Neurology Reviews

Nearly half of older adults with dementia experience falls, suggests new research that also identifies multiple risk factors for these falls.

In a study of more than 5,500 participants, 45.5% of those with dementia experienced one or more falls, compared with 30.9% of their peers without dementia.

Vision impairment and living with a spouse were among the strongest predictors of future fall risk among participants living with dementia. Interestingly, high neighborhood social deprivation, which is reflected by such things as income and education, was associated with lower odds of falling.

Overall, the results highlight the need for a multidisciplinary approach to preventing falls among elderly individuals with dementia, said lead author Safiyyah M. Okoye, PhD, assistant professor, College of Nursing and Health Professions, Drexel University, Philadelphia.

“We need to consider different dimensions and figure out how we can try to go beyond the clinic in our interactions,” she said.

Dr. Okoye noted that in addition to reviewing medications that may contribute to falls and screening for vision problems, clinicians might also consider resources to improve the home environment and ensure that families have appropriate caregiving.

The findings were published online  in Alzheimer’s and Dementia: The Journal of the Alzheimer’s Association.
 

No ‘silver bullet’

Every year, falls cause millions of injuries in older adults, and those with dementia are especially vulnerable. This population has twice the risk of falling and up to three times the risk of incurring serious fall-related injuries, such as fractures, the researchers noted.

Falls are a leading cause of hospitalization among those with dementia. Previous evidence has shown that persons with dementia are more likely to experience negative health consequences, such as delirium, while in hospital, compared with those without dementia. Even minor fall-related injuries are associated with the patient’s being discharged to a nursing home rather than returning home.

Dr. Okoye stressed that many factors contribute to falls, including health status; function, such as the ability to walk and balance; medications; home environment; and activity level.

“There are multidimensional aspects, and we can’t just find one silver bullet to address falls. It should be addressed comprehensively,” she said.

Existing studies “overwhelmingly” focus on factors related to health and function that could be addressed in the doctor’s office or with a referral, rather than on environmental and social factors, Dr. Okoye noted.

And even though the risk of falling is high among community-dwelling seniors with dementia, very few studies have addressed the risk of falls among these adults, she added.

The new analysis included a nationally representative sample of 5,581 community-dwelling adults who participated in both the 2015 and 2016 National Health and Aging Trends Study (NHATS). The NHATS is a population-based survey of health and disability trends and trajectories among Americans aged 65 years and older.

During interviews, participants were asked, personally or by proxy, about falls during the previous 12 months. Having fallen at baseline was evaluated as a possible predictor of falls in the subsequent 12 months.

To determine probable dementia, researchers asked whether a doctor had ever told the participants that they had dementia or Alzheimer’s disease. They also used a dementia screening questionnaire and neuropsychological tests of memory, orientation, and executive function.

Of the total sample, most (n = 5,093) did not have dementia.

Physical environmental factors that were assessed included conditions at home, such as clutter, tripping hazards, and structural issues, as well as neighborhood social and economic deprivation – such as income, education levels, and employment status.
 

Fall rates and counterintuitive findings

Results showed that significantly more of those with dementia than without experienced one or more falls (45.5% vs. 30.9%; P < .001).

In addition, a history of falling was significantly associated with subsequent falls among those with dementia (odds ratio, 6.20; 95% confidence interval, 3.81-10.09), as was vision impairment (OR, 2.22; 95% CI, 1.12-4.40) and living with a spouse versus alone (OR, 2.43; 95% CI, 1.09-5.43).

A possible explanation for higher fall risk among those living with a partner is that those living alone usually have better functioning, the investigators noted. Also, live-in partners tend to be of a similar age as the person with dementia and may have challenges of their own.

Interestingly, high neighborhood social deprivation was associated with lower odds of falling (OR, 0.55 for the highest deprivation scores; 95% CI, 0.31-0.98), a finding Dr. Okoye said was “counterintuitive.”

This result could be related to the social environment, she noted. “Maybe there are more people around in the house, more people with eyes on the person, or more people in the community who know the person. Despite the low economic resources, there could be social resources there,” she said.

The new findings underscore the idea that falling is a multidimensional phenomenon among older adults with dementia as well as those without dementia, Dr. Okoye noted.

Doctors can play a role in reducing falls among patients with dementia by asking about falls, possibly eliminating medications that are associated with risk of falling, and screening for and correcting vision and hearing impairments, she suggested.

They may also help determine household hazards for a patient, such as clutter and poor lighting, and ensure that these are addressed, Dr. Okoye added.
 

No surprise

Commenting on the study, David S. Knopman, MD, a clinical neurologist at Mayo Clinic, Rochester, Minn., said the finding that visual impairment and a prior history of falling are predictive of subsequent falls “comes as no surprise.”

Dr. Knopman, whose research focuses on late-life cognitive disorders, was not involved with the current study.

Risk reduction is “of course” a key management goal, he said. “Vigilance and optimizing the patient’s living space to reduce fall risks are the major strategies,” he added.

Dr. Knopman reiterated that falls among those with dementia are associated with higher mortality and often lead to loss of the capacity to live outside of an institution.

The study was supported by the National Institute on Aging. The investigators and Dr. Knopman report no relevant financial relationships.

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

Nearly half of older adults with dementia experience falls, suggests new research that also identifies multiple risk factors for these falls.

In a study of more than 5,500 participants, 45.5% of those with dementia experienced one or more falls, compared with 30.9% of their peers without dementia.

Vision impairment and living with a spouse were among the strongest predictors of future fall risk among participants living with dementia. Interestingly, high neighborhood social deprivation, which is reflected by such things as income and education, was associated with lower odds of falling.

Overall, the results highlight the need for a multidisciplinary approach to preventing falls among elderly individuals with dementia, said lead author Safiyyah M. Okoye, PhD, assistant professor, College of Nursing and Health Professions, Drexel University, Philadelphia.

“We need to consider different dimensions and figure out how we can try to go beyond the clinic in our interactions,” she said.

Dr. Okoye noted that in addition to reviewing medications that may contribute to falls and screening for vision problems, clinicians might also consider resources to improve the home environment and ensure that families have appropriate caregiving.

The findings were published online  in Alzheimer’s and Dementia: The Journal of the Alzheimer’s Association.
 

No ‘silver bullet’

Every year, falls cause millions of injuries in older adults, and those with dementia are especially vulnerable. This population has twice the risk of falling and up to three times the risk of incurring serious fall-related injuries, such as fractures, the researchers noted.

Falls are a leading cause of hospitalization among those with dementia. Previous evidence has shown that persons with dementia are more likely to experience negative health consequences, such as delirium, while in hospital, compared with those without dementia. Even minor fall-related injuries are associated with the patient’s being discharged to a nursing home rather than returning home.

Dr. Okoye stressed that many factors contribute to falls, including health status; function, such as the ability to walk and balance; medications; home environment; and activity level.

“There are multidimensional aspects, and we can’t just find one silver bullet to address falls. It should be addressed comprehensively,” she said.

Existing studies “overwhelmingly” focus on factors related to health and function that could be addressed in the doctor’s office or with a referral, rather than on environmental and social factors, Dr. Okoye noted.

And even though the risk of falling is high among community-dwelling seniors with dementia, very few studies have addressed the risk of falls among these adults, she added.

The new analysis included a nationally representative sample of 5,581 community-dwelling adults who participated in both the 2015 and 2016 National Health and Aging Trends Study (NHATS). The NHATS is a population-based survey of health and disability trends and trajectories among Americans aged 65 years and older.

During interviews, participants were asked, personally or by proxy, about falls during the previous 12 months. Having fallen at baseline was evaluated as a possible predictor of falls in the subsequent 12 months.

To determine probable dementia, researchers asked whether a doctor had ever told the participants that they had dementia or Alzheimer’s disease. They also used a dementia screening questionnaire and neuropsychological tests of memory, orientation, and executive function.

Of the total sample, most (n = 5,093) did not have dementia.

Physical environmental factors that were assessed included conditions at home, such as clutter, tripping hazards, and structural issues, as well as neighborhood social and economic deprivation – such as income, education levels, and employment status.
 

Fall rates and counterintuitive findings

Results showed that significantly more of those with dementia than without experienced one or more falls (45.5% vs. 30.9%; P < .001).

In addition, a history of falling was significantly associated with subsequent falls among those with dementia (odds ratio, 6.20; 95% confidence interval, 3.81-10.09), as was vision impairment (OR, 2.22; 95% CI, 1.12-4.40) and living with a spouse versus alone (OR, 2.43; 95% CI, 1.09-5.43).

A possible explanation for higher fall risk among those living with a partner is that those living alone usually have better functioning, the investigators noted. Also, live-in partners tend to be of a similar age as the person with dementia and may have challenges of their own.

Interestingly, high neighborhood social deprivation was associated with lower odds of falling (OR, 0.55 for the highest deprivation scores; 95% CI, 0.31-0.98), a finding Dr. Okoye said was “counterintuitive.”

This result could be related to the social environment, she noted. “Maybe there are more people around in the house, more people with eyes on the person, or more people in the community who know the person. Despite the low economic resources, there could be social resources there,” she said.

The new findings underscore the idea that falling is a multidimensional phenomenon among older adults with dementia as well as those without dementia, Dr. Okoye noted.

Doctors can play a role in reducing falls among patients with dementia by asking about falls, possibly eliminating medications that are associated with risk of falling, and screening for and correcting vision and hearing impairments, she suggested.

They may also help determine household hazards for a patient, such as clutter and poor lighting, and ensure that these are addressed, Dr. Okoye added.
 

No surprise

Commenting on the study, David S. Knopman, MD, a clinical neurologist at Mayo Clinic, Rochester, Minn., said the finding that visual impairment and a prior history of falling are predictive of subsequent falls “comes as no surprise.”

Dr. Knopman, whose research focuses on late-life cognitive disorders, was not involved with the current study.

Risk reduction is “of course” a key management goal, he said. “Vigilance and optimizing the patient’s living space to reduce fall risks are the major strategies,” he added.

Dr. Knopman reiterated that falls among those with dementia are associated with higher mortality and often lead to loss of the capacity to live outside of an institution.

The study was supported by the National Institute on Aging. The investigators and Dr. Knopman report no relevant financial relationships.

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

Nearly half of older adults with dementia experience falls, suggests new research that also identifies multiple risk factors for these falls.

In a study of more than 5,500 participants, 45.5% of those with dementia experienced one or more falls, compared with 30.9% of their peers without dementia.

Vision impairment and living with a spouse were among the strongest predictors of future fall risk among participants living with dementia. Interestingly, high neighborhood social deprivation, which is reflected by such things as income and education, was associated with lower odds of falling.

Overall, the results highlight the need for a multidisciplinary approach to preventing falls among elderly individuals with dementia, said lead author Safiyyah M. Okoye, PhD, assistant professor, College of Nursing and Health Professions, Drexel University, Philadelphia.

“We need to consider different dimensions and figure out how we can try to go beyond the clinic in our interactions,” she said.

Dr. Okoye noted that in addition to reviewing medications that may contribute to falls and screening for vision problems, clinicians might also consider resources to improve the home environment and ensure that families have appropriate caregiving.

The findings were published online  in Alzheimer’s and Dementia: The Journal of the Alzheimer’s Association.
 

No ‘silver bullet’

Every year, falls cause millions of injuries in older adults, and those with dementia are especially vulnerable. This population has twice the risk of falling and up to three times the risk of incurring serious fall-related injuries, such as fractures, the researchers noted.

Falls are a leading cause of hospitalization among those with dementia. Previous evidence has shown that persons with dementia are more likely to experience negative health consequences, such as delirium, while in hospital, compared with those without dementia. Even minor fall-related injuries are associated with the patient’s being discharged to a nursing home rather than returning home.

Dr. Okoye stressed that many factors contribute to falls, including health status; function, such as the ability to walk and balance; medications; home environment; and activity level.

“There are multidimensional aspects, and we can’t just find one silver bullet to address falls. It should be addressed comprehensively,” she said.

Existing studies “overwhelmingly” focus on factors related to health and function that could be addressed in the doctor’s office or with a referral, rather than on environmental and social factors, Dr. Okoye noted.

And even though the risk of falling is high among community-dwelling seniors with dementia, very few studies have addressed the risk of falls among these adults, she added.

The new analysis included a nationally representative sample of 5,581 community-dwelling adults who participated in both the 2015 and 2016 National Health and Aging Trends Study (NHATS). The NHATS is a population-based survey of health and disability trends and trajectories among Americans aged 65 years and older.

During interviews, participants were asked, personally or by proxy, about falls during the previous 12 months. Having fallen at baseline was evaluated as a possible predictor of falls in the subsequent 12 months.

To determine probable dementia, researchers asked whether a doctor had ever told the participants that they had dementia or Alzheimer’s disease. They also used a dementia screening questionnaire and neuropsychological tests of memory, orientation, and executive function.

Of the total sample, most (n = 5,093) did not have dementia.

Physical environmental factors that were assessed included conditions at home, such as clutter, tripping hazards, and structural issues, as well as neighborhood social and economic deprivation – such as income, education levels, and employment status.
 

Fall rates and counterintuitive findings

Results showed that significantly more of those with dementia than without experienced one or more falls (45.5% vs. 30.9%; P < .001).

In addition, a history of falling was significantly associated with subsequent falls among those with dementia (odds ratio, 6.20; 95% confidence interval, 3.81-10.09), as was vision impairment (OR, 2.22; 95% CI, 1.12-4.40) and living with a spouse versus alone (OR, 2.43; 95% CI, 1.09-5.43).

A possible explanation for higher fall risk among those living with a partner is that those living alone usually have better functioning, the investigators noted. Also, live-in partners tend to be of a similar age as the person with dementia and may have challenges of their own.

Interestingly, high neighborhood social deprivation was associated with lower odds of falling (OR, 0.55 for the highest deprivation scores; 95% CI, 0.31-0.98), a finding Dr. Okoye said was “counterintuitive.”

This result could be related to the social environment, she noted. “Maybe there are more people around in the house, more people with eyes on the person, or more people in the community who know the person. Despite the low economic resources, there could be social resources there,” she said.

The new findings underscore the idea that falling is a multidimensional phenomenon among older adults with dementia as well as those without dementia, Dr. Okoye noted.

Doctors can play a role in reducing falls among patients with dementia by asking about falls, possibly eliminating medications that are associated with risk of falling, and screening for and correcting vision and hearing impairments, she suggested.

They may also help determine household hazards for a patient, such as clutter and poor lighting, and ensure that these are addressed, Dr. Okoye added.
 

No surprise

Commenting on the study, David S. Knopman, MD, a clinical neurologist at Mayo Clinic, Rochester, Minn., said the finding that visual impairment and a prior history of falling are predictive of subsequent falls “comes as no surprise.”

Dr. Knopman, whose research focuses on late-life cognitive disorders, was not involved with the current study.

Risk reduction is “of course” a key management goal, he said. “Vigilance and optimizing the patient’s living space to reduce fall risks are the major strategies,” he added.

Dr. Knopman reiterated that falls among those with dementia are associated with higher mortality and often lead to loss of the capacity to live outside of an institution.

The study was supported by the National Institute on Aging. The investigators and Dr. Knopman report no relevant financial relationships.

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

Ecopipam, in development for Tourette syndrome in children and adolescents, has shown in a randomized, controlled trial that, compared with placebo, it reduced tics and reduced the risk for some of the common side effects of other treatments, including weight gain.

Findings of the multicenter, double-blind, trial funded by the drug maker, Emalex Biosciences, were published online in Pediatrics. The trial was conducted at 68 sites in the United States, Canada, Germany, France, and Poland between May 2019 and September 2021.

Donald L. Gilbert, MD, MS, with the division of neurology at Cincinnati Children’s Hospital, and colleagues noted that all Food and Drug Administration–approved medications for Tourette syndrome are antipsychotics. The medications carry a risk of weight gain, electrocardiogram abnormalities, metabolic changes, and drug-induced movement disorders.

First-in-class medication ecopipam, targets the D1 dopamine receptor, while currently approved medications block the D2 receptor. It “may be a safe and effective treatment of Tourette syndrome with advantages over other currently approved therapeutic agents,” the authors wrote.

The study included 153 individuals at least 6 years old up to age 18 with a baseline Yale Global Tic Severity Score Total Tic Score of at least 20.

They were randomly assigned 1:1 to ecopipam or placebo.
 

Significant reduction in tic severity

Researchers saw a 30% reduction in the tic severity score from baseline to week 12 for the ecopipam group compared with the placebo group.

The data showed a least-squares mean difference of 3.44 (95% confidence interval [CI], 6.09-0.79, P = .01). Researchers also saw improvement in Clinical Global Impression of Tourette Syndrome Severity in the ecopipam group (P = .03).

Sara Pawlowski, MD, division chief for primary care mental health integration at University of Vermont Health Network and assistant professor of psychiatry, University of Vermont, Burlington, said in an interview that several things should be considered with this research.

One is that, though the results show a reduction in tics, the study lasted only 12 weeks and “tics can last a lifetime,” she noted.

“They also can ebb and flow with major life events, stressors, and various other variables. So, I wonder how the effects of improvement can be teased out from the natural ebb and flow of the condition in a 3-month window, which is a snapshot into the course of a known relapsing, remitting, lifetime, and chronically variable condition,” she said.
 

Headaches, insomnia among side effects

Weight gain was larger in the placebo group than in the ecopipam group: 17.1% in the ecopipam group and 20.3% of those who got a placebo had a weight gain of more than 7% over the study period.

The most common side effects of the study drug were headache (15.8%), insomnia (14.5%), fatigue (7.9%), and somnolence (7.9%).

A limitation of the study was lack of racial and ethnic diversity, as 93.5% of those in the placebo group and 86.8% in the ecopipam group were White.

Guidelines in North America and Europe agree that behavioral treatments should be the first-line therapy.

Dr. Pawlowski said that although effective medications are needed, she urges focusing on better access to nonmedication treatments “that work for children and adolescents” as children who start taking the medications early may take them for the rest of their lives.

Also, while the research didn’t find weight gain in the ecopipam group, the side effects they did find in the group, including headache and insomnia, “do impact a child’s life,” she noted.

“We also can’t be reassured that over the course of chronic treatment there wouldn’t be movement disorders or metabolic disorders that emerge. Those are side effects or disorders that can emerge surreptitiously over time, and more time than 12 weeks,” she said.

The study was funded by Emalex Biosciences. Dr. Gilbert has received consulting fees from Biogen and PTC therapeutics. Study coauthors disclosed ties with Emalex, Alkermes, and Paragon Biosciences. Dr. Pawlowski reports no relevant financial relationships.

Ecopipam, in development for Tourette syndrome in children and adolescents, has shown in a randomized, controlled trial that, compared with placebo, it reduced tics and reduced the risk for some of the common side effects of other treatments, including weight gain.

Findings of the multicenter, double-blind, trial funded by the drug maker, Emalex Biosciences, were published online in Pediatrics. The trial was conducted at 68 sites in the United States, Canada, Germany, France, and Poland between May 2019 and September 2021.

Donald L. Gilbert, MD, MS, with the division of neurology at Cincinnati Children’s Hospital, and colleagues noted that all Food and Drug Administration–approved medications for Tourette syndrome are antipsychotics. The medications carry a risk of weight gain, electrocardiogram abnormalities, metabolic changes, and drug-induced movement disorders.

First-in-class medication ecopipam, targets the D1 dopamine receptor, while currently approved medications block the D2 receptor. It “may be a safe and effective treatment of Tourette syndrome with advantages over other currently approved therapeutic agents,” the authors wrote.

The study included 153 individuals at least 6 years old up to age 18 with a baseline Yale Global Tic Severity Score Total Tic Score of at least 20.

They were randomly assigned 1:1 to ecopipam or placebo.
 

Significant reduction in tic severity

Researchers saw a 30% reduction in the tic severity score from baseline to week 12 for the ecopipam group compared with the placebo group.

The data showed a least-squares mean difference of 3.44 (95% confidence interval [CI], 6.09-0.79, P = .01). Researchers also saw improvement in Clinical Global Impression of Tourette Syndrome Severity in the ecopipam group (P = .03).

Sara Pawlowski, MD, division chief for primary care mental health integration at University of Vermont Health Network and assistant professor of psychiatry, University of Vermont, Burlington, said in an interview that several things should be considered with this research.

One is that, though the results show a reduction in tics, the study lasted only 12 weeks and “tics can last a lifetime,” she noted.

“They also can ebb and flow with major life events, stressors, and various other variables. So, I wonder how the effects of improvement can be teased out from the natural ebb and flow of the condition in a 3-month window, which is a snapshot into the course of a known relapsing, remitting, lifetime, and chronically variable condition,” she said.
 

Headaches, insomnia among side effects

Weight gain was larger in the placebo group than in the ecopipam group: 17.1% in the ecopipam group and 20.3% of those who got a placebo had a weight gain of more than 7% over the study period.

The most common side effects of the study drug were headache (15.8%), insomnia (14.5%), fatigue (7.9%), and somnolence (7.9%).

A limitation of the study was lack of racial and ethnic diversity, as 93.5% of those in the placebo group and 86.8% in the ecopipam group were White.

Guidelines in North America and Europe agree that behavioral treatments should be the first-line therapy.

Dr. Pawlowski said that although effective medications are needed, she urges focusing on better access to nonmedication treatments “that work for children and adolescents” as children who start taking the medications early may take them for the rest of their lives.

Also, while the research didn’t find weight gain in the ecopipam group, the side effects they did find in the group, including headache and insomnia, “do impact a child’s life,” she noted.

“We also can’t be reassured that over the course of chronic treatment there wouldn’t be movement disorders or metabolic disorders that emerge. Those are side effects or disorders that can emerge surreptitiously over time, and more time than 12 weeks,” she said.

The study was funded by Emalex Biosciences. Dr. Gilbert has received consulting fees from Biogen and PTC therapeutics. Study coauthors disclosed ties with Emalex, Alkermes, and Paragon Biosciences. Dr. Pawlowski reports no relevant financial relationships.

Ecopipam, in development for Tourette syndrome in children and adolescents, has shown in a randomized, controlled trial that, compared with placebo, it reduced tics and reduced the risk for some of the common side effects of other treatments, including weight gain.

Findings of the multicenter, double-blind, trial funded by the drug maker, Emalex Biosciences, were published online in Pediatrics. The trial was conducted at 68 sites in the United States, Canada, Germany, France, and Poland between May 2019 and September 2021.

Donald L. Gilbert, MD, MS, with the division of neurology at Cincinnati Children’s Hospital, and colleagues noted that all Food and Drug Administration–approved medications for Tourette syndrome are antipsychotics. The medications carry a risk of weight gain, electrocardiogram abnormalities, metabolic changes, and drug-induced movement disorders.

First-in-class medication ecopipam, targets the D1 dopamine receptor, while currently approved medications block the D2 receptor. It “may be a safe and effective treatment of Tourette syndrome with advantages over other currently approved therapeutic agents,” the authors wrote.

The study included 153 individuals at least 6 years old up to age 18 with a baseline Yale Global Tic Severity Score Total Tic Score of at least 20.

They were randomly assigned 1:1 to ecopipam or placebo.
 

Significant reduction in tic severity

Researchers saw a 30% reduction in the tic severity score from baseline to week 12 for the ecopipam group compared with the placebo group.

The data showed a least-squares mean difference of 3.44 (95% confidence interval [CI], 6.09-0.79, P = .01). Researchers also saw improvement in Clinical Global Impression of Tourette Syndrome Severity in the ecopipam group (P = .03).

Sara Pawlowski, MD, division chief for primary care mental health integration at University of Vermont Health Network and assistant professor of psychiatry, University of Vermont, Burlington, said in an interview that several things should be considered with this research.

One is that, though the results show a reduction in tics, the study lasted only 12 weeks and “tics can last a lifetime,” she noted.

“They also can ebb and flow with major life events, stressors, and various other variables. So, I wonder how the effects of improvement can be teased out from the natural ebb and flow of the condition in a 3-month window, which is a snapshot into the course of a known relapsing, remitting, lifetime, and chronically variable condition,” she said.
 

Headaches, insomnia among side effects

Weight gain was larger in the placebo group than in the ecopipam group: 17.1% in the ecopipam group and 20.3% of those who got a placebo had a weight gain of more than 7% over the study period.

The most common side effects of the study drug were headache (15.8%), insomnia (14.5%), fatigue (7.9%), and somnolence (7.9%).

A limitation of the study was lack of racial and ethnic diversity, as 93.5% of those in the placebo group and 86.8% in the ecopipam group were White.

Guidelines in North America and Europe agree that behavioral treatments should be the first-line therapy.

Dr. Pawlowski said that although effective medications are needed, she urges focusing on better access to nonmedication treatments “that work for children and adolescents” as children who start taking the medications early may take them for the rest of their lives.

Also, while the research didn’t find weight gain in the ecopipam group, the side effects they did find in the group, including headache and insomnia, “do impact a child’s life,” she noted.

“We also can’t be reassured that over the course of chronic treatment there wouldn’t be movement disorders or metabolic disorders that emerge. Those are side effects or disorders that can emerge surreptitiously over time, and more time than 12 weeks,” she said.

The study was funded by Emalex Biosciences. Dr. Gilbert has received consulting fees from Biogen and PTC therapeutics. Study coauthors disclosed ties with Emalex, Alkermes, and Paragon Biosciences. Dr. Pawlowski reports no relevant financial relationships.

Dementia prevalence is 61% higher among older people with moderate to severe hearing loss compared with those with normal hearing, new national data show. Investigators also found that even mild hearing loss was associated with increased dementia risk, although it was not statistically significant, and that hearing aid use was tied to a 32% decrease in dementia prevalence.

“Every 10-decibel increase in hearing loss was associated with 16% greater prevalence of dementia, such that prevalence of dementia in older adults with moderate or greater hearing loss was 61% higher than prevalence in those with normal hearing,” said lead investigator Alison Huang, PhD, senior research associate in epidemiology at Johns Hopkins Bloomberg School of Public Health and core faculty in the Cochlear Center for Hearing and Public Health, Baltimore.

The findings were published online in JAMA.
 

Dose dependent effect

For their study, researchers analyzed data on 2,413 community-dwelling participants in the National Health and Aging Trends Study, a nationally representative, continuous panel study of U.S. Medicare beneficiaries aged 65 and older.

Data from the study was collected during in-home interviews, setting it apart from previous work that relied on data collected in a clinical setting, Dr. Huang said.

“This study was able to capture more vulnerable populations, such as the oldest old and older adults with disabilities, typically excluded from prior epidemiologic studies of the hearing loss–dementia association that use clinic-based data collection, which only captures people who have the ability and means to get to clinics,” Dr. Huang said.

Weighted hearing loss prevalence was 36.7% for mild and 29.8% for moderate to severe hearing loss, and weighted prevalence of dementia was 10.3%.

Those with moderate to severe hearing loss were 61% more likely to have dementia than were those with normal hearing (prevalence ratio, 1.61; 95% confidence interval [CI], 1.09-2.38).

Dementia prevalence increased with increasing severity of hearing loss: Normal hearing: 6.19% (95% CI, 4.31-8.80); mild hearing loss: 8.93% (95% CI, 6.99-11.34); moderate to severe hearing loss: 16.52% (95% CI, 13.81-19.64). But only moderate to severe hearing loss showed a statistically significant association with dementia (P = .02).

Dementia prevalence increased 16% per 10-decibel increase in hearing loss (prevalence ratio 1.16; P < .001).

Among the 853 individuals in the study with moderate to severe hearing loss, those who used hearing aids (n = 414) had a 32% lower risk of dementia compared with those who didn’t use assisted devices (prevalence ratio, 0.68; 95% CI, 0.47-1.00). Similar data were published in JAMA Neurology, suggesting that hearing aids reduce dementia risk.

“With this study, we were able to refine our understanding of the strength of the hearing loss–dementia association in a study more representative of older adults in the United States,” said Dr. Huang.
 

Robust association

Commenting on the findings, Justin S. Golub, MD, associate professor in the department of otolaryngology–head and neck surgery at Columbia University, New York, said the study supports earlier research and suggests a “robust” association between hearing loss and dementia.

“The particular advantage of this study was that it was high quality and nationally representative,” Dr. Golub said. “It is also among a smaller set of studies that have shown hearing aid use to be associated with lower risk of dementia.”

Although not statistically significant, researchers did find increasing prevalence of dementia among people with only mild hearing loss, and clinicians should take note, said Dr. Golub, who was not involved with this study.

“We would expect the relationship between mild hearing loss and dementia to be weaker than severe hearing loss and dementia and, as a result, it might take more participants to show an association among the mild group,” Dr. Golub said.

“Even though this particular study did not specifically find a relationship between mild hearing loss and dementia, I would still recommend people to start treating their hearing loss when it is early,” Dr. Golub added.

The study was funded by the National Institute on Aging. Dr. Golub reports no relevant financial relationships. Full disclosures for study authors are included in the original article.

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

Dementia prevalence is 61% higher among older people with moderate to severe hearing loss compared with those with normal hearing, new national data show. Investigators also found that even mild hearing loss was associated with increased dementia risk, although it was not statistically significant, and that hearing aid use was tied to a 32% decrease in dementia prevalence.

“Every 10-decibel increase in hearing loss was associated with 16% greater prevalence of dementia, such that prevalence of dementia in older adults with moderate or greater hearing loss was 61% higher than prevalence in those with normal hearing,” said lead investigator Alison Huang, PhD, senior research associate in epidemiology at Johns Hopkins Bloomberg School of Public Health and core faculty in the Cochlear Center for Hearing and Public Health, Baltimore.

The findings were published online in JAMA.
 

Dose dependent effect

For their study, researchers analyzed data on 2,413 community-dwelling participants in the National Health and Aging Trends Study, a nationally representative, continuous panel study of U.S. Medicare beneficiaries aged 65 and older.

Data from the study was collected during in-home interviews, setting it apart from previous work that relied on data collected in a clinical setting, Dr. Huang said.

“This study was able to capture more vulnerable populations, such as the oldest old and older adults with disabilities, typically excluded from prior epidemiologic studies of the hearing loss–dementia association that use clinic-based data collection, which only captures people who have the ability and means to get to clinics,” Dr. Huang said.

Weighted hearing loss prevalence was 36.7% for mild and 29.8% for moderate to severe hearing loss, and weighted prevalence of dementia was 10.3%.

Those with moderate to severe hearing loss were 61% more likely to have dementia than were those with normal hearing (prevalence ratio, 1.61; 95% confidence interval [CI], 1.09-2.38).

Dementia prevalence increased with increasing severity of hearing loss: Normal hearing: 6.19% (95% CI, 4.31-8.80); mild hearing loss: 8.93% (95% CI, 6.99-11.34); moderate to severe hearing loss: 16.52% (95% CI, 13.81-19.64). But only moderate to severe hearing loss showed a statistically significant association with dementia (P = .02).

Dementia prevalence increased 16% per 10-decibel increase in hearing loss (prevalence ratio 1.16; P < .001).

Among the 853 individuals in the study with moderate to severe hearing loss, those who used hearing aids (n = 414) had a 32% lower risk of dementia compared with those who didn’t use assisted devices (prevalence ratio, 0.68; 95% CI, 0.47-1.00). Similar data were published in JAMA Neurology, suggesting that hearing aids reduce dementia risk.

“With this study, we were able to refine our understanding of the strength of the hearing loss–dementia association in a study more representative of older adults in the United States,” said Dr. Huang.
 

Robust association

Commenting on the findings, Justin S. Golub, MD, associate professor in the department of otolaryngology–head and neck surgery at Columbia University, New York, said the study supports earlier research and suggests a “robust” association between hearing loss and dementia.

“The particular advantage of this study was that it was high quality and nationally representative,” Dr. Golub said. “It is also among a smaller set of studies that have shown hearing aid use to be associated with lower risk of dementia.”

Although not statistically significant, researchers did find increasing prevalence of dementia among people with only mild hearing loss, and clinicians should take note, said Dr. Golub, who was not involved with this study.

“We would expect the relationship between mild hearing loss and dementia to be weaker than severe hearing loss and dementia and, as a result, it might take more participants to show an association among the mild group,” Dr. Golub said.

“Even though this particular study did not specifically find a relationship between mild hearing loss and dementia, I would still recommend people to start treating their hearing loss when it is early,” Dr. Golub added.

The study was funded by the National Institute on Aging. Dr. Golub reports no relevant financial relationships. Full disclosures for study authors are included in the original article.

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

Dementia prevalence is 61% higher among older people with moderate to severe hearing loss compared with those with normal hearing, new national data show. Investigators also found that even mild hearing loss was associated with increased dementia risk, although it was not statistically significant, and that hearing aid use was tied to a 32% decrease in dementia prevalence.

“Every 10-decibel increase in hearing loss was associated with 16% greater prevalence of dementia, such that prevalence of dementia in older adults with moderate or greater hearing loss was 61% higher than prevalence in those with normal hearing,” said lead investigator Alison Huang, PhD, senior research associate in epidemiology at Johns Hopkins Bloomberg School of Public Health and core faculty in the Cochlear Center for Hearing and Public Health, Baltimore.

The findings were published online in JAMA.
 

Dose dependent effect

For their study, researchers analyzed data on 2,413 community-dwelling participants in the National Health and Aging Trends Study, a nationally representative, continuous panel study of U.S. Medicare beneficiaries aged 65 and older.

Data from the study was collected during in-home interviews, setting it apart from previous work that relied on data collected in a clinical setting, Dr. Huang said.

“This study was able to capture more vulnerable populations, such as the oldest old and older adults with disabilities, typically excluded from prior epidemiologic studies of the hearing loss–dementia association that use clinic-based data collection, which only captures people who have the ability and means to get to clinics,” Dr. Huang said.

Weighted hearing loss prevalence was 36.7% for mild and 29.8% for moderate to severe hearing loss, and weighted prevalence of dementia was 10.3%.

Those with moderate to severe hearing loss were 61% more likely to have dementia than were those with normal hearing (prevalence ratio, 1.61; 95% confidence interval [CI], 1.09-2.38).

Dementia prevalence increased with increasing severity of hearing loss: Normal hearing: 6.19% (95% CI, 4.31-8.80); mild hearing loss: 8.93% (95% CI, 6.99-11.34); moderate to severe hearing loss: 16.52% (95% CI, 13.81-19.64). But only moderate to severe hearing loss showed a statistically significant association with dementia (P = .02).

Dementia prevalence increased 16% per 10-decibel increase in hearing loss (prevalence ratio 1.16; P < .001).

Among the 853 individuals in the study with moderate to severe hearing loss, those who used hearing aids (n = 414) had a 32% lower risk of dementia compared with those who didn’t use assisted devices (prevalence ratio, 0.68; 95% CI, 0.47-1.00). Similar data were published in JAMA Neurology, suggesting that hearing aids reduce dementia risk.

“With this study, we were able to refine our understanding of the strength of the hearing loss–dementia association in a study more representative of older adults in the United States,” said Dr. Huang.
 

Robust association

Commenting on the findings, Justin S. Golub, MD, associate professor in the department of otolaryngology–head and neck surgery at Columbia University, New York, said the study supports earlier research and suggests a “robust” association between hearing loss and dementia.

“The particular advantage of this study was that it was high quality and nationally representative,” Dr. Golub said. “It is also among a smaller set of studies that have shown hearing aid use to be associated with lower risk of dementia.”

Although not statistically significant, researchers did find increasing prevalence of dementia among people with only mild hearing loss, and clinicians should take note, said Dr. Golub, who was not involved with this study.

“We would expect the relationship between mild hearing loss and dementia to be weaker than severe hearing loss and dementia and, as a result, it might take more participants to show an association among the mild group,” Dr. Golub said.

“Even though this particular study did not specifically find a relationship between mild hearing loss and dementia, I would still recommend people to start treating their hearing loss when it is early,” Dr. Golub added.

The study was funded by the National Institute on Aging. Dr. Golub reports no relevant financial relationships. Full disclosures for study authors are included in the original article.

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

Physicians and other clinicians could more easily exit contracts and change jobs under the Federal Trade Commission’s new proposed rule that would block companies from limiting employees’ ability to work for a rival.

The proposed rule seeks to ban companies from enforcing noncompete clauses in employment contracts, a practice that represents an “unfair method of competition” with “exploitative and widespread” impacts, including suppression of wages, innovation, and entrepreneurial spirit, the FTC said. The public has 60 days to submit comments on the proposal before the FTC issues the final rule.

Employers often include noncompete clauses in physician contracts because they want to avoid having patients leave their health care system and follow a doctor to a competitor. A 2018 survey of primary care physicians found that about half of office-based physicians and 37% of physicians employed at hospitals or freestanding care centers were bound by restrictive covenants.

“A federal ban on noncompete agreements will ensure that physicians nationwide can finally change jobs without fear of being sued,” Erik B. Smith, MD, JD, clinical assistant professor of anesthesiology at the University of Southern California, Los Angeles, said in an interview.

Many doctors would like to see noncompete agreements vanish, but some physicians still favor them.

“As a small-practice owner, I am personally against this. The noncompete helps me take a risk and hire a physician. It typically takes 2-3 years for me to break even. I think this will further consolidate employment with large hospital systems unfortunately,” Texas cardiologist Rishin Shah, MD, recently tweeted in response to the FTC announcement.

Dr. Smith, who has advocated for noncompete reform, said about half of states currently allow the controversial clauses.

However, several states have recently passed laws restricting their use. California, North Dakota, and Oklahoma ban noncompetes, although some narrowly defined exceptions, such as the sale of a business, remain.

Other states, like Colorado, Illinois, and Oregon, broadly ban noncompete clauses, except for workers earning above a certain threshold. For example, in Colorado, noncompete agreements are permitted for highly compensated employees earning more than $101,250.

Despite additional restrictions on noncompete agreements for workers in the District of Columbia, the new legislation does not apply to physicians earning total compensation of $250,000 or more. However, their employers must define the geographic parameters of the noncompete and limit postemployment restrictions to 2 years.

Restrictive covenants are “uniquely challenging to family medicine’s emphasis on longitudinal care and the patient-physician relationship,” said Tochi Iroku-Malize, MD, MPH, president of the American Academy of Family Physicians. The limitations imposed by noncompete agreements “potentially reduce patient choice, lower the quality of care for patients, and ultimately harm the foundation of family medicine – our relationships with our patients.”

Although the proposed rule aligns with President Biden’s executive order promoting economic competition, Dr. Smith said a national ban on noncompete agreements may push the limits of FTC authority.

“This new rule will certainly result in a ‘major questions doctrine’ Supreme Court challenge,” said Dr. Smith, and possibly be struck down if the court determines an administrative overstep into areas of “vast economic or political significance.”
 

A controversial policy

The American Medical Association’s code of ethics discourages covenants that “unreasonably restrict” the ability of physicians to practice following contract termination. And in 2022, the AMA cited “overly broad” noncompete language as a red flag young physicians should watch out for during contract negotiations.

But in 2020, the AMA asked the FTC not to use its rulemaking authority to regulate noncompete clauses in physician employment contracts, and instead, relegate enforcement of such agreements to each state. The American Hospital Association expressed similar views.

Still, the FTC said that eliminating noncompete clauses will increase annual wages by $300 billion, allow 30 million Americans to pursue better job opportunities, and encourage hiring competition among employers. It will also save consumers up to $148 billion in health care costs annually.

“Noncompetes block workers from freely switching jobs, depriving them of higher wages and better working conditions, and depriving businesses of a talent pool that they need to build and expand,” Lina M. Khan, FTC chair, said in a press release about the proposal.

A national ban on noncompetes would keep more physicians in the industry and practicing in their communities, a win for patients and providers, said Dr. Smith. It could also compel employers to offer more competitive employment packages, including fair wages, better work conditions, and a culture of well-being and patient safety.

“Whatever the final rule is, I’m certain it will be legally challenged,” said Dr. Smith, adding that the nation’s most prominent business lobbying group, the Chamber of Commerce, has already issued a statement calling the rule “blatantly unlawful."

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

Physicians and other clinicians could more easily exit contracts and change jobs under the Federal Trade Commission’s new proposed rule that would block companies from limiting employees’ ability to work for a rival.

The proposed rule seeks to ban companies from enforcing noncompete clauses in employment contracts, a practice that represents an “unfair method of competition” with “exploitative and widespread” impacts, including suppression of wages, innovation, and entrepreneurial spirit, the FTC said. The public has 60 days to submit comments on the proposal before the FTC issues the final rule.

Employers often include noncompete clauses in physician contracts because they want to avoid having patients leave their health care system and follow a doctor to a competitor. A 2018 survey of primary care physicians found that about half of office-based physicians and 37% of physicians employed at hospitals or freestanding care centers were bound by restrictive covenants.

“A federal ban on noncompete agreements will ensure that physicians nationwide can finally change jobs without fear of being sued,” Erik B. Smith, MD, JD, clinical assistant professor of anesthesiology at the University of Southern California, Los Angeles, said in an interview.

Many doctors would like to see noncompete agreements vanish, but some physicians still favor them.

“As a small-practice owner, I am personally against this. The noncompete helps me take a risk and hire a physician. It typically takes 2-3 years for me to break even. I think this will further consolidate employment with large hospital systems unfortunately,” Texas cardiologist Rishin Shah, MD, recently tweeted in response to the FTC announcement.

Dr. Smith, who has advocated for noncompete reform, said about half of states currently allow the controversial clauses.

However, several states have recently passed laws restricting their use. California, North Dakota, and Oklahoma ban noncompetes, although some narrowly defined exceptions, such as the sale of a business, remain.

Other states, like Colorado, Illinois, and Oregon, broadly ban noncompete clauses, except for workers earning above a certain threshold. For example, in Colorado, noncompete agreements are permitted for highly compensated employees earning more than $101,250.

Despite additional restrictions on noncompete agreements for workers in the District of Columbia, the new legislation does not apply to physicians earning total compensation of $250,000 or more. However, their employers must define the geographic parameters of the noncompete and limit postemployment restrictions to 2 years.

Restrictive covenants are “uniquely challenging to family medicine’s emphasis on longitudinal care and the patient-physician relationship,” said Tochi Iroku-Malize, MD, MPH, president of the American Academy of Family Physicians. The limitations imposed by noncompete agreements “potentially reduce patient choice, lower the quality of care for patients, and ultimately harm the foundation of family medicine – our relationships with our patients.”

Although the proposed rule aligns with President Biden’s executive order promoting economic competition, Dr. Smith said a national ban on noncompete agreements may push the limits of FTC authority.

“This new rule will certainly result in a ‘major questions doctrine’ Supreme Court challenge,” said Dr. Smith, and possibly be struck down if the court determines an administrative overstep into areas of “vast economic or political significance.”
 

A controversial policy

The American Medical Association’s code of ethics discourages covenants that “unreasonably restrict” the ability of physicians to practice following contract termination. And in 2022, the AMA cited “overly broad” noncompete language as a red flag young physicians should watch out for during contract negotiations.

But in 2020, the AMA asked the FTC not to use its rulemaking authority to regulate noncompete clauses in physician employment contracts, and instead, relegate enforcement of such agreements to each state. The American Hospital Association expressed similar views.

Still, the FTC said that eliminating noncompete clauses will increase annual wages by $300 billion, allow 30 million Americans to pursue better job opportunities, and encourage hiring competition among employers. It will also save consumers up to $148 billion in health care costs annually.

“Noncompetes block workers from freely switching jobs, depriving them of higher wages and better working conditions, and depriving businesses of a talent pool that they need to build and expand,” Lina M. Khan, FTC chair, said in a press release about the proposal.

A national ban on noncompetes would keep more physicians in the industry and practicing in their communities, a win for patients and providers, said Dr. Smith. It could also compel employers to offer more competitive employment packages, including fair wages, better work conditions, and a culture of well-being and patient safety.

“Whatever the final rule is, I’m certain it will be legally challenged,” said Dr. Smith, adding that the nation’s most prominent business lobbying group, the Chamber of Commerce, has already issued a statement calling the rule “blatantly unlawful."

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

Physicians and other clinicians could more easily exit contracts and change jobs under the Federal Trade Commission’s new proposed rule that would block companies from limiting employees’ ability to work for a rival.

The proposed rule seeks to ban companies from enforcing noncompete clauses in employment contracts, a practice that represents an “unfair method of competition” with “exploitative and widespread” impacts, including suppression of wages, innovation, and entrepreneurial spirit, the FTC said. The public has 60 days to submit comments on the proposal before the FTC issues the final rule.

Employers often include noncompete clauses in physician contracts because they want to avoid having patients leave their health care system and follow a doctor to a competitor. A 2018 survey of primary care physicians found that about half of office-based physicians and 37% of physicians employed at hospitals or freestanding care centers were bound by restrictive covenants.

“A federal ban on noncompete agreements will ensure that physicians nationwide can finally change jobs without fear of being sued,” Erik B. Smith, MD, JD, clinical assistant professor of anesthesiology at the University of Southern California, Los Angeles, said in an interview.

Many doctors would like to see noncompete agreements vanish, but some physicians still favor them.

“As a small-practice owner, I am personally against this. The noncompete helps me take a risk and hire a physician. It typically takes 2-3 years for me to break even. I think this will further consolidate employment with large hospital systems unfortunately,” Texas cardiologist Rishin Shah, MD, recently tweeted in response to the FTC announcement.

Dr. Smith, who has advocated for noncompete reform, said about half of states currently allow the controversial clauses.

However, several states have recently passed laws restricting their use. California, North Dakota, and Oklahoma ban noncompetes, although some narrowly defined exceptions, such as the sale of a business, remain.

Other states, like Colorado, Illinois, and Oregon, broadly ban noncompete clauses, except for workers earning above a certain threshold. For example, in Colorado, noncompete agreements are permitted for highly compensated employees earning more than $101,250.

Despite additional restrictions on noncompete agreements for workers in the District of Columbia, the new legislation does not apply to physicians earning total compensation of $250,000 or more. However, their employers must define the geographic parameters of the noncompete and limit postemployment restrictions to 2 years.

Restrictive covenants are “uniquely challenging to family medicine’s emphasis on longitudinal care and the patient-physician relationship,” said Tochi Iroku-Malize, MD, MPH, president of the American Academy of Family Physicians. The limitations imposed by noncompete agreements “potentially reduce patient choice, lower the quality of care for patients, and ultimately harm the foundation of family medicine – our relationships with our patients.”

Although the proposed rule aligns with President Biden’s executive order promoting economic competition, Dr. Smith said a national ban on noncompete agreements may push the limits of FTC authority.

“This new rule will certainly result in a ‘major questions doctrine’ Supreme Court challenge,” said Dr. Smith, and possibly be struck down if the court determines an administrative overstep into areas of “vast economic or political significance.”
 

A controversial policy

The American Medical Association’s code of ethics discourages covenants that “unreasonably restrict” the ability of physicians to practice following contract termination. And in 2022, the AMA cited “overly broad” noncompete language as a red flag young physicians should watch out for during contract negotiations.

But in 2020, the AMA asked the FTC not to use its rulemaking authority to regulate noncompete clauses in physician employment contracts, and instead, relegate enforcement of such agreements to each state. The American Hospital Association expressed similar views.

Still, the FTC said that eliminating noncompete clauses will increase annual wages by $300 billion, allow 30 million Americans to pursue better job opportunities, and encourage hiring competition among employers. It will also save consumers up to $148 billion in health care costs annually.

“Noncompetes block workers from freely switching jobs, depriving them of higher wages and better working conditions, and depriving businesses of a talent pool that they need to build and expand,” Lina M. Khan, FTC chair, said in a press release about the proposal.

A national ban on noncompetes would keep more physicians in the industry and practicing in their communities, a win for patients and providers, said Dr. Smith. It could also compel employers to offer more competitive employment packages, including fair wages, better work conditions, and a culture of well-being and patient safety.

“Whatever the final rule is, I’m certain it will be legally challenged,” said Dr. Smith, adding that the nation’s most prominent business lobbying group, the Chamber of Commerce, has already issued a statement calling the rule “blatantly unlawful."

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

When I was a resident (back in the Cretaceous era), the idea of autoimmune encephalitis was just beginning to take hold. It was kind of like Bigfoot. A few reports, vague articles, the occasional sighting of what may or may not be a case. …

Unlike Bigfoot, however, the evidence quickly added up until there was no question that such a disorder existed. Then disorder became disorders, and now it seems a few more types are added to the list each year.

This doesn’t change the fact that they’re still, in the grand scheme of general neurology, relatively rare, though no one questions that they exist.

Today people still wishfully take pictures of Bigfoot, but they turn out to be images of bears or other animals, or tricks of light and shadow.

This is an issue with human thought. Many times we see what we want to see, especially if it’s more interesting than a mundane alternative.

An autoimmune encephalitis article in the January 2023 issue of JAMA Neurology looked into this. On reviewing 393 patients diagnosed with the disorder, the researchers found that 27% of them actually didn’t have it at all. Such things as functional disorders, neurodegenerative diseases, and primary psychiatric diagnoses were, instead, the culprits.

I’m not criticizing those who made an incorrect diagnosis. We all do. That’s the nature of medicine.

Which is worse? Missing the diagnosis entirely and not treating, or diagnosing a patient with something else and treating incorrectly? I guess it depends on the disease and nature of treatment.

Certainly, finding a case of autoimmune encephalitis is more interesting than, say toxic-metabolic encephalopathy from a bladder infection, just as getting a picture of Bigfoot is way more cool than one of a bear with mange.

But we need to be careful when faced with equivocal labs and data lest we read too much into them. There are too many gray zones in medicine to lead you astray. Not to say we won’t be. Even well-intentioned physicians (which I assume is pretty much all of us) are going to make mistakes.

But it’s not just rare diseases. In the early 1990s two different studies found that 24% of patients diagnosed with Parkinson’s disease were found to have something else on autopsy.

That was 30 years ago. Now we have DaT scans to help. Maybe our abilities as neurologists have also gotten better (though I don’t think the neurological exam has changed much since Charcot).

Our gadgets, labs, and treatments get better every year. We have tools available to us now that were unthinkable a generation ago. For that matter, they were unthinkable when I began my career.

But they don’t change the fact that human error never goes away. All of us are susceptible to it, and all of us make mistakes.

Such is the way of medicine now, and likely always. All we can do is our best and keep moving forward.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

When I was a resident (back in the Cretaceous era), the idea of autoimmune encephalitis was just beginning to take hold. It was kind of like Bigfoot. A few reports, vague articles, the occasional sighting of what may or may not be a case. …

Unlike Bigfoot, however, the evidence quickly added up until there was no question that such a disorder existed. Then disorder became disorders, and now it seems a few more types are added to the list each year.

This doesn’t change the fact that they’re still, in the grand scheme of general neurology, relatively rare, though no one questions that they exist.

Today people still wishfully take pictures of Bigfoot, but they turn out to be images of bears or other animals, or tricks of light and shadow.

This is an issue with human thought. Many times we see what we want to see, especially if it’s more interesting than a mundane alternative.

An autoimmune encephalitis article in the January 2023 issue of JAMA Neurology looked into this. On reviewing 393 patients diagnosed with the disorder, the researchers found that 27% of them actually didn’t have it at all. Such things as functional disorders, neurodegenerative diseases, and primary psychiatric diagnoses were, instead, the culprits.

I’m not criticizing those who made an incorrect diagnosis. We all do. That’s the nature of medicine.

Which is worse? Missing the diagnosis entirely and not treating, or diagnosing a patient with something else and treating incorrectly? I guess it depends on the disease and nature of treatment.

Certainly, finding a case of autoimmune encephalitis is more interesting than, say toxic-metabolic encephalopathy from a bladder infection, just as getting a picture of Bigfoot is way more cool than one of a bear with mange.

But we need to be careful when faced with equivocal labs and data lest we read too much into them. There are too many gray zones in medicine to lead you astray. Not to say we won’t be. Even well-intentioned physicians (which I assume is pretty much all of us) are going to make mistakes.

But it’s not just rare diseases. In the early 1990s two different studies found that 24% of patients diagnosed with Parkinson’s disease were found to have something else on autopsy.

That was 30 years ago. Now we have DaT scans to help. Maybe our abilities as neurologists have also gotten better (though I don’t think the neurological exam has changed much since Charcot).

Our gadgets, labs, and treatments get better every year. We have tools available to us now that were unthinkable a generation ago. For that matter, they were unthinkable when I began my career.

But they don’t change the fact that human error never goes away. All of us are susceptible to it, and all of us make mistakes.

Such is the way of medicine now, and likely always. All we can do is our best and keep moving forward.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

When I was a resident (back in the Cretaceous era), the idea of autoimmune encephalitis was just beginning to take hold. It was kind of like Bigfoot. A few reports, vague articles, the occasional sighting of what may or may not be a case. …

Unlike Bigfoot, however, the evidence quickly added up until there was no question that such a disorder existed. Then disorder became disorders, and now it seems a few more types are added to the list each year.

This doesn’t change the fact that they’re still, in the grand scheme of general neurology, relatively rare, though no one questions that they exist.

Today people still wishfully take pictures of Bigfoot, but they turn out to be images of bears or other animals, or tricks of light and shadow.

This is an issue with human thought. Many times we see what we want to see, especially if it’s more interesting than a mundane alternative.

An autoimmune encephalitis article in the January 2023 issue of JAMA Neurology looked into this. On reviewing 393 patients diagnosed with the disorder, the researchers found that 27% of them actually didn’t have it at all. Such things as functional disorders, neurodegenerative diseases, and primary psychiatric diagnoses were, instead, the culprits.

I’m not criticizing those who made an incorrect diagnosis. We all do. That’s the nature of medicine.

Which is worse? Missing the diagnosis entirely and not treating, or diagnosing a patient with something else and treating incorrectly? I guess it depends on the disease and nature of treatment.

Certainly, finding a case of autoimmune encephalitis is more interesting than, say toxic-metabolic encephalopathy from a bladder infection, just as getting a picture of Bigfoot is way more cool than one of a bear with mange.

But we need to be careful when faced with equivocal labs and data lest we read too much into them. There are too many gray zones in medicine to lead you astray. Not to say we won’t be. Even well-intentioned physicians (which I assume is pretty much all of us) are going to make mistakes.

But it’s not just rare diseases. In the early 1990s two different studies found that 24% of patients diagnosed with Parkinson’s disease were found to have something else on autopsy.

That was 30 years ago. Now we have DaT scans to help. Maybe our abilities as neurologists have also gotten better (though I don’t think the neurological exam has changed much since Charcot).

Our gadgets, labs, and treatments get better every year. We have tools available to us now that were unthinkable a generation ago. For that matter, they were unthinkable when I began my career.

But they don’t change the fact that human error never goes away. All of us are susceptible to it, and all of us make mistakes.

Such is the way of medicine now, and likely always. All we can do is our best and keep moving forward.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

People with higher dietary zinc intake have a nearly one-third lower risk of migraine than those who get little zinc in their diets, according to results from a cross-sectional study of more than 11,000 American adults.

For their research, published online in Headache, Huanxian Liu, MD, and colleagues at Chinese PLA General Hospital in Beijing, analyzed publicly available data from the U.S. National Health and Nutrition Examination Survey to determine whether people self-reporting migraine or severe headache saw lower zinc intake, compared with people without migraine. The data used in the analysis was collected between 1999 and 2004, and contained information on foods and drinks consumed by participants in a 24-hour period, along with additional health information.
 

An inverse relationship

The investigators divided their study’s 11,088 participants (mean age, 46.5 years; 50% female) into quintiles based on dietary zinc consumption as inferred from foods eaten. They also considered zinc supplementation, for which data was available for 4,324 participants, of whom 2,607 reported use of supplements containing zinc.

Some 20% of the cohort (n = 2,236) reported migraine or severe headache within the previous 3 months. Pregnant women were excluded from analysis, and the investigators adjusted for a range of covariates, including age, sex, ethnicity, education level, body mass, smoking, diabetes, cardiovascular disease, and nutritional factors.

Dr. Liu and colleagues reported an inverse association between dietary zinc consumption and migraine, with the highest-consuming quintile of the cohort (15.8 mg or more zinc per day) seeing lowest risk of migraine (odds ratio, 0.70; 95% confidence interval, 0.52-0.94; P = .029), compared with the low-consuming quintile (5.9 mg or less daily). Among people getting high levels of zinc (19.3-32.5 mg daily) through supplements, risk of migraine was lower still, to between an OR of 0.62 (95% CI: 0.46–0.83, P = 0.019) and an OR of 0.67 (95% CI, 0.49–0.91; P = .045).

While the investigators acknowledged limitations of the study, including its cross-sectional design and use of a broad question to discern prevalence of migraine, the findings suggest that “zinc is an important nutrient that influences migraine,” they wrote, citing evidence for its antioxidant and anti-inflammatory properties.
 

The importance of nutritional factors

Commenting on the research findings, Deborah I. Friedman, MD, MPH, a headache specialist in Dallas, said that Dr. Liu and colleagues’ findings added to a growing information base about nutritional factors and migraine. For example, “low magnesium levels are common in people with migraine, and magnesium supplementation is a recommended preventive treatment for migraine.”

Dr. Friedman cited a recent study showing that vitamin B₁₂ and magnesium supplementation in women (, combined with high-intensity interval training, “silenced” the inflammation signaling pathway, helped migraine pain and decreased levels of calcitonin gene-related peptide. A 2022 randomized trial found that alpha lipoic acid supplementation reduced migraine severity, frequency and disability in women with episodic migraine.

Vitamin D levels are also lower in people with migraine, compared with controls, Dr. Friedman noted, and a randomized trial of 2,000 IU of vitamin D₃ daily saw reduced monthly headache days, attack duration, severe headaches, and analgesic use, compared with placebo. Other nutrients implicated in migraine include coenzyme Q10, calcium, folic acid, vitamin B₆, and vitamin B₁.

“What should a patient with migraine do with all of this information? First, eat a healthy and balanced diet,” Dr. Friedman said. “Sources of dietary zinc include red meat, nuts, legumes, poultry, shellfish (especially oysters), whole grains, some cereals, and even dark chocolate. The recommended daily dosage of zinc is 9.5 mg in men and 7 mg in women. Most people get enough zinc in their diet; vegetarians, vegans, pregnant or breastfeeding women, and adults over age 65 may need to take supplemental zinc.”

Dr. Liu and colleagues’ work was supported by China’s National Natural Science Foundation. The investigators reported no financial conflicts of interest. Dr. Friedman has received financial support from Alder, Allergan, Amgen, Biohaven, Eli Lilly, Merck, Teva, and other pharmaceutical manufacturers.

People with higher dietary zinc intake have a nearly one-third lower risk of migraine than those who get little zinc in their diets, according to results from a cross-sectional study of more than 11,000 American adults.

For their research, published online in Headache, Huanxian Liu, MD, and colleagues at Chinese PLA General Hospital in Beijing, analyzed publicly available data from the U.S. National Health and Nutrition Examination Survey to determine whether people self-reporting migraine or severe headache saw lower zinc intake, compared with people without migraine. The data used in the analysis was collected between 1999 and 2004, and contained information on foods and drinks consumed by participants in a 24-hour period, along with additional health information.
 

An inverse relationship

The investigators divided their study’s 11,088 participants (mean age, 46.5 years; 50% female) into quintiles based on dietary zinc consumption as inferred from foods eaten. They also considered zinc supplementation, for which data was available for 4,324 participants, of whom 2,607 reported use of supplements containing zinc.

Some 20% of the cohort (n = 2,236) reported migraine or severe headache within the previous 3 months. Pregnant women were excluded from analysis, and the investigators adjusted for a range of covariates, including age, sex, ethnicity, education level, body mass, smoking, diabetes, cardiovascular disease, and nutritional factors.

Dr. Liu and colleagues reported an inverse association between dietary zinc consumption and migraine, with the highest-consuming quintile of the cohort (15.8 mg or more zinc per day) seeing lowest risk of migraine (odds ratio, 0.70; 95% confidence interval, 0.52-0.94; P = .029), compared with the low-consuming quintile (5.9 mg or less daily). Among people getting high levels of zinc (19.3-32.5 mg daily) through supplements, risk of migraine was lower still, to between an OR of 0.62 (95% CI: 0.46–0.83, P = 0.019) and an OR of 0.67 (95% CI, 0.49–0.91; P = .045).

While the investigators acknowledged limitations of the study, including its cross-sectional design and use of a broad question to discern prevalence of migraine, the findings suggest that “zinc is an important nutrient that influences migraine,” they wrote, citing evidence for its antioxidant and anti-inflammatory properties.
 

The importance of nutritional factors

Commenting on the research findings, Deborah I. Friedman, MD, MPH, a headache specialist in Dallas, said that Dr. Liu and colleagues’ findings added to a growing information base about nutritional factors and migraine. For example, “low magnesium levels are common in people with migraine, and magnesium supplementation is a recommended preventive treatment for migraine.”

Dr. Friedman cited a recent study showing that vitamin B₁₂ and magnesium supplementation in women (, combined with high-intensity interval training, “silenced” the inflammation signaling pathway, helped migraine pain and decreased levels of calcitonin gene-related peptide. A 2022 randomized trial found that alpha lipoic acid supplementation reduced migraine severity, frequency and disability in women with episodic migraine.

Vitamin D levels are also lower in people with migraine, compared with controls, Dr. Friedman noted, and a randomized trial of 2,000 IU of vitamin D₃ daily saw reduced monthly headache days, attack duration, severe headaches, and analgesic use, compared with placebo. Other nutrients implicated in migraine include coenzyme Q10, calcium, folic acid, vitamin B₆, and vitamin B₁.

“What should a patient with migraine do with all of this information? First, eat a healthy and balanced diet,” Dr. Friedman said. “Sources of dietary zinc include red meat, nuts, legumes, poultry, shellfish (especially oysters), whole grains, some cereals, and even dark chocolate. The recommended daily dosage of zinc is 9.5 mg in men and 7 mg in women. Most people get enough zinc in their diet; vegetarians, vegans, pregnant or breastfeeding women, and adults over age 65 may need to take supplemental zinc.”

Dr. Liu and colleagues’ work was supported by China’s National Natural Science Foundation. The investigators reported no financial conflicts of interest. Dr. Friedman has received financial support from Alder, Allergan, Amgen, Biohaven, Eli Lilly, Merck, Teva, and other pharmaceutical manufacturers.

People with higher dietary zinc intake have a nearly one-third lower risk of migraine than those who get little zinc in their diets, according to results from a cross-sectional study of more than 11,000 American adults.

For their research, published online in Headache, Huanxian Liu, MD, and colleagues at Chinese PLA General Hospital in Beijing, analyzed publicly available data from the U.S. National Health and Nutrition Examination Survey to determine whether people self-reporting migraine or severe headache saw lower zinc intake, compared with people without migraine. The data used in the analysis was collected between 1999 and 2004, and contained information on foods and drinks consumed by participants in a 24-hour period, along with additional health information.
 

An inverse relationship

The investigators divided their study’s 11,088 participants (mean age, 46.5 years; 50% female) into quintiles based on dietary zinc consumption as inferred from foods eaten. They also considered zinc supplementation, for which data was available for 4,324 participants, of whom 2,607 reported use of supplements containing zinc.

Some 20% of the cohort (n = 2,236) reported migraine or severe headache within the previous 3 months. Pregnant women were excluded from analysis, and the investigators adjusted for a range of covariates, including age, sex, ethnicity, education level, body mass, smoking, diabetes, cardiovascular disease, and nutritional factors.

Dr. Liu and colleagues reported an inverse association between dietary zinc consumption and migraine, with the highest-consuming quintile of the cohort (15.8 mg or more zinc per day) seeing lowest risk of migraine (odds ratio, 0.70; 95% confidence interval, 0.52-0.94; P = .029), compared with the low-consuming quintile (5.9 mg or less daily). Among people getting high levels of zinc (19.3-32.5 mg daily) through supplements, risk of migraine was lower still, to between an OR of 0.62 (95% CI: 0.46–0.83, P = 0.019) and an OR of 0.67 (95% CI, 0.49–0.91; P = .045).

While the investigators acknowledged limitations of the study, including its cross-sectional design and use of a broad question to discern prevalence of migraine, the findings suggest that “zinc is an important nutrient that influences migraine,” they wrote, citing evidence for its antioxidant and anti-inflammatory properties.
 

The importance of nutritional factors

Commenting on the research findings, Deborah I. Friedman, MD, MPH, a headache specialist in Dallas, said that Dr. Liu and colleagues’ findings added to a growing information base about nutritional factors and migraine. For example, “low magnesium levels are common in people with migraine, and magnesium supplementation is a recommended preventive treatment for migraine.”

Dr. Friedman cited a recent study showing that vitamin B₁₂ and magnesium supplementation in women (, combined with high-intensity interval training, “silenced” the inflammation signaling pathway, helped migraine pain and decreased levels of calcitonin gene-related peptide. A 2022 randomized trial found that alpha lipoic acid supplementation reduced migraine severity, frequency and disability in women with episodic migraine.

Vitamin D levels are also lower in people with migraine, compared with controls, Dr. Friedman noted, and a randomized trial of 2,000 IU of vitamin D₃ daily saw reduced monthly headache days, attack duration, severe headaches, and analgesic use, compared with placebo. Other nutrients implicated in migraine include coenzyme Q10, calcium, folic acid, vitamin B₆, and vitamin B₁.

“What should a patient with migraine do with all of this information? First, eat a healthy and balanced diet,” Dr. Friedman said. “Sources of dietary zinc include red meat, nuts, legumes, poultry, shellfish (especially oysters), whole grains, some cereals, and even dark chocolate. The recommended daily dosage of zinc is 9.5 mg in men and 7 mg in women. Most people get enough zinc in their diet; vegetarians, vegans, pregnant or breastfeeding women, and adults over age 65 may need to take supplemental zinc.”

Dr. Liu and colleagues’ work was supported by China’s National Natural Science Foundation. The investigators reported no financial conflicts of interest. Dr. Friedman has received financial support from Alder, Allergan, Amgen, Biohaven, Eli Lilly, Merck, Teva, and other pharmaceutical manufacturers.

Short bouts of intense exercise may help protect the brain from age-related cognitive decline by increasing production of a key protein involved in neuroplasticity, learning, and memory, new research suggests.

In a small study of healthy adults, 6 minutes of high-intensity cycling increased circulating levels of brain-derived neurotrophic factor (BDNF) to a significantly greater extent than prolonged light cycling or fasting.

However, the data do not suggest that 6 minutes of high-intensity exercise “wards off dementia,” cautioned lead investigator Travis Gibbons, MSc, PhD candidate in environmental physiology at the University of Otago (New Zealand), Dunedin, and now postdoctoral fellow at the University of British Columbia – Okanagan, Kelowna.

“Like all science, this is just a small piece that supports a potential mechanistic role for how exercise might improve brain health,” Dr. Gibbons told this news organization.

The findings were published online in the Journal of Physiology.
 

Targeting BDNF

Both intermittent fasting and exercise have previously been shown to have potent neuroprotective effects; and an acute upregulation of BDNF appears to be a common mechanistic link.

To tease apart the influence of fasting and exercise on BDNF production, Dr. Gibbons and colleagues studied 12 aerobically fit, healthy men (n = 6) and women (n = 6) aged 20-40 years.

In a study that employed a repeated-measures crossover design, they assessed circulating BDNF levels after a 20-hour fast, prolonged (90-min) light cycling, short (6-min) high-intensity cycling, and combined fasting and exercise.

Six minutes of high-intensity exercise appeared to be the most efficient way to increase BDNF.

Fasting for 20 hours led to a ninefold increase in ketone body delivery to the brain but had no effect on any metric of BDNF in peripheral circulation at rest or during exercise.

Six minutes of high-intensity exercise increased every metric of circulating BDNF four to five times more than prolonged low-intensity exercise.

In addition, the increase in plasma-derived BDNF correlated with a sixfold increase in circulating lactate irrespective of feeding or fasting state.
 

Lactate delivery?

“My leading theory is that, during and following intense exercise, lactate produced by muscles is delivered and consumed by the brain,” Dr. Gibbons noted.

“It takes high-intensity exercise to provoke this ‘cerebral substrate switch’ from glucose to lactate. Critically, this cerebral substrate switch has been shown to contribute to the early processes that upregulate BDNF production in the brain,” he said.

However, “Whether this translates to ‘warding off dementia’ is not clear,” Dr. Gibbons added.

The study also suggests that increases in plasma volume and platelet concentration appear to play a role in concentrating BDNF in the circulation during exercise.

The investigators note that BDNF and other neurotrophic-based pharmaceutical therapies have shown “great promise” in slowing and even arresting neurodegenerative processes in animals, but attempts to harness the protective power of BDNF in human neurodegeneration have thus far failed.

“Whether episodically upregulating BDNF production with intense exercise is an effective strategy to curb age-related cognitive decline in humans is unknown, but animal models indicate that it is and that BDNF plays a primary role,” the researchers write.

Funding for the study was provided by the Healthcare Otago Charitable Trust. The investigators have reported no relevant financial relationships.

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

Short bouts of intense exercise may help protect the brain from age-related cognitive decline by increasing production of a key protein involved in neuroplasticity, learning, and memory, new research suggests.

In a small study of healthy adults, 6 minutes of high-intensity cycling increased circulating levels of brain-derived neurotrophic factor (BDNF) to a significantly greater extent than prolonged light cycling or fasting.

However, the data do not suggest that 6 minutes of high-intensity exercise “wards off dementia,” cautioned lead investigator Travis Gibbons, MSc, PhD candidate in environmental physiology at the University of Otago (New Zealand), Dunedin, and now postdoctoral fellow at the University of British Columbia – Okanagan, Kelowna.

“Like all science, this is just a small piece that supports a potential mechanistic role for how exercise might improve brain health,” Dr. Gibbons told this news organization.

The findings were published online in the Journal of Physiology.
 

Targeting BDNF

Both intermittent fasting and exercise have previously been shown to have potent neuroprotective effects; and an acute upregulation of BDNF appears to be a common mechanistic link.

To tease apart the influence of fasting and exercise on BDNF production, Dr. Gibbons and colleagues studied 12 aerobically fit, healthy men (n = 6) and women (n = 6) aged 20-40 years.

In a study that employed a repeated-measures crossover design, they assessed circulating BDNF levels after a 20-hour fast, prolonged (90-min) light cycling, short (6-min) high-intensity cycling, and combined fasting and exercise.

Six minutes of high-intensity exercise appeared to be the most efficient way to increase BDNF.

Fasting for 20 hours led to a ninefold increase in ketone body delivery to the brain but had no effect on any metric of BDNF in peripheral circulation at rest or during exercise.

Six minutes of high-intensity exercise increased every metric of circulating BDNF four to five times more than prolonged low-intensity exercise.

In addition, the increase in plasma-derived BDNF correlated with a sixfold increase in circulating lactate irrespective of feeding or fasting state.
 

Lactate delivery?

“My leading theory is that, during and following intense exercise, lactate produced by muscles is delivered and consumed by the brain,” Dr. Gibbons noted.

“It takes high-intensity exercise to provoke this ‘cerebral substrate switch’ from glucose to lactate. Critically, this cerebral substrate switch has been shown to contribute to the early processes that upregulate BDNF production in the brain,” he said.

However, “Whether this translates to ‘warding off dementia’ is not clear,” Dr. Gibbons added.

The study also suggests that increases in plasma volume and platelet concentration appear to play a role in concentrating BDNF in the circulation during exercise.

The investigators note that BDNF and other neurotrophic-based pharmaceutical therapies have shown “great promise” in slowing and even arresting neurodegenerative processes in animals, but attempts to harness the protective power of BDNF in human neurodegeneration have thus far failed.

“Whether episodically upregulating BDNF production with intense exercise is an effective strategy to curb age-related cognitive decline in humans is unknown, but animal models indicate that it is and that BDNF plays a primary role,” the researchers write.

Funding for the study was provided by the Healthcare Otago Charitable Trust. The investigators have reported no relevant financial relationships.

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

Short bouts of intense exercise may help protect the brain from age-related cognitive decline by increasing production of a key protein involved in neuroplasticity, learning, and memory, new research suggests.

In a small study of healthy adults, 6 minutes of high-intensity cycling increased circulating levels of brain-derived neurotrophic factor (BDNF) to a significantly greater extent than prolonged light cycling or fasting.

However, the data do not suggest that 6 minutes of high-intensity exercise “wards off dementia,” cautioned lead investigator Travis Gibbons, MSc, PhD candidate in environmental physiology at the University of Otago (New Zealand), Dunedin, and now postdoctoral fellow at the University of British Columbia – Okanagan, Kelowna.

“Like all science, this is just a small piece that supports a potential mechanistic role for how exercise might improve brain health,” Dr. Gibbons told this news organization.

The findings were published online in the Journal of Physiology.
 

Targeting BDNF

Both intermittent fasting and exercise have previously been shown to have potent neuroprotective effects; and an acute upregulation of BDNF appears to be a common mechanistic link.

To tease apart the influence of fasting and exercise on BDNF production, Dr. Gibbons and colleagues studied 12 aerobically fit, healthy men (n = 6) and women (n = 6) aged 20-40 years.

In a study that employed a repeated-measures crossover design, they assessed circulating BDNF levels after a 20-hour fast, prolonged (90-min) light cycling, short (6-min) high-intensity cycling, and combined fasting and exercise.

Six minutes of high-intensity exercise appeared to be the most efficient way to increase BDNF.

Fasting for 20 hours led to a ninefold increase in ketone body delivery to the brain but had no effect on any metric of BDNF in peripheral circulation at rest or during exercise.

Six minutes of high-intensity exercise increased every metric of circulating BDNF four to five times more than prolonged low-intensity exercise.

In addition, the increase in plasma-derived BDNF correlated with a sixfold increase in circulating lactate irrespective of feeding or fasting state.
 

Lactate delivery?

“My leading theory is that, during and following intense exercise, lactate produced by muscles is delivered and consumed by the brain,” Dr. Gibbons noted.

“It takes high-intensity exercise to provoke this ‘cerebral substrate switch’ from glucose to lactate. Critically, this cerebral substrate switch has been shown to contribute to the early processes that upregulate BDNF production in the brain,” he said.

However, “Whether this translates to ‘warding off dementia’ is not clear,” Dr. Gibbons added.

The study also suggests that increases in plasma volume and platelet concentration appear to play a role in concentrating BDNF in the circulation during exercise.

The investigators note that BDNF and other neurotrophic-based pharmaceutical therapies have shown “great promise” in slowing and even arresting neurodegenerative processes in animals, but attempts to harness the protective power of BDNF in human neurodegeneration have thus far failed.

“Whether episodically upregulating BDNF production with intense exercise is an effective strategy to curb age-related cognitive decline in humans is unknown, but animal models indicate that it is and that BDNF plays a primary role,” the researchers write.

Funding for the study was provided by the Healthcare Otago Charitable Trust. The investigators have reported no relevant financial relationships.

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

Delay in treatment will cost hospital millions

A Texas hospital must pay a multimillion-dollar judgment for failing to treat a woman’s spinal injury in time to prevent paralysis, according to a report on WFAA.com, among other news sites.

On March 21, 2019, Judy “Jessie” Adams, then part of a singing-songwriting duo with her husband, Richard, went to Premier Interventional Pain Management, in Flower Mound, Tex., prior to the couple’s drive to Ohio for a funeral. At Premier, Jesse received an epidural steroid injection (ESI) that she hoped would ease her back pain during the long drive.

Instead, the injection ended up increasing her pain.

“He [the pain physician] gave me the shot, but I couldn’t feel my legs. They were tingling, but I couldn’t feel them,” Mrs. Adams explained. “The pain was so bad in my back.” In their suit, Adams and her husband alleged that the doctor had probably “nicked a blood vessel during the ESI procedure, causing Jessie to hemorrhage.” (The couple’s suit against the doctor was settled prior to trial.)

Mrs. Adams remained under observation at the pain facility for about 1½ hours, at which point she was taken by ambulance to nearby Texas Health Presbyterian Hospital. There, in the emergency department, staff ordered a “STAT MRI” in preparation for an emergency laminectomy.

For reasons that remain murky, the MRI wasn’t performed for 1 hour and 37 minutes. The emergency laminectomy itself wasn’t started until more than 5 hours after Adams had been admitted to the ED. This was a direct violation of hospital protocol, which required that emergency surgeries be performed within 1 hour of admittance in the first available surgical suite. (At trial, Mrs. Adams’s attorneys from Lyons & Simmons offered evidence that a suite became available 49 minutes after Adams had arrived at the ED.)

During the wait, Mrs. Adams continued to experience excruciating pain. “I kept screaming: ‘Help me,’ ” she recalled. At trial, her attorneys argued that the hospital’s delay in addressing her spinal emergency led directly to her current paralysis, which keeps her confined to a wheelchair and renders her incontinent.

The hospital disagreed. In court, it maintained that Mrs. Adams was already paralyzed when she arrived at the ED and that there was no delay in care.

The jury saw things differently, however. Siding with the plaintiffs, it awarded Mrs. Adams and her husband $10.1 million, including $500,000 for Mr. Adams’s loss of future earnings and $1 million for his “loss of consortium” with his wife.

Their music career now effectively over, Mr. Adams spends most of his time taking care of Mrs. Adams.

“Music was our lifeblood for so many years, and he can’t do it anymore,” Mrs. Adams said. “He goes upstairs to play his guitar and write, and suddenly I need him to come and cath me. I just feel like I’m going to wake up from this bad dream, but it’s the same routine.”
 

Two doctors are absolved in woman’s sudden death

In a 3-2 decision in December 2022, the Pennsylvania Supreme Court ruled that the state’s 2-year statute of limitations in wrongful-death cases applies even in cases in which plaintiffs fail to identify the cause of death in a timely manner, as a report in the Claims Journal indicates.

The decision stems from a lawsuit filed by Linda Reibenstein on behalf of her mother, Mary Ann Whitman, who died in late April 2010 from a ruptured aortic aneurysm.

On April 12, 2010, Ms. Whitman visited Patrick D. Conaboy, MD, a Scranton family physician, complaining of a persistent cough, fever, and lower-back pain. Following an initial examination, Dr. Conaboy ordered an aortic duplex ultrasound scan and a CT scan of the patient’s abdomen.

The ultrasound was performed by radiologist Charles Barax, MD, who reviewed both scans. He identified a “poorly visualized aortic aneurysm.” At this point, Dr. Conaboy referred Ms. Whitman to a vascular surgeon. But before this visit could take place, Whitman’s aneurysm ruptured, killing her. This was listed as the medical cause of death on the patient’s death certificate.

In April 2011, Ms. Reibenstein filed a claim against Dr. Barax, alleging that he had failed to gauge the severity of her mother’s condition. Ms. Reibenstein’s attorney wasn’t able to question Dr. Barax on the record until well after the state’s 2-year statute of limitations had elapsed. When he did testify, Dr. Barax explained that the scans’ image quality prevented him from determining whether Whitman’s aneurysm was rupturing or simply bleeding. Despite this, he insisted that he had warned Dr. Conaboy of the potential for Ms. Whitman’s aneurysm to rupture.

In March 2016, nearly 6 years after her mother’s death, Ms. Reibenstein filed a new lawsuit, this one against Dr. Conaboy, whom she alleged had failed to properly treat her mother’s condition. Dr. Conaboy, in turn, asked the court for summary judgment – that is, a judgment in his favor without a full trial – arguing that the state’s window for filing a wrongful-death claim had long since closed. For their part, Ms. Reibenstein and her attorney argued that the state’s 2-year statute of limitations didn’t start until the plaintiff had discovered the cause of her mother’s death.

Initially refusing to dismiss the case, a lower court reconsidered Dr. Conaboy’s motion for summary judgment and ruled that Ms. Reibenstein had failed to present any evidence of “affirmative misrepresentation or fraudulent concealment.” In other words, in the absence of any willful attempt on the part of the defendant to hide the legal cause of death, which includes “acts, omissions, or events having some causative connection with the death,” the statute of limitations remained in effect, and the defendant’s motion was thereby granted.

Continuing the legal seesaw, a state appeals court reversed the lower-court ruling. Noting that the Pennsylvania malpractice statute was ambiguous, the court argued that it should be interpreted in a way that protects plaintiffs who seek “fair compensation” but encounter willfully erected obstacles in pursuit of their claim.

Dr. Conaboy then took his case to the state’s highest court. In its majority decision, the Pennsylvania Supreme Court staked out a narrow definition of cause of death – one based on the death certificate – and ruled that only willful fraud in that document would constitute the necessary condition for halting the claim’s clock. Furthermore, the high court said, when lawmakers adopted the Medical Care Availability and Reduction of Error Act in 2002, they did so with no guarantee “that all of the information necessary to sustain a claim will be gathered in the limitations period.”

Similarly, the court ruled, “at some point the clock must run out, lest health care providers remain subject to liability exposure indefinitely, with the prospect of a trial marred by the death or diminished memory of material witnesses or the loss of critical evidence.”

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

Delay in treatment will cost hospital millions

A Texas hospital must pay a multimillion-dollar judgment for failing to treat a woman’s spinal injury in time to prevent paralysis, according to a report on WFAA.com, among other news sites.

On March 21, 2019, Judy “Jessie” Adams, then part of a singing-songwriting duo with her husband, Richard, went to Premier Interventional Pain Management, in Flower Mound, Tex., prior to the couple’s drive to Ohio for a funeral. At Premier, Jesse received an epidural steroid injection (ESI) that she hoped would ease her back pain during the long drive.

Instead, the injection ended up increasing her pain.

“He [the pain physician] gave me the shot, but I couldn’t feel my legs. They were tingling, but I couldn’t feel them,” Mrs. Adams explained. “The pain was so bad in my back.” In their suit, Adams and her husband alleged that the doctor had probably “nicked a blood vessel during the ESI procedure, causing Jessie to hemorrhage.” (The couple’s suit against the doctor was settled prior to trial.)

Mrs. Adams remained under observation at the pain facility for about 1½ hours, at which point she was taken by ambulance to nearby Texas Health Presbyterian Hospital. There, in the emergency department, staff ordered a “STAT MRI” in preparation for an emergency laminectomy.

For reasons that remain murky, the MRI wasn’t performed for 1 hour and 37 minutes. The emergency laminectomy itself wasn’t started until more than 5 hours after Adams had been admitted to the ED. This was a direct violation of hospital protocol, which required that emergency surgeries be performed within 1 hour of admittance in the first available surgical suite. (At trial, Mrs. Adams’s attorneys from Lyons & Simmons offered evidence that a suite became available 49 minutes after Adams had arrived at the ED.)

During the wait, Mrs. Adams continued to experience excruciating pain. “I kept screaming: ‘Help me,’ ” she recalled. At trial, her attorneys argued that the hospital’s delay in addressing her spinal emergency led directly to her current paralysis, which keeps her confined to a wheelchair and renders her incontinent.

The hospital disagreed. In court, it maintained that Mrs. Adams was already paralyzed when she arrived at the ED and that there was no delay in care.

The jury saw things differently, however. Siding with the plaintiffs, it awarded Mrs. Adams and her husband $10.1 million, including $500,000 for Mr. Adams’s loss of future earnings and $1 million for his “loss of consortium” with his wife.

Their music career now effectively over, Mr. Adams spends most of his time taking care of Mrs. Adams.

“Music was our lifeblood for so many years, and he can’t do it anymore,” Mrs. Adams said. “He goes upstairs to play his guitar and write, and suddenly I need him to come and cath me. I just feel like I’m going to wake up from this bad dream, but it’s the same routine.”
 

Two doctors are absolved in woman’s sudden death

In a 3-2 decision in December 2022, the Pennsylvania Supreme Court ruled that the state’s 2-year statute of limitations in wrongful-death cases applies even in cases in which plaintiffs fail to identify the cause of death in a timely manner, as a report in the Claims Journal indicates.

The decision stems from a lawsuit filed by Linda Reibenstein on behalf of her mother, Mary Ann Whitman, who died in late April 2010 from a ruptured aortic aneurysm.

On April 12, 2010, Ms. Whitman visited Patrick D. Conaboy, MD, a Scranton family physician, complaining of a persistent cough, fever, and lower-back pain. Following an initial examination, Dr. Conaboy ordered an aortic duplex ultrasound scan and a CT scan of the patient’s abdomen.

The ultrasound was performed by radiologist Charles Barax, MD, who reviewed both scans. He identified a “poorly visualized aortic aneurysm.” At this point, Dr. Conaboy referred Ms. Whitman to a vascular surgeon. But before this visit could take place, Whitman’s aneurysm ruptured, killing her. This was listed as the medical cause of death on the patient’s death certificate.

In April 2011, Ms. Reibenstein filed a claim against Dr. Barax, alleging that he had failed to gauge the severity of her mother’s condition. Ms. Reibenstein’s attorney wasn’t able to question Dr. Barax on the record until well after the state’s 2-year statute of limitations had elapsed. When he did testify, Dr. Barax explained that the scans’ image quality prevented him from determining whether Whitman’s aneurysm was rupturing or simply bleeding. Despite this, he insisted that he had warned Dr. Conaboy of the potential for Ms. Whitman’s aneurysm to rupture.

In March 2016, nearly 6 years after her mother’s death, Ms. Reibenstein filed a new lawsuit, this one against Dr. Conaboy, whom she alleged had failed to properly treat her mother’s condition. Dr. Conaboy, in turn, asked the court for summary judgment – that is, a judgment in his favor without a full trial – arguing that the state’s window for filing a wrongful-death claim had long since closed. For their part, Ms. Reibenstein and her attorney argued that the state’s 2-year statute of limitations didn’t start until the plaintiff had discovered the cause of her mother’s death.

Initially refusing to dismiss the case, a lower court reconsidered Dr. Conaboy’s motion for summary judgment and ruled that Ms. Reibenstein had failed to present any evidence of “affirmative misrepresentation or fraudulent concealment.” In other words, in the absence of any willful attempt on the part of the defendant to hide the legal cause of death, which includes “acts, omissions, or events having some causative connection with the death,” the statute of limitations remained in effect, and the defendant’s motion was thereby granted.

Continuing the legal seesaw, a state appeals court reversed the lower-court ruling. Noting that the Pennsylvania malpractice statute was ambiguous, the court argued that it should be interpreted in a way that protects plaintiffs who seek “fair compensation” but encounter willfully erected obstacles in pursuit of their claim.

Dr. Conaboy then took his case to the state’s highest court. In its majority decision, the Pennsylvania Supreme Court staked out a narrow definition of cause of death – one based on the death certificate – and ruled that only willful fraud in that document would constitute the necessary condition for halting the claim’s clock. Furthermore, the high court said, when lawmakers adopted the Medical Care Availability and Reduction of Error Act in 2002, they did so with no guarantee “that all of the information necessary to sustain a claim will be gathered in the limitations period.”

Similarly, the court ruled, “at some point the clock must run out, lest health care providers remain subject to liability exposure indefinitely, with the prospect of a trial marred by the death or diminished memory of material witnesses or the loss of critical evidence.”

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

Delay in treatment will cost hospital millions

A Texas hospital must pay a multimillion-dollar judgment for failing to treat a woman’s spinal injury in time to prevent paralysis, according to a report on WFAA.com, among other news sites.

On March 21, 2019, Judy “Jessie” Adams, then part of a singing-songwriting duo with her husband, Richard, went to Premier Interventional Pain Management, in Flower Mound, Tex., prior to the couple’s drive to Ohio for a funeral. At Premier, Jesse received an epidural steroid injection (ESI) that she hoped would ease her back pain during the long drive.

Instead, the injection ended up increasing her pain.

“He [the pain physician] gave me the shot, but I couldn’t feel my legs. They were tingling, but I couldn’t feel them,” Mrs. Adams explained. “The pain was so bad in my back.” In their suit, Adams and her husband alleged that the doctor had probably “nicked a blood vessel during the ESI procedure, causing Jessie to hemorrhage.” (The couple’s suit against the doctor was settled prior to trial.)

Mrs. Adams remained under observation at the pain facility for about 1½ hours, at which point she was taken by ambulance to nearby Texas Health Presbyterian Hospital. There, in the emergency department, staff ordered a “STAT MRI” in preparation for an emergency laminectomy.

For reasons that remain murky, the MRI wasn’t performed for 1 hour and 37 minutes. The emergency laminectomy itself wasn’t started until more than 5 hours after Adams had been admitted to the ED. This was a direct violation of hospital protocol, which required that emergency surgeries be performed within 1 hour of admittance in the first available surgical suite. (At trial, Mrs. Adams’s attorneys from Lyons & Simmons offered evidence that a suite became available 49 minutes after Adams had arrived at the ED.)

During the wait, Mrs. Adams continued to experience excruciating pain. “I kept screaming: ‘Help me,’ ” she recalled. At trial, her attorneys argued that the hospital’s delay in addressing her spinal emergency led directly to her current paralysis, which keeps her confined to a wheelchair and renders her incontinent.

The hospital disagreed. In court, it maintained that Mrs. Adams was already paralyzed when she arrived at the ED and that there was no delay in care.

The jury saw things differently, however. Siding with the plaintiffs, it awarded Mrs. Adams and her husband $10.1 million, including $500,000 for Mr. Adams’s loss of future earnings and $1 million for his “loss of consortium” with his wife.

Their music career now effectively over, Mr. Adams spends most of his time taking care of Mrs. Adams.

“Music was our lifeblood for so many years, and he can’t do it anymore,” Mrs. Adams said. “He goes upstairs to play his guitar and write, and suddenly I need him to come and cath me. I just feel like I’m going to wake up from this bad dream, but it’s the same routine.”
 

Two doctors are absolved in woman’s sudden death

In a 3-2 decision in December 2022, the Pennsylvania Supreme Court ruled that the state’s 2-year statute of limitations in wrongful-death cases applies even in cases in which plaintiffs fail to identify the cause of death in a timely manner, as a report in the Claims Journal indicates.

The decision stems from a lawsuit filed by Linda Reibenstein on behalf of her mother, Mary Ann Whitman, who died in late April 2010 from a ruptured aortic aneurysm.

On April 12, 2010, Ms. Whitman visited Patrick D. Conaboy, MD, a Scranton family physician, complaining of a persistent cough, fever, and lower-back pain. Following an initial examination, Dr. Conaboy ordered an aortic duplex ultrasound scan and a CT scan of the patient’s abdomen.

The ultrasound was performed by radiologist Charles Barax, MD, who reviewed both scans. He identified a “poorly visualized aortic aneurysm.” At this point, Dr. Conaboy referred Ms. Whitman to a vascular surgeon. But before this visit could take place, Whitman’s aneurysm ruptured, killing her. This was listed as the medical cause of death on the patient’s death certificate.

In April 2011, Ms. Reibenstein filed a claim against Dr. Barax, alleging that he had failed to gauge the severity of her mother’s condition. Ms. Reibenstein’s attorney wasn’t able to question Dr. Barax on the record until well after the state’s 2-year statute of limitations had elapsed. When he did testify, Dr. Barax explained that the scans’ image quality prevented him from determining whether Whitman’s aneurysm was rupturing or simply bleeding. Despite this, he insisted that he had warned Dr. Conaboy of the potential for Ms. Whitman’s aneurysm to rupture.

In March 2016, nearly 6 years after her mother’s death, Ms. Reibenstein filed a new lawsuit, this one against Dr. Conaboy, whom she alleged had failed to properly treat her mother’s condition. Dr. Conaboy, in turn, asked the court for summary judgment – that is, a judgment in his favor without a full trial – arguing that the state’s window for filing a wrongful-death claim had long since closed. For their part, Ms. Reibenstein and her attorney argued that the state’s 2-year statute of limitations didn’t start until the plaintiff had discovered the cause of her mother’s death.

Initially refusing to dismiss the case, a lower court reconsidered Dr. Conaboy’s motion for summary judgment and ruled that Ms. Reibenstein had failed to present any evidence of “affirmative misrepresentation or fraudulent concealment.” In other words, in the absence of any willful attempt on the part of the defendant to hide the legal cause of death, which includes “acts, omissions, or events having some causative connection with the death,” the statute of limitations remained in effect, and the defendant’s motion was thereby granted.

Continuing the legal seesaw, a state appeals court reversed the lower-court ruling. Noting that the Pennsylvania malpractice statute was ambiguous, the court argued that it should be interpreted in a way that protects plaintiffs who seek “fair compensation” but encounter willfully erected obstacles in pursuit of their claim.

Dr. Conaboy then took his case to the state’s highest court. In its majority decision, the Pennsylvania Supreme Court staked out a narrow definition of cause of death – one based on the death certificate – and ruled that only willful fraud in that document would constitute the necessary condition for halting the claim’s clock. Furthermore, the high court said, when lawmakers adopted the Medical Care Availability and Reduction of Error Act in 2002, they did so with no guarantee “that all of the information necessary to sustain a claim will be gathered in the limitations period.”

Similarly, the court ruled, “at some point the clock must run out, lest health care providers remain subject to liability exposure indefinitely, with the prospect of a trial marred by the death or diminished memory of material witnesses or the loss of critical evidence.”

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

Persistent postconcussion symptoms (PPCS) are tied to a significantly increased risk of developing subsequent depressive symptoms, new research shows.

Results of a large meta-analysis that included 18 studies and more than 9,000 patients showed a fourfold higher risk of developing depressive symptoms in those with PPCS versus those without PPCS.

“In this meta-analysis, experiencing PPCS was associated with a higher risk of experiencing depressive symptoms,” write the investigators, led by Maude Lambert, PhD, of the School of Psychology, University of Ottawa, and Bloorview Research Institute, Toronto.

“There are several important clinical and health policy implications of the findings. Most notably, the development of strategies for effective prevention and earlier intervention to optimize mental health recovery following a concussion should be supported,” they add.

The study was published online  in JAMA Network Open.
 

‘Important minority’

An “important minority” of 15%-30% of those with concussions continue to experience symptoms for months, or even years, following the injury, the investigators note.

Symptoms vary but can include headaches, fatigue, dizziness, cognitive difficulties, and emotional changes, which can “significantly impact an individual’s everyday functioning.”

The association between PPCS and mental health outcomes “has emerged as an area of interest” over the past decade, with multiple studies pointing to bidirectional associations between depressive symptoms and PPCS, the researchers note. Individuals with PPCS are at significantly higher risk of experiencing depressive symptoms, and depressive symptoms, in turn, predict more prolonged postconcussion recovery, they add.

The authors conducted a previous scoping review that showed individuals with PPCS had “greater mental health difficulties than individuals who recovered from concussion or healthy controls.”

But “quantitative summaries evaluating the magnitude and nature of the association between PPCS and mental health outcomes were not conducted,” so they decided to conduct a follow-up meta-analysis to corroborate the hypothesis that PPCS may be associated with depressive symptoms.

The researchers also wanted to “investigate potential moderators of that association and determine whether the association between depressive symptoms and PPCS differed based on age, sex, mental illness, history of concussion, and time since the injury.”

This could have “significant public health implications” as it represents an “important step” toward understanding the association between PPCS and mental health, paving the way for the “development of optimal postconcussion intervention strategies, targeting effective prevention and earlier intervention to enhance recovery trajectories, improve mental health, and promote well-being following concussion.”

To be included in the meta-analysis, a study had to focus on participants who had experienced a concussion, diagnosed by a health care professional, or as classified by diagnostic measures, and who experienced greater than or equal to 1 concussion symptom lasting greater than 4 weeks.

There was no explicit upper limit on duration, and individuals of all ages were eligible.

Depressive symptoms were defined as “an outcome that must be measured by a validated and standardized measure of depression.”
 

Biopsychosocial model

Of 580 reports assessed for eligibility, 18 were included in the meta-analysis, incorporating a total of 9,101 participants, with a median (range) sample size of 154 (48-4,462) participants and a mean (SD) participant age of 33.7 (14.4) years.

The mean length of time since the concussion was 21.3 (18.7) weeks. Of the participants, a mean of 36.1% (11.1%) had a history of greater than or equal to 2 concussions.

Close to three-quarters of the studies (72%) used a cross-sectional design, with most studies conducted in North America, and the remaining conducted in Europe, China, and New Zealand.

The researchers found a “significant positive association” between PPCS and postinjury depressive symptoms (odds ratio, 4.87; 95% confidence interval, 3.01-7.90; P < .001), “representing a large effect size.”

Funnel plot and Egger test analyses “suggested the presence of a publication bias.” However, even after accounting for publication bias, the effect size “of large magnitude” remained, the authors report (OR, 4.56; 95% CI, 2.82-7.37; P < .001).

No significant moderators were identified, “likely due to the small number of studies included,” they speculate.

They note that the current study “does not allow inference about the causal directionality of the association” between PPCS and postinjury depressive symptoms, so the question remains: Do PPCS induce depressive symptoms, or do depressive symptoms induce PPCS?”

Despite this unanswered question, the findings still have important clinical and public health implications, highlighting “the need for a greater understanding of the mechanisms of development and etiology of depressive symptoms postconcussion” and emphasizing “the necessary emergence for timely and effective treatment interventions for depressive symptoms to optimize the long-term prognosis of concussion,” the authors note.

They add that several research teams “have aimed to gain more insight into the etiology and underlying mechanisms of development and course of mental health difficulties in individuals who experience a concussion” and have arrived at a biopsychosocial framework, in light of “the myriad of contributing physiological, biological, and psychosocial factors.”

They recommend the establishment of “specialized multidisciplinary or interdisciplinary concussion care programs should include health care professionals with strong clinical foundations and training in mental health conditions.”
 

Speedy multidisciplinary care

Commenting on the research, Charles Tator, MD, PhD, professor of neurosurgery, University of Toronto, Division of Neurosurgery, Toronto Western Hospital, said the researchers “performed a thorough systematic review” showing “emphatically that depression occurs in this population.”

Dr. Tator, the director of the Canadian Concussion Centre, who was not involved with the current study, continued: “Nowadays clinical discoveries are validated through a progression of case reports, single-center retrospective cohort studies like ours, referenced by [Dr.] Lambert et al., and then confirmatory systematic reviews, each adding important layers of evidence.”

“This evaluative process has now endorsed the importance of early treatment of mental health symptoms in patients with persisting symptoms, which can include depression, anxiety, and PTSD,” he said.

He recommended that treatment should start with family physicians and nurse practitioners “but may require escalation to psychologists and social workers and then to psychiatrists who are often more skilled in medication selection.”

He encouraged “speedy multidisciplinary care,” noting that the possibility of suicide is worrisome.

No source of study funding was listed. A study coauthor, Shannon Scratch, PhD, has reported receiving funds from the Holland Bloorview Kids Rehabilitation Hospital Foundation (via the Holland Family Professorship in Acquired Brain Injury) during the conduct of this study. No other disclosures were reported. Dr. Tator has reported no relevant financial relationships.

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

Persistent postconcussion symptoms (PPCS) are tied to a significantly increased risk of developing subsequent depressive symptoms, new research shows.

Results of a large meta-analysis that included 18 studies and more than 9,000 patients showed a fourfold higher risk of developing depressive symptoms in those with PPCS versus those without PPCS.

“In this meta-analysis, experiencing PPCS was associated with a higher risk of experiencing depressive symptoms,” write the investigators, led by Maude Lambert, PhD, of the School of Psychology, University of Ottawa, and Bloorview Research Institute, Toronto.

“There are several important clinical and health policy implications of the findings. Most notably, the development of strategies for effective prevention and earlier intervention to optimize mental health recovery following a concussion should be supported,” they add.

The study was published online  in JAMA Network Open.
 

‘Important minority’

An “important minority” of 15%-30% of those with concussions continue to experience symptoms for months, or even years, following the injury, the investigators note.

Symptoms vary but can include headaches, fatigue, dizziness, cognitive difficulties, and emotional changes, which can “significantly impact an individual’s everyday functioning.”

The association between PPCS and mental health outcomes “has emerged as an area of interest” over the past decade, with multiple studies pointing to bidirectional associations between depressive symptoms and PPCS, the researchers note. Individuals with PPCS are at significantly higher risk of experiencing depressive symptoms, and depressive symptoms, in turn, predict more prolonged postconcussion recovery, they add.

The authors conducted a previous scoping review that showed individuals with PPCS had “greater mental health difficulties than individuals who recovered from concussion or healthy controls.”

But “quantitative summaries evaluating the magnitude and nature of the association between PPCS and mental health outcomes were not conducted,” so they decided to conduct a follow-up meta-analysis to corroborate the hypothesis that PPCS may be associated with depressive symptoms.

The researchers also wanted to “investigate potential moderators of that association and determine whether the association between depressive symptoms and PPCS differed based on age, sex, mental illness, history of concussion, and time since the injury.”

This could have “significant public health implications” as it represents an “important step” toward understanding the association between PPCS and mental health, paving the way for the “development of optimal postconcussion intervention strategies, targeting effective prevention and earlier intervention to enhance recovery trajectories, improve mental health, and promote well-being following concussion.”

To be included in the meta-analysis, a study had to focus on participants who had experienced a concussion, diagnosed by a health care professional, or as classified by diagnostic measures, and who experienced greater than or equal to 1 concussion symptom lasting greater than 4 weeks.

There was no explicit upper limit on duration, and individuals of all ages were eligible.

Depressive symptoms were defined as “an outcome that must be measured by a validated and standardized measure of depression.”
 

Biopsychosocial model

Of 580 reports assessed for eligibility, 18 were included in the meta-analysis, incorporating a total of 9,101 participants, with a median (range) sample size of 154 (48-4,462) participants and a mean (SD) participant age of 33.7 (14.4) years.

The mean length of time since the concussion was 21.3 (18.7) weeks. Of the participants, a mean of 36.1% (11.1%) had a history of greater than or equal to 2 concussions.

Close to three-quarters of the studies (72%) used a cross-sectional design, with most studies conducted in North America, and the remaining conducted in Europe, China, and New Zealand.

The researchers found a “significant positive association” between PPCS and postinjury depressive symptoms (odds ratio, 4.87; 95% confidence interval, 3.01-7.90; P < .001), “representing a large effect size.”

Funnel plot and Egger test analyses “suggested the presence of a publication bias.” However, even after accounting for publication bias, the effect size “of large magnitude” remained, the authors report (OR, 4.56; 95% CI, 2.82-7.37; P < .001).

No significant moderators were identified, “likely due to the small number of studies included,” they speculate.

They note that the current study “does not allow inference about the causal directionality of the association” between PPCS and postinjury depressive symptoms, so the question remains: Do PPCS induce depressive symptoms, or do depressive symptoms induce PPCS?”

Despite this unanswered question, the findings still have important clinical and public health implications, highlighting “the need for a greater understanding of the mechanisms of development and etiology of depressive symptoms postconcussion” and emphasizing “the necessary emergence for timely and effective treatment interventions for depressive symptoms to optimize the long-term prognosis of concussion,” the authors note.

They add that several research teams “have aimed to gain more insight into the etiology and underlying mechanisms of development and course of mental health difficulties in individuals who experience a concussion” and have arrived at a biopsychosocial framework, in light of “the myriad of contributing physiological, biological, and psychosocial factors.”

They recommend the establishment of “specialized multidisciplinary or interdisciplinary concussion care programs should include health care professionals with strong clinical foundations and training in mental health conditions.”
 

Speedy multidisciplinary care

Commenting on the research, Charles Tator, MD, PhD, professor of neurosurgery, University of Toronto, Division of Neurosurgery, Toronto Western Hospital, said the researchers “performed a thorough systematic review” showing “emphatically that depression occurs in this population.”

Dr. Tator, the director of the Canadian Concussion Centre, who was not involved with the current study, continued: “Nowadays clinical discoveries are validated through a progression of case reports, single-center retrospective cohort studies like ours, referenced by [Dr.] Lambert et al., and then confirmatory systematic reviews, each adding important layers of evidence.”

“This evaluative process has now endorsed the importance of early treatment of mental health symptoms in patients with persisting symptoms, which can include depression, anxiety, and PTSD,” he said.

He recommended that treatment should start with family physicians and nurse practitioners “but may require escalation to psychologists and social workers and then to psychiatrists who are often more skilled in medication selection.”

He encouraged “speedy multidisciplinary care,” noting that the possibility of suicide is worrisome.

No source of study funding was listed. A study coauthor, Shannon Scratch, PhD, has reported receiving funds from the Holland Bloorview Kids Rehabilitation Hospital Foundation (via the Holland Family Professorship in Acquired Brain Injury) during the conduct of this study. No other disclosures were reported. Dr. Tator has reported no relevant financial relationships.

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

Persistent postconcussion symptoms (PPCS) are tied to a significantly increased risk of developing subsequent depressive symptoms, new research shows.

Results of a large meta-analysis that included 18 studies and more than 9,000 patients showed a fourfold higher risk of developing depressive symptoms in those with PPCS versus those without PPCS.

“In this meta-analysis, experiencing PPCS was associated with a higher risk of experiencing depressive symptoms,” write the investigators, led by Maude Lambert, PhD, of the School of Psychology, University of Ottawa, and Bloorview Research Institute, Toronto.

“There are several important clinical and health policy implications of the findings. Most notably, the development of strategies for effective prevention and earlier intervention to optimize mental health recovery following a concussion should be supported,” they add.

The study was published online  in JAMA Network Open.
 

‘Important minority’

An “important minority” of 15%-30% of those with concussions continue to experience symptoms for months, or even years, following the injury, the investigators note.

Symptoms vary but can include headaches, fatigue, dizziness, cognitive difficulties, and emotional changes, which can “significantly impact an individual’s everyday functioning.”

The association between PPCS and mental health outcomes “has emerged as an area of interest” over the past decade, with multiple studies pointing to bidirectional associations between depressive symptoms and PPCS, the researchers note. Individuals with PPCS are at significantly higher risk of experiencing depressive symptoms, and depressive symptoms, in turn, predict more prolonged postconcussion recovery, they add.

The authors conducted a previous scoping review that showed individuals with PPCS had “greater mental health difficulties than individuals who recovered from concussion or healthy controls.”

But “quantitative summaries evaluating the magnitude and nature of the association between PPCS and mental health outcomes were not conducted,” so they decided to conduct a follow-up meta-analysis to corroborate the hypothesis that PPCS may be associated with depressive symptoms.

The researchers also wanted to “investigate potential moderators of that association and determine whether the association between depressive symptoms and PPCS differed based on age, sex, mental illness, history of concussion, and time since the injury.”

This could have “significant public health implications” as it represents an “important step” toward understanding the association between PPCS and mental health, paving the way for the “development of optimal postconcussion intervention strategies, targeting effective prevention and earlier intervention to enhance recovery trajectories, improve mental health, and promote well-being following concussion.”

To be included in the meta-analysis, a study had to focus on participants who had experienced a concussion, diagnosed by a health care professional, or as classified by diagnostic measures, and who experienced greater than or equal to 1 concussion symptom lasting greater than 4 weeks.

There was no explicit upper limit on duration, and individuals of all ages were eligible.

Depressive symptoms were defined as “an outcome that must be measured by a validated and standardized measure of depression.”
 

Biopsychosocial model

Of 580 reports assessed for eligibility, 18 were included in the meta-analysis, incorporating a total of 9,101 participants, with a median (range) sample size of 154 (48-4,462) participants and a mean (SD) participant age of 33.7 (14.4) years.

The mean length of time since the concussion was 21.3 (18.7) weeks. Of the participants, a mean of 36.1% (11.1%) had a history of greater than or equal to 2 concussions.

Close to three-quarters of the studies (72%) used a cross-sectional design, with most studies conducted in North America, and the remaining conducted in Europe, China, and New Zealand.

The researchers found a “significant positive association” between PPCS and postinjury depressive symptoms (odds ratio, 4.87; 95% confidence interval, 3.01-7.90; P < .001), “representing a large effect size.”

Funnel plot and Egger test analyses “suggested the presence of a publication bias.” However, even after accounting for publication bias, the effect size “of large magnitude” remained, the authors report (OR, 4.56; 95% CI, 2.82-7.37; P < .001).

No significant moderators were identified, “likely due to the small number of studies included,” they speculate.

They note that the current study “does not allow inference about the causal directionality of the association” between PPCS and postinjury depressive symptoms, so the question remains: Do PPCS induce depressive symptoms, or do depressive symptoms induce PPCS?”

Despite this unanswered question, the findings still have important clinical and public health implications, highlighting “the need for a greater understanding of the mechanisms of development and etiology of depressive symptoms postconcussion” and emphasizing “the necessary emergence for timely and effective treatment interventions for depressive symptoms to optimize the long-term prognosis of concussion,” the authors note.

They add that several research teams “have aimed to gain more insight into the etiology and underlying mechanisms of development and course of mental health difficulties in individuals who experience a concussion” and have arrived at a biopsychosocial framework, in light of “the myriad of contributing physiological, biological, and psychosocial factors.”

They recommend the establishment of “specialized multidisciplinary or interdisciplinary concussion care programs should include health care professionals with strong clinical foundations and training in mental health conditions.”
 

Speedy multidisciplinary care

Commenting on the research, Charles Tator, MD, PhD, professor of neurosurgery, University of Toronto, Division of Neurosurgery, Toronto Western Hospital, said the researchers “performed a thorough systematic review” showing “emphatically that depression occurs in this population.”

Dr. Tator, the director of the Canadian Concussion Centre, who was not involved with the current study, continued: “Nowadays clinical discoveries are validated through a progression of case reports, single-center retrospective cohort studies like ours, referenced by [Dr.] Lambert et al., and then confirmatory systematic reviews, each adding important layers of evidence.”

“This evaluative process has now endorsed the importance of early treatment of mental health symptoms in patients with persisting symptoms, which can include depression, anxiety, and PTSD,” he said.

He recommended that treatment should start with family physicians and nurse practitioners “but may require escalation to psychologists and social workers and then to psychiatrists who are often more skilled in medication selection.”

He encouraged “speedy multidisciplinary care,” noting that the possibility of suicide is worrisome.

No source of study funding was listed. A study coauthor, Shannon Scratch, PhD, has reported receiving funds from the Holland Bloorview Kids Rehabilitation Hospital Foundation (via the Holland Family Professorship in Acquired Brain Injury) during the conduct of this study. No other disclosures were reported. Dr. Tator has reported no relevant financial relationships.

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

Sleep complaints by patients with a major depressive episode (MDE) may be a red flag signaling a higher risk for developing other psychiatric disorders, new research suggests.

Investigators studied 3-year incidence rates of psychiatric disorders in almost 3,000 patients experiencing an MDE. Results showed that having a history of difficulty falling asleep, early morning awakening, and hypersomnia increased risk for incident psychiatric disorders.

“The findings of this study suggest the potential value of including insomnia and hypersomnia in clinical assessments of all psychiatric disorders,” write the investigators, led by Bénédicte Barbotin, MD, Département de Psychiatrie et d’Addictologie, Assistance Publique-Hôpitaux de Paris, Hôpital Bichat-Claude Bernard, France.

“Insomnia and hypersomnia symptoms may be prodromal transdiagnostic biomarkers and easily modifiable therapeutic targets for the prevention of psychiatric disorders,” they add.

The findings were published online recently in the Journal of Clinical Psychiatry.


 

Bidirectional association

The researchers note that sleep disturbance is “one of the most common symptoms” associated with major depressive disorder (MDD) and may be “both a consequence and a cause.”

Moreover, improving sleep disturbances for patients with an MDE “tends to improve depressive symptom and outcomes,” they add.

Although the possibility of a bidirectional association between MDEs and sleep disturbances “offers a new perspective that sleep complaints might be a predictive prodromal symptom,” the association of sleep complaints with the subsequent development of other psychiatric disorders in MDEs “remains poorly documented,” the investigators write.

The observation that sleep complaints are associated with psychiatric complications and adverse outcomes, such as suicidality and substance overdose, suggests that longitudinal studies “may help to better understand these relationships.”

To investigate these issues, the researchers examined three sleep complaints among patients with MDE: trouble falling asleep, early morning awakening, and hypersomnia. They adjusted for an array of variables, including antisocial personality disorders, use of sedatives or tranquilizers, sociodemographic characteristics, MDE severity, poverty, obesity, educational level, and stressful life events.

They also used a “bifactor latent variable approach” to “disentangle” a number of effects, including those shared by all psychiatric disorders; those specific to dimensions of psychopathology, such as internalizing dimension; and those specific to individual psychiatric disorders, such as dysthymia.

“To our knowledge, this is the most extensive prospective assessment [ever conducted] of associations between sleep complaints and incident psychiatric disorders,” the investigators write.

They drew on data from Waves 1 and 2 of the National Epidemiological Survey on Alcohol and Related Conditions, a large nationally representative survey conducted in 2001-2002 (Wave 1) and 2004-2005 (Wave 2) by the National Institute on Alcoholism and Alcohol Abuse.

The analysis included 2,864 participants who experienced MDE in the year prior to Wave 1 and who completed interviews at both waves.

Researchers assessed past-year DSM-IV Axis I disorders and baseline sleep complaints at Wave 1, as well as incident DSM-IV Axis I disorders between the two waves – including substance use, mood, and anxiety disorders.
 

Screening needed?

Results showed a wide range of incidence rates for psychiatric disorders between Wave 1 and Wave 2, ranging from 2.7% for cannabis use to 8.2% for generalized anxiety disorder.

The lifetime prevalence of sleep complaints was higher among participants who developed a psychiatric disorder between the two waves than among those who did not have sleep complaints. The range (from lowest to highest percentage) is shown in the accompanying table.

A higher number of sleep complaints was also associated with higher percentages of psychiatric disorders.

Hypersomnia, in particular, significantly increased the odds of having another psychiatric disorder. For patients with MDD who reported hypersomnia, the mean number of sleep disorders was significantly higher than for patients without hypersomnia (2.08 vs. 1.32; P < .001).

“This explains why hypersomnia appears more strongly associated with the incidence of psychiatric disorders,” the investigators write.

After adjusting for sociodemographic and clinical characteristics and antisocial personality disorder, the effects shared across all sleep complaints were “significantly associated with the incident general psychopathology factor, representing mechanisms that may lead to incidence of all psychiatric disorder in the model,” they add.

The researchers note that insomnia and hypersomnia can impair cognitive function, decision-making, problem-solving, and emotion processing networks, thereby increasing the onset of psychiatric disorders in vulnerable individuals.

Shared biological determinants, such as monoamine neurotransmitters that play a major role in depression, anxiety, substance use disorders, and the regulation of sleep stages, may also underlie both sleep disturbances and psychiatric disorders, they speculate.

“These results suggest the importance of systematically assessing insomnia and hypersomnia when evaluating psychiatric disorders and considering these symptoms as nonspecific prodromal or at-risk symptoms, also shared with suicidal behaviors,” the investigators write.

“In addition, since most individuals who developed a psychiatric disorder had at least one sleep complaint, all psychiatric disorders should be carefully screened among individuals with sleep complaints,” they add.
 

Transdiagnostic phenomenon

In a comment, Roger McIntyre, MD, professor of psychiatry and pharmacology at the University of Toronto, and head of the Mood Disorders Psychopharmacology Unit, noted that the study replicates previous observations that a bidirectional relationship exists between sleep disturbances and mental disorders and that there “seems to be a relationship between sleep disturbance and suicidality that is bidirectional.”

He added that he appreciated the fact that the investigators “took this knowledge one step further; and what they are saying is that within the syndrome of depression, it is the sleep disturbance that is predicting future problems.”

Dr. McIntyre, who is also chairman and executive director of the Brain and Cognitive Discover Foundation in Toronto, was not involved with the study.

The data suggest that, “conceptually, sleep disturbance is a transdiagnostic phenomenon that may also be the nexus when multiple comorbid mental disorders occur,” he said.

“If this is the case, clinically, there is an opportunity here to prevent incident mental disorders in persons with depression and sleep disturbance, prioritizing sleep management in any patient with a mood disorder,” Dr. McIntyre added.

He noted that “the testable hypothesis” is how this is occurring mechanistically.

“I would conjecture that it could be inflammation and/or insulin resistance that is part of sleep disturbance that could predispose and portend other mental illnesses – and likely other medical conditions too, such as obesity and diabetes,” he said.

The study received no specific funding from any funding agency, commercial, or not-for-profit sectors. The investigators’ relevant financial relationships are listed in the original article. Dr. McIntyre has received research grant support from CIHR/GACD/National Natural Science Foundation of China and the Milken Institute; has received speaker/consultation fees from Lundbeck, Janssen, Alkermes,Neumora Therapeutics, Boehringer Ingelheim, Sage, Biogen, Mitsubishi Tanabe, Purdue, Pfizer, Otsuka, Takeda, Neurocrine, Sunovion, Bausch Health, Axsome, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular, NewBridge Pharmaceuticals, Viatris, AbbVie, and Atai Life Sciences; and is a CEO of Braxia Scientific Corp.

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

Sleep complaints by patients with a major depressive episode (MDE) may be a red flag signaling a higher risk for developing other psychiatric disorders, new research suggests.

Investigators studied 3-year incidence rates of psychiatric disorders in almost 3,000 patients experiencing an MDE. Results showed that having a history of difficulty falling asleep, early morning awakening, and hypersomnia increased risk for incident psychiatric disorders.

“The findings of this study suggest the potential value of including insomnia and hypersomnia in clinical assessments of all psychiatric disorders,” write the investigators, led by Bénédicte Barbotin, MD, Département de Psychiatrie et d’Addictologie, Assistance Publique-Hôpitaux de Paris, Hôpital Bichat-Claude Bernard, France.

“Insomnia and hypersomnia symptoms may be prodromal transdiagnostic biomarkers and easily modifiable therapeutic targets for the prevention of psychiatric disorders,” they add.

The findings were published online recently in the Journal of Clinical Psychiatry.


 

Bidirectional association

The researchers note that sleep disturbance is “one of the most common symptoms” associated with major depressive disorder (MDD) and may be “both a consequence and a cause.”

Moreover, improving sleep disturbances for patients with an MDE “tends to improve depressive symptom and outcomes,” they add.

Although the possibility of a bidirectional association between MDEs and sleep disturbances “offers a new perspective that sleep complaints might be a predictive prodromal symptom,” the association of sleep complaints with the subsequent development of other psychiatric disorders in MDEs “remains poorly documented,” the investigators write.

The observation that sleep complaints are associated with psychiatric complications and adverse outcomes, such as suicidality and substance overdose, suggests that longitudinal studies “may help to better understand these relationships.”

To investigate these issues, the researchers examined three sleep complaints among patients with MDE: trouble falling asleep, early morning awakening, and hypersomnia. They adjusted for an array of variables, including antisocial personality disorders, use of sedatives or tranquilizers, sociodemographic characteristics, MDE severity, poverty, obesity, educational level, and stressful life events.

They also used a “bifactor latent variable approach” to “disentangle” a number of effects, including those shared by all psychiatric disorders; those specific to dimensions of psychopathology, such as internalizing dimension; and those specific to individual psychiatric disorders, such as dysthymia.

“To our knowledge, this is the most extensive prospective assessment [ever conducted] of associations between sleep complaints and incident psychiatric disorders,” the investigators write.

They drew on data from Waves 1 and 2 of the National Epidemiological Survey on Alcohol and Related Conditions, a large nationally representative survey conducted in 2001-2002 (Wave 1) and 2004-2005 (Wave 2) by the National Institute on Alcoholism and Alcohol Abuse.

The analysis included 2,864 participants who experienced MDE in the year prior to Wave 1 and who completed interviews at both waves.

Researchers assessed past-year DSM-IV Axis I disorders and baseline sleep complaints at Wave 1, as well as incident DSM-IV Axis I disorders between the two waves – including substance use, mood, and anxiety disorders.
 

Screening needed?

Results showed a wide range of incidence rates for psychiatric disorders between Wave 1 and Wave 2, ranging from 2.7% for cannabis use to 8.2% for generalized anxiety disorder.

The lifetime prevalence of sleep complaints was higher among participants who developed a psychiatric disorder between the two waves than among those who did not have sleep complaints. The range (from lowest to highest percentage) is shown in the accompanying table.

A higher number of sleep complaints was also associated with higher percentages of psychiatric disorders.

Hypersomnia, in particular, significantly increased the odds of having another psychiatric disorder. For patients with MDD who reported hypersomnia, the mean number of sleep disorders was significantly higher than for patients without hypersomnia (2.08 vs. 1.32; P < .001).

“This explains why hypersomnia appears more strongly associated with the incidence of psychiatric disorders,” the investigators write.

After adjusting for sociodemographic and clinical characteristics and antisocial personality disorder, the effects shared across all sleep complaints were “significantly associated with the incident general psychopathology factor, representing mechanisms that may lead to incidence of all psychiatric disorder in the model,” they add.

The researchers note that insomnia and hypersomnia can impair cognitive function, decision-making, problem-solving, and emotion processing networks, thereby increasing the onset of psychiatric disorders in vulnerable individuals.

Shared biological determinants, such as monoamine neurotransmitters that play a major role in depression, anxiety, substance use disorders, and the regulation of sleep stages, may also underlie both sleep disturbances and psychiatric disorders, they speculate.

“These results suggest the importance of systematically assessing insomnia and hypersomnia when evaluating psychiatric disorders and considering these symptoms as nonspecific prodromal or at-risk symptoms, also shared with suicidal behaviors,” the investigators write.

“In addition, since most individuals who developed a psychiatric disorder had at least one sleep complaint, all psychiatric disorders should be carefully screened among individuals with sleep complaints,” they add.
 

Transdiagnostic phenomenon

In a comment, Roger McIntyre, MD, professor of psychiatry and pharmacology at the University of Toronto, and head of the Mood Disorders Psychopharmacology Unit, noted that the study replicates previous observations that a bidirectional relationship exists between sleep disturbances and mental disorders and that there “seems to be a relationship between sleep disturbance and suicidality that is bidirectional.”

He added that he appreciated the fact that the investigators “took this knowledge one step further; and what they are saying is that within the syndrome of depression, it is the sleep disturbance that is predicting future problems.”

Dr. McIntyre, who is also chairman and executive director of the Brain and Cognitive Discover Foundation in Toronto, was not involved with the study.

The data suggest that, “conceptually, sleep disturbance is a transdiagnostic phenomenon that may also be the nexus when multiple comorbid mental disorders occur,” he said.

“If this is the case, clinically, there is an opportunity here to prevent incident mental disorders in persons with depression and sleep disturbance, prioritizing sleep management in any patient with a mood disorder,” Dr. McIntyre added.

He noted that “the testable hypothesis” is how this is occurring mechanistically.

“I would conjecture that it could be inflammation and/or insulin resistance that is part of sleep disturbance that could predispose and portend other mental illnesses – and likely other medical conditions too, such as obesity and diabetes,” he said.

The study received no specific funding from any funding agency, commercial, or not-for-profit sectors. The investigators’ relevant financial relationships are listed in the original article. Dr. McIntyre has received research grant support from CIHR/GACD/National Natural Science Foundation of China and the Milken Institute; has received speaker/consultation fees from Lundbeck, Janssen, Alkermes,Neumora Therapeutics, Boehringer Ingelheim, Sage, Biogen, Mitsubishi Tanabe, Purdue, Pfizer, Otsuka, Takeda, Neurocrine, Sunovion, Bausch Health, Axsome, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular, NewBridge Pharmaceuticals, Viatris, AbbVie, and Atai Life Sciences; and is a CEO of Braxia Scientific Corp.

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

Sleep complaints by patients with a major depressive episode (MDE) may be a red flag signaling a higher risk for developing other psychiatric disorders, new research suggests.

Investigators studied 3-year incidence rates of psychiatric disorders in almost 3,000 patients experiencing an MDE. Results showed that having a history of difficulty falling asleep, early morning awakening, and hypersomnia increased risk for incident psychiatric disorders.

“The findings of this study suggest the potential value of including insomnia and hypersomnia in clinical assessments of all psychiatric disorders,” write the investigators, led by Bénédicte Barbotin, MD, Département de Psychiatrie et d’Addictologie, Assistance Publique-Hôpitaux de Paris, Hôpital Bichat-Claude Bernard, France.

“Insomnia and hypersomnia symptoms may be prodromal transdiagnostic biomarkers and easily modifiable therapeutic targets for the prevention of psychiatric disorders,” they add.

The findings were published online recently in the Journal of Clinical Psychiatry.


 

Bidirectional association

The researchers note that sleep disturbance is “one of the most common symptoms” associated with major depressive disorder (MDD) and may be “both a consequence and a cause.”

Moreover, improving sleep disturbances for patients with an MDE “tends to improve depressive symptom and outcomes,” they add.

Although the possibility of a bidirectional association between MDEs and sleep disturbances “offers a new perspective that sleep complaints might be a predictive prodromal symptom,” the association of sleep complaints with the subsequent development of other psychiatric disorders in MDEs “remains poorly documented,” the investigators write.

The observation that sleep complaints are associated with psychiatric complications and adverse outcomes, such as suicidality and substance overdose, suggests that longitudinal studies “may help to better understand these relationships.”

To investigate these issues, the researchers examined three sleep complaints among patients with MDE: trouble falling asleep, early morning awakening, and hypersomnia. They adjusted for an array of variables, including antisocial personality disorders, use of sedatives or tranquilizers, sociodemographic characteristics, MDE severity, poverty, obesity, educational level, and stressful life events.

They also used a “bifactor latent variable approach” to “disentangle” a number of effects, including those shared by all psychiatric disorders; those specific to dimensions of psychopathology, such as internalizing dimension; and those specific to individual psychiatric disorders, such as dysthymia.

“To our knowledge, this is the most extensive prospective assessment [ever conducted] of associations between sleep complaints and incident psychiatric disorders,” the investigators write.

They drew on data from Waves 1 and 2 of the National Epidemiological Survey on Alcohol and Related Conditions, a large nationally representative survey conducted in 2001-2002 (Wave 1) and 2004-2005 (Wave 2) by the National Institute on Alcoholism and Alcohol Abuse.

The analysis included 2,864 participants who experienced MDE in the year prior to Wave 1 and who completed interviews at both waves.

Researchers assessed past-year DSM-IV Axis I disorders and baseline sleep complaints at Wave 1, as well as incident DSM-IV Axis I disorders between the two waves – including substance use, mood, and anxiety disorders.
 

Screening needed?

Results showed a wide range of incidence rates for psychiatric disorders between Wave 1 and Wave 2, ranging from 2.7% for cannabis use to 8.2% for generalized anxiety disorder.

The lifetime prevalence of sleep complaints was higher among participants who developed a psychiatric disorder between the two waves than among those who did not have sleep complaints. The range (from lowest to highest percentage) is shown in the accompanying table.

A higher number of sleep complaints was also associated with higher percentages of psychiatric disorders.

Hypersomnia, in particular, significantly increased the odds of having another psychiatric disorder. For patients with MDD who reported hypersomnia, the mean number of sleep disorders was significantly higher than for patients without hypersomnia (2.08 vs. 1.32; P < .001).

“This explains why hypersomnia appears more strongly associated with the incidence of psychiatric disorders,” the investigators write.

After adjusting for sociodemographic and clinical characteristics and antisocial personality disorder, the effects shared across all sleep complaints were “significantly associated with the incident general psychopathology factor, representing mechanisms that may lead to incidence of all psychiatric disorder in the model,” they add.

The researchers note that insomnia and hypersomnia can impair cognitive function, decision-making, problem-solving, and emotion processing networks, thereby increasing the onset of psychiatric disorders in vulnerable individuals.

Shared biological determinants, such as monoamine neurotransmitters that play a major role in depression, anxiety, substance use disorders, and the regulation of sleep stages, may also underlie both sleep disturbances and psychiatric disorders, they speculate.

“These results suggest the importance of systematically assessing insomnia and hypersomnia when evaluating psychiatric disorders and considering these symptoms as nonspecific prodromal or at-risk symptoms, also shared with suicidal behaviors,” the investigators write.

“In addition, since most individuals who developed a psychiatric disorder had at least one sleep complaint, all psychiatric disorders should be carefully screened among individuals with sleep complaints,” they add.
 

Transdiagnostic phenomenon

In a comment, Roger McIntyre, MD, professor of psychiatry and pharmacology at the University of Toronto, and head of the Mood Disorders Psychopharmacology Unit, noted that the study replicates previous observations that a bidirectional relationship exists between sleep disturbances and mental disorders and that there “seems to be a relationship between sleep disturbance and suicidality that is bidirectional.”

He added that he appreciated the fact that the investigators “took this knowledge one step further; and what they are saying is that within the syndrome of depression, it is the sleep disturbance that is predicting future problems.”

Dr. McIntyre, who is also chairman and executive director of the Brain and Cognitive Discover Foundation in Toronto, was not involved with the study.

The data suggest that, “conceptually, sleep disturbance is a transdiagnostic phenomenon that may also be the nexus when multiple comorbid mental disorders occur,” he said.

“If this is the case, clinically, there is an opportunity here to prevent incident mental disorders in persons with depression and sleep disturbance, prioritizing sleep management in any patient with a mood disorder,” Dr. McIntyre added.

He noted that “the testable hypothesis” is how this is occurring mechanistically.

“I would conjecture that it could be inflammation and/or insulin resistance that is part of sleep disturbance that could predispose and portend other mental illnesses – and likely other medical conditions too, such as obesity and diabetes,” he said.

The study received no specific funding from any funding agency, commercial, or not-for-profit sectors. The investigators’ relevant financial relationships are listed in the original article. Dr. McIntyre has received research grant support from CIHR/GACD/National Natural Science Foundation of China and the Milken Institute; has received speaker/consultation fees from Lundbeck, Janssen, Alkermes,Neumora Therapeutics, Boehringer Ingelheim, Sage, Biogen, Mitsubishi Tanabe, Purdue, Pfizer, Otsuka, Takeda, Neurocrine, Sunovion, Bausch Health, Axsome, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular, NewBridge Pharmaceuticals, Viatris, AbbVie, and Atai Life Sciences; and is a CEO of Braxia Scientific Corp.

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