Kelli Whitlock Burton

New guidelines on determining brain death offer the first updated recommendations in more than a decade for adult and pediatric patients.

The consensus practice guideline on brain death, also known as death by neurologic criteria (BD/DNC), was developed by a panel of 20 experts from different specialties, institutions, and medical societies.

As with previous guidelines, the updated version stipulates that brain death should be declared when a patient with a known cause of catastrophic brain injury has permanent loss of function of the brain, including the brain stem, which results in coma, brain stem areflexia, and apnea in the setting of an adequate stimulus.

But the updated version also clarifies questions on neurological examinations and apnea testing and offers new guidance on pre-evaluation targets for blood pressure and body temperature and evaluating brain death in patients who are pregnant, are on extracorporeal membrane oxygenation, or have an injury to the base of the brain.

Also, for the first time, the guidance clarifies that clinicians don’t need to obtain consent before performing a brain death evaluation, unless institutional policy, state laws, or regulations stipulate otherwise.

“The 2023 guidelines will be considered the standard of care in the U.S.,” lead author David M. Greer, MD, chair and chief of neurology, Boston University, and chief of neurology, Boston Medical Center, said in an interview. “Each hospital in the U.S. is responsible for its own policy for BD/DNC determination, and our hope is that they will quickly revise their policies in accordance with this new national standard.”

The guidelines, which are accompanied by a three-page checklist and a free digital app, were published online in Neurology.
 

Four years in the making

Work on the 85 recommendations in the new report began more than 4 years ago as a collaborative effort by the American Academy of Neurology, the American Academy of Pediatrics, the Child Neurology Society, and the Society of Critical Care Medicine.

A lack of high-quality evidence on brain death determination led panelists to devise an evidence-informed formal consensus process to develop the guidelines, which involved three rounds of anonymous voting on each recommendation and the rationales behind them.

The strength of each recommendation was based on the level of consensus reached through voting, with Level A denoting a recommendation that “must” be followed, Level B one that “should” be followed, and Level C one that “may” be followed.

The majority of recommendations received an A or B rating. Only one recommendation, about whether a second clinical exam is needed in adults, garnered a C rating.

In children, the guidelines recommend that clinicians must perform two clinical examinations and two apnea tests 12 hours apart. In adults, only one exam is required. Both of those recommendations were rated Level A. A recommendation for a second exam in adults received the single Level C rating.
 

A uniform set of guidelines?

The new guidelines replace adult practice guidance published by AAN in 2010 and guideline for infants and children released in 2011 by AAP, CNS, and SCCM, and for the first time combine brain death guidelines for adult and pediatric patients into one document.

“It is important for clinicians to review the new guideline carefully and ensure their hospital brain death guidelines are updated to be consistent with the new guideline in order to prevent inaccurate determinations of death,” guidelines coauthor Ariane Lewis, MD, NYU Langone Health, New York, said in an interview.

The 1981 Uniform Determination of Death Act (UDDA) is the legal foundation for the declaration of BD/DNC in the United States, but it only stipulates that brain death determination must be made in accordance with accepted medical standards.

There is no single national standard, and states and hospitals are free to adopt their own, which many have done. One goal of the new guidelines was to create a uniform set of guidelines that all institutions follow.

“This is a step toward having a set of guidelines that are accepted by most of the societies and clinical specialties involved in this sort of diagnosis,” that could lead to a national-level policy, Fernando Goldenberg, MD, professor of neurology and director of neuroscience critical care, University of Chicago Medicine, said in an interview.

Dr. Goldenberg was not part of the panel that developed the updated guidelines, but was a coauthor of a consensus statement from the World Brain Death Project in 2020.

Developing a singular global guideline for brain death determination is unlikely, Dr. Goldenberg said. Policies vary widely across the world, and some countries don’t even recognize brain death.

“But this attempts to unify things at the U.S. level, which is very important,” he said.
 

Permanent vs. irreversible

Dr. Goldenberg said that combining adult and pediatric guidelines into one document will be very helpful for clinicians like him who treat patients from age 16 years and up.

The expanded guidance on apnea testing, recommendations on specific ancillary tests to use or avoid, and inclusion of language stipulating that prior consent is not needed to perform a brain death evaluation are also useful.

He also noted that the section on credentialing and training of clinicians who perform BD/DNC evaluations recognizes advanced practice providers, the first time he recalls seeing these professionals included in brain death guidelines.

However, the panel’s decision to use the term “permanent” to describe loss of brain function instead of “irreversible” gave Dr. Goldenberg pause.

The UDDA provides that an individual is declared legally dead when “circulatory and respiratory functions irreversibly stop; or all functions of the entire brain, including the brain stem, irreversibly stop.”

Earlier in October, the American College of Physicians released a position paper on cardiorespiratory death determination that called for a revision of the UDDA language.

The ACP suggested that “irreversibly” be replaced with “permanently” with regard to the cessation of circulatory and respiratory functions, but that “irreversible” be kept in the description of brain death.

“Permanent means that there is damage that is potentially reversible and irreversible means that the damage is so profound, it cannot be reversed even if an attempt to do so is performed,” Dr. Goldenberg said.

Even though the World Brain Death Project, on which he worked, also used “permanent” to describe brain function loss, Dr. Goldenberg said he aligns with ACP’s position.

“The understanding of brain death is that the damage is so profound, it is irreversible, even if you were to try,” he said. “Therefore, I think that the most appropriate term for brain death should be irreversible as opposed to permanent.”

The report was funded by the American Academy of Neurology. Dr. Greer has received travel funding from Boston University; serves as editor-in-chief for Seminars in Neurology; receives publishing royalties for 50 Studies Every Neurologist Should Know and Successful Leadership in Academic Medicine; has received honoraria from AAN; has received research funding from Becton, Dickinson, and Company; and has served as expert witness in legal proceedings. Dr. Lewis has received honoraria from AAN and Neurodiem, serves as Neurology deputy editor of disputes and debates, and serves as deputy editor of seminars in Neurology. Dr. Goldenberg reported no relevant financial relationships.

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

New guidelines on determining brain death offer the first updated recommendations in more than a decade for adult and pediatric patients.

The consensus practice guideline on brain death, also known as death by neurologic criteria (BD/DNC), was developed by a panel of 20 experts from different specialties, institutions, and medical societies.

As with previous guidelines, the updated version stipulates that brain death should be declared when a patient with a known cause of catastrophic brain injury has permanent loss of function of the brain, including the brain stem, which results in coma, brain stem areflexia, and apnea in the setting of an adequate stimulus.

But the updated version also clarifies questions on neurological examinations and apnea testing and offers new guidance on pre-evaluation targets for blood pressure and body temperature and evaluating brain death in patients who are pregnant, are on extracorporeal membrane oxygenation, or have an injury to the base of the brain.

Also, for the first time, the guidance clarifies that clinicians don’t need to obtain consent before performing a brain death evaluation, unless institutional policy, state laws, or regulations stipulate otherwise.

“The 2023 guidelines will be considered the standard of care in the U.S.,” lead author David M. Greer, MD, chair and chief of neurology, Boston University, and chief of neurology, Boston Medical Center, said in an interview. “Each hospital in the U.S. is responsible for its own policy for BD/DNC determination, and our hope is that they will quickly revise their policies in accordance with this new national standard.”

The guidelines, which are accompanied by a three-page checklist and a free digital app, were published online in Neurology.
 

Four years in the making

Work on the 85 recommendations in the new report began more than 4 years ago as a collaborative effort by the American Academy of Neurology, the American Academy of Pediatrics, the Child Neurology Society, and the Society of Critical Care Medicine.

A lack of high-quality evidence on brain death determination led panelists to devise an evidence-informed formal consensus process to develop the guidelines, which involved three rounds of anonymous voting on each recommendation and the rationales behind them.

The strength of each recommendation was based on the level of consensus reached through voting, with Level A denoting a recommendation that “must” be followed, Level B one that “should” be followed, and Level C one that “may” be followed.

The majority of recommendations received an A or B rating. Only one recommendation, about whether a second clinical exam is needed in adults, garnered a C rating.

In children, the guidelines recommend that clinicians must perform two clinical examinations and two apnea tests 12 hours apart. In adults, only one exam is required. Both of those recommendations were rated Level A. A recommendation for a second exam in adults received the single Level C rating.
 

A uniform set of guidelines?

The new guidelines replace adult practice guidance published by AAN in 2010 and guideline for infants and children released in 2011 by AAP, CNS, and SCCM, and for the first time combine brain death guidelines for adult and pediatric patients into one document.

“It is important for clinicians to review the new guideline carefully and ensure their hospital brain death guidelines are updated to be consistent with the new guideline in order to prevent inaccurate determinations of death,” guidelines coauthor Ariane Lewis, MD, NYU Langone Health, New York, said in an interview.

The 1981 Uniform Determination of Death Act (UDDA) is the legal foundation for the declaration of BD/DNC in the United States, but it only stipulates that brain death determination must be made in accordance with accepted medical standards.

There is no single national standard, and states and hospitals are free to adopt their own, which many have done. One goal of the new guidelines was to create a uniform set of guidelines that all institutions follow.

“This is a step toward having a set of guidelines that are accepted by most of the societies and clinical specialties involved in this sort of diagnosis,” that could lead to a national-level policy, Fernando Goldenberg, MD, professor of neurology and director of neuroscience critical care, University of Chicago Medicine, said in an interview.

Dr. Goldenberg was not part of the panel that developed the updated guidelines, but was a coauthor of a consensus statement from the World Brain Death Project in 2020.

Developing a singular global guideline for brain death determination is unlikely, Dr. Goldenberg said. Policies vary widely across the world, and some countries don’t even recognize brain death.

“But this attempts to unify things at the U.S. level, which is very important,” he said.
 

Permanent vs. irreversible

Dr. Goldenberg said that combining adult and pediatric guidelines into one document will be very helpful for clinicians like him who treat patients from age 16 years and up.

The expanded guidance on apnea testing, recommendations on specific ancillary tests to use or avoid, and inclusion of language stipulating that prior consent is not needed to perform a brain death evaluation are also useful.

He also noted that the section on credentialing and training of clinicians who perform BD/DNC evaluations recognizes advanced practice providers, the first time he recalls seeing these professionals included in brain death guidelines.

However, the panel’s decision to use the term “permanent” to describe loss of brain function instead of “irreversible” gave Dr. Goldenberg pause.

The UDDA provides that an individual is declared legally dead when “circulatory and respiratory functions irreversibly stop; or all functions of the entire brain, including the brain stem, irreversibly stop.”

Earlier in October, the American College of Physicians released a position paper on cardiorespiratory death determination that called for a revision of the UDDA language.

The ACP suggested that “irreversibly” be replaced with “permanently” with regard to the cessation of circulatory and respiratory functions, but that “irreversible” be kept in the description of brain death.

“Permanent means that there is damage that is potentially reversible and irreversible means that the damage is so profound, it cannot be reversed even if an attempt to do so is performed,” Dr. Goldenberg said.

Even though the World Brain Death Project, on which he worked, also used “permanent” to describe brain function loss, Dr. Goldenberg said he aligns with ACP’s position.

“The understanding of brain death is that the damage is so profound, it is irreversible, even if you were to try,” he said. “Therefore, I think that the most appropriate term for brain death should be irreversible as opposed to permanent.”

The report was funded by the American Academy of Neurology. Dr. Greer has received travel funding from Boston University; serves as editor-in-chief for Seminars in Neurology; receives publishing royalties for 50 Studies Every Neurologist Should Know and Successful Leadership in Academic Medicine; has received honoraria from AAN; has received research funding from Becton, Dickinson, and Company; and has served as expert witness in legal proceedings. Dr. Lewis has received honoraria from AAN and Neurodiem, serves as Neurology deputy editor of disputes and debates, and serves as deputy editor of seminars in Neurology. Dr. Goldenberg reported no relevant financial relationships.

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

New guidelines on determining brain death offer the first updated recommendations in more than a decade for adult and pediatric patients.

The consensus practice guideline on brain death, also known as death by neurologic criteria (BD/DNC), was developed by a panel of 20 experts from different specialties, institutions, and medical societies.

As with previous guidelines, the updated version stipulates that brain death should be declared when a patient with a known cause of catastrophic brain injury has permanent loss of function of the brain, including the brain stem, which results in coma, brain stem areflexia, and apnea in the setting of an adequate stimulus.

But the updated version also clarifies questions on neurological examinations and apnea testing and offers new guidance on pre-evaluation targets for blood pressure and body temperature and evaluating brain death in patients who are pregnant, are on extracorporeal membrane oxygenation, or have an injury to the base of the brain.

Also, for the first time, the guidance clarifies that clinicians don’t need to obtain consent before performing a brain death evaluation, unless institutional policy, state laws, or regulations stipulate otherwise.

“The 2023 guidelines will be considered the standard of care in the U.S.,” lead author David M. Greer, MD, chair and chief of neurology, Boston University, and chief of neurology, Boston Medical Center, said in an interview. “Each hospital in the U.S. is responsible for its own policy for BD/DNC determination, and our hope is that they will quickly revise their policies in accordance with this new national standard.”

The guidelines, which are accompanied by a three-page checklist and a free digital app, were published online in Neurology.
 

Four years in the making

Work on the 85 recommendations in the new report began more than 4 years ago as a collaborative effort by the American Academy of Neurology, the American Academy of Pediatrics, the Child Neurology Society, and the Society of Critical Care Medicine.

A lack of high-quality evidence on brain death determination led panelists to devise an evidence-informed formal consensus process to develop the guidelines, which involved three rounds of anonymous voting on each recommendation and the rationales behind them.

The strength of each recommendation was based on the level of consensus reached through voting, with Level A denoting a recommendation that “must” be followed, Level B one that “should” be followed, and Level C one that “may” be followed.

The majority of recommendations received an A or B rating. Only one recommendation, about whether a second clinical exam is needed in adults, garnered a C rating.

In children, the guidelines recommend that clinicians must perform two clinical examinations and two apnea tests 12 hours apart. In adults, only one exam is required. Both of those recommendations were rated Level A. A recommendation for a second exam in adults received the single Level C rating.
 

A uniform set of guidelines?

The new guidelines replace adult practice guidance published by AAN in 2010 and guideline for infants and children released in 2011 by AAP, CNS, and SCCM, and for the first time combine brain death guidelines for adult and pediatric patients into one document.

“It is important for clinicians to review the new guideline carefully and ensure their hospital brain death guidelines are updated to be consistent with the new guideline in order to prevent inaccurate determinations of death,” guidelines coauthor Ariane Lewis, MD, NYU Langone Health, New York, said in an interview.

The 1981 Uniform Determination of Death Act (UDDA) is the legal foundation for the declaration of BD/DNC in the United States, but it only stipulates that brain death determination must be made in accordance with accepted medical standards.

There is no single national standard, and states and hospitals are free to adopt their own, which many have done. One goal of the new guidelines was to create a uniform set of guidelines that all institutions follow.

“This is a step toward having a set of guidelines that are accepted by most of the societies and clinical specialties involved in this sort of diagnosis,” that could lead to a national-level policy, Fernando Goldenberg, MD, professor of neurology and director of neuroscience critical care, University of Chicago Medicine, said in an interview.

Dr. Goldenberg was not part of the panel that developed the updated guidelines, but was a coauthor of a consensus statement from the World Brain Death Project in 2020.

Developing a singular global guideline for brain death determination is unlikely, Dr. Goldenberg said. Policies vary widely across the world, and some countries don’t even recognize brain death.

“But this attempts to unify things at the U.S. level, which is very important,” he said.
 

Permanent vs. irreversible

Dr. Goldenberg said that combining adult and pediatric guidelines into one document will be very helpful for clinicians like him who treat patients from age 16 years and up.

The expanded guidance on apnea testing, recommendations on specific ancillary tests to use or avoid, and inclusion of language stipulating that prior consent is not needed to perform a brain death evaluation are also useful.

He also noted that the section on credentialing and training of clinicians who perform BD/DNC evaluations recognizes advanced practice providers, the first time he recalls seeing these professionals included in brain death guidelines.

However, the panel’s decision to use the term “permanent” to describe loss of brain function instead of “irreversible” gave Dr. Goldenberg pause.

The UDDA provides that an individual is declared legally dead when “circulatory and respiratory functions irreversibly stop; or all functions of the entire brain, including the brain stem, irreversibly stop.”

Earlier in October, the American College of Physicians released a position paper on cardiorespiratory death determination that called for a revision of the UDDA language.

The ACP suggested that “irreversibly” be replaced with “permanently” with regard to the cessation of circulatory and respiratory functions, but that “irreversible” be kept in the description of brain death.

“Permanent means that there is damage that is potentially reversible and irreversible means that the damage is so profound, it cannot be reversed even if an attempt to do so is performed,” Dr. Goldenberg said.

Even though the World Brain Death Project, on which he worked, also used “permanent” to describe brain function loss, Dr. Goldenberg said he aligns with ACP’s position.

“The understanding of brain death is that the damage is so profound, it is irreversible, even if you were to try,” he said. “Therefore, I think that the most appropriate term for brain death should be irreversible as opposed to permanent.”

The report was funded by the American Academy of Neurology. Dr. Greer has received travel funding from Boston University; serves as editor-in-chief for Seminars in Neurology; receives publishing royalties for 50 Studies Every Neurologist Should Know and Successful Leadership in Academic Medicine; has received honoraria from AAN; has received research funding from Becton, Dickinson, and Company; and has served as expert witness in legal proceedings. Dr. Lewis has received honoraria from AAN and Neurodiem, serves as Neurology deputy editor of disputes and debates, and serves as deputy editor of seminars in Neurology. Dr. Goldenberg reported no relevant financial relationships.

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

TOPLINE:

The risk for dementia before age 90 years was significantly higher among people with a history of proton pump inhibitor (PPI) use and was highest among those diagnosed before age 70 years regardless of when PPI treatment was initiated.

METHODOLOGY:

• Researchers used four Danish registries to collect data on dementia diagnoses and prescription PPI use among 1,983,785 individuals aged 60-75 years between 2000 and 2018.
• The median follow-up time was 10.3 years.

TAKEAWAY:

• There were 99,384 (5.0%) cases of all-cause dementia during follow-up, with a median age of diagnosis of 79 years.
• Twenty-one-point-two percent of dementia cases and 18.9% of controls reported a history of PPI use.
• Risk for all-cause dementia before age 90 years was 36% higher with PPI use in people aged 60-69 years at baseline (adjusted incidence rate ratio, 1.36; 95% confidence interval, 1.29-1.43) and 6% higher in those who were age 80-89 years at baseline (aIRR, 1.06; 95% CI, 1.03-1.09).
• Investigators found significant increased dementia risk before age 90 years with PPI use regardless of when PPI treatment began and found no link between PPI use and dementia diagnoses after age 90 years.

IN PRACTICE:

“The association between PPI use and dementia was unambiguously largest among the youngest cases of dementia, potentially suggestive of a critical window of exposure where midlife PPI use affects dementia risk to a larger degree compared to late-life use,” the authors wrote. “Further, the finding could signify a declining impact of individual risk factors with advancing age owing to lengthy ongoing neuropathological processes.”

SOURCE:

Lead author of the study was Nelsan Pourhadi, MD, Danish Dementia Research Centre, department of neurology, Copenhagen University Hospital–Rigshospitalet. It was published online in Alzheimer’s and Dementia.

LIMITATIONS:

The study did not include data on PPI prescriptions before 1995, over-the-counter PPI use, and in-hospital intravenous use of PPI during the study period.

DISCLOSURES:

The study was funded by the Danish Ministry of Health. The authors reported no relevant conflicts.

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

TOPLINE:

The risk for dementia before age 90 years was significantly higher among people with a history of proton pump inhibitor (PPI) use and was highest among those diagnosed before age 70 years regardless of when PPI treatment was initiated.

METHODOLOGY:

• Researchers used four Danish registries to collect data on dementia diagnoses and prescription PPI use among 1,983,785 individuals aged 60-75 years between 2000 and 2018.
• The median follow-up time was 10.3 years.

TAKEAWAY:

• There were 99,384 (5.0%) cases of all-cause dementia during follow-up, with a median age of diagnosis of 79 years.
• Twenty-one-point-two percent of dementia cases and 18.9% of controls reported a history of PPI use.
• Risk for all-cause dementia before age 90 years was 36% higher with PPI use in people aged 60-69 years at baseline (adjusted incidence rate ratio, 1.36; 95% confidence interval, 1.29-1.43) and 6% higher in those who were age 80-89 years at baseline (aIRR, 1.06; 95% CI, 1.03-1.09).
• Investigators found significant increased dementia risk before age 90 years with PPI use regardless of when PPI treatment began and found no link between PPI use and dementia diagnoses after age 90 years.

IN PRACTICE:

“The association between PPI use and dementia was unambiguously largest among the youngest cases of dementia, potentially suggestive of a critical window of exposure where midlife PPI use affects dementia risk to a larger degree compared to late-life use,” the authors wrote. “Further, the finding could signify a declining impact of individual risk factors with advancing age owing to lengthy ongoing neuropathological processes.”

SOURCE:

Lead author of the study was Nelsan Pourhadi, MD, Danish Dementia Research Centre, department of neurology, Copenhagen University Hospital–Rigshospitalet. It was published online in Alzheimer’s and Dementia.

LIMITATIONS:

The study did not include data on PPI prescriptions before 1995, over-the-counter PPI use, and in-hospital intravenous use of PPI during the study period.

DISCLOSURES:

The study was funded by the Danish Ministry of Health. The authors reported no relevant conflicts.

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

TOPLINE:

The risk for dementia before age 90 years was significantly higher among people with a history of proton pump inhibitor (PPI) use and was highest among those diagnosed before age 70 years regardless of when PPI treatment was initiated.

METHODOLOGY:

• Researchers used four Danish registries to collect data on dementia diagnoses and prescription PPI use among 1,983,785 individuals aged 60-75 years between 2000 and 2018.
• The median follow-up time was 10.3 years.

TAKEAWAY:

• There were 99,384 (5.0%) cases of all-cause dementia during follow-up, with a median age of diagnosis of 79 years.
• Twenty-one-point-two percent of dementia cases and 18.9% of controls reported a history of PPI use.
• Risk for all-cause dementia before age 90 years was 36% higher with PPI use in people aged 60-69 years at baseline (adjusted incidence rate ratio, 1.36; 95% confidence interval, 1.29-1.43) and 6% higher in those who were age 80-89 years at baseline (aIRR, 1.06; 95% CI, 1.03-1.09).
• Investigators found significant increased dementia risk before age 90 years with PPI use regardless of when PPI treatment began and found no link between PPI use and dementia diagnoses after age 90 years.

IN PRACTICE:

“The association between PPI use and dementia was unambiguously largest among the youngest cases of dementia, potentially suggestive of a critical window of exposure where midlife PPI use affects dementia risk to a larger degree compared to late-life use,” the authors wrote. “Further, the finding could signify a declining impact of individual risk factors with advancing age owing to lengthy ongoing neuropathological processes.”

SOURCE:

Lead author of the study was Nelsan Pourhadi, MD, Danish Dementia Research Centre, department of neurology, Copenhagen University Hospital–Rigshospitalet. It was published online in Alzheimer’s and Dementia.

LIMITATIONS:

The study did not include data on PPI prescriptions before 1995, over-the-counter PPI use, and in-hospital intravenous use of PPI during the study period.

DISCLOSURES:

The study was funded by the Danish Ministry of Health. The authors reported no relevant conflicts.

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

TOPLINE:

People with a history of depression or stress were significantly more likely to be diagnosed with mild cognitive impairment (MCI) or Alzheimer’s disease (AD) later in life compared with those without either condition, a new study found.

METHODOLOGY:

• Longitudinal cohort study of 1,362,548 people with records in the Region Stockholm administrative health care database with a diagnosis of stress-induced exhaustion disorder (SED), depression, or both between 2012 and 2013.
• Cohort followed for diagnosis of MCI or AD between 2014 and 2022.

TAKEAWAY:

• SED diagnosed in 0.3%, depression in 2.9% and both SED and depression in 0.1%
• Compared with people without SED or depression, AD risk was more than double in patients with SED (adjusted odds ratio [aOR], 2.45; 99% confidence interval [CI], 1.22-4.91) or depression (aOR, 2.32; 99% CI, 1.85-2.90) and four times higher in patients with both SED and depression (aOR, 4.00; 99% CI, 1.67-9.58)
• Risk for MCI was also higher in people with SED (aOR, 1.87; 99% CI,1.20-2.91), depression (aOR, 2.85; 99% CI, 2.53-3.22) or both SED and depression (aOR, 3.87; 99% CI, 2.39-6.27) vs patients with no history of SED or depression.
• Only patients with depression had a higher risk for another dementia type (aOR, 2.39; 99% CI, 1.92-2.96).

[embed:render:related:node:262640]

IN PRACTICE:

“Future studies should examine the possibility that symptoms of depression and/or chronic stress could be prodromal symptoms of dementia rather than risk factors,” study authors wrote.

SOURCE:

The study was conducted by Johanna Wallensten, doctoral student, department of clinical sciences, Danderyd Hospital, Stockholm, and colleagues and funded by the Karolinska Institute. It was published online in Alzheimer’s Research and Therapy.

LIMITATIONS:

Use of a health care registry could have led to over- or underestimation of depression, MCI and AD. The study probably captures most people with depression but not most people with depressive symptoms.

DISCLOSURES:

The authors reported no relevant conflicts.

A version of this article appeared on Medscape.com.

TOPLINE:

People with a history of depression or stress were significantly more likely to be diagnosed with mild cognitive impairment (MCI) or Alzheimer’s disease (AD) later in life compared with those without either condition, a new study found.

METHODOLOGY:

• Longitudinal cohort study of 1,362,548 people with records in the Region Stockholm administrative health care database with a diagnosis of stress-induced exhaustion disorder (SED), depression, or both between 2012 and 2013.
• Cohort followed for diagnosis of MCI or AD between 2014 and 2022.

TAKEAWAY:

• SED diagnosed in 0.3%, depression in 2.9% and both SED and depression in 0.1%
• Compared with people without SED or depression, AD risk was more than double in patients with SED (adjusted odds ratio [aOR], 2.45; 99% confidence interval [CI], 1.22-4.91) or depression (aOR, 2.32; 99% CI, 1.85-2.90) and four times higher in patients with both SED and depression (aOR, 4.00; 99% CI, 1.67-9.58)
• Risk for MCI was also higher in people with SED (aOR, 1.87; 99% CI,1.20-2.91), depression (aOR, 2.85; 99% CI, 2.53-3.22) or both SED and depression (aOR, 3.87; 99% CI, 2.39-6.27) vs patients with no history of SED or depression.
• Only patients with depression had a higher risk for another dementia type (aOR, 2.39; 99% CI, 1.92-2.96).

[embed:render:related:node:262640]

IN PRACTICE:

“Future studies should examine the possibility that symptoms of depression and/or chronic stress could be prodromal symptoms of dementia rather than risk factors,” study authors wrote.

SOURCE:

The study was conducted by Johanna Wallensten, doctoral student, department of clinical sciences, Danderyd Hospital, Stockholm, and colleagues and funded by the Karolinska Institute. It was published online in Alzheimer’s Research and Therapy.

LIMITATIONS:

Use of a health care registry could have led to over- or underestimation of depression, MCI and AD. The study probably captures most people with depression but not most people with depressive symptoms.

DISCLOSURES:

The authors reported no relevant conflicts.

A version of this article appeared on Medscape.com.

TOPLINE:

People with a history of depression or stress were significantly more likely to be diagnosed with mild cognitive impairment (MCI) or Alzheimer’s disease (AD) later in life compared with those without either condition, a new study found.

METHODOLOGY:

• Longitudinal cohort study of 1,362,548 people with records in the Region Stockholm administrative health care database with a diagnosis of stress-induced exhaustion disorder (SED), depression, or both between 2012 and 2013.
• Cohort followed for diagnosis of MCI or AD between 2014 and 2022.

TAKEAWAY:

• SED diagnosed in 0.3%, depression in 2.9% and both SED and depression in 0.1%
• Compared with people without SED or depression, AD risk was more than double in patients with SED (adjusted odds ratio [aOR], 2.45; 99% confidence interval [CI], 1.22-4.91) or depression (aOR, 2.32; 99% CI, 1.85-2.90) and four times higher in patients with both SED and depression (aOR, 4.00; 99% CI, 1.67-9.58)
• Risk for MCI was also higher in people with SED (aOR, 1.87; 99% CI,1.20-2.91), depression (aOR, 2.85; 99% CI, 2.53-3.22) or both SED and depression (aOR, 3.87; 99% CI, 2.39-6.27) vs patients with no history of SED or depression.
• Only patients with depression had a higher risk for another dementia type (aOR, 2.39; 99% CI, 1.92-2.96).

[embed:render:related:node:262640]

IN PRACTICE:

“Future studies should examine the possibility that symptoms of depression and/or chronic stress could be prodromal symptoms of dementia rather than risk factors,” study authors wrote.

SOURCE:

The study was conducted by Johanna Wallensten, doctoral student, department of clinical sciences, Danderyd Hospital, Stockholm, and colleagues and funded by the Karolinska Institute. It was published online in Alzheimer’s Research and Therapy.

LIMITATIONS:

Use of a health care registry could have led to over- or underestimation of depression, MCI and AD. The study probably captures most people with depression but not most people with depressive symptoms.

DISCLOSURES:

The authors reported no relevant conflicts.

A version of this article appeared on Medscape.com.

A national shortage of neurologists is creating “neurology deserts” around the country, forcing patients to wait longer and drive farther for care, news that comes as no revelation to Thomas Vidic, MD, clinical associate professor of neurology at Indiana University, South Bend.

In 2013, Dr. Vidic and other members of an American Academy of Neurology Workforce Task Force coauthored a report that predicted the demand for neurologists would outstrip supply by 2025. A decade later, it appears the situation is even more dire than anticipated.

While a nationwide physician shortage is affecting all specialties, neurology is facing a particularly difficult confluence of events. Advances in treatments for migraine, epilepsy, multiple sclerosis, and other neurological disorders have created a growing demand for care of pediatric and adult patients.

Over the next 7-27 years, as the number of Americans over age 65 increases, the incidences of Parkinson’s and dementia are set to double, and stroke cases are expected to rise by 20%.

At the same time, physician retirement and burnout are siphoning off neurologists from a workforce that isn’t growing fast enough. The American Medical Association reports the number of neurologists who treat patients in the United States grew by only 598 over the last decade, from 12,761 to 13,359.

This perfect storm has created what another AAN report calls a “grave threat” to patient care. The neurologist shortage “reduces access to care, worsens patient outcomes, and erodes career satisfaction and quality of life for neurologists as they face increasingly insurmountable demands,” write the authors of that 2019 report.

“We’re in trouble,” said Dr. Vidic. “We have a tremendous need for neurologists that we’re just not supporting.”
 

How did we get here?

Some of the challenges related to neurologist recruitment and retention are similar to those in other specialties. Compensation is certainly a factor, Dr. Vidic said.

Although neurologists’ incomes have increased significantly over the past decade, they still rank in the lower half of all medical specialties. In addition, only 50% of neurologists believe they are fairly compensated.

Burnout is another significant challenge. In 2019, before the pandemic, 53% of neurologists surveyed in Medscape’s National Physician Burnout, Depression, and Suicide Report indicated they were burned out. That percentage increased slightly in 2023, to 55%, with most respondents reporting a strong to severe impact on their lives.

The most common reason for burnout was administration and paperwork that cuts into neurologists’ time with patients. Charting and completing prior authorization and step therapy forms required by most insurers take an average of 17.6 hours a week for neurologists – much longer than the overall physician average and higher than almost all other specialties.

But perhaps the biggest contributor to the nationwide neurologist shortage is a 26-year cap on Medicare funding for medical residency. Enacted as part of the 1997 Balanced Budget Act, the legislation limits Medicare funding for medical residency training at 1996 levels. Most medical residencies are funded by the federal government and Medicare is the largest participating program.

As a result of the cap, the number of total residents in the United States – which grew by 20.6% between 1987 and 1997 – increased by only 8% from 1997 to 2007.

A new study on patients’ long travel times to neurology clinics, published in Neurology, is the latest to illustrate the real-world impact of too few neurologists amid growing caseloads.

Researchers found that 17% of the 563,216 Medicare beneficiaries who visited a neurologist in 2018 had to travel an average of 81 miles one way. Those long distances were endured most often by patients with brain and spinal cord cancers, amyotrophic lateral sclerosis, and multiple sclerosis.

While the neurologist shortage affects every state, a 2020 study suggests rural areas are most affected. This analysis of Medicare recipients showed that just 21% of rural residents with a neurological condition had access to a nearby specialist, compared with 27% of urban dwellers. The findings are similar to those of a 2017 report that identified “neurology deserts” in a number of states across the country.

Wait times for new neurology patients are reported to be among the longest of all specialties, with an average of 30 days for adult patients and 5-6 months for pediatric patients.


 

More neurology instruction needed

“It’s really hard knowing there are families out there who need the care but can’t get to it in a timely manner,” said Tyler Allison, MD, associate professor of pediatrics at the University of Missouri–Kansas City.

Working in a rural state means Dr. Allison has patients who drive 6 hours or more for an appointment. Although telemedicine has reduced the number of trips for many of his existing pediatric cases, it has had little impact on new patients. This is particularly frustrating, he said, when he sees a new patient with a condition that could have been treated by a primary care physician in their home community.

“One of the biggest problems we have in the child neurology world is that we don’t have enough primary care physicians who feel they are adequately trained to care for these patients,” said Dr. Allison, who also is the program director of the Child Neurology Residency Program at Children’s Mercy Kansas City.

“Sometimes I see patients where, frankly, I only need to see them once to provide reassurance to the family and then they go back to their primary care doctor,” he said. “It’s the kind of thing that if we trained people appropriately from the beginning, it would shorten our wait list.”

Indeed, increasing neurology instruction during medical school is one recommendation offered in a 2019 report that characterized the neurologist shortage as a “grave threat.”

Data from the Association of American Medical Colleges show U.S. medical schools required an average of 4.4 weeks of neurology instruction in 2019-2020. Of the disciplines included in the AAMC report, only radiology and surgical specialties required a shorter clinical course. Many medical schools also require a neurology rotation, usually during the third year.

“There are still medical schools that do not require a neurology rotation,” said Dr. Vidic. Indiana University’s medical school requires a 1-month neurology rotation. “Per capita, we turn out more neurologists than any other medical school in the country because we give the exposure.”
 

General neurologists needed

The 2019 AAN report also calls for a renewed focus on general neurology in residency training as a way to ease patient wait times.

“General neurologists in the community can care for 75%-85% of patients with neurological disease,” said Michael Markowski, DO, a general neurologist in Cape Cod, Mass., who chaired the AAN’s general neurology task force from 2019 to 2020.

“Our residency training programs aren’t doing anything wrong, but we have data that show we have to start doing something different if we’re going to care for the one in three Americans with neurological disease who deserve care in their community rather than having to travel to subspecialty centers, which are primarily located in larger cities,” he said.

Based on an AAN survey, only about one-third of U.S. neurologists identify as general neurologists; most focus on movement disorders, dementia or Alzheimer’s, epilepsy, or another neurology subspecialty. It’s a sharp contrast from Europe, where the vast majority of neurologists identify as general neurologists.

“It was striking, the difference between the neurologists across Europe who identify as general neurologists, in comparison to the U.S.,” said Dr. Markowski, who was the AAN representative for the European Academy of Neurology General Neurology Task Force. “Close to 28% of U.S. neurologists identify as general neurologists, but across 37 European nations, that [percentage] is 76%.”

In Europe, general neurology rotations make up at least half of the first year of medical residency, Dr. Markowski said, adding that in the United States, there is more focus on inpatient rather than outpatient neurology rotations.

“If you never see that role model during your training who is a general neurologist, who can see the vast majority of all neurology patients, why would you think you could do that when you graduate?” Dr. Markowski said.
 

A legislative solution

While expanding neurology instruction in medical school and increasing exposure to general neurology rotations in residency could help, the clearest path to increasing the number of neurologists in the United States is to lift the decades-old residency cap.

The Resident Physician Shortage Reduction Act of 2023 would do just that, adding 14,000 new medical residency positions over 7 years. The bill has bipartisan support, with hundreds of cosponsors from both sides of the aisle. Nearly 100 professional societies and medical and hospital groups have submitted testimony in support.

Similar legislation has been introduced at least six times since 2007 and no bill has ever made it out of committee. It’s unclear whether the latest version will meet a similar fate, but its expected price tag of $10-$12 billion over 10 years is a large hurdle to overcome.

Congress did take a small step in 2021 to increase residency spots, with legislation that allocated funding for 1,000 new positions over 5 years. Congress added another 200 spots to that total in a bill passed last year.

Critics say the slots are tied up in Medicare red tape and it’s a far cry from the 14,000 new positions experts say are needed to address the physician shortage.

“We absolutely want the larger bill, and we think that’s the way to go, but we’ll continue to work and try to add as many positions as we can,” said Leonard Marquez, senior director of government relations and legislative advocacy for AAMC.

Congress is also considering legislation to speed up prior reauthorization for Medicare, something the Centers for Medicare & Medicaid Services is also seeking to do through rule changes. Nearly 30 state legislatures are debating similar legislation at the state level. And another bill in Congress would expand the Conrad State 30 program, which allows states to request J-1 visa waivers for international physicians to work in underserved areas.

“The solutions to this problem are multifactorial, and the answer that worked 10 years ago won’t be the right answer today, and the answer that works today won’t be the right answer 10 years from now,” Dr. Vidic said. “All we have to do is keep making changes, keep evolving, and the playing field continually changes.”

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

A national shortage of neurologists is creating “neurology deserts” around the country, forcing patients to wait longer and drive farther for care, news that comes as no revelation to Thomas Vidic, MD, clinical associate professor of neurology at Indiana University, South Bend.

In 2013, Dr. Vidic and other members of an American Academy of Neurology Workforce Task Force coauthored a report that predicted the demand for neurologists would outstrip supply by 2025. A decade later, it appears the situation is even more dire than anticipated.

While a nationwide physician shortage is affecting all specialties, neurology is facing a particularly difficult confluence of events. Advances in treatments for migraine, epilepsy, multiple sclerosis, and other neurological disorders have created a growing demand for care of pediatric and adult patients.

Over the next 7-27 years, as the number of Americans over age 65 increases, the incidences of Parkinson’s and dementia are set to double, and stroke cases are expected to rise by 20%.

At the same time, physician retirement and burnout are siphoning off neurologists from a workforce that isn’t growing fast enough. The American Medical Association reports the number of neurologists who treat patients in the United States grew by only 598 over the last decade, from 12,761 to 13,359.

This perfect storm has created what another AAN report calls a “grave threat” to patient care. The neurologist shortage “reduces access to care, worsens patient outcomes, and erodes career satisfaction and quality of life for neurologists as they face increasingly insurmountable demands,” write the authors of that 2019 report.

“We’re in trouble,” said Dr. Vidic. “We have a tremendous need for neurologists that we’re just not supporting.”
 

How did we get here?

Some of the challenges related to neurologist recruitment and retention are similar to those in other specialties. Compensation is certainly a factor, Dr. Vidic said.

Although neurologists’ incomes have increased significantly over the past decade, they still rank in the lower half of all medical specialties. In addition, only 50% of neurologists believe they are fairly compensated.

Burnout is another significant challenge. In 2019, before the pandemic, 53% of neurologists surveyed in Medscape’s National Physician Burnout, Depression, and Suicide Report indicated they were burned out. That percentage increased slightly in 2023, to 55%, with most respondents reporting a strong to severe impact on their lives.

The most common reason for burnout was administration and paperwork that cuts into neurologists’ time with patients. Charting and completing prior authorization and step therapy forms required by most insurers take an average of 17.6 hours a week for neurologists – much longer than the overall physician average and higher than almost all other specialties.

But perhaps the biggest contributor to the nationwide neurologist shortage is a 26-year cap on Medicare funding for medical residency. Enacted as part of the 1997 Balanced Budget Act, the legislation limits Medicare funding for medical residency training at 1996 levels. Most medical residencies are funded by the federal government and Medicare is the largest participating program.

As a result of the cap, the number of total residents in the United States – which grew by 20.6% between 1987 and 1997 – increased by only 8% from 1997 to 2007.

A new study on patients’ long travel times to neurology clinics, published in Neurology, is the latest to illustrate the real-world impact of too few neurologists amid growing caseloads.

Researchers found that 17% of the 563,216 Medicare beneficiaries who visited a neurologist in 2018 had to travel an average of 81 miles one way. Those long distances were endured most often by patients with brain and spinal cord cancers, amyotrophic lateral sclerosis, and multiple sclerosis.

While the neurologist shortage affects every state, a 2020 study suggests rural areas are most affected. This analysis of Medicare recipients showed that just 21% of rural residents with a neurological condition had access to a nearby specialist, compared with 27% of urban dwellers. The findings are similar to those of a 2017 report that identified “neurology deserts” in a number of states across the country.

Wait times for new neurology patients are reported to be among the longest of all specialties, with an average of 30 days for adult patients and 5-6 months for pediatric patients.


 

More neurology instruction needed

“It’s really hard knowing there are families out there who need the care but can’t get to it in a timely manner,” said Tyler Allison, MD, associate professor of pediatrics at the University of Missouri–Kansas City.

Working in a rural state means Dr. Allison has patients who drive 6 hours or more for an appointment. Although telemedicine has reduced the number of trips for many of his existing pediatric cases, it has had little impact on new patients. This is particularly frustrating, he said, when he sees a new patient with a condition that could have been treated by a primary care physician in their home community.

“One of the biggest problems we have in the child neurology world is that we don’t have enough primary care physicians who feel they are adequately trained to care for these patients,” said Dr. Allison, who also is the program director of the Child Neurology Residency Program at Children’s Mercy Kansas City.

“Sometimes I see patients where, frankly, I only need to see them once to provide reassurance to the family and then they go back to their primary care doctor,” he said. “It’s the kind of thing that if we trained people appropriately from the beginning, it would shorten our wait list.”

Indeed, increasing neurology instruction during medical school is one recommendation offered in a 2019 report that characterized the neurologist shortage as a “grave threat.”

Data from the Association of American Medical Colleges show U.S. medical schools required an average of 4.4 weeks of neurology instruction in 2019-2020. Of the disciplines included in the AAMC report, only radiology and surgical specialties required a shorter clinical course. Many medical schools also require a neurology rotation, usually during the third year.

“There are still medical schools that do not require a neurology rotation,” said Dr. Vidic. Indiana University’s medical school requires a 1-month neurology rotation. “Per capita, we turn out more neurologists than any other medical school in the country because we give the exposure.”
 

General neurologists needed

The 2019 AAN report also calls for a renewed focus on general neurology in residency training as a way to ease patient wait times.

“General neurologists in the community can care for 75%-85% of patients with neurological disease,” said Michael Markowski, DO, a general neurologist in Cape Cod, Mass., who chaired the AAN’s general neurology task force from 2019 to 2020.

“Our residency training programs aren’t doing anything wrong, but we have data that show we have to start doing something different if we’re going to care for the one in three Americans with neurological disease who deserve care in their community rather than having to travel to subspecialty centers, which are primarily located in larger cities,” he said.

Based on an AAN survey, only about one-third of U.S. neurologists identify as general neurologists; most focus on movement disorders, dementia or Alzheimer’s, epilepsy, or another neurology subspecialty. It’s a sharp contrast from Europe, where the vast majority of neurologists identify as general neurologists.

“It was striking, the difference between the neurologists across Europe who identify as general neurologists, in comparison to the U.S.,” said Dr. Markowski, who was the AAN representative for the European Academy of Neurology General Neurology Task Force. “Close to 28% of U.S. neurologists identify as general neurologists, but across 37 European nations, that [percentage] is 76%.”

In Europe, general neurology rotations make up at least half of the first year of medical residency, Dr. Markowski said, adding that in the United States, there is more focus on inpatient rather than outpatient neurology rotations.

“If you never see that role model during your training who is a general neurologist, who can see the vast majority of all neurology patients, why would you think you could do that when you graduate?” Dr. Markowski said.
 

A legislative solution

While expanding neurology instruction in medical school and increasing exposure to general neurology rotations in residency could help, the clearest path to increasing the number of neurologists in the United States is to lift the decades-old residency cap.

The Resident Physician Shortage Reduction Act of 2023 would do just that, adding 14,000 new medical residency positions over 7 years. The bill has bipartisan support, with hundreds of cosponsors from both sides of the aisle. Nearly 100 professional societies and medical and hospital groups have submitted testimony in support.

Similar legislation has been introduced at least six times since 2007 and no bill has ever made it out of committee. It’s unclear whether the latest version will meet a similar fate, but its expected price tag of $10-$12 billion over 10 years is a large hurdle to overcome.

Congress did take a small step in 2021 to increase residency spots, with legislation that allocated funding for 1,000 new positions over 5 years. Congress added another 200 spots to that total in a bill passed last year.

Critics say the slots are tied up in Medicare red tape and it’s a far cry from the 14,000 new positions experts say are needed to address the physician shortage.

“We absolutely want the larger bill, and we think that’s the way to go, but we’ll continue to work and try to add as many positions as we can,” said Leonard Marquez, senior director of government relations and legislative advocacy for AAMC.

Congress is also considering legislation to speed up prior reauthorization for Medicare, something the Centers for Medicare & Medicaid Services is also seeking to do through rule changes. Nearly 30 state legislatures are debating similar legislation at the state level. And another bill in Congress would expand the Conrad State 30 program, which allows states to request J-1 visa waivers for international physicians to work in underserved areas.

“The solutions to this problem are multifactorial, and the answer that worked 10 years ago won’t be the right answer today, and the answer that works today won’t be the right answer 10 years from now,” Dr. Vidic said. “All we have to do is keep making changes, keep evolving, and the playing field continually changes.”

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

A national shortage of neurologists is creating “neurology deserts” around the country, forcing patients to wait longer and drive farther for care, news that comes as no revelation to Thomas Vidic, MD, clinical associate professor of neurology at Indiana University, South Bend.

In 2013, Dr. Vidic and other members of an American Academy of Neurology Workforce Task Force coauthored a report that predicted the demand for neurologists would outstrip supply by 2025. A decade later, it appears the situation is even more dire than anticipated.

While a nationwide physician shortage is affecting all specialties, neurology is facing a particularly difficult confluence of events. Advances in treatments for migraine, epilepsy, multiple sclerosis, and other neurological disorders have created a growing demand for care of pediatric and adult patients.

Over the next 7-27 years, as the number of Americans over age 65 increases, the incidences of Parkinson’s and dementia are set to double, and stroke cases are expected to rise by 20%.

At the same time, physician retirement and burnout are siphoning off neurologists from a workforce that isn’t growing fast enough. The American Medical Association reports the number of neurologists who treat patients in the United States grew by only 598 over the last decade, from 12,761 to 13,359.

This perfect storm has created what another AAN report calls a “grave threat” to patient care. The neurologist shortage “reduces access to care, worsens patient outcomes, and erodes career satisfaction and quality of life for neurologists as they face increasingly insurmountable demands,” write the authors of that 2019 report.

“We’re in trouble,” said Dr. Vidic. “We have a tremendous need for neurologists that we’re just not supporting.”
 

How did we get here?

Some of the challenges related to neurologist recruitment and retention are similar to those in other specialties. Compensation is certainly a factor, Dr. Vidic said.

Although neurologists’ incomes have increased significantly over the past decade, they still rank in the lower half of all medical specialties. In addition, only 50% of neurologists believe they are fairly compensated.

Burnout is another significant challenge. In 2019, before the pandemic, 53% of neurologists surveyed in Medscape’s National Physician Burnout, Depression, and Suicide Report indicated they were burned out. That percentage increased slightly in 2023, to 55%, with most respondents reporting a strong to severe impact on their lives.

The most common reason for burnout was administration and paperwork that cuts into neurologists’ time with patients. Charting and completing prior authorization and step therapy forms required by most insurers take an average of 17.6 hours a week for neurologists – much longer than the overall physician average and higher than almost all other specialties.

But perhaps the biggest contributor to the nationwide neurologist shortage is a 26-year cap on Medicare funding for medical residency. Enacted as part of the 1997 Balanced Budget Act, the legislation limits Medicare funding for medical residency training at 1996 levels. Most medical residencies are funded by the federal government and Medicare is the largest participating program.

As a result of the cap, the number of total residents in the United States – which grew by 20.6% between 1987 and 1997 – increased by only 8% from 1997 to 2007.

A new study on patients’ long travel times to neurology clinics, published in Neurology, is the latest to illustrate the real-world impact of too few neurologists amid growing caseloads.

Researchers found that 17% of the 563,216 Medicare beneficiaries who visited a neurologist in 2018 had to travel an average of 81 miles one way. Those long distances were endured most often by patients with brain and spinal cord cancers, amyotrophic lateral sclerosis, and multiple sclerosis.

While the neurologist shortage affects every state, a 2020 study suggests rural areas are most affected. This analysis of Medicare recipients showed that just 21% of rural residents with a neurological condition had access to a nearby specialist, compared with 27% of urban dwellers. The findings are similar to those of a 2017 report that identified “neurology deserts” in a number of states across the country.

Wait times for new neurology patients are reported to be among the longest of all specialties, with an average of 30 days for adult patients and 5-6 months for pediatric patients.


 

More neurology instruction needed

“It’s really hard knowing there are families out there who need the care but can’t get to it in a timely manner,” said Tyler Allison, MD, associate professor of pediatrics at the University of Missouri–Kansas City.

Working in a rural state means Dr. Allison has patients who drive 6 hours or more for an appointment. Although telemedicine has reduced the number of trips for many of his existing pediatric cases, it has had little impact on new patients. This is particularly frustrating, he said, when he sees a new patient with a condition that could have been treated by a primary care physician in their home community.

“One of the biggest problems we have in the child neurology world is that we don’t have enough primary care physicians who feel they are adequately trained to care for these patients,” said Dr. Allison, who also is the program director of the Child Neurology Residency Program at Children’s Mercy Kansas City.

“Sometimes I see patients where, frankly, I only need to see them once to provide reassurance to the family and then they go back to their primary care doctor,” he said. “It’s the kind of thing that if we trained people appropriately from the beginning, it would shorten our wait list.”

Indeed, increasing neurology instruction during medical school is one recommendation offered in a 2019 report that characterized the neurologist shortage as a “grave threat.”

Data from the Association of American Medical Colleges show U.S. medical schools required an average of 4.4 weeks of neurology instruction in 2019-2020. Of the disciplines included in the AAMC report, only radiology and surgical specialties required a shorter clinical course. Many medical schools also require a neurology rotation, usually during the third year.

“There are still medical schools that do not require a neurology rotation,” said Dr. Vidic. Indiana University’s medical school requires a 1-month neurology rotation. “Per capita, we turn out more neurologists than any other medical school in the country because we give the exposure.”
 

General neurologists needed

The 2019 AAN report also calls for a renewed focus on general neurology in residency training as a way to ease patient wait times.

“General neurologists in the community can care for 75%-85% of patients with neurological disease,” said Michael Markowski, DO, a general neurologist in Cape Cod, Mass., who chaired the AAN’s general neurology task force from 2019 to 2020.

“Our residency training programs aren’t doing anything wrong, but we have data that show we have to start doing something different if we’re going to care for the one in three Americans with neurological disease who deserve care in their community rather than having to travel to subspecialty centers, which are primarily located in larger cities,” he said.

Based on an AAN survey, only about one-third of U.S. neurologists identify as general neurologists; most focus on movement disorders, dementia or Alzheimer’s, epilepsy, or another neurology subspecialty. It’s a sharp contrast from Europe, where the vast majority of neurologists identify as general neurologists.

“It was striking, the difference between the neurologists across Europe who identify as general neurologists, in comparison to the U.S.,” said Dr. Markowski, who was the AAN representative for the European Academy of Neurology General Neurology Task Force. “Close to 28% of U.S. neurologists identify as general neurologists, but across 37 European nations, that [percentage] is 76%.”

In Europe, general neurology rotations make up at least half of the first year of medical residency, Dr. Markowski said, adding that in the United States, there is more focus on inpatient rather than outpatient neurology rotations.

“If you never see that role model during your training who is a general neurologist, who can see the vast majority of all neurology patients, why would you think you could do that when you graduate?” Dr. Markowski said.
 

A legislative solution

While expanding neurology instruction in medical school and increasing exposure to general neurology rotations in residency could help, the clearest path to increasing the number of neurologists in the United States is to lift the decades-old residency cap.

The Resident Physician Shortage Reduction Act of 2023 would do just that, adding 14,000 new medical residency positions over 7 years. The bill has bipartisan support, with hundreds of cosponsors from both sides of the aisle. Nearly 100 professional societies and medical and hospital groups have submitted testimony in support.

Similar legislation has been introduced at least six times since 2007 and no bill has ever made it out of committee. It’s unclear whether the latest version will meet a similar fate, but its expected price tag of $10-$12 billion over 10 years is a large hurdle to overcome.

Congress did take a small step in 2021 to increase residency spots, with legislation that allocated funding for 1,000 new positions over 5 years. Congress added another 200 spots to that total in a bill passed last year.

Critics say the slots are tied up in Medicare red tape and it’s a far cry from the 14,000 new positions experts say are needed to address the physician shortage.

“We absolutely want the larger bill, and we think that’s the way to go, but we’ll continue to work and try to add as many positions as we can,” said Leonard Marquez, senior director of government relations and legislative advocacy for AAMC.

Congress is also considering legislation to speed up prior reauthorization for Medicare, something the Centers for Medicare & Medicaid Services is also seeking to do through rule changes. Nearly 30 state legislatures are debating similar legislation at the state level. And another bill in Congress would expand the Conrad State 30 program, which allows states to request J-1 visa waivers for international physicians to work in underserved areas.

“The solutions to this problem are multifactorial, and the answer that worked 10 years ago won’t be the right answer today, and the answer that works today won’t be the right answer 10 years from now,” Dr. Vidic said. “All we have to do is keep making changes, keep evolving, and the playing field continually changes.”

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

TOPLINE:

Young adults who simultaneously use alcohol and marijuana (SAM) consume more drinks, are high for more hours in the day, and report more negative alcohol-related consequences.

METHODOLOGY:

• The 2-year study included 409 people aged 18-25 years with a history of simultaneous alcohol and marijuana use (50.9% were women; 48.2% were non-Hispanic White; 48.9% were college students).
• Participants completed daily online surveys about substance use and negative substance-related consequences for 14 continuous days every 4 months.

TAKEAWAY:

• Alcohol use was reported on 36.1% of survey days, marijuana use on 28.0%, and alcohol and marijuana use on 15.0%.
• Negative substance-related consequences were reported on 28.0% of drinking days and 56.4% of marijuana days.
• SAM use was reported in 81.7% of alcohol users and 86.6% of marijuana users.
• On SAM use days, participants consumed an average of 37% more drinks, with 43% more negative alcohol consequences; were high for 10% more hours; and were more likely to feel clumsy or dizzy, compared with non-SAM use days.

IN PRACTICE:

“This finding should be integrated into psychoeducational programs highlighting the risk of combining alcohol and marijuana,” the authors write. “A more nuanced harm-reduction [approach] could also encourage young adults to closely monitor and limit the amount of each substance being used if they choose to combine substances.”

SOURCE:

The study was conducted by Anne M. Fairlie, PhD, University of Washington, Seattle, and colleagues, and funded by the National Institute on Alcohol Abuse and Alcoholism. The study was published online in Alcohol Clinical and Experimental Research.

LIMITATIONS:

Study participants were recruited based on their substance use and lived in a region where recreational marijuana is legal, so the findings may not be generalizable to other populations. Substance use and consequences were self-reported and subject to bias.

DISCLOSURES:

The authors have reported no relevant financial relationships.

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

TOPLINE:

Young adults who simultaneously use alcohol and marijuana (SAM) consume more drinks, are high for more hours in the day, and report more negative alcohol-related consequences.

METHODOLOGY:

• The 2-year study included 409 people aged 18-25 years with a history of simultaneous alcohol and marijuana use (50.9% were women; 48.2% were non-Hispanic White; 48.9% were college students).
• Participants completed daily online surveys about substance use and negative substance-related consequences for 14 continuous days every 4 months.

TAKEAWAY:

• Alcohol use was reported on 36.1% of survey days, marijuana use on 28.0%, and alcohol and marijuana use on 15.0%.
• Negative substance-related consequences were reported on 28.0% of drinking days and 56.4% of marijuana days.
• SAM use was reported in 81.7% of alcohol users and 86.6% of marijuana users.
• On SAM use days, participants consumed an average of 37% more drinks, with 43% more negative alcohol consequences; were high for 10% more hours; and were more likely to feel clumsy or dizzy, compared with non-SAM use days.

IN PRACTICE:

“This finding should be integrated into psychoeducational programs highlighting the risk of combining alcohol and marijuana,” the authors write. “A more nuanced harm-reduction [approach] could also encourage young adults to closely monitor and limit the amount of each substance being used if they choose to combine substances.”

SOURCE:

The study was conducted by Anne M. Fairlie, PhD, University of Washington, Seattle, and colleagues, and funded by the National Institute on Alcohol Abuse and Alcoholism. The study was published online in Alcohol Clinical and Experimental Research.

LIMITATIONS:

Study participants were recruited based on their substance use and lived in a region where recreational marijuana is legal, so the findings may not be generalizable to other populations. Substance use and consequences were self-reported and subject to bias.

DISCLOSURES:

The authors have reported no relevant financial relationships.

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

TOPLINE:

Young adults who simultaneously use alcohol and marijuana (SAM) consume more drinks, are high for more hours in the day, and report more negative alcohol-related consequences.

METHODOLOGY:

• The 2-year study included 409 people aged 18-25 years with a history of simultaneous alcohol and marijuana use (50.9% were women; 48.2% were non-Hispanic White; 48.9% were college students).
• Participants completed daily online surveys about substance use and negative substance-related consequences for 14 continuous days every 4 months.

TAKEAWAY:

• Alcohol use was reported on 36.1% of survey days, marijuana use on 28.0%, and alcohol and marijuana use on 15.0%.
• Negative substance-related consequences were reported on 28.0% of drinking days and 56.4% of marijuana days.
• SAM use was reported in 81.7% of alcohol users and 86.6% of marijuana users.
• On SAM use days, participants consumed an average of 37% more drinks, with 43% more negative alcohol consequences; were high for 10% more hours; and were more likely to feel clumsy or dizzy, compared with non-SAM use days.

IN PRACTICE:

“This finding should be integrated into psychoeducational programs highlighting the risk of combining alcohol and marijuana,” the authors write. “A more nuanced harm-reduction [approach] could also encourage young adults to closely monitor and limit the amount of each substance being used if they choose to combine substances.”

SOURCE:

The study was conducted by Anne M. Fairlie, PhD, University of Washington, Seattle, and colleagues, and funded by the National Institute on Alcohol Abuse and Alcoholism. The study was published online in Alcohol Clinical and Experimental Research.

LIMITATIONS:

Study participants were recruited based on their substance use and lived in a region where recreational marijuana is legal, so the findings may not be generalizable to other populations. Substance use and consequences were self-reported and subject to bias.

DISCLOSURES:

The authors have reported no relevant financial relationships.

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

More than 10 hours a day of sedentary behavior significantly increases the risk of dementia in older adults, a new study suggests.

The study of nearly 50,000 adults in the UK Biobank shows that dementia risk increased 8% with 10 hours of sedentary time and 63% with 12 hours. That’s particularly concerning because Americans spend an average of 9.5 hours a day sitting.

Sleep wasn’t factored into the sedentary time and how someone accumulated the 10 hours – either in one continuous block or broken up throughout the day – was irrelevant.

“Our analysis cannot determine whether there is a causal link, so prescriptive conclusions are not really possible; however. I think it is very reasonable to conclude that sitting less and moving more may help reduce risk of dementia,” lead investigator David Raichlen, PhD, professor of biological sciences and anthropology, University of Southern California, Los Angeles, said in an interview.

The findings were published online in JAMA.
 

A surprising find?

The study is a retrospective analysis of prospectively collected data from the UK Biobank of 49,841 adults aged 60 years or older who wore an accelerometer on their wrists 24 hours a day for a week. Participants had no history of dementia when they wore the movement monitoring device.

Investigators used machine-based learning to determine sedentary time based on readings from the accelerometers. Sleep was not included as sedentary behavior.

Over a mean follow-up of 6.72 years, 414 participants were diagnosed with dementia.

Investigators found that dementia risk rises by 8% at 10 hours a day (adjusted hazard ratio, 1.08; P < .001) and 63% at 12 hours a day (aHR, 1.63; P < .001), compared with 9.27 hours a day. Those who logged 15 hours of sedentary behavior a day had more than triple the dementia risk (aHR, 3.21; P < .001).

Although previous studies had found that breaking up sedentary periods with short bursts of activity help offset some negative health effects of sitting, that wasn’t the case here. Dementia risk was elevated whether participants were sedentary for 10 uninterrupted hours or multiple sedentary periods that totaled 10 hours over the whole day.

“This was surprising,” Dr. Raichlen said. “We expected to find that patterns of sedentary behavior would play a role in risk of dementia, but once you take into account the daily volume of time spent sedentary, how you get there doesn’t seem to matter as much.”

The study did not examine how participants spent sedentary time, but an earlier study by Dr. Raichlen found that watching TV was associated with a greater risk of dementia in older adults, compared with working on a computer.
 

More research welcome

Dr. Raichlen noted that the number of dementia cases in the study is low and that the view of sedentary behavior is based on 1 week of accelerometer readings. A longitudinal study is needed to determine if the findings last over a longer time period.

In a comment, Claire Sexton, DPhil, senior director of scientific programs and outreach for the Alzheimer’s Association, says that earlier studies reported an association between sedentary time and dementia, so these results aren’t “particularly surprising.”

“However, reports that did not find an association have also been published, so additional research on possible associations is welcome,” she said.

It’s also important to note that this observational study doesn’t establish a causal relationship between inactivity and cognitive function, which Dr. Sexton said means the influence of other dementia risk factors that are also exacerbated by sedentary behavior can’t be ruled out.

“Although results remained significant after adjusting for several of these factors, further research is required to better understand the various elements that may influence the observed relationship,” noted Dr. Sexton, who was not part of the study. “Reverse causality – that changes in the brain related to dementia are causing the sedentary behavior – cannot be ruled out.”

The study was funded by the National Institutes of Health, the state of Arizona, the Arizona Department of Health Services, and the McKnight Brain Research Foundation. Dr. Raichlen and Dr. Sexton report no relevant financial relationships.

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

More than 10 hours a day of sedentary behavior significantly increases the risk of dementia in older adults, a new study suggests.

The study of nearly 50,000 adults in the UK Biobank shows that dementia risk increased 8% with 10 hours of sedentary time and 63% with 12 hours. That’s particularly concerning because Americans spend an average of 9.5 hours a day sitting.

Sleep wasn’t factored into the sedentary time and how someone accumulated the 10 hours – either in one continuous block or broken up throughout the day – was irrelevant.

“Our analysis cannot determine whether there is a causal link, so prescriptive conclusions are not really possible; however. I think it is very reasonable to conclude that sitting less and moving more may help reduce risk of dementia,” lead investigator David Raichlen, PhD, professor of biological sciences and anthropology, University of Southern California, Los Angeles, said in an interview.

The findings were published online in JAMA.
 

A surprising find?

The study is a retrospective analysis of prospectively collected data from the UK Biobank of 49,841 adults aged 60 years or older who wore an accelerometer on their wrists 24 hours a day for a week. Participants had no history of dementia when they wore the movement monitoring device.

Investigators used machine-based learning to determine sedentary time based on readings from the accelerometers. Sleep was not included as sedentary behavior.

Over a mean follow-up of 6.72 years, 414 participants were diagnosed with dementia.

Investigators found that dementia risk rises by 8% at 10 hours a day (adjusted hazard ratio, 1.08; P < .001) and 63% at 12 hours a day (aHR, 1.63; P < .001), compared with 9.27 hours a day. Those who logged 15 hours of sedentary behavior a day had more than triple the dementia risk (aHR, 3.21; P < .001).

Although previous studies had found that breaking up sedentary periods with short bursts of activity help offset some negative health effects of sitting, that wasn’t the case here. Dementia risk was elevated whether participants were sedentary for 10 uninterrupted hours or multiple sedentary periods that totaled 10 hours over the whole day.

“This was surprising,” Dr. Raichlen said. “We expected to find that patterns of sedentary behavior would play a role in risk of dementia, but once you take into account the daily volume of time spent sedentary, how you get there doesn’t seem to matter as much.”

The study did not examine how participants spent sedentary time, but an earlier study by Dr. Raichlen found that watching TV was associated with a greater risk of dementia in older adults, compared with working on a computer.
 

More research welcome

Dr. Raichlen noted that the number of dementia cases in the study is low and that the view of sedentary behavior is based on 1 week of accelerometer readings. A longitudinal study is needed to determine if the findings last over a longer time period.

In a comment, Claire Sexton, DPhil, senior director of scientific programs and outreach for the Alzheimer’s Association, says that earlier studies reported an association between sedentary time and dementia, so these results aren’t “particularly surprising.”

“However, reports that did not find an association have also been published, so additional research on possible associations is welcome,” she said.

It’s also important to note that this observational study doesn’t establish a causal relationship between inactivity and cognitive function, which Dr. Sexton said means the influence of other dementia risk factors that are also exacerbated by sedentary behavior can’t be ruled out.

“Although results remained significant after adjusting for several of these factors, further research is required to better understand the various elements that may influence the observed relationship,” noted Dr. Sexton, who was not part of the study. “Reverse causality – that changes in the brain related to dementia are causing the sedentary behavior – cannot be ruled out.”

The study was funded by the National Institutes of Health, the state of Arizona, the Arizona Department of Health Services, and the McKnight Brain Research Foundation. Dr. Raichlen and Dr. Sexton report no relevant financial relationships.

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

More than 10 hours a day of sedentary behavior significantly increases the risk of dementia in older adults, a new study suggests.

The study of nearly 50,000 adults in the UK Biobank shows that dementia risk increased 8% with 10 hours of sedentary time and 63% with 12 hours. That’s particularly concerning because Americans spend an average of 9.5 hours a day sitting.

Sleep wasn’t factored into the sedentary time and how someone accumulated the 10 hours – either in one continuous block or broken up throughout the day – was irrelevant.

“Our analysis cannot determine whether there is a causal link, so prescriptive conclusions are not really possible; however. I think it is very reasonable to conclude that sitting less and moving more may help reduce risk of dementia,” lead investigator David Raichlen, PhD, professor of biological sciences and anthropology, University of Southern California, Los Angeles, said in an interview.

The findings were published online in JAMA.
 

A surprising find?

The study is a retrospective analysis of prospectively collected data from the UK Biobank of 49,841 adults aged 60 years or older who wore an accelerometer on their wrists 24 hours a day for a week. Participants had no history of dementia when they wore the movement monitoring device.

Investigators used machine-based learning to determine sedentary time based on readings from the accelerometers. Sleep was not included as sedentary behavior.

Over a mean follow-up of 6.72 years, 414 participants were diagnosed with dementia.

Investigators found that dementia risk rises by 8% at 10 hours a day (adjusted hazard ratio, 1.08; P < .001) and 63% at 12 hours a day (aHR, 1.63; P < .001), compared with 9.27 hours a day. Those who logged 15 hours of sedentary behavior a day had more than triple the dementia risk (aHR, 3.21; P < .001).

Although previous studies had found that breaking up sedentary periods with short bursts of activity help offset some negative health effects of sitting, that wasn’t the case here. Dementia risk was elevated whether participants were sedentary for 10 uninterrupted hours or multiple sedentary periods that totaled 10 hours over the whole day.

“This was surprising,” Dr. Raichlen said. “We expected to find that patterns of sedentary behavior would play a role in risk of dementia, but once you take into account the daily volume of time spent sedentary, how you get there doesn’t seem to matter as much.”

The study did not examine how participants spent sedentary time, but an earlier study by Dr. Raichlen found that watching TV was associated with a greater risk of dementia in older adults, compared with working on a computer.
 

More research welcome

Dr. Raichlen noted that the number of dementia cases in the study is low and that the view of sedentary behavior is based on 1 week of accelerometer readings. A longitudinal study is needed to determine if the findings last over a longer time period.

In a comment, Claire Sexton, DPhil, senior director of scientific programs and outreach for the Alzheimer’s Association, says that earlier studies reported an association between sedentary time and dementia, so these results aren’t “particularly surprising.”

“However, reports that did not find an association have also been published, so additional research on possible associations is welcome,” she said.

It’s also important to note that this observational study doesn’t establish a causal relationship between inactivity and cognitive function, which Dr. Sexton said means the influence of other dementia risk factors that are also exacerbated by sedentary behavior can’t be ruled out.

“Although results remained significant after adjusting for several of these factors, further research is required to better understand the various elements that may influence the observed relationship,” noted Dr. Sexton, who was not part of the study. “Reverse causality – that changes in the brain related to dementia are causing the sedentary behavior – cannot be ruled out.”

The study was funded by the National Institutes of Health, the state of Arizona, the Arizona Department of Health Services, and the McKnight Brain Research Foundation. Dr. Raichlen and Dr. Sexton report no relevant financial relationships.

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

A single dose of an experimental psilocybin drug offered significant sustained improvement in symptoms and disability in patients with major depressive disorder (MDD) over a 6-week period, results of a study suggest.

The randomized, phase 2 trial was conducted at 11 sites across the United States and is the latest to demonstrate the psychedelic drug’s potential as a treatment for depression.

The project was funded by Usona Institute, a nonprofit medical research organization based in Madison, Wisc. The institute issued a press statement, but researchers did not comment further on the findings.

“As the largest and most rigorous study conducted across a wide spectrum of individuals with major depressive disorder, the results show promise for all people struggling with this condition,” lead author Charles Raison, MD, director of clinical and translational research at Usona, said in the statement. 

The 34 coauthors on the study are affiliated with public universities, research centers, and private companies. Eight of the investigators are identified as employees of Usona Institute.

Declining further comment, an institute spokesperson told this news organization that, “Usona has chosen the approach of no interviews, and this applies for all coauthors.”

The findings were published online in JAMA.
 

Largest study to date

Usona’s investigational psilocybin drug has been granted a breakthrough designation by the Food and Drug Administration, a process designed to speed drug development and review.

Previous smaller studies have suggested a rapid antidepressant response with psilocybin, but they have been small, unblinded, and have had short duration of follow-up, they write. This randomized, double-blind, phase 2 clinical trial is the largest study of psilocybin for depression to date, the researchers note.

It included 104 adults aged 21-65 years with MDD who had a current depressive episode of at least 60 days and a Montgomery-Åsberg Depression Rating Scale (MADRS) total score of 28 or more at baseline.

Participants had to be free of psychedelic drugs for at least 5 years, have had no active suicidal ideation or suicidal behavior in the prior 12 months, no personal or first-degree family history of psychosis or mania, and no history of moderate/severe alcohol or drug use disorder.

Before the study, participants had a 7- to 35-day screening period for psychiatric medication tapering, underwent baseline assessments, and received 6-8 hours of preparation with two facilitators who would be with them during dosing.

Dosing occurred within 7 days of baseline assessments. During the 6- to 8-hour session, participants received either a single 25-mg oral dose of psilocybin or 100-mg dose of niacin. One participant randomly assigned to receive psilocybin received the incorrect treatment, resulting in 50 participants receiving psilocybin and 54 receiving niacin.

Participants returned the next day, the next week, and then every 2 weeks for assessments, for a follow-up of 6 weeks.
 

Psychosocial support

Participants who received psilocybin reported significantly greater improvements in MDD symptoms, compared with those who received niacin. MADRS scores – a scale from 0 to 60 where higher scores indicate more severe depression – showed greater reductions with treatment vs. placebo at 8 days (mean difference, −12.0; 95% confidence interval, −16.6 to −7.4; P < .001), and at day 43 (mean difference, −12.3; 95% CI, −17.5 to −7.2; P < .001).

More participants receiving psilocybin had sustained depressive symptom response (42% vs. 11%; P = .002) and more improvement in the Sheehan Disability Scale score, which measures functional disability, 43 days after treatment (P < .001).

The effects persisted through the end of the study, although the differences between groups were no longer significant by week 6.

Fonzo_Greg_TX_web.jpg

“This is another exciting piece of evidence that adds to the current literature regarding the potential efficacy of psilocybin for the treatment of mental health conditions, particularly depression,” said Greg Fonzo, MD, codirector of the Center for Psychedelic Research and Therapy at the University of Texas at Austin, who commented on the findings.

Significantly more people in the psilocybin group reported at least one treatment-related adverse event (AE, 82% vs. 44%), although most were mild to moderate. Headache and nausea were the most common side effects and most resolved within 1 day of dosing.

While those numbers are high, Dr. Fonzo said they’re not out of line with AEs reported in other studies.

“Particularly with the types of adverse events reported here, like headache and nausea, those are things you would typically expect to see in this treatment,” said Dr. Fonzo, who was not part of the research.

“But it is high, and it underscores that this is not a treatment without certain risks, even though it was good that they were primarily mild in severity,” he added.
 

A ‘stepping stone’ to FDA approval?

The use of tools to measure disability in addition to symptoms of depression severity is a strength of the study, Dr. Fonzo added. The use of an active comparator and the 6-week follow-up also offer something new over previous studies.

Despite the longer follow up, questions remain about the durability of response, something only a longer study could answer, Dr. Fonzo said. The small and homogeneous sample-size are also a concern. Nearly 90% of participants were White, and more than half had an income of $75,000 a year or higher.

“It’s another stepping stone in the process to FDA approval, but the next step in that process would be much larger phase 3 trials that would have much larger samples, a longer follow-up, and hopefully have a more inclusive swath of the population,” Dr. Fonzo said.

But perhaps one of the most significant limitations is the use of niacin as an active comparator, said Caleb Alexander, MD, codirector of the Center for Drug Safety and Effectiveness at Johns Hopkins University in Baltimore.

Alexander_Caleb_MD_web.jpg

The use of an agent that doesn’t produce effects similar to those expected from a psychedelic introduced the potential for functional unblinding, Dr. Alexander said. Investigators did not ask participants to guess whether they received psilocybin or niacin, so the quality of the blinding was not assessed in the study.

“We’d like to see the use of [an] active comparator that might have a chance of obscuring to people as to whether they’ve been randomized to the treatment arm or control arm,” said Dr. Alexander, who wasn’t involved in the study. “Why not use a benzodiazepine or another drug that produces a transient euphoria that would better obscure whether or not people were receiving the psilocybin?”

The authors of an accompanying editorial shared these concerns, also noting that the study included “a significant number of patients who did not respond to therapy.”

“It is important to analyze and understand adverse outcomes in psychedelic trials and conduct longitudinal studies to determine how sustained the effects will be and what may initiate a recrudescence of symptoms,” write Rachel Yehuda, PhD, and Amy Lehrner, PhD, both of the Peters VA Medical Center and Icahn School of Medicine at Mount Sinai, New York.

Yehuda_Rachel_NY_web.jpg

“Future studies will help identify who is most likely to benefit from psychedelics, whether booster or repeated treatment is safe and beneficial, and what the optimal dose and therapeutic frameworks are.”

A long-term follow-up of the current trial was terminated last year because of low enrollment. The spokesperson with Usona Institute did not respond to questions about that study, and the institute’s statement only added that preparations are underway to launch another study that “will provide additional safety and efficacy data to support submission of a new drug application to the FDA.”

Usona published its manufacturing process that it used to synthesize psilocybin in an open-access journal and signed a statement on “open science and open praxis” with psilocybin and similar substances, which appears on their website. That statement was signed by 31 research and service organizations around the world and nearly 150 scientists, scholars, and practitioners.

The study was funded by Usona Institute. Dr. Raison reported receiving personal fees from Usona Institute and grants to Usona Institute from Dr. Bronner’s All-One, Fournier Family Foundation, Good Ventures, Steven and Alexandra Cohen Foundation, Tiny Blue Dot Foundation, Turnbull Family Foundation, and William A. Linton during the conduct of the study; and personal fees from Novartis, Sage/Biogen, Emory Healthcare, and Vail Health outside the submitted work. Dr. Fonzo and Dr. Alexander report no relevant financial relationships. Dr. Yehuda reports receiving nonfinancial support from the Multidisciplinary Association for Psychedelic Studies Public Benefit (MAPS PBC) and grants from COMPASS Pathways. Dr. Lehrner is an investigator on trials sponsored by MAPS PBC and COMPASS Pathways.

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

A single dose of an experimental psilocybin drug offered significant sustained improvement in symptoms and disability in patients with major depressive disorder (MDD) over a 6-week period, results of a study suggest.

The randomized, phase 2 trial was conducted at 11 sites across the United States and is the latest to demonstrate the psychedelic drug’s potential as a treatment for depression.

The project was funded by Usona Institute, a nonprofit medical research organization based in Madison, Wisc. The institute issued a press statement, but researchers did not comment further on the findings.

“As the largest and most rigorous study conducted across a wide spectrum of individuals with major depressive disorder, the results show promise for all people struggling with this condition,” lead author Charles Raison, MD, director of clinical and translational research at Usona, said in the statement. 

The 34 coauthors on the study are affiliated with public universities, research centers, and private companies. Eight of the investigators are identified as employees of Usona Institute.

Declining further comment, an institute spokesperson told this news organization that, “Usona has chosen the approach of no interviews, and this applies for all coauthors.”

The findings were published online in JAMA.
 

Largest study to date

Usona’s investigational psilocybin drug has been granted a breakthrough designation by the Food and Drug Administration, a process designed to speed drug development and review.

Previous smaller studies have suggested a rapid antidepressant response with psilocybin, but they have been small, unblinded, and have had short duration of follow-up, they write. This randomized, double-blind, phase 2 clinical trial is the largest study of psilocybin for depression to date, the researchers note.

It included 104 adults aged 21-65 years with MDD who had a current depressive episode of at least 60 days and a Montgomery-Åsberg Depression Rating Scale (MADRS) total score of 28 or more at baseline.

Participants had to be free of psychedelic drugs for at least 5 years, have had no active suicidal ideation or suicidal behavior in the prior 12 months, no personal or first-degree family history of psychosis or mania, and no history of moderate/severe alcohol or drug use disorder.

Before the study, participants had a 7- to 35-day screening period for psychiatric medication tapering, underwent baseline assessments, and received 6-8 hours of preparation with two facilitators who would be with them during dosing.

Dosing occurred within 7 days of baseline assessments. During the 6- to 8-hour session, participants received either a single 25-mg oral dose of psilocybin or 100-mg dose of niacin. One participant randomly assigned to receive psilocybin received the incorrect treatment, resulting in 50 participants receiving psilocybin and 54 receiving niacin.

Participants returned the next day, the next week, and then every 2 weeks for assessments, for a follow-up of 6 weeks.
 

Psychosocial support

Participants who received psilocybin reported significantly greater improvements in MDD symptoms, compared with those who received niacin. MADRS scores – a scale from 0 to 60 where higher scores indicate more severe depression – showed greater reductions with treatment vs. placebo at 8 days (mean difference, −12.0; 95% confidence interval, −16.6 to −7.4; P < .001), and at day 43 (mean difference, −12.3; 95% CI, −17.5 to −7.2; P < .001).

More participants receiving psilocybin had sustained depressive symptom response (42% vs. 11%; P = .002) and more improvement in the Sheehan Disability Scale score, which measures functional disability, 43 days after treatment (P < .001).

The effects persisted through the end of the study, although the differences between groups were no longer significant by week 6.

Fonzo_Greg_TX_web.jpg

“This is another exciting piece of evidence that adds to the current literature regarding the potential efficacy of psilocybin for the treatment of mental health conditions, particularly depression,” said Greg Fonzo, MD, codirector of the Center for Psychedelic Research and Therapy at the University of Texas at Austin, who commented on the findings.

Significantly more people in the psilocybin group reported at least one treatment-related adverse event (AE, 82% vs. 44%), although most were mild to moderate. Headache and nausea were the most common side effects and most resolved within 1 day of dosing.

While those numbers are high, Dr. Fonzo said they’re not out of line with AEs reported in other studies.

“Particularly with the types of adverse events reported here, like headache and nausea, those are things you would typically expect to see in this treatment,” said Dr. Fonzo, who was not part of the research.

“But it is high, and it underscores that this is not a treatment without certain risks, even though it was good that they were primarily mild in severity,” he added.
 

A ‘stepping stone’ to FDA approval?

The use of tools to measure disability in addition to symptoms of depression severity is a strength of the study, Dr. Fonzo added. The use of an active comparator and the 6-week follow-up also offer something new over previous studies.

Despite the longer follow up, questions remain about the durability of response, something only a longer study could answer, Dr. Fonzo said. The small and homogeneous sample-size are also a concern. Nearly 90% of participants were White, and more than half had an income of $75,000 a year or higher.

“It’s another stepping stone in the process to FDA approval, but the next step in that process would be much larger phase 3 trials that would have much larger samples, a longer follow-up, and hopefully have a more inclusive swath of the population,” Dr. Fonzo said.

But perhaps one of the most significant limitations is the use of niacin as an active comparator, said Caleb Alexander, MD, codirector of the Center for Drug Safety and Effectiveness at Johns Hopkins University in Baltimore.

Alexander_Caleb_MD_web.jpg

The use of an agent that doesn’t produce effects similar to those expected from a psychedelic introduced the potential for functional unblinding, Dr. Alexander said. Investigators did not ask participants to guess whether they received psilocybin or niacin, so the quality of the blinding was not assessed in the study.

“We’d like to see the use of [an] active comparator that might have a chance of obscuring to people as to whether they’ve been randomized to the treatment arm or control arm,” said Dr. Alexander, who wasn’t involved in the study. “Why not use a benzodiazepine or another drug that produces a transient euphoria that would better obscure whether or not people were receiving the psilocybin?”

The authors of an accompanying editorial shared these concerns, also noting that the study included “a significant number of patients who did not respond to therapy.”

“It is important to analyze and understand adverse outcomes in psychedelic trials and conduct longitudinal studies to determine how sustained the effects will be and what may initiate a recrudescence of symptoms,” write Rachel Yehuda, PhD, and Amy Lehrner, PhD, both of the Peters VA Medical Center and Icahn School of Medicine at Mount Sinai, New York.

Yehuda_Rachel_NY_web.jpg

“Future studies will help identify who is most likely to benefit from psychedelics, whether booster or repeated treatment is safe and beneficial, and what the optimal dose and therapeutic frameworks are.”

A long-term follow-up of the current trial was terminated last year because of low enrollment. The spokesperson with Usona Institute did not respond to questions about that study, and the institute’s statement only added that preparations are underway to launch another study that “will provide additional safety and efficacy data to support submission of a new drug application to the FDA.”

Usona published its manufacturing process that it used to synthesize psilocybin in an open-access journal and signed a statement on “open science and open praxis” with psilocybin and similar substances, which appears on their website. That statement was signed by 31 research and service organizations around the world and nearly 150 scientists, scholars, and practitioners.

The study was funded by Usona Institute. Dr. Raison reported receiving personal fees from Usona Institute and grants to Usona Institute from Dr. Bronner’s All-One, Fournier Family Foundation, Good Ventures, Steven and Alexandra Cohen Foundation, Tiny Blue Dot Foundation, Turnbull Family Foundation, and William A. Linton during the conduct of the study; and personal fees from Novartis, Sage/Biogen, Emory Healthcare, and Vail Health outside the submitted work. Dr. Fonzo and Dr. Alexander report no relevant financial relationships. Dr. Yehuda reports receiving nonfinancial support from the Multidisciplinary Association for Psychedelic Studies Public Benefit (MAPS PBC) and grants from COMPASS Pathways. Dr. Lehrner is an investigator on trials sponsored by MAPS PBC and COMPASS Pathways.

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

A single dose of an experimental psilocybin drug offered significant sustained improvement in symptoms and disability in patients with major depressive disorder (MDD) over a 6-week period, results of a study suggest.

The randomized, phase 2 trial was conducted at 11 sites across the United States and is the latest to demonstrate the psychedelic drug’s potential as a treatment for depression.

The project was funded by Usona Institute, a nonprofit medical research organization based in Madison, Wisc. The institute issued a press statement, but researchers did not comment further on the findings.

“As the largest and most rigorous study conducted across a wide spectrum of individuals with major depressive disorder, the results show promise for all people struggling with this condition,” lead author Charles Raison, MD, director of clinical and translational research at Usona, said in the statement. 

The 34 coauthors on the study are affiliated with public universities, research centers, and private companies. Eight of the investigators are identified as employees of Usona Institute.

Declining further comment, an institute spokesperson told this news organization that, “Usona has chosen the approach of no interviews, and this applies for all coauthors.”

The findings were published online in JAMA.
 

Largest study to date

Usona’s investigational psilocybin drug has been granted a breakthrough designation by the Food and Drug Administration, a process designed to speed drug development and review.

Previous smaller studies have suggested a rapid antidepressant response with psilocybin, but they have been small, unblinded, and have had short duration of follow-up, they write. This randomized, double-blind, phase 2 clinical trial is the largest study of psilocybin for depression to date, the researchers note.

It included 104 adults aged 21-65 years with MDD who had a current depressive episode of at least 60 days and a Montgomery-Åsberg Depression Rating Scale (MADRS) total score of 28 or more at baseline.

Participants had to be free of psychedelic drugs for at least 5 years, have had no active suicidal ideation or suicidal behavior in the prior 12 months, no personal or first-degree family history of psychosis or mania, and no history of moderate/severe alcohol or drug use disorder.

Before the study, participants had a 7- to 35-day screening period for psychiatric medication tapering, underwent baseline assessments, and received 6-8 hours of preparation with two facilitators who would be with them during dosing.

Dosing occurred within 7 days of baseline assessments. During the 6- to 8-hour session, participants received either a single 25-mg oral dose of psilocybin or 100-mg dose of niacin. One participant randomly assigned to receive psilocybin received the incorrect treatment, resulting in 50 participants receiving psilocybin and 54 receiving niacin.

Participants returned the next day, the next week, and then every 2 weeks for assessments, for a follow-up of 6 weeks.
 

Psychosocial support

Participants who received psilocybin reported significantly greater improvements in MDD symptoms, compared with those who received niacin. MADRS scores – a scale from 0 to 60 where higher scores indicate more severe depression – showed greater reductions with treatment vs. placebo at 8 days (mean difference, −12.0; 95% confidence interval, −16.6 to −7.4; P < .001), and at day 43 (mean difference, −12.3; 95% CI, −17.5 to −7.2; P < .001).

More participants receiving psilocybin had sustained depressive symptom response (42% vs. 11%; P = .002) and more improvement in the Sheehan Disability Scale score, which measures functional disability, 43 days after treatment (P < .001).

The effects persisted through the end of the study, although the differences between groups were no longer significant by week 6.

Fonzo_Greg_TX_web.jpg

“This is another exciting piece of evidence that adds to the current literature regarding the potential efficacy of psilocybin for the treatment of mental health conditions, particularly depression,” said Greg Fonzo, MD, codirector of the Center for Psychedelic Research and Therapy at the University of Texas at Austin, who commented on the findings.

Significantly more people in the psilocybin group reported at least one treatment-related adverse event (AE, 82% vs. 44%), although most were mild to moderate. Headache and nausea were the most common side effects and most resolved within 1 day of dosing.

While those numbers are high, Dr. Fonzo said they’re not out of line with AEs reported in other studies.

“Particularly with the types of adverse events reported here, like headache and nausea, those are things you would typically expect to see in this treatment,” said Dr. Fonzo, who was not part of the research.

“But it is high, and it underscores that this is not a treatment without certain risks, even though it was good that they were primarily mild in severity,” he added.
 

A ‘stepping stone’ to FDA approval?

The use of tools to measure disability in addition to symptoms of depression severity is a strength of the study, Dr. Fonzo added. The use of an active comparator and the 6-week follow-up also offer something new over previous studies.

Despite the longer follow up, questions remain about the durability of response, something only a longer study could answer, Dr. Fonzo said. The small and homogeneous sample-size are also a concern. Nearly 90% of participants were White, and more than half had an income of $75,000 a year or higher.

“It’s another stepping stone in the process to FDA approval, but the next step in that process would be much larger phase 3 trials that would have much larger samples, a longer follow-up, and hopefully have a more inclusive swath of the population,” Dr. Fonzo said.

But perhaps one of the most significant limitations is the use of niacin as an active comparator, said Caleb Alexander, MD, codirector of the Center for Drug Safety and Effectiveness at Johns Hopkins University in Baltimore.

Alexander_Caleb_MD_web.jpg

The use of an agent that doesn’t produce effects similar to those expected from a psychedelic introduced the potential for functional unblinding, Dr. Alexander said. Investigators did not ask participants to guess whether they received psilocybin or niacin, so the quality of the blinding was not assessed in the study.

“We’d like to see the use of [an] active comparator that might have a chance of obscuring to people as to whether they’ve been randomized to the treatment arm or control arm,” said Dr. Alexander, who wasn’t involved in the study. “Why not use a benzodiazepine or another drug that produces a transient euphoria that would better obscure whether or not people were receiving the psilocybin?”

The authors of an accompanying editorial shared these concerns, also noting that the study included “a significant number of patients who did not respond to therapy.”

“It is important to analyze and understand adverse outcomes in psychedelic trials and conduct longitudinal studies to determine how sustained the effects will be and what may initiate a recrudescence of symptoms,” write Rachel Yehuda, PhD, and Amy Lehrner, PhD, both of the Peters VA Medical Center and Icahn School of Medicine at Mount Sinai, New York.

Yehuda_Rachel_NY_web.jpg

“Future studies will help identify who is most likely to benefit from psychedelics, whether booster or repeated treatment is safe and beneficial, and what the optimal dose and therapeutic frameworks are.”

A long-term follow-up of the current trial was terminated last year because of low enrollment. The spokesperson with Usona Institute did not respond to questions about that study, and the institute’s statement only added that preparations are underway to launch another study that “will provide additional safety and efficacy data to support submission of a new drug application to the FDA.”

Usona published its manufacturing process that it used to synthesize psilocybin in an open-access journal and signed a statement on “open science and open praxis” with psilocybin and similar substances, which appears on their website. That statement was signed by 31 research and service organizations around the world and nearly 150 scientists, scholars, and practitioners.

The study was funded by Usona Institute. Dr. Raison reported receiving personal fees from Usona Institute and grants to Usona Institute from Dr. Bronner’s All-One, Fournier Family Foundation, Good Ventures, Steven and Alexandra Cohen Foundation, Tiny Blue Dot Foundation, Turnbull Family Foundation, and William A. Linton during the conduct of the study; and personal fees from Novartis, Sage/Biogen, Emory Healthcare, and Vail Health outside the submitted work. Dr. Fonzo and Dr. Alexander report no relevant financial relationships. Dr. Yehuda reports receiving nonfinancial support from the Multidisciplinary Association for Psychedelic Studies Public Benefit (MAPS PBC) and grants from COMPASS Pathways. Dr. Lehrner is an investigator on trials sponsored by MAPS PBC and COMPASS Pathways.

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

The largest study to date of chronic traumatic encephalopathy (CTE) in young athletes shows that 41% had the neurodegenerative disease, caused by repetitive head impacts (RHIs).

Analysis of brain tissue from athletes who were exposed to RHIs and died before the age of 30 revealed neuropathological evidence of shrinkage of the brain and microscopic changes that indicate a breach of the blood-brain barrier. The case series also identified the first known American female athlete with CTE.

Nearly all of those with CTE had a mild form of the disease and 71% played only at the amateur level in youth, high school, or college sports.

“A lot of people think CTE is a result of high-level, professional play such as football, ice hockey, and boxing, but it can affect amateur athletes and can affect people at a young age,” lead author Ann McKee, MD, professor of neurology and pathology and director of the Chronic Traumatic Encephalopathy Center at Boston University, said in an interview.

The findings were published online in JAMA Neurology.
 

A rare look

Brain donation at younger ages is rare, so most of what is known about CTE comes from studies in older athletes.

“We’ve always known that young people could develop this disease early after just amateur high school, youth, and college exposure, but this is the largest study of donor brains at this age,” Dr. McKee said.

The case series included 152 brains of athletes who played contact sports, experienced RHIs, and died before age 30. The tissues are part of the Understanding Neurologic Injury and Traumatic Encephalopathy (UNITE) Brain Bank and were donated between February 2008 and September 2022.

Researchers reviewed the donors’ medical records and conducted retrospective interviews with the donors’ next of kin to assess cognitive symptoms, mood disturbances, and neurobehavioral issues.

Donors died between the ages of 13 and 29 years, 92.8% were male and 73% were White. In 57.2% of the cases, suicide was the cause of death, with no difference between those with or without CTE.

CTE was neuropathologically diagnosed in 41.4% of athletes, using diagnostic criteria developed by the National Institute of Neurological Disorders and Stroke. 

More than 95% had mild CTE. Diagnosis was associated with older age (mean difference, 3.92 years; P < .001) and significantly more years of exposure to contact sports (11.6 vs. 8.8 years).

Among those with CTE, 71.4% played amateur sports, including football (60.9%), soccer (17.2%), hockey (7.8%), and wrestling (7%).

The cohort includes the first known American female athlete with CTE. Recruiting female brain donors has always been a challenge, Dr. McKee said. In this study, females comprised about 7% of the entire cohort and tended to be younger and play fewer years of a sport, compared with their male counterparts. All of that could lower their risk for CTE, Dr. McKee said.

“We don’t have enough brain donations to make any comments about differences between the genders, but we’ve always known that women can develop CTE,” she said. “It’s been reported after domestic violence and in an autistic woman who was a headbanger, so it was just a matter of time before we found our first case.”
 

Early stage of CTE?

Neuropathological analysis revealed neuronal p-tau aggregates in all CTE cases, a hallmark of the disease.

Young athletes with CTE had significantly more ventricular dilatation, suggesting atrophy or shrinkage of the brain, and more cavum septum pellucidum.

“I was surprised that even at this very young age group we could see structural changes to the gross pathology,” Dr. McKee said.

Investigators also found evidence of perivascular macrophages in the deep white matter, a microscopic change that correlated with CTE and years of play and indicates a breach of the blood-brain barrier that could allow pro-inflammatory molecules to enter the brain, setting up a neuroinflammatory response.

“Neuroinflammation is a very early change after repetitive head impacts, as well as in CTE,” Dr. McKee said. “This may be one of the mechanisms by which the inflammation starts, meaning microvascular injury might be an integral part of the pathogenesis of CTE.”
 

A message for clinicians

All athletes had symptoms of mood and neurobehavioral dysfunction common in people with RHIs. There were no significant differences in those clinical symptoms based on CTE diagnosis, which is likely related to the retrospective nature of the clinical evaluations, Dr. McKee said.

While the study leaves many questions about CTE in younger athletes unanswered, there is a message for clinicians and for patients in the findings, she said.

For clinicians, it’s important to note that “this young population of amateur athletes can be very symptomatic, and in all likelihood, a lot of these symptoms are reversible with proper care and management,” Dr. McKee said.

“For individual athletes, it’s important to note that 58% of this cohort did not have CTE, so just because you have these symptoms is not an indication that you have a neurodegenerative disease,” she added.

The study was funded by Andlinger Foundation, the National Football League, Mac Parkman Foundation, National Operating Committee on Standards for Athletic Equipment, and the Nick and Lynn Buoniconti Foundation, World Wrestling Entertainment, Alzheimer’s Association, National Institutes of Health, Concussion Legacy Foundation, U.S. Department of Defense and the U.S. Department of Veterans Affairs. Dr. McKee is a member of the Mackey-White Health and Safety Committee of the National Football League Players Association and reported receiving grants from the NIH and Department of Veteran Affairs and other funding from the Buoniconti Foundation and Mac Parkman Foundation during the conduct of the study.

A version of this article appeared on Medscape.com.

The largest study to date of chronic traumatic encephalopathy (CTE) in young athletes shows that 41% had the neurodegenerative disease, caused by repetitive head impacts (RHIs).

Analysis of brain tissue from athletes who were exposed to RHIs and died before the age of 30 revealed neuropathological evidence of shrinkage of the brain and microscopic changes that indicate a breach of the blood-brain barrier. The case series also identified the first known American female athlete with CTE.

Nearly all of those with CTE had a mild form of the disease and 71% played only at the amateur level in youth, high school, or college sports.

“A lot of people think CTE is a result of high-level, professional play such as football, ice hockey, and boxing, but it can affect amateur athletes and can affect people at a young age,” lead author Ann McKee, MD, professor of neurology and pathology and director of the Chronic Traumatic Encephalopathy Center at Boston University, said in an interview.

The findings were published online in JAMA Neurology.
 

A rare look

Brain donation at younger ages is rare, so most of what is known about CTE comes from studies in older athletes.

“We’ve always known that young people could develop this disease early after just amateur high school, youth, and college exposure, but this is the largest study of donor brains at this age,” Dr. McKee said.

The case series included 152 brains of athletes who played contact sports, experienced RHIs, and died before age 30. The tissues are part of the Understanding Neurologic Injury and Traumatic Encephalopathy (UNITE) Brain Bank and were donated between February 2008 and September 2022.

Researchers reviewed the donors’ medical records and conducted retrospective interviews with the donors’ next of kin to assess cognitive symptoms, mood disturbances, and neurobehavioral issues.

Donors died between the ages of 13 and 29 years, 92.8% were male and 73% were White. In 57.2% of the cases, suicide was the cause of death, with no difference between those with or without CTE.

CTE was neuropathologically diagnosed in 41.4% of athletes, using diagnostic criteria developed by the National Institute of Neurological Disorders and Stroke. 

More than 95% had mild CTE. Diagnosis was associated with older age (mean difference, 3.92 years; P < .001) and significantly more years of exposure to contact sports (11.6 vs. 8.8 years).

Among those with CTE, 71.4% played amateur sports, including football (60.9%), soccer (17.2%), hockey (7.8%), and wrestling (7%).

The cohort includes the first known American female athlete with CTE. Recruiting female brain donors has always been a challenge, Dr. McKee said. In this study, females comprised about 7% of the entire cohort and tended to be younger and play fewer years of a sport, compared with their male counterparts. All of that could lower their risk for CTE, Dr. McKee said.

“We don’t have enough brain donations to make any comments about differences between the genders, but we’ve always known that women can develop CTE,” she said. “It’s been reported after domestic violence and in an autistic woman who was a headbanger, so it was just a matter of time before we found our first case.”
 

Early stage of CTE?

Neuropathological analysis revealed neuronal p-tau aggregates in all CTE cases, a hallmark of the disease.

Young athletes with CTE had significantly more ventricular dilatation, suggesting atrophy or shrinkage of the brain, and more cavum septum pellucidum.

“I was surprised that even at this very young age group we could see structural changes to the gross pathology,” Dr. McKee said.

Investigators also found evidence of perivascular macrophages in the deep white matter, a microscopic change that correlated with CTE and years of play and indicates a breach of the blood-brain barrier that could allow pro-inflammatory molecules to enter the brain, setting up a neuroinflammatory response.

“Neuroinflammation is a very early change after repetitive head impacts, as well as in CTE,” Dr. McKee said. “This may be one of the mechanisms by which the inflammation starts, meaning microvascular injury might be an integral part of the pathogenesis of CTE.”
 

A message for clinicians

All athletes had symptoms of mood and neurobehavioral dysfunction common in people with RHIs. There were no significant differences in those clinical symptoms based on CTE diagnosis, which is likely related to the retrospective nature of the clinical evaluations, Dr. McKee said.

While the study leaves many questions about CTE in younger athletes unanswered, there is a message for clinicians and for patients in the findings, she said.

For clinicians, it’s important to note that “this young population of amateur athletes can be very symptomatic, and in all likelihood, a lot of these symptoms are reversible with proper care and management,” Dr. McKee said.

“For individual athletes, it’s important to note that 58% of this cohort did not have CTE, so just because you have these symptoms is not an indication that you have a neurodegenerative disease,” she added.

The study was funded by Andlinger Foundation, the National Football League, Mac Parkman Foundation, National Operating Committee on Standards for Athletic Equipment, and the Nick and Lynn Buoniconti Foundation, World Wrestling Entertainment, Alzheimer’s Association, National Institutes of Health, Concussion Legacy Foundation, U.S. Department of Defense and the U.S. Department of Veterans Affairs. Dr. McKee is a member of the Mackey-White Health and Safety Committee of the National Football League Players Association and reported receiving grants from the NIH and Department of Veteran Affairs and other funding from the Buoniconti Foundation and Mac Parkman Foundation during the conduct of the study.

A version of this article appeared on Medscape.com.

The largest study to date of chronic traumatic encephalopathy (CTE) in young athletes shows that 41% had the neurodegenerative disease, caused by repetitive head impacts (RHIs).

Analysis of brain tissue from athletes who were exposed to RHIs and died before the age of 30 revealed neuropathological evidence of shrinkage of the brain and microscopic changes that indicate a breach of the blood-brain barrier. The case series also identified the first known American female athlete with CTE.

Nearly all of those with CTE had a mild form of the disease and 71% played only at the amateur level in youth, high school, or college sports.

“A lot of people think CTE is a result of high-level, professional play such as football, ice hockey, and boxing, but it can affect amateur athletes and can affect people at a young age,” lead author Ann McKee, MD, professor of neurology and pathology and director of the Chronic Traumatic Encephalopathy Center at Boston University, said in an interview.

The findings were published online in JAMA Neurology.
 

A rare look

Brain donation at younger ages is rare, so most of what is known about CTE comes from studies in older athletes.

“We’ve always known that young people could develop this disease early after just amateur high school, youth, and college exposure, but this is the largest study of donor brains at this age,” Dr. McKee said.

The case series included 152 brains of athletes who played contact sports, experienced RHIs, and died before age 30. The tissues are part of the Understanding Neurologic Injury and Traumatic Encephalopathy (UNITE) Brain Bank and were donated between February 2008 and September 2022.

Researchers reviewed the donors’ medical records and conducted retrospective interviews with the donors’ next of kin to assess cognitive symptoms, mood disturbances, and neurobehavioral issues.

Donors died between the ages of 13 and 29 years, 92.8% were male and 73% were White. In 57.2% of the cases, suicide was the cause of death, with no difference between those with or without CTE.

CTE was neuropathologically diagnosed in 41.4% of athletes, using diagnostic criteria developed by the National Institute of Neurological Disorders and Stroke. 

More than 95% had mild CTE. Diagnosis was associated with older age (mean difference, 3.92 years; P < .001) and significantly more years of exposure to contact sports (11.6 vs. 8.8 years).

Among those with CTE, 71.4% played amateur sports, including football (60.9%), soccer (17.2%), hockey (7.8%), and wrestling (7%).

The cohort includes the first known American female athlete with CTE. Recruiting female brain donors has always been a challenge, Dr. McKee said. In this study, females comprised about 7% of the entire cohort and tended to be younger and play fewer years of a sport, compared with their male counterparts. All of that could lower their risk for CTE, Dr. McKee said.

“We don’t have enough brain donations to make any comments about differences between the genders, but we’ve always known that women can develop CTE,” she said. “It’s been reported after domestic violence and in an autistic woman who was a headbanger, so it was just a matter of time before we found our first case.”
 

Early stage of CTE?

Neuropathological analysis revealed neuronal p-tau aggregates in all CTE cases, a hallmark of the disease.

Young athletes with CTE had significantly more ventricular dilatation, suggesting atrophy or shrinkage of the brain, and more cavum septum pellucidum.

“I was surprised that even at this very young age group we could see structural changes to the gross pathology,” Dr. McKee said.

Investigators also found evidence of perivascular macrophages in the deep white matter, a microscopic change that correlated with CTE and years of play and indicates a breach of the blood-brain barrier that could allow pro-inflammatory molecules to enter the brain, setting up a neuroinflammatory response.

“Neuroinflammation is a very early change after repetitive head impacts, as well as in CTE,” Dr. McKee said. “This may be one of the mechanisms by which the inflammation starts, meaning microvascular injury might be an integral part of the pathogenesis of CTE.”
 

A message for clinicians

All athletes had symptoms of mood and neurobehavioral dysfunction common in people with RHIs. There were no significant differences in those clinical symptoms based on CTE diagnosis, which is likely related to the retrospective nature of the clinical evaluations, Dr. McKee said.

While the study leaves many questions about CTE in younger athletes unanswered, there is a message for clinicians and for patients in the findings, she said.

For clinicians, it’s important to note that “this young population of amateur athletes can be very symptomatic, and in all likelihood, a lot of these symptoms are reversible with proper care and management,” Dr. McKee said.

“For individual athletes, it’s important to note that 58% of this cohort did not have CTE, so just because you have these symptoms is not an indication that you have a neurodegenerative disease,” she added.

The study was funded by Andlinger Foundation, the National Football League, Mac Parkman Foundation, National Operating Committee on Standards for Athletic Equipment, and the Nick and Lynn Buoniconti Foundation, World Wrestling Entertainment, Alzheimer’s Association, National Institutes of Health, Concussion Legacy Foundation, U.S. Department of Defense and the U.S. Department of Veterans Affairs. Dr. McKee is a member of the Mackey-White Health and Safety Committee of the National Football League Players Association and reported receiving grants from the NIH and Department of Veteran Affairs and other funding from the Buoniconti Foundation and Mac Parkman Foundation during the conduct of the study.

A version of this article appeared on Medscape.com.

Changes in retinal tissues known to be associated with Parkinson’s disease (PD) may occur up to 7 years before clinical symptoms of the disease appear, a new study suggests. 

Researchers used artificial intelligence (AI) to analyze data from two population-level data sets and the world’s largest database of retinal images and associated clinical data to detect the retinal changes in patients with PD and in healthy individuals who developed the disease years later. 

Prior research had shown that PD is associated with a thinning of the ganglion cell-inner plexiform layer (GCIPL) in the retina, something that investigators confirmed in this new study. But they also identified changes in the inner nuclear layer (INL), which is a new finding. 

The study is the largest to date on retinal markers in PD and the first to show these changes in living patients.

“I think we are still several years away from converting these findings into individual level prediction for patients,” lead author, Siegfried Wagner, MD, MsC, Honorary Clinical Senior Research Fellow at Moorfields Eye Hospital and University College of London Institute of Ophthalmology in London, told this news organization. “The most important takeaway is that there are observable differences in the retina of individuals who go on to develop Parkinson’s disease.”

The findings were published online in Neurology. 
 

Another look at OCT

Researchers used data from retinal eye scans taken by optical coherence tomography (OCT), a noninvasive three-dimensional imaging technology that is widely used by opticians. 

Other studies have used OCT to detect retinal changes in multiple sclerosis and cognitive decline. 

For this research, investigators identified markers in people with PD using ophthalmic imaging data from 700 patients and 105,770 controls who participated in the retrospective AlzEye study. 

After adjustment for age, sex, ethnicity, hypertension, and diabetes, individuals with PD had significantly thinner GCIPL and reduced thickness of the INL.

To evaluate retinal changes in patients before a PD diagnosis, researchers then turned to 50,405 participants in the UK Biobank with no history of PD who received a retinal scan as part of their baseline visit. Of that group, 53 were diagnosed with PD during the study period. 

Researchers found an association between new diagnoses of PD and reduced thickness of the GCIPL (hazard ratio [HR], 0.62; P = .002) and thinner INL, especially at the inferior subfield (HR, 0.66; P = .002). That association persisted even in people whose clinical symptoms developed within 2 years of the retinal scan. 

“We wonder if the reduced INL thickness is indicating a direct dopaminergic impairment occurring within the inner retina,” Dr. Wagner said. “Dopaminergic amacrine cells only account for a small proportion of the cells in this layer but previous work in the laboratory shows observable abnormalities in Parkinson’s disease.”
 

Too early for diagnostics?

Commenting on the findings, Rebecca Gilbert, MD, PhD, chief scientific officer, American Parkinson Disease Association, noted that the changes in the retinal thickness identified in the study were too small to be useful in the clinic as a screening tool for early PD. 

“In order for that to happen, the specificity and sensitivity needs to be established,” she said. “Both specificity and sensitivity need to be high enough so that the test can be used to give clinically meaningful results – and reliably tell an individual with PD that he or she does have the disease and individual without PD that he or she doesn’t have the disease.”

Authors of an accompanying editorial agreed. Valeria Koska, MD, and Philipp Albrecht, MD, both of Heinrich Heine University Düsseldorf in Germany, noted that though the effect sizes of retinal changes were small, the study “sets new standards for the role of retinal morphology as potential biomarker in neurodegenerative disease.”

The study was funded by Fight for Sight UK, Medical Research Council, UK Research & Innovation, Basque Health Department, and the Wellcome Trust Study. Dr. Wagner reported funding from the Medical Research Council and the Rank Prize. Dr. Gilbert is employed by the American Parkinson Disease Association. Dr. Albrecht has received grant and personal fees and nonfinancial support from Allergan, Biogen, Celgene, Ipsen, Janssen Cilag, Merck, Merz Pharmaceuticals, Novartis, Roche, and Teva, outside the submitted work. Dr. Koska reported no relevant disclosures. 
 

A version of this article appeared on Medscape.com.

Changes in retinal tissues known to be associated with Parkinson’s disease (PD) may occur up to 7 years before clinical symptoms of the disease appear, a new study suggests. 

Researchers used artificial intelligence (AI) to analyze data from two population-level data sets and the world’s largest database of retinal images and associated clinical data to detect the retinal changes in patients with PD and in healthy individuals who developed the disease years later. 

Prior research had shown that PD is associated with a thinning of the ganglion cell-inner plexiform layer (GCIPL) in the retina, something that investigators confirmed in this new study. But they also identified changes in the inner nuclear layer (INL), which is a new finding. 

The study is the largest to date on retinal markers in PD and the first to show these changes in living patients.

“I think we are still several years away from converting these findings into individual level prediction for patients,” lead author, Siegfried Wagner, MD, MsC, Honorary Clinical Senior Research Fellow at Moorfields Eye Hospital and University College of London Institute of Ophthalmology in London, told this news organization. “The most important takeaway is that there are observable differences in the retina of individuals who go on to develop Parkinson’s disease.”

The findings were published online in Neurology. 
 

Another look at OCT

Researchers used data from retinal eye scans taken by optical coherence tomography (OCT), a noninvasive three-dimensional imaging technology that is widely used by opticians. 

Other studies have used OCT to detect retinal changes in multiple sclerosis and cognitive decline. 

For this research, investigators identified markers in people with PD using ophthalmic imaging data from 700 patients and 105,770 controls who participated in the retrospective AlzEye study. 

After adjustment for age, sex, ethnicity, hypertension, and diabetes, individuals with PD had significantly thinner GCIPL and reduced thickness of the INL.

To evaluate retinal changes in patients before a PD diagnosis, researchers then turned to 50,405 participants in the UK Biobank with no history of PD who received a retinal scan as part of their baseline visit. Of that group, 53 were diagnosed with PD during the study period. 

Researchers found an association between new diagnoses of PD and reduced thickness of the GCIPL (hazard ratio [HR], 0.62; P = .002) and thinner INL, especially at the inferior subfield (HR, 0.66; P = .002). That association persisted even in people whose clinical symptoms developed within 2 years of the retinal scan. 

“We wonder if the reduced INL thickness is indicating a direct dopaminergic impairment occurring within the inner retina,” Dr. Wagner said. “Dopaminergic amacrine cells only account for a small proportion of the cells in this layer but previous work in the laboratory shows observable abnormalities in Parkinson’s disease.”
 

Too early for diagnostics?

Commenting on the findings, Rebecca Gilbert, MD, PhD, chief scientific officer, American Parkinson Disease Association, noted that the changes in the retinal thickness identified in the study were too small to be useful in the clinic as a screening tool for early PD. 

“In order for that to happen, the specificity and sensitivity needs to be established,” she said. “Both specificity and sensitivity need to be high enough so that the test can be used to give clinically meaningful results – and reliably tell an individual with PD that he or she does have the disease and individual without PD that he or she doesn’t have the disease.”

Authors of an accompanying editorial agreed. Valeria Koska, MD, and Philipp Albrecht, MD, both of Heinrich Heine University Düsseldorf in Germany, noted that though the effect sizes of retinal changes were small, the study “sets new standards for the role of retinal morphology as potential biomarker in neurodegenerative disease.”

The study was funded by Fight for Sight UK, Medical Research Council, UK Research & Innovation, Basque Health Department, and the Wellcome Trust Study. Dr. Wagner reported funding from the Medical Research Council and the Rank Prize. Dr. Gilbert is employed by the American Parkinson Disease Association. Dr. Albrecht has received grant and personal fees and nonfinancial support from Allergan, Biogen, Celgene, Ipsen, Janssen Cilag, Merck, Merz Pharmaceuticals, Novartis, Roche, and Teva, outside the submitted work. Dr. Koska reported no relevant disclosures. 
 

A version of this article appeared on Medscape.com.

Changes in retinal tissues known to be associated with Parkinson’s disease (PD) may occur up to 7 years before clinical symptoms of the disease appear, a new study suggests. 

Researchers used artificial intelligence (AI) to analyze data from two population-level data sets and the world’s largest database of retinal images and associated clinical data to detect the retinal changes in patients with PD and in healthy individuals who developed the disease years later. 

Prior research had shown that PD is associated with a thinning of the ganglion cell-inner plexiform layer (GCIPL) in the retina, something that investigators confirmed in this new study. But they also identified changes in the inner nuclear layer (INL), which is a new finding. 

The study is the largest to date on retinal markers in PD and the first to show these changes in living patients.

“I think we are still several years away from converting these findings into individual level prediction for patients,” lead author, Siegfried Wagner, MD, MsC, Honorary Clinical Senior Research Fellow at Moorfields Eye Hospital and University College of London Institute of Ophthalmology in London, told this news organization. “The most important takeaway is that there are observable differences in the retina of individuals who go on to develop Parkinson’s disease.”

The findings were published online in Neurology. 
 

Another look at OCT

Researchers used data from retinal eye scans taken by optical coherence tomography (OCT), a noninvasive three-dimensional imaging technology that is widely used by opticians. 

Other studies have used OCT to detect retinal changes in multiple sclerosis and cognitive decline. 

For this research, investigators identified markers in people with PD using ophthalmic imaging data from 700 patients and 105,770 controls who participated in the retrospective AlzEye study. 

After adjustment for age, sex, ethnicity, hypertension, and diabetes, individuals with PD had significantly thinner GCIPL and reduced thickness of the INL.

To evaluate retinal changes in patients before a PD diagnosis, researchers then turned to 50,405 participants in the UK Biobank with no history of PD who received a retinal scan as part of their baseline visit. Of that group, 53 were diagnosed with PD during the study period. 

Researchers found an association between new diagnoses of PD and reduced thickness of the GCIPL (hazard ratio [HR], 0.62; P = .002) and thinner INL, especially at the inferior subfield (HR, 0.66; P = .002). That association persisted even in people whose clinical symptoms developed within 2 years of the retinal scan. 

“We wonder if the reduced INL thickness is indicating a direct dopaminergic impairment occurring within the inner retina,” Dr. Wagner said. “Dopaminergic amacrine cells only account for a small proportion of the cells in this layer but previous work in the laboratory shows observable abnormalities in Parkinson’s disease.”
 

Too early for diagnostics?

Commenting on the findings, Rebecca Gilbert, MD, PhD, chief scientific officer, American Parkinson Disease Association, noted that the changes in the retinal thickness identified in the study were too small to be useful in the clinic as a screening tool for early PD. 

“In order for that to happen, the specificity and sensitivity needs to be established,” she said. “Both specificity and sensitivity need to be high enough so that the test can be used to give clinically meaningful results – and reliably tell an individual with PD that he or she does have the disease and individual without PD that he or she doesn’t have the disease.”

Authors of an accompanying editorial agreed. Valeria Koska, MD, and Philipp Albrecht, MD, both of Heinrich Heine University Düsseldorf in Germany, noted that though the effect sizes of retinal changes were small, the study “sets new standards for the role of retinal morphology as potential biomarker in neurodegenerative disease.”

The study was funded by Fight for Sight UK, Medical Research Council, UK Research & Innovation, Basque Health Department, and the Wellcome Trust Study. Dr. Wagner reported funding from the Medical Research Council and the Rank Prize. Dr. Gilbert is employed by the American Parkinson Disease Association. Dr. Albrecht has received grant and personal fees and nonfinancial support from Allergan, Biogen, Celgene, Ipsen, Janssen Cilag, Merck, Merz Pharmaceuticals, Novartis, Roche, and Teva, outside the submitted work. Dr. Koska reported no relevant disclosures. 
 

A version of this article appeared on Medscape.com.

Among military veterans who die by suicide, those who experience a traumatic brain injury (TBI) during service take their lives 21% sooner after deployment than those without a TBI history, a new study shows.

Investigators also found that increases in new mental health diagnoses are significantly higher in soldiers with a history of TBI – in some cases, strikingly higher. For example, cases of substance use disorder rose by 100% among veterans with TBI compared to just 14.5% in those with no brain injury.

Brenner_Lisa_CO_web.jpg

“We had had pieces of these findings for a long time but to be able to lay out this longitudinal story over time is the part that’s new and important to really switch the focus to people’s whole lives and things that happen over time, both psychological and physical,” lead author Lisa Brenner, PhD, director of the Veterans Health Administration (VHA) Rocky Mountain Mental Illness Research Education and Clinical Center, Aurora, Colo., said in an interview.

“If we take that life-course view, it’s a very different way about thinking about conceptualizing exposures and conceptualizing risk and it’s a different way of thinking about treatment and prevention,” added Dr. Brenner, professor of physical medicine and rehabilitation, psychiatry, and neurology at the University of Colorado, Aurora. “I think that definitely applies to civilian populations.”

The findings were published online in JAMA Network Open.
 

Largest, longest study to date

Researchers have long suspected that TBI and a higher rate of new mental illness and a shorter time to suicide are all somehow linked. But this study examined all three components longitudinally, in what is thought to be the largest and longest study on the topic to date, including more than 860,000 people who were followed for up to a decade.

Investigators studied health data from the Substance Use and Psychological Injury Combat Study database on 860,892 U.S. Army soldiers who returned from deployment in Iraq or Afghanistan between 2008 and 2014 and were 18-24 years old at the end of that deployment. They then examined new mental health diagnoses and suicide trends over time.

Nearly 109,000 (12.6%) experienced a TBI during deployment, and 2,695 had died by suicide through the end of 2018.

New-onset diagnoses of anxiety, mood disorders, posttraumatic stress disorder, alcohol use, and substance use disorder (SUD) after deployment were all more common in soldiers who experienced PTSD while serving compared with those with no history of TBI.

There was a 67.7% increase in mood disorders in participants with TBI compared with a 37.5% increase in those without TBI. The increase in new cases of alcohol use disorder was also greater in the TBI group (a 31.9% increase vs. a 10.3% increase).

But the sharpest difference was the increase in substance use disorder among those with TBI, which rose 100% compared with a 14.5% increase in solders with no history of TBI.
 

Sharp differences in time to suicide

Death by suicide was only slightly more common in those with TBI compared with those without (0.4% vs. 0.3%, respectively). But those with a brain injury committed suicide 21.3% sooner than did those without a head injury, after the researchers controlled for sex, age, race, ethnicity, and fiscal year of return from deployment.

Time to suicide was faster in those with a TBI and two or more new mental health diagnoses and fastest among those with TBI and a new SUD diagnosis, who took their own lives 62.8% faster than did those without a TBI.

The findings offer an important message to medical professionals in many different specialties, Dr. Brenner said.

“Folks in mental health probably have a lot of patients who have brain injury in their practice, and they don’t know it and that’s an important thing to know,” she said, adding that “neurologists should screen for depression and other mental health conditions and make sure those people have evidence-based treatments for those mental health conditions while they’re addressing the TBI-related symptoms.”
 

Applicable to civilians?

“The complex interplay between TBI, its potential effects on mental health, and risk of suicide remains a vexing focus of ongoing investigations and academic inquiry,” Ross Zafonte, DO, president of Spaulding Rehabilitation Hospital Network and professor and chair of physical medicine and rehabilitation at Harvard Medical School, Boston, and colleagues, wrote in an accompanying editorial.

The study builds on earlier work, they added, and praised the study’s longitudinal design and large cohort as key to the findings. The data on increased rates of new-onset substance use disorder, which was also associated with a faster time to suicide in the TBI group, were of particular interest.

“In this work, Brenner and colleagues identified substance use disorder as a key factor in faster time to suicide for active-duty service members with a history of TBI compared with those without TBI and theorized that a multiple stress or exposure burden may enhance risk,” they wrote. “This theory is reasonable and has been postulated among individuals with medical sequelae linked to TBI.”

However, the authors caution against applying these findings in military veterans to civilians.

“While this work is critical in the military population, caution should be given to avoid direct generalization to other populations, such as athletes, for whom the linkage to suicidal ideation is less understood,” they wrote.

The study was funded by National Institute of Mental Health and Office of the Director at National Institutes of Health. Dr. Brenner has received personal fees from Wolters Kluwer, Rand, American Psychological Association, and Oxford University Press and serves as a consultant to sports leagues via her university affiliation. Dr. Zafonte reported receiving royalties from Springer/Demos; serving as a member of the editorial boards of Journal of Neurotrauma and Frontiers in Neurology and scientific advisory boards of Myomo, Nanodiagnostics, Onecare.ai, and Kisbee; and evaluating patients in the MGH Brain and Body-TRUST Program, which is funded by the National Football League Players Association.
 

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

Among military veterans who die by suicide, those who experience a traumatic brain injury (TBI) during service take their lives 21% sooner after deployment than those without a TBI history, a new study shows.

Investigators also found that increases in new mental health diagnoses are significantly higher in soldiers with a history of TBI – in some cases, strikingly higher. For example, cases of substance use disorder rose by 100% among veterans with TBI compared to just 14.5% in those with no brain injury.

Brenner_Lisa_CO_web.jpg

“We had had pieces of these findings for a long time but to be able to lay out this longitudinal story over time is the part that’s new and important to really switch the focus to people’s whole lives and things that happen over time, both psychological and physical,” lead author Lisa Brenner, PhD, director of the Veterans Health Administration (VHA) Rocky Mountain Mental Illness Research Education and Clinical Center, Aurora, Colo., said in an interview.

“If we take that life-course view, it’s a very different way about thinking about conceptualizing exposures and conceptualizing risk and it’s a different way of thinking about treatment and prevention,” added Dr. Brenner, professor of physical medicine and rehabilitation, psychiatry, and neurology at the University of Colorado, Aurora. “I think that definitely applies to civilian populations.”

The findings were published online in JAMA Network Open.
 

Largest, longest study to date

Researchers have long suspected that TBI and a higher rate of new mental illness and a shorter time to suicide are all somehow linked. But this study examined all three components longitudinally, in what is thought to be the largest and longest study on the topic to date, including more than 860,000 people who were followed for up to a decade.

Investigators studied health data from the Substance Use and Psychological Injury Combat Study database on 860,892 U.S. Army soldiers who returned from deployment in Iraq or Afghanistan between 2008 and 2014 and were 18-24 years old at the end of that deployment. They then examined new mental health diagnoses and suicide trends over time.

Nearly 109,000 (12.6%) experienced a TBI during deployment, and 2,695 had died by suicide through the end of 2018.

New-onset diagnoses of anxiety, mood disorders, posttraumatic stress disorder, alcohol use, and substance use disorder (SUD) after deployment were all more common in soldiers who experienced PTSD while serving compared with those with no history of TBI.

There was a 67.7% increase in mood disorders in participants with TBI compared with a 37.5% increase in those without TBI. The increase in new cases of alcohol use disorder was also greater in the TBI group (a 31.9% increase vs. a 10.3% increase).

But the sharpest difference was the increase in substance use disorder among those with TBI, which rose 100% compared with a 14.5% increase in solders with no history of TBI.
 

Sharp differences in time to suicide

Death by suicide was only slightly more common in those with TBI compared with those without (0.4% vs. 0.3%, respectively). But those with a brain injury committed suicide 21.3% sooner than did those without a head injury, after the researchers controlled for sex, age, race, ethnicity, and fiscal year of return from deployment.

Time to suicide was faster in those with a TBI and two or more new mental health diagnoses and fastest among those with TBI and a new SUD diagnosis, who took their own lives 62.8% faster than did those without a TBI.

The findings offer an important message to medical professionals in many different specialties, Dr. Brenner said.

“Folks in mental health probably have a lot of patients who have brain injury in their practice, and they don’t know it and that’s an important thing to know,” she said, adding that “neurologists should screen for depression and other mental health conditions and make sure those people have evidence-based treatments for those mental health conditions while they’re addressing the TBI-related symptoms.”
 

Applicable to civilians?

“The complex interplay between TBI, its potential effects on mental health, and risk of suicide remains a vexing focus of ongoing investigations and academic inquiry,” Ross Zafonte, DO, president of Spaulding Rehabilitation Hospital Network and professor and chair of physical medicine and rehabilitation at Harvard Medical School, Boston, and colleagues, wrote in an accompanying editorial.

The study builds on earlier work, they added, and praised the study’s longitudinal design and large cohort as key to the findings. The data on increased rates of new-onset substance use disorder, which was also associated with a faster time to suicide in the TBI group, were of particular interest.

“In this work, Brenner and colleagues identified substance use disorder as a key factor in faster time to suicide for active-duty service members with a history of TBI compared with those without TBI and theorized that a multiple stress or exposure burden may enhance risk,” they wrote. “This theory is reasonable and has been postulated among individuals with medical sequelae linked to TBI.”

However, the authors caution against applying these findings in military veterans to civilians.

“While this work is critical in the military population, caution should be given to avoid direct generalization to other populations, such as athletes, for whom the linkage to suicidal ideation is less understood,” they wrote.

The study was funded by National Institute of Mental Health and Office of the Director at National Institutes of Health. Dr. Brenner has received personal fees from Wolters Kluwer, Rand, American Psychological Association, and Oxford University Press and serves as a consultant to sports leagues via her university affiliation. Dr. Zafonte reported receiving royalties from Springer/Demos; serving as a member of the editorial boards of Journal of Neurotrauma and Frontiers in Neurology and scientific advisory boards of Myomo, Nanodiagnostics, Onecare.ai, and Kisbee; and evaluating patients in the MGH Brain and Body-TRUST Program, which is funded by the National Football League Players Association.
 

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

Among military veterans who die by suicide, those who experience a traumatic brain injury (TBI) during service take their lives 21% sooner after deployment than those without a TBI history, a new study shows.

Investigators also found that increases in new mental health diagnoses are significantly higher in soldiers with a history of TBI – in some cases, strikingly higher. For example, cases of substance use disorder rose by 100% among veterans with TBI compared to just 14.5% in those with no brain injury.

Brenner_Lisa_CO_web.jpg

“We had had pieces of these findings for a long time but to be able to lay out this longitudinal story over time is the part that’s new and important to really switch the focus to people’s whole lives and things that happen over time, both psychological and physical,” lead author Lisa Brenner, PhD, director of the Veterans Health Administration (VHA) Rocky Mountain Mental Illness Research Education and Clinical Center, Aurora, Colo., said in an interview.

“If we take that life-course view, it’s a very different way about thinking about conceptualizing exposures and conceptualizing risk and it’s a different way of thinking about treatment and prevention,” added Dr. Brenner, professor of physical medicine and rehabilitation, psychiatry, and neurology at the University of Colorado, Aurora. “I think that definitely applies to civilian populations.”

The findings were published online in JAMA Network Open.
 

Largest, longest study to date

Researchers have long suspected that TBI and a higher rate of new mental illness and a shorter time to suicide are all somehow linked. But this study examined all three components longitudinally, in what is thought to be the largest and longest study on the topic to date, including more than 860,000 people who were followed for up to a decade.

Investigators studied health data from the Substance Use and Psychological Injury Combat Study database on 860,892 U.S. Army soldiers who returned from deployment in Iraq or Afghanistan between 2008 and 2014 and were 18-24 years old at the end of that deployment. They then examined new mental health diagnoses and suicide trends over time.

Nearly 109,000 (12.6%) experienced a TBI during deployment, and 2,695 had died by suicide through the end of 2018.

New-onset diagnoses of anxiety, mood disorders, posttraumatic stress disorder, alcohol use, and substance use disorder (SUD) after deployment were all more common in soldiers who experienced PTSD while serving compared with those with no history of TBI.

There was a 67.7% increase in mood disorders in participants with TBI compared with a 37.5% increase in those without TBI. The increase in new cases of alcohol use disorder was also greater in the TBI group (a 31.9% increase vs. a 10.3% increase).

But the sharpest difference was the increase in substance use disorder among those with TBI, which rose 100% compared with a 14.5% increase in solders with no history of TBI.
 

Sharp differences in time to suicide

Death by suicide was only slightly more common in those with TBI compared with those without (0.4% vs. 0.3%, respectively). But those with a brain injury committed suicide 21.3% sooner than did those without a head injury, after the researchers controlled for sex, age, race, ethnicity, and fiscal year of return from deployment.

Time to suicide was faster in those with a TBI and two or more new mental health diagnoses and fastest among those with TBI and a new SUD diagnosis, who took their own lives 62.8% faster than did those without a TBI.

The findings offer an important message to medical professionals in many different specialties, Dr. Brenner said.

“Folks in mental health probably have a lot of patients who have brain injury in their practice, and they don’t know it and that’s an important thing to know,” she said, adding that “neurologists should screen for depression and other mental health conditions and make sure those people have evidence-based treatments for those mental health conditions while they’re addressing the TBI-related symptoms.”
 

Applicable to civilians?

“The complex interplay between TBI, its potential effects on mental health, and risk of suicide remains a vexing focus of ongoing investigations and academic inquiry,” Ross Zafonte, DO, president of Spaulding Rehabilitation Hospital Network and professor and chair of physical medicine and rehabilitation at Harvard Medical School, Boston, and colleagues, wrote in an accompanying editorial.

The study builds on earlier work, they added, and praised the study’s longitudinal design and large cohort as key to the findings. The data on increased rates of new-onset substance use disorder, which was also associated with a faster time to suicide in the TBI group, were of particular interest.

“In this work, Brenner and colleagues identified substance use disorder as a key factor in faster time to suicide for active-duty service members with a history of TBI compared with those without TBI and theorized that a multiple stress or exposure burden may enhance risk,” they wrote. “This theory is reasonable and has been postulated among individuals with medical sequelae linked to TBI.”

However, the authors caution against applying these findings in military veterans to civilians.

“While this work is critical in the military population, caution should be given to avoid direct generalization to other populations, such as athletes, for whom the linkage to suicidal ideation is less understood,” they wrote.

The study was funded by National Institute of Mental Health and Office of the Director at National Institutes of Health. Dr. Brenner has received personal fees from Wolters Kluwer, Rand, American Psychological Association, and Oxford University Press and serves as a consultant to sports leagues via her university affiliation. Dr. Zafonte reported receiving royalties from Springer/Demos; serving as a member of the editorial boards of Journal of Neurotrauma and Frontiers in Neurology and scientific advisory boards of Myomo, Nanodiagnostics, Onecare.ai, and Kisbee; and evaluating patients in the MGH Brain and Body-TRUST Program, which is funded by the National Football League Players Association.
 

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