they became participants in the UK Biobank.

Age at menopause was categorized as premature (younger than age 40), early (40 to 44 years), reference (45 to 51), 52 to 55 years, and 55+ years.

Compared with women who entered menopause around age 50 years (reference), women who experienced premature menopause were 35% more likely to develop some type of dementia later in life (hazard ratio, 1.35; 95% confidence interval, 1.22 to 1.91).

Women with early menopause were also more likely to develop early-onset dementia, that is, before age 65 (HR, 1.31; 95% confidence interval, 1.07 to 1.72).

Women who entered menopause later (at age 52+) had dementia risk similar to women who entered menopause at the average age of 50 to 51 years.

The results were adjusted for relevant cofactors, including age at last exam, race, educational level, cigarette and alcohol use, body mass index, cardiovascular disease, diabetes, income, and leisure and physical activities.

Blame it on estrogen?

Reduced estrogen levels may be a factor in the possible connection between early menopause and dementia, Dr. Hao and her colleagues say.

Estradiol plays a key role in a range of neurological functions, so the reduction of endogenous estrogen at menopause may aggravate brain changes related to neurodegenerative disease and speed up progression of dementia, they explain.

“We know that the lack of estrogen over the long term enhances oxidative stress, which may increase brain aging and lead to cognitive impairment,” Dr. Hao adds.

Limitations of the study include reliance on self-reported information about age at menopause onset.

Also, the researchers did not evaluate dementia rates in women who had a naturally occurring early menopause separate from the women with surgery-induced menopause, which may affect the results.

Finally, the data used for this study included mostly White women living in the U.K. and may not generalize to other populations.
 

Supportive evidence, critical area of research

The U.K. study supports results of a previously reported Kaiser Permanente study, which showed women who entered menopause at age 45 or younger were at 28% greater dementia risk, compared with women who experienced menopause after age 45.

Reached for comment, Heather Snyder, PhD, Alzheimer’s Association vice president of medical and scientific relations, noted that nearly two-thirds of Americans with Alzheimer’s are women.

“We know Alzheimer’s and other dementias impact a greater number of women than men, but we don’t know why,” she told this news organization.

“Lifelong differences in women may affect their risk or affect what is contributing to their underlying biology of the disease, and we need more research to better understand what may be these contributing factors,” said Dr. Snyder.

“Reproductive history is one critical area being studied. The physical and hormonal changes that occur during menopause – as well as other hormonal changes throughout life – are considerable, and it’s important to understand what impact, if any, these changes may have on the brain,” Dr. Snyder added.

“The potential link between reproduction history and brain health is intriguing, but much more research in this area is needed to understand these links,” she said.

The study was funded by the Start-up Foundation for Scientific Research at Shandong University. Dr. Hao and Dr. Snyder have disclosed no relevant financial relationships.

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

Earlier menopause appears to be associated with a higher risk of dementia, and earlier onset of dementia, compared with menopause at normal age or later, according to a large study.

“Being aware of this increased risk can help women practice strategies to prevent dementia and to work with their physicians to closely monitor their cognitive status as they age,” study investigator Wenting Hao, MD, with Shandong University, Jinan, China, says in a news release.

The findings were presented in an e-poster March 1 at the Epidemiology, Prevention, Lifestyle & Cardiometabolic Health (EPI|Lifestyle) 2022 conference sponsored by the American Heart Association.
 

UK Biobank data

Dr. Hao and colleagues examined health data for 153,291 women who were 60 years old on average when they became participants in the UK Biobank.

Age at menopause was categorized as premature (younger than age 40), early (40 to 44 years), reference (45 to 51), 52 to 55 years, and 55+ years.

Compared with women who entered menopause around age 50 years (reference), women who experienced premature menopause were 35% more likely to develop some type of dementia later in life (hazard ratio, 1.35; 95% confidence interval, 1.22 to 1.91).

Women with early menopause were also more likely to develop early-onset dementia, that is, before age 65 (HR, 1.31; 95% confidence interval, 1.07 to 1.72).

Women who entered menopause later (at age 52+) had dementia risk similar to women who entered menopause at the average age of 50 to 51 years.

The results were adjusted for relevant cofactors, including age at last exam, race, educational level, cigarette and alcohol use, body mass index, cardiovascular disease, diabetes, income, and leisure and physical activities.

Blame it on estrogen?

Reduced estrogen levels may be a factor in the possible connection between early menopause and dementia, Dr. Hao and her colleagues say.

Estradiol plays a key role in a range of neurological functions, so the reduction of endogenous estrogen at menopause may aggravate brain changes related to neurodegenerative disease and speed up progression of dementia, they explain.

“We know that the lack of estrogen over the long term enhances oxidative stress, which may increase brain aging and lead to cognitive impairment,” Dr. Hao adds.

Limitations of the study include reliance on self-reported information about age at menopause onset.

Also, the researchers did not evaluate dementia rates in women who had a naturally occurring early menopause separate from the women with surgery-induced menopause, which may affect the results.

Finally, the data used for this study included mostly White women living in the U.K. and may not generalize to other populations.
 

Supportive evidence, critical area of research

The U.K. study supports results of a previously reported Kaiser Permanente study, which showed women who entered menopause at age 45 or younger were at 28% greater dementia risk, compared with women who experienced menopause after age 45.

Reached for comment, Heather Snyder, PhD, Alzheimer’s Association vice president of medical and scientific relations, noted that nearly two-thirds of Americans with Alzheimer’s are women.

“We know Alzheimer’s and other dementias impact a greater number of women than men, but we don’t know why,” she told this news organization.

“Lifelong differences in women may affect their risk or affect what is contributing to their underlying biology of the disease, and we need more research to better understand what may be these contributing factors,” said Dr. Snyder.

“Reproductive history is one critical area being studied. The physical and hormonal changes that occur during menopause – as well as other hormonal changes throughout life – are considerable, and it’s important to understand what impact, if any, these changes may have on the brain,” Dr. Snyder added.

“The potential link between reproduction history and brain health is intriguing, but much more research in this area is needed to understand these links,” she said.

The study was funded by the Start-up Foundation for Scientific Research at Shandong University. Dr. Hao and Dr. Snyder have disclosed no relevant financial relationships.

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

Earlier menopause appears to be associated with a higher risk of dementia, and earlier onset of dementia, compared with menopause at normal age or later, according to a large study.

“Being aware of this increased risk can help women practice strategies to prevent dementia and to work with their physicians to closely monitor their cognitive status as they age,” study investigator Wenting Hao, MD, with Shandong University, Jinan, China, says in a news release.

The findings were presented in an e-poster March 1 at the Epidemiology, Prevention, Lifestyle & Cardiometabolic Health (EPI|Lifestyle) 2022 conference sponsored by the American Heart Association.
 

UK Biobank data

Dr. Hao and colleagues examined health data for 153,291 women who were 60 years old on average when they became participants in the UK Biobank.

Age at menopause was categorized as premature (younger than age 40), early (40 to 44 years), reference (45 to 51), 52 to 55 years, and 55+ years.

Compared with women who entered menopause around age 50 years (reference), women who experienced premature menopause were 35% more likely to develop some type of dementia later in life (hazard ratio, 1.35; 95% confidence interval, 1.22 to 1.91).

Women with early menopause were also more likely to develop early-onset dementia, that is, before age 65 (HR, 1.31; 95% confidence interval, 1.07 to 1.72).

Women who entered menopause later (at age 52+) had dementia risk similar to women who entered menopause at the average age of 50 to 51 years.

The results were adjusted for relevant cofactors, including age at last exam, race, educational level, cigarette and alcohol use, body mass index, cardiovascular disease, diabetes, income, and leisure and physical activities.

Blame it on estrogen?

Reduced estrogen levels may be a factor in the possible connection between early menopause and dementia, Dr. Hao and her colleagues say.

Estradiol plays a key role in a range of neurological functions, so the reduction of endogenous estrogen at menopause may aggravate brain changes related to neurodegenerative disease and speed up progression of dementia, they explain.

“We know that the lack of estrogen over the long term enhances oxidative stress, which may increase brain aging and lead to cognitive impairment,” Dr. Hao adds.

Limitations of the study include reliance on self-reported information about age at menopause onset.

Also, the researchers did not evaluate dementia rates in women who had a naturally occurring early menopause separate from the women with surgery-induced menopause, which may affect the results.

Finally, the data used for this study included mostly White women living in the U.K. and may not generalize to other populations.
 

Supportive evidence, critical area of research

The U.K. study supports results of a previously reported Kaiser Permanente study, which showed women who entered menopause at age 45 or younger were at 28% greater dementia risk, compared with women who experienced menopause after age 45.

Reached for comment, Heather Snyder, PhD, Alzheimer’s Association vice president of medical and scientific relations, noted that nearly two-thirds of Americans with Alzheimer’s are women.

“We know Alzheimer’s and other dementias impact a greater number of women than men, but we don’t know why,” she told this news organization.

“Lifelong differences in women may affect their risk or affect what is contributing to their underlying biology of the disease, and we need more research to better understand what may be these contributing factors,” said Dr. Snyder.

“Reproductive history is one critical area being studied. The physical and hormonal changes that occur during menopause – as well as other hormonal changes throughout life – are considerable, and it’s important to understand what impact, if any, these changes may have on the brain,” Dr. Snyder added.

“The potential link between reproduction history and brain health is intriguing, but much more research in this area is needed to understand these links,” she said.

The study was funded by the Start-up Foundation for Scientific Research at Shandong University. Dr. Hao and Dr. Snyder have disclosed no relevant financial relationships.

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

Mental disorders in early life are associated with a significantly increased risk of dementia in later years.

Results of a large, longitudinal, population-based study show that individuals hospitalized for a mental health disorder had a fourfold increased relative risk (RR) for developing dementia, compared with those who were not hospitalized with a mental illness.

In addition, those with dementia plus a mental disorder developed dementia almost 6 years earlier than those without a mental illness.

The findings were consistent among men and women, in patients with early- and late-onset dementia, in those with Alzheimer’s and non-Alzheimer’s dementia, and across all mental health disorders – and remained so after accounting for pre-existing physical illness and socioeconomic factors.

“Dementia is not typically treated until later in life, but our study suggests that we need to be thinking about dementia prevention much earlier in the life course,” study investigator Leah Richmond-Rakerd, PhD, assistant professor, department of psychology, University of Michigan, said in an interview.

“Supporting young people’s mental health could be a window of opportunity to help reduce the burden of dementia in older adults,” she said.

The findings were published online Feb. 16.
 

Underappreciated risk factor

“Recognition of the outsized influence of dementia on later-life functioning has fueled research into modifiable risk factors and prevention targets,” the investigators write.

Previous research suggests mental disorders may “comprise an underappreciated category of modifiable risk factors.” However, those studies focused primarily on midlife and older individuals, not on capturing mental disorders during young adulthood, which is the time of “peak prevalence,” they add. In addition, most studies have not explored the full range of mental disorders.

Dr. Richmond-Rakerd noted that it is well known that mental health disorders peak in adolescence and young adulthood – and are treatable.

“If the same people who have mental disorders when they are young tend to develop dementia when they are older, that would mean that preventing mental health problems in younger people might reduce or delay the burden of dementia in older people,” she said.

The investigators assessed records from the New Zealand Integrated Data Infrastructure, which is a de-identified register that includes the entire New Zealand population. They also examined information about hospitalizations and diagnoses from records kept by the New Zealand Ministry of Health.

The researchers followed 1,711,386 individuals born between 1928 and 1967 (50.6% men, aged 21 to 60 years at baseline) for 30 years. The population was subdivided into age groups based on birth years: 1928-1937 (14.8%), 1938-1947 (20.85%), 1948-1957 (29.35%), and 1958-1967 (35.1%).
 

Earlier onset

During the study period, 3.8% of individuals were identified as having a mental disorder, and 2% were identified as having dementia. Similar percentages of men and women had a mental disorder, and similar percentages had dementia.

Dementia was “over-represented” among participants with versus without a mental disorder (6.1% vs. 1.8%). This finding held across all age groups.

Those diagnosed with a mental disorder were also more likely to develop dementia, compared with their peers without a mental disorder (RR, 3.51; 95% confidence interval, 3.39-3.64), which is a larger association than that between physical diseases and dementia (RR, 1.19; 95% CI, 1.16-1.21).

These associations were present in both sexes and in all age groups, although the associations were stronger in more recently born cohorts.

A sixfold higher risk for dementia remained even after adjusting for pre-existing physical illnesses (HR, 6.49; 95% CI, 6.25-6.73); and the elevated risk was evident across different lengths of follow-up from the index mental disorder.

When the researchers focused specifically on individuals diagnosed with dementia, they found that those diagnosed with a mental disorder developed dementia a mean of 5.60 years earlier than those without a mental disorder diagnosis – an association observed across both sexes and all age groups.

“Individuals diagnosed with psychotic, substance use, mood, neurotic, and all other mental disorders and who engaged in self-harm were all more likely than those without a mental disorder to be diagnosed with subsequent dementia, even after accounting for their physical disease histories,” the investigators write.

Although there was a link between mental disorders in both Alzheimer’s and non-Alzheimer’s dementias, the association was larger in non-Alzheimer’s.

The researchers note that the study has several limitations, including the fact that it was conducted in New Zealand and therefore the results may not be generalizable to other regions. In addition, inpatient hospital records do not capture less severe mental disorder cases treated in the outpatient setting.

Dr. Richmond-Rakerd suggested several potential mechanisms that could account for the link between mental illness and dementia, including poor lifestyle choices and metabolic side effects associated with some psychiatric medications.

“There could also be shared risk factors for both mental disorders and dementia, such as shared genetics, or individuals may experience a lifelong brain vulnerability that shows up as mental health problems earlier in life and shows up as dementia later in life,” she said.
 

An important risk factor

Commenting for this article, Ken Duckworth, MD, chief medical officer of the National Alliance on Mental Illness, said a major strength of the study was its longitudinal scope and large population size.

He described the study as allowing clinicians to “watch the movie,” as opposed to looking at a “snapshot” of data.

“Although you can learn things from snapshots, a large, comprehensive public health system looking at 30 years of claims – something not possible in the U.S. because of our more fragmented health care system – offers more insight,” said Dr. Duckworth, who was not involved with the research.

The investigators are “painting a picture of a correlation of risk, and to me, that’s the beginning of further inquiry,” he added. “Would preventive efforts targeting dementia, such as exercise and socialization, be helpful? It’s a great study that raises these interesting questions.”

Also commenting in an interview, Claire Sexton, DPhil, director of scientific programs and outreach at the Alzheimer’s Association, said the study “adds a wealth of data to our understanding” of mental disorders as a dementia risk factor.

However, the study was observational, so “the findings cannot imply causation, [and just] because someone has depression, that does not mean they will go on to develop Alzheimer’s,” said Dr. Sexton, who also was not involved with the research.

Still, “these data support the idea that taking care of one’s mental health is incredibly important for overall wellbeing. For providers, it’s important to have mental health evaluation be a part of your patient’s regular checkups,” she added.

Dr. Richmond-Rakerd noted that even if mental health conditions are not a causal risk factor for dementia, “the presence of a mental health problem is still an important indicator of risk. Mental health providers may wish to target other risk factors for dementia that are more common in individuals with mental health conditions, such as social disconnection.”

The study was funded by grants from the National Institute on Aging, the U.K. Medical Research Council, the National Institute of Child Health and Development through the Duke Population Research Center, and the National Institute on Aging through the Center for Advancing Sociodemographic and Economic Study of Alzheimer’s Disease and Related Dementias. Dr. Richmond-Rakerd reports no relevant financial relationships. The other investigators’ disclosures are listed in the original article. Dr. Sexton and Dr. Duckworth report no relevant financial relationships.

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

Mental disorders in early life are associated with a significantly increased risk of dementia in later years.

Results of a large, longitudinal, population-based study show that individuals hospitalized for a mental health disorder had a fourfold increased relative risk (RR) for developing dementia, compared with those who were not hospitalized with a mental illness.

In addition, those with dementia plus a mental disorder developed dementia almost 6 years earlier than those without a mental illness.

The findings were consistent among men and women, in patients with early- and late-onset dementia, in those with Alzheimer’s and non-Alzheimer’s dementia, and across all mental health disorders – and remained so after accounting for pre-existing physical illness and socioeconomic factors.

“Dementia is not typically treated until later in life, but our study suggests that we need to be thinking about dementia prevention much earlier in the life course,” study investigator Leah Richmond-Rakerd, PhD, assistant professor, department of psychology, University of Michigan, said in an interview.

“Supporting young people’s mental health could be a window of opportunity to help reduce the burden of dementia in older adults,” she said.

The findings were published online Feb. 16.
 

Underappreciated risk factor

“Recognition of the outsized influence of dementia on later-life functioning has fueled research into modifiable risk factors and prevention targets,” the investigators write.

Previous research suggests mental disorders may “comprise an underappreciated category of modifiable risk factors.” However, those studies focused primarily on midlife and older individuals, not on capturing mental disorders during young adulthood, which is the time of “peak prevalence,” they add. In addition, most studies have not explored the full range of mental disorders.

Dr. Richmond-Rakerd noted that it is well known that mental health disorders peak in adolescence and young adulthood – and are treatable.

“If the same people who have mental disorders when they are young tend to develop dementia when they are older, that would mean that preventing mental health problems in younger people might reduce or delay the burden of dementia in older people,” she said.

The investigators assessed records from the New Zealand Integrated Data Infrastructure, which is a de-identified register that includes the entire New Zealand population. They also examined information about hospitalizations and diagnoses from records kept by the New Zealand Ministry of Health.

The researchers followed 1,711,386 individuals born between 1928 and 1967 (50.6% men, aged 21 to 60 years at baseline) for 30 years. The population was subdivided into age groups based on birth years: 1928-1937 (14.8%), 1938-1947 (20.85%), 1948-1957 (29.35%), and 1958-1967 (35.1%).
 

Earlier onset

During the study period, 3.8% of individuals were identified as having a mental disorder, and 2% were identified as having dementia. Similar percentages of men and women had a mental disorder, and similar percentages had dementia.

Dementia was “over-represented” among participants with versus without a mental disorder (6.1% vs. 1.8%). This finding held across all age groups.

Those diagnosed with a mental disorder were also more likely to develop dementia, compared with their peers without a mental disorder (RR, 3.51; 95% confidence interval, 3.39-3.64), which is a larger association than that between physical diseases and dementia (RR, 1.19; 95% CI, 1.16-1.21).

These associations were present in both sexes and in all age groups, although the associations were stronger in more recently born cohorts.

A sixfold higher risk for dementia remained even after adjusting for pre-existing physical illnesses (HR, 6.49; 95% CI, 6.25-6.73); and the elevated risk was evident across different lengths of follow-up from the index mental disorder.

When the researchers focused specifically on individuals diagnosed with dementia, they found that those diagnosed with a mental disorder developed dementia a mean of 5.60 years earlier than those without a mental disorder diagnosis – an association observed across both sexes and all age groups.

“Individuals diagnosed with psychotic, substance use, mood, neurotic, and all other mental disorders and who engaged in self-harm were all more likely than those without a mental disorder to be diagnosed with subsequent dementia, even after accounting for their physical disease histories,” the investigators write.

Although there was a link between mental disorders in both Alzheimer’s and non-Alzheimer’s dementias, the association was larger in non-Alzheimer’s.

The researchers note that the study has several limitations, including the fact that it was conducted in New Zealand and therefore the results may not be generalizable to other regions. In addition, inpatient hospital records do not capture less severe mental disorder cases treated in the outpatient setting.

Dr. Richmond-Rakerd suggested several potential mechanisms that could account for the link between mental illness and dementia, including poor lifestyle choices and metabolic side effects associated with some psychiatric medications.

“There could also be shared risk factors for both mental disorders and dementia, such as shared genetics, or individuals may experience a lifelong brain vulnerability that shows up as mental health problems earlier in life and shows up as dementia later in life,” she said.
 

An important risk factor

Commenting for this article, Ken Duckworth, MD, chief medical officer of the National Alliance on Mental Illness, said a major strength of the study was its longitudinal scope and large population size.

He described the study as allowing clinicians to “watch the movie,” as opposed to looking at a “snapshot” of data.

“Although you can learn things from snapshots, a large, comprehensive public health system looking at 30 years of claims – something not possible in the U.S. because of our more fragmented health care system – offers more insight,” said Dr. Duckworth, who was not involved with the research.

The investigators are “painting a picture of a correlation of risk, and to me, that’s the beginning of further inquiry,” he added. “Would preventive efforts targeting dementia, such as exercise and socialization, be helpful? It’s a great study that raises these interesting questions.”

Also commenting in an interview, Claire Sexton, DPhil, director of scientific programs and outreach at the Alzheimer’s Association, said the study “adds a wealth of data to our understanding” of mental disorders as a dementia risk factor.

However, the study was observational, so “the findings cannot imply causation, [and just] because someone has depression, that does not mean they will go on to develop Alzheimer’s,” said Dr. Sexton, who also was not involved with the research.

Still, “these data support the idea that taking care of one’s mental health is incredibly important for overall wellbeing. For providers, it’s important to have mental health evaluation be a part of your patient’s regular checkups,” she added.

Dr. Richmond-Rakerd noted that even if mental health conditions are not a causal risk factor for dementia, “the presence of a mental health problem is still an important indicator of risk. Mental health providers may wish to target other risk factors for dementia that are more common in individuals with mental health conditions, such as social disconnection.”

The study was funded by grants from the National Institute on Aging, the U.K. Medical Research Council, the National Institute of Child Health and Development through the Duke Population Research Center, and the National Institute on Aging through the Center for Advancing Sociodemographic and Economic Study of Alzheimer’s Disease and Related Dementias. Dr. Richmond-Rakerd reports no relevant financial relationships. The other investigators’ disclosures are listed in the original article. Dr. Sexton and Dr. Duckworth report no relevant financial relationships.

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

Mental disorders in early life are associated with a significantly increased risk of dementia in later years.

Results of a large, longitudinal, population-based study show that individuals hospitalized for a mental health disorder had a fourfold increased relative risk (RR) for developing dementia, compared with those who were not hospitalized with a mental illness.

In addition, those with dementia plus a mental disorder developed dementia almost 6 years earlier than those without a mental illness.

The findings were consistent among men and women, in patients with early- and late-onset dementia, in those with Alzheimer’s and non-Alzheimer’s dementia, and across all mental health disorders – and remained so after accounting for pre-existing physical illness and socioeconomic factors.

“Dementia is not typically treated until later in life, but our study suggests that we need to be thinking about dementia prevention much earlier in the life course,” study investigator Leah Richmond-Rakerd, PhD, assistant professor, department of psychology, University of Michigan, said in an interview.

“Supporting young people’s mental health could be a window of opportunity to help reduce the burden of dementia in older adults,” she said.

The findings were published online Feb. 16.
 

Underappreciated risk factor

“Recognition of the outsized influence of dementia on later-life functioning has fueled research into modifiable risk factors and prevention targets,” the investigators write.

Previous research suggests mental disorders may “comprise an underappreciated category of modifiable risk factors.” However, those studies focused primarily on midlife and older individuals, not on capturing mental disorders during young adulthood, which is the time of “peak prevalence,” they add. In addition, most studies have not explored the full range of mental disorders.

Dr. Richmond-Rakerd noted that it is well known that mental health disorders peak in adolescence and young adulthood – and are treatable.

“If the same people who have mental disorders when they are young tend to develop dementia when they are older, that would mean that preventing mental health problems in younger people might reduce or delay the burden of dementia in older people,” she said.

The investigators assessed records from the New Zealand Integrated Data Infrastructure, which is a de-identified register that includes the entire New Zealand population. They also examined information about hospitalizations and diagnoses from records kept by the New Zealand Ministry of Health.

The researchers followed 1,711,386 individuals born between 1928 and 1967 (50.6% men, aged 21 to 60 years at baseline) for 30 years. The population was subdivided into age groups based on birth years: 1928-1937 (14.8%), 1938-1947 (20.85%), 1948-1957 (29.35%), and 1958-1967 (35.1%).
 

Earlier onset

During the study period, 3.8% of individuals were identified as having a mental disorder, and 2% were identified as having dementia. Similar percentages of men and women had a mental disorder, and similar percentages had dementia.

Dementia was “over-represented” among participants with versus without a mental disorder (6.1% vs. 1.8%). This finding held across all age groups.

Those diagnosed with a mental disorder were also more likely to develop dementia, compared with their peers without a mental disorder (RR, 3.51; 95% confidence interval, 3.39-3.64), which is a larger association than that between physical diseases and dementia (RR, 1.19; 95% CI, 1.16-1.21).

These associations were present in both sexes and in all age groups, although the associations were stronger in more recently born cohorts.

A sixfold higher risk for dementia remained even after adjusting for pre-existing physical illnesses (HR, 6.49; 95% CI, 6.25-6.73); and the elevated risk was evident across different lengths of follow-up from the index mental disorder.

When the researchers focused specifically on individuals diagnosed with dementia, they found that those diagnosed with a mental disorder developed dementia a mean of 5.60 years earlier than those without a mental disorder diagnosis – an association observed across both sexes and all age groups.

“Individuals diagnosed with psychotic, substance use, mood, neurotic, and all other mental disorders and who engaged in self-harm were all more likely than those without a mental disorder to be diagnosed with subsequent dementia, even after accounting for their physical disease histories,” the investigators write.

Although there was a link between mental disorders in both Alzheimer’s and non-Alzheimer’s dementias, the association was larger in non-Alzheimer’s.

The researchers note that the study has several limitations, including the fact that it was conducted in New Zealand and therefore the results may not be generalizable to other regions. In addition, inpatient hospital records do not capture less severe mental disorder cases treated in the outpatient setting.

Dr. Richmond-Rakerd suggested several potential mechanisms that could account for the link between mental illness and dementia, including poor lifestyle choices and metabolic side effects associated with some psychiatric medications.

“There could also be shared risk factors for both mental disorders and dementia, such as shared genetics, or individuals may experience a lifelong brain vulnerability that shows up as mental health problems earlier in life and shows up as dementia later in life,” she said.
 

An important risk factor

Commenting for this article, Ken Duckworth, MD, chief medical officer of the National Alliance on Mental Illness, said a major strength of the study was its longitudinal scope and large population size.

He described the study as allowing clinicians to “watch the movie,” as opposed to looking at a “snapshot” of data.

“Although you can learn things from snapshots, a large, comprehensive public health system looking at 30 years of claims – something not possible in the U.S. because of our more fragmented health care system – offers more insight,” said Dr. Duckworth, who was not involved with the research.

The investigators are “painting a picture of a correlation of risk, and to me, that’s the beginning of further inquiry,” he added. “Would preventive efforts targeting dementia, such as exercise and socialization, be helpful? It’s a great study that raises these interesting questions.”

Also commenting in an interview, Claire Sexton, DPhil, director of scientific programs and outreach at the Alzheimer’s Association, said the study “adds a wealth of data to our understanding” of mental disorders as a dementia risk factor.

However, the study was observational, so “the findings cannot imply causation, [and just] because someone has depression, that does not mean they will go on to develop Alzheimer’s,” said Dr. Sexton, who also was not involved with the research.

Still, “these data support the idea that taking care of one’s mental health is incredibly important for overall wellbeing. For providers, it’s important to have mental health evaluation be a part of your patient’s regular checkups,” she added.

Dr. Richmond-Rakerd noted that even if mental health conditions are not a causal risk factor for dementia, “the presence of a mental health problem is still an important indicator of risk. Mental health providers may wish to target other risk factors for dementia that are more common in individuals with mental health conditions, such as social disconnection.”

The study was funded by grants from the National Institute on Aging, the U.K. Medical Research Council, the National Institute of Child Health and Development through the Duke Population Research Center, and the National Institute on Aging through the Center for Advancing Sociodemographic and Economic Study of Alzheimer’s Disease and Related Dementias. Dr. Richmond-Rakerd reports no relevant financial relationships. The other investigators’ disclosures are listed in the original article. Dr. Sexton and Dr. Duckworth report no relevant financial relationships.

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