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Recently Incarcerated Account for Nearly 20% of US Suicides
Nearly one-fifth of suicides in the United States occur in people who were incarcerated in the previous year, a new study showed.
An analysis of more than seven million recently incarcerated US adults revealed a nearly ninefold increased risk for suicide within 1 year after release and an almost sevenfold higher risk during the 2 years following release compared with nonincarcerated people.
The findings suggest that recent incarceration should be considered a risk factor for suicide, investigators said.
“Suicide prevention efforts should focus on people who have spent at least 1 night in jail in the past year,” investigator Ted R. Miller, PhD, of the Pacific Institute for Research and Evaluation, Beltsville, Maryland, and Curtin University School of Public Health, Silver Spring, Maryland, and colleagues wrote. “Health systems could develop infrastructure to identify these high-risk adults and provide community-based suicide screening and prevention.”
The study was published online on May 10, 2024, in JAMA Network Open.
To address the lack of data on suicide risk after recent incarceration, researchers used estimates from meta-analyses and jail census counts.
In 2019, a little more than seven million people (77% male), or 2.8% of the US adult population, were released from US jails at least once, typically after brief pretrial stays. Of those, 9121 died by suicide.
Compared with suicide risk in people who had never been incarcerated, risk was nearly nine times higher within 1 year of release (relative risk [RR], 8.95; 95% CI, 7.21-10.69) and nearly seven times higher during the second year after release (RR, 6.98; 95% CI, 4.21-9.76), researchers found.
Over a quarter (27%) of all adult suicides in the United States occurred in formerly incarcerated people within 2 years of jail release, and one fifth occurred within 1 year of release.
“The results suggest that better integration of suicide risk detection and prevention across health and criminal justice systems is critical to advancing population-level suicide-prevention efforts,” the authors wrote.
High volumes of jail admissions and discharges, short jail stays, and understaffing limit the capacity of many jails to coordinate care with outside health agencies, researchers acknowledged.
“The suicide rate after the return to the community after jail stay is higher than the suicide rate in jail, but local jails have limited capacity to coordinate postrelease health activities,” authors wrote. “Thus, a comprehensive approach to reducing the population-level US suicide rate would include health systems screening their subscribers or patients for recent arrest or police involvement and reaching out to those recently released to prevent suicide.”
In an accompanying editorial, Stuart A. Kinner, PhD, and Rohan Borschmann, PhD, both with the Melbourne School of Population and Global Health, University of Melbourne, Australia, noted that people who experience incarceration “are distinguished by complex health problems that necessitate coordinated, multisectoral care.”
“Miller and colleagues’ findings provide further evidence that incarceration serves as an important marker for disease vulnerability and risk,” Dr. Kinner and Borschmann wrote. “Yet, all too often, the health care provided to these individuals before, during, and after incarceration is underresourced, interrupted, and fragmented.”
Coordinating care for recently incarcerated individuals will require a coordinated effort by all stakeholders, including those in the criminal justice system, they argued.
“The systems that incarcerate 7.1 million people in the United States each year should not be given a get-out-of-jail-free card,” they wrote.
This study was supported by grants from the National Institutes of Mental Health (NIMH)/National Institutes of Health (NIH) and from the National Center for Health and Justice Integration for Suicide Prevention. Dr. Miller reported receiving grants from the NIMH/NIH with his employer as a subcontractor during the conduct of the study and a contract from government plaintiffs in Opioid Litigation: Epidemiology/Abatement Planning outside the submitted work. The other authors’ disclosures are listed on the original paper. Dr. Kinner and Borschmann declared no relevant financial relationships.
A version of this article appeared on Medscape.com.
Nearly one-fifth of suicides in the United States occur in people who were incarcerated in the previous year, a new study showed.
An analysis of more than seven million recently incarcerated US adults revealed a nearly ninefold increased risk for suicide within 1 year after release and an almost sevenfold higher risk during the 2 years following release compared with nonincarcerated people.
The findings suggest that recent incarceration should be considered a risk factor for suicide, investigators said.
“Suicide prevention efforts should focus on people who have spent at least 1 night in jail in the past year,” investigator Ted R. Miller, PhD, of the Pacific Institute for Research and Evaluation, Beltsville, Maryland, and Curtin University School of Public Health, Silver Spring, Maryland, and colleagues wrote. “Health systems could develop infrastructure to identify these high-risk adults and provide community-based suicide screening and prevention.”
The study was published online on May 10, 2024, in JAMA Network Open.
To address the lack of data on suicide risk after recent incarceration, researchers used estimates from meta-analyses and jail census counts.
In 2019, a little more than seven million people (77% male), or 2.8% of the US adult population, were released from US jails at least once, typically after brief pretrial stays. Of those, 9121 died by suicide.
Compared with suicide risk in people who had never been incarcerated, risk was nearly nine times higher within 1 year of release (relative risk [RR], 8.95; 95% CI, 7.21-10.69) and nearly seven times higher during the second year after release (RR, 6.98; 95% CI, 4.21-9.76), researchers found.
Over a quarter (27%) of all adult suicides in the United States occurred in formerly incarcerated people within 2 years of jail release, and one fifth occurred within 1 year of release.
“The results suggest that better integration of suicide risk detection and prevention across health and criminal justice systems is critical to advancing population-level suicide-prevention efforts,” the authors wrote.
High volumes of jail admissions and discharges, short jail stays, and understaffing limit the capacity of many jails to coordinate care with outside health agencies, researchers acknowledged.
“The suicide rate after the return to the community after jail stay is higher than the suicide rate in jail, but local jails have limited capacity to coordinate postrelease health activities,” authors wrote. “Thus, a comprehensive approach to reducing the population-level US suicide rate would include health systems screening their subscribers or patients for recent arrest or police involvement and reaching out to those recently released to prevent suicide.”
In an accompanying editorial, Stuart A. Kinner, PhD, and Rohan Borschmann, PhD, both with the Melbourne School of Population and Global Health, University of Melbourne, Australia, noted that people who experience incarceration “are distinguished by complex health problems that necessitate coordinated, multisectoral care.”
“Miller and colleagues’ findings provide further evidence that incarceration serves as an important marker for disease vulnerability and risk,” Dr. Kinner and Borschmann wrote. “Yet, all too often, the health care provided to these individuals before, during, and after incarceration is underresourced, interrupted, and fragmented.”
Coordinating care for recently incarcerated individuals will require a coordinated effort by all stakeholders, including those in the criminal justice system, they argued.
“The systems that incarcerate 7.1 million people in the United States each year should not be given a get-out-of-jail-free card,” they wrote.
This study was supported by grants from the National Institutes of Mental Health (NIMH)/National Institutes of Health (NIH) and from the National Center for Health and Justice Integration for Suicide Prevention. Dr. Miller reported receiving grants from the NIMH/NIH with his employer as a subcontractor during the conduct of the study and a contract from government plaintiffs in Opioid Litigation: Epidemiology/Abatement Planning outside the submitted work. The other authors’ disclosures are listed on the original paper. Dr. Kinner and Borschmann declared no relevant financial relationships.
A version of this article appeared on Medscape.com.
Nearly one-fifth of suicides in the United States occur in people who were incarcerated in the previous year, a new study showed.
An analysis of more than seven million recently incarcerated US adults revealed a nearly ninefold increased risk for suicide within 1 year after release and an almost sevenfold higher risk during the 2 years following release compared with nonincarcerated people.
The findings suggest that recent incarceration should be considered a risk factor for suicide, investigators said.
“Suicide prevention efforts should focus on people who have spent at least 1 night in jail in the past year,” investigator Ted R. Miller, PhD, of the Pacific Institute for Research and Evaluation, Beltsville, Maryland, and Curtin University School of Public Health, Silver Spring, Maryland, and colleagues wrote. “Health systems could develop infrastructure to identify these high-risk adults and provide community-based suicide screening and prevention.”
The study was published online on May 10, 2024, in JAMA Network Open.
To address the lack of data on suicide risk after recent incarceration, researchers used estimates from meta-analyses and jail census counts.
In 2019, a little more than seven million people (77% male), or 2.8% of the US adult population, were released from US jails at least once, typically after brief pretrial stays. Of those, 9121 died by suicide.
Compared with suicide risk in people who had never been incarcerated, risk was nearly nine times higher within 1 year of release (relative risk [RR], 8.95; 95% CI, 7.21-10.69) and nearly seven times higher during the second year after release (RR, 6.98; 95% CI, 4.21-9.76), researchers found.
Over a quarter (27%) of all adult suicides in the United States occurred in formerly incarcerated people within 2 years of jail release, and one fifth occurred within 1 year of release.
“The results suggest that better integration of suicide risk detection and prevention across health and criminal justice systems is critical to advancing population-level suicide-prevention efforts,” the authors wrote.
High volumes of jail admissions and discharges, short jail stays, and understaffing limit the capacity of many jails to coordinate care with outside health agencies, researchers acknowledged.
“The suicide rate after the return to the community after jail stay is higher than the suicide rate in jail, but local jails have limited capacity to coordinate postrelease health activities,” authors wrote. “Thus, a comprehensive approach to reducing the population-level US suicide rate would include health systems screening their subscribers or patients for recent arrest or police involvement and reaching out to those recently released to prevent suicide.”
In an accompanying editorial, Stuart A. Kinner, PhD, and Rohan Borschmann, PhD, both with the Melbourne School of Population and Global Health, University of Melbourne, Australia, noted that people who experience incarceration “are distinguished by complex health problems that necessitate coordinated, multisectoral care.”
“Miller and colleagues’ findings provide further evidence that incarceration serves as an important marker for disease vulnerability and risk,” Dr. Kinner and Borschmann wrote. “Yet, all too often, the health care provided to these individuals before, during, and after incarceration is underresourced, interrupted, and fragmented.”
Coordinating care for recently incarcerated individuals will require a coordinated effort by all stakeholders, including those in the criminal justice system, they argued.
“The systems that incarcerate 7.1 million people in the United States each year should not be given a get-out-of-jail-free card,” they wrote.
This study was supported by grants from the National Institutes of Mental Health (NIMH)/National Institutes of Health (NIH) and from the National Center for Health and Justice Integration for Suicide Prevention. Dr. Miller reported receiving grants from the NIMH/NIH with his employer as a subcontractor during the conduct of the study and a contract from government plaintiffs in Opioid Litigation: Epidemiology/Abatement Planning outside the submitted work. The other authors’ disclosures are listed on the original paper. Dr. Kinner and Borschmann declared no relevant financial relationships.
A version of this article appeared on Medscape.com.
Migraine Disability Nearly Doubled in US Between 2005 and 2018
, a new systematic review showed.
“The disability trend could reflect changes in reporting, study methodology, social, and societal changes, or changes in exacerbating or remediating factors that make migraine more disabling,” wrote lead investigator Fred Cohen, MD, of Center for Headache and Facial Pain, Department of Neurology, Icahn School of Medicine, Mount Sinai, New York City, and colleagues.
The study was published online in Headache.
Researchers conducted a systematic review of population-based US epidemiologic studies focusing on the prevalence and/or burden of migraine, all published before February 2022. Studies on migraine, episodic migraine, and/or chronic migraine were included.
The primary measure of disease burden was the Migraine Disability Assessment Scale (MIDAS), which measures days lost to migraine over a 3-month period in three domains and defines groups with moderate or severe disability (grades III and IV, respectively), using cut-scores.
Of 1609 studies initially reviewed, the researchers included 26 publications from 11 US population-based studies.
For the past 30 years, the prevalence of migraine in the population has remained largely stable, ranging from 12% to 15% in the overall population, from 17% to 19% in women, and from 6% to 7% in men.
In adults overall, chronic migraine prevalence is 0.91% (1.3% in women and 0.5% in men), while in adolescents, the prevalence is 0.8%.
Although prevalence remained roughly the same during the 30 years, the proportion of people with migraine and moderate to severe MIDAS disability (grades III-IV) has trended upward across studies during part of the study period, increasing from 22% in 2005 to 42% in 2018.
Throughout the years studied, a consistently higher proportion of women versus men were assigned MIDAS grades III-IV.
Although researchers said the exact reason for the increase is unknown, possible explanations include changes in study methodology from mailed questionnaires to web surveys or the decline in participation rate in web surveys. It is also possible that people with migraine may be more willing to report disability than they used to be, authors wrote.
Increased MIDAS scores may be attributable to some environmental risk factor that exacerbates migraine without modifying its prevalence, such as worsening air quality, an increase in natural disasters, or increased opioid use for migraine, they added.
The reason for increased moderate to severe disability in women may be attributable to the fact that migraine is “most common in mid-life, a period characterized by familial and work responsibilities, which may engender a higher risk of burden for working women,” authors wrote. The link between migraine attacks and menstrual cycles may also explain observed gender differences in disability.
In general, the most frequently reported burdens associated with migraine included missed work and school and family and social functioning.
It is “surprising that improvements in treatment have not been associated with reductions in disability,” researchers noted.
No financial support was provided for this study. Dr. Cohen serves as an assistant editor for Headache. He has received honoraria from Springer Nature and MedLink Neurology. Other authors’ disclosures are listed on the original paper.
A version of this article appeared on Medscape.com.
, a new systematic review showed.
“The disability trend could reflect changes in reporting, study methodology, social, and societal changes, or changes in exacerbating or remediating factors that make migraine more disabling,” wrote lead investigator Fred Cohen, MD, of Center for Headache and Facial Pain, Department of Neurology, Icahn School of Medicine, Mount Sinai, New York City, and colleagues.
The study was published online in Headache.
Researchers conducted a systematic review of population-based US epidemiologic studies focusing on the prevalence and/or burden of migraine, all published before February 2022. Studies on migraine, episodic migraine, and/or chronic migraine were included.
The primary measure of disease burden was the Migraine Disability Assessment Scale (MIDAS), which measures days lost to migraine over a 3-month period in three domains and defines groups with moderate or severe disability (grades III and IV, respectively), using cut-scores.
Of 1609 studies initially reviewed, the researchers included 26 publications from 11 US population-based studies.
For the past 30 years, the prevalence of migraine in the population has remained largely stable, ranging from 12% to 15% in the overall population, from 17% to 19% in women, and from 6% to 7% in men.
In adults overall, chronic migraine prevalence is 0.91% (1.3% in women and 0.5% in men), while in adolescents, the prevalence is 0.8%.
Although prevalence remained roughly the same during the 30 years, the proportion of people with migraine and moderate to severe MIDAS disability (grades III-IV) has trended upward across studies during part of the study period, increasing from 22% in 2005 to 42% in 2018.
Throughout the years studied, a consistently higher proportion of women versus men were assigned MIDAS grades III-IV.
Although researchers said the exact reason for the increase is unknown, possible explanations include changes in study methodology from mailed questionnaires to web surveys or the decline in participation rate in web surveys. It is also possible that people with migraine may be more willing to report disability than they used to be, authors wrote.
Increased MIDAS scores may be attributable to some environmental risk factor that exacerbates migraine without modifying its prevalence, such as worsening air quality, an increase in natural disasters, or increased opioid use for migraine, they added.
The reason for increased moderate to severe disability in women may be attributable to the fact that migraine is “most common in mid-life, a period characterized by familial and work responsibilities, which may engender a higher risk of burden for working women,” authors wrote. The link between migraine attacks and menstrual cycles may also explain observed gender differences in disability.
In general, the most frequently reported burdens associated with migraine included missed work and school and family and social functioning.
It is “surprising that improvements in treatment have not been associated with reductions in disability,” researchers noted.
No financial support was provided for this study. Dr. Cohen serves as an assistant editor for Headache. He has received honoraria from Springer Nature and MedLink Neurology. Other authors’ disclosures are listed on the original paper.
A version of this article appeared on Medscape.com.
, a new systematic review showed.
“The disability trend could reflect changes in reporting, study methodology, social, and societal changes, or changes in exacerbating or remediating factors that make migraine more disabling,” wrote lead investigator Fred Cohen, MD, of Center for Headache and Facial Pain, Department of Neurology, Icahn School of Medicine, Mount Sinai, New York City, and colleagues.
The study was published online in Headache.
Researchers conducted a systematic review of population-based US epidemiologic studies focusing on the prevalence and/or burden of migraine, all published before February 2022. Studies on migraine, episodic migraine, and/or chronic migraine were included.
The primary measure of disease burden was the Migraine Disability Assessment Scale (MIDAS), which measures days lost to migraine over a 3-month period in three domains and defines groups with moderate or severe disability (grades III and IV, respectively), using cut-scores.
Of 1609 studies initially reviewed, the researchers included 26 publications from 11 US population-based studies.
For the past 30 years, the prevalence of migraine in the population has remained largely stable, ranging from 12% to 15% in the overall population, from 17% to 19% in women, and from 6% to 7% in men.
In adults overall, chronic migraine prevalence is 0.91% (1.3% in women and 0.5% in men), while in adolescents, the prevalence is 0.8%.
Although prevalence remained roughly the same during the 30 years, the proportion of people with migraine and moderate to severe MIDAS disability (grades III-IV) has trended upward across studies during part of the study period, increasing from 22% in 2005 to 42% in 2018.
Throughout the years studied, a consistently higher proportion of women versus men were assigned MIDAS grades III-IV.
Although researchers said the exact reason for the increase is unknown, possible explanations include changes in study methodology from mailed questionnaires to web surveys or the decline in participation rate in web surveys. It is also possible that people with migraine may be more willing to report disability than they used to be, authors wrote.
Increased MIDAS scores may be attributable to some environmental risk factor that exacerbates migraine without modifying its prevalence, such as worsening air quality, an increase in natural disasters, or increased opioid use for migraine, they added.
The reason for increased moderate to severe disability in women may be attributable to the fact that migraine is “most common in mid-life, a period characterized by familial and work responsibilities, which may engender a higher risk of burden for working women,” authors wrote. The link between migraine attacks and menstrual cycles may also explain observed gender differences in disability.
In general, the most frequently reported burdens associated with migraine included missed work and school and family and social functioning.
It is “surprising that improvements in treatment have not been associated with reductions in disability,” researchers noted.
No financial support was provided for this study. Dr. Cohen serves as an assistant editor for Headache. He has received honoraria from Springer Nature and MedLink Neurology. Other authors’ disclosures are listed on the original paper.
A version of this article appeared on Medscape.com.
FROM HEADACHE
New Expert Guidance on Antiseizure Medication Use During Pregnancy
New expert guidance to help clinicians manage the treatment of patients with epilepsy during pregnancy has been released.
Issued by the American Academy of Neurology, the American Epilepsy Society, and the Society for Maternal-Fetal Medicine, the new practice guideline covers the use of antiseizure medications (ASMs) and folic acid supplementation before conception and during pregnancy.
“Most children born to people with epilepsy are healthy, but there is a small risk of pregnancy-related problems, partly due to seizures and partly due to the effects of antiseizure medications,” the guidelines’ lead author Alison M. Pack, MD, MPH, professor of neurology and chief of the Epilepsy and Sleep Division, Columbia University, New York City, said in a news release.
“This guideline provides recommendations regarding the effects of antiseizure medications and folic acid supplementation on malformations at birth and the development of children during pregnancy, so that doctors and people with epilepsy can determine which treatments may be best for them,” she added.
The guideline was published online in Neurology.
Why Now?
The new guideline updates the 2009 guidance on epilepsy management during pregnancy. Since then, Dr. Pack told this news organization, there has been a wealth of new data on differential effects of different ASMs — notably, lamotrigine and levetiracetam — the most commonly prescribed medications in this population.
“In this guideline, we were able to assess differential effects of different ASMs on outcomes of interest, including major congenital malformations [MCMs], perinatal outcomes, and neurodevelopmental outcomes. In addition, we looked at the effect of folic acid supplementation on each of these outcomes,” she said.
The overarching goals of care for patients are to “optimize health outcomes both for individuals and their future offspring,” the authors wrote. Shared decision-making, they add, leads to better decision-making by providing a better understanding of the available treatment options and their potential risks, resulting in enhanced decision-making that aligns with personal values.
Clinicians should recommend ASMs that optimize seizure control and fetal outcomes, in the event of a pregnancy, at the earliest possible preconception time, the guideline authors note.
“Overall, treating clinicians need to balance treating the person with epilepsy to control convulsive seizures (generalized tonic-clonic seizures and focal-to-bilateral tonic-clonic seizures) to minimize potential risks to the birth parent and the possible risks of certain ASMs on the fetus if pregnancy occurs,” they wrote.
If a patient is already pregnant, the experts recommend that clinicians “exercise caution” in removing or replacing an ASM that controls convulsive seizures, even if it’s “not an optimal choice” for the fetus.
In addition, they advise that ASM levels should be monitored throughout the pregnancy, guided by individual ASM pharmacokinetics and an individual patient’s clinical presentation. ASM dose, they note, should be adjusted during pregnancy in response to decreasing serum ASM levels or worsening seizure control.
The authors point out that there are limited data on “pregnancy-related outcomes with respect to acetazolamide, eslicarbazepine, ethosuximide, lacosamide, nitrazepam, perampanel, piracetam, pregabalin, rufinamide, stiripentol, tiagabine, and vigabatrin.”
Patients should be informed that the birth prevalence of any major congenital malformation in the general population ranges between 2.4% and 2.9%.
If Feasible, Avoid Valproic Acid
“One of the most important take-home messages is that valproic acid has the highest unadjusted birth prevalence of all major congenital malformations — 9.7% — and the highest unadjusted birth prevalence of neural tube defects at 1.4%,” Dr. Pack said. As a result, the guideline authors advise against using valproic acid, if clinically feasible.
Valproic acid also has the highest prevalence of negative neurodevelopmental outcomes, including a reduction in global IQ and an increased prevalence of autism spectrum disorder (ASD). Patients should be counseled accordingly and advised of the increased risk for ASD and decreased IQ resulting from valproic acid.
Clinicians should consider using lamotrigine, levetiracetam, or oxcarbazepine when appropriate. Serum concentrations of most ASMs have a “defined therapeutic window” for effective seizure control and that concentration may decrease during pregnancy, particularly with lamotrigine and levetiracetam, the authors note.
Phenobarbital, topiramate, and valproic acid should because of the increased risk for cardiac malformations, oral clefts, and urogenital and renal malformations.
Fetal screening for major congenital malformations is recommended to enable early detection and timely intervention in patients treated with any ASM during pregnancy Patients receiving phenobarbital during pregnancy should also undergo fetal cardiac screenings.
Valproic acid and topiramate are also associated with children who are small for their gestational age. To enable early identification of fetal growth restriction, patients taking valproic acid or topiramate should be monitored. In addition, children exposed to these medications in utero should be monitored during childhood to ensure they are meeting age-appropriate developmental milestones.
Folic acid taken during pregnancy can reduce the prevalence of negative neurodevelopment outcomes, but not major congenital malformations, Dr. Pack noted.
“Due to limited available data, we were unable to define an optimal dose of folic acid supplementation beyond at least 0.4 mg/d,” Dr. Pack said. “Future studies, preferably randomized clinical trials, are needed to better define the optimal dose.”
She emphasized that epilepsy is one of the most common neurologic disorders, and 1 in 5 of those affected are people of childbearing potential. Understanding the effects of ASMs on pregnancy outcomes is critical for physicians who manage these patients.
Uncertainty Remains
Commenting for this news organization, Kimford Meador, MD, a professor in the Department of Neurology and Neurological Sciences at Stanford University School of Medicine , Stanford Neuroscience Health Center, Palo Alto, California, noted that the new guidelines reflect the gains in knowledge since 2009 and that the recommendations are “reasonable, based on available data.”
However, “one very important point is how much remains unknown,” said Dr. Meador, who was not involved in writing the current guideline. “Many ASMs have no data, and several have estimates based on small samples or a single observational study.” Thus, “the risks for the majority of ASMs are uncertain.”
Given that randomized trials “are not possible in this population, and that all observational studies are subject to residual confounding, a reliable signal across multiple studies in humans is required to be certain of findings,” he stated.
This practice guideline was developed with financial support from the American Academy of Neurology. Dr. Pack serves on the editorial board for the journal Epilepsy Currents, receives royalties from UpToDate, receives funding from the National Institutes of Health for serving as coinvestigator and site principal investigator for the Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study, and receives funding from Bayer for serving as a co-investigator on a study on women with epilepsy initiating a progestin intrauterine device. One of Dr. Pack’s immediate family members has received personal compensation for serving as an employee of REGENEXBIO. The other authors’ disclosures are listed on the original paper. Dr. Meador has received research support from the National Institutes of Health, Veterans Administration, Eisai, Inc, and Suno Medtronic Navigation, Inc, and the Epilepsy Study Consortium pays Dr. Meador’s university for his research on the Human Epilepsy Project and consultant time related to Eisai, UCB Pharma, and Xenon.
A version of this article first appeared on Medscape.com.
New expert guidance to help clinicians manage the treatment of patients with epilepsy during pregnancy has been released.
Issued by the American Academy of Neurology, the American Epilepsy Society, and the Society for Maternal-Fetal Medicine, the new practice guideline covers the use of antiseizure medications (ASMs) and folic acid supplementation before conception and during pregnancy.
“Most children born to people with epilepsy are healthy, but there is a small risk of pregnancy-related problems, partly due to seizures and partly due to the effects of antiseizure medications,” the guidelines’ lead author Alison M. Pack, MD, MPH, professor of neurology and chief of the Epilepsy and Sleep Division, Columbia University, New York City, said in a news release.
“This guideline provides recommendations regarding the effects of antiseizure medications and folic acid supplementation on malformations at birth and the development of children during pregnancy, so that doctors and people with epilepsy can determine which treatments may be best for them,” she added.
The guideline was published online in Neurology.
Why Now?
The new guideline updates the 2009 guidance on epilepsy management during pregnancy. Since then, Dr. Pack told this news organization, there has been a wealth of new data on differential effects of different ASMs — notably, lamotrigine and levetiracetam — the most commonly prescribed medications in this population.
“In this guideline, we were able to assess differential effects of different ASMs on outcomes of interest, including major congenital malformations [MCMs], perinatal outcomes, and neurodevelopmental outcomes. In addition, we looked at the effect of folic acid supplementation on each of these outcomes,” she said.
The overarching goals of care for patients are to “optimize health outcomes both for individuals and their future offspring,” the authors wrote. Shared decision-making, they add, leads to better decision-making by providing a better understanding of the available treatment options and their potential risks, resulting in enhanced decision-making that aligns with personal values.
Clinicians should recommend ASMs that optimize seizure control and fetal outcomes, in the event of a pregnancy, at the earliest possible preconception time, the guideline authors note.
“Overall, treating clinicians need to balance treating the person with epilepsy to control convulsive seizures (generalized tonic-clonic seizures and focal-to-bilateral tonic-clonic seizures) to minimize potential risks to the birth parent and the possible risks of certain ASMs on the fetus if pregnancy occurs,” they wrote.
If a patient is already pregnant, the experts recommend that clinicians “exercise caution” in removing or replacing an ASM that controls convulsive seizures, even if it’s “not an optimal choice” for the fetus.
In addition, they advise that ASM levels should be monitored throughout the pregnancy, guided by individual ASM pharmacokinetics and an individual patient’s clinical presentation. ASM dose, they note, should be adjusted during pregnancy in response to decreasing serum ASM levels or worsening seizure control.
The authors point out that there are limited data on “pregnancy-related outcomes with respect to acetazolamide, eslicarbazepine, ethosuximide, lacosamide, nitrazepam, perampanel, piracetam, pregabalin, rufinamide, stiripentol, tiagabine, and vigabatrin.”
Patients should be informed that the birth prevalence of any major congenital malformation in the general population ranges between 2.4% and 2.9%.
If Feasible, Avoid Valproic Acid
“One of the most important take-home messages is that valproic acid has the highest unadjusted birth prevalence of all major congenital malformations — 9.7% — and the highest unadjusted birth prevalence of neural tube defects at 1.4%,” Dr. Pack said. As a result, the guideline authors advise against using valproic acid, if clinically feasible.
Valproic acid also has the highest prevalence of negative neurodevelopmental outcomes, including a reduction in global IQ and an increased prevalence of autism spectrum disorder (ASD). Patients should be counseled accordingly and advised of the increased risk for ASD and decreased IQ resulting from valproic acid.
Clinicians should consider using lamotrigine, levetiracetam, or oxcarbazepine when appropriate. Serum concentrations of most ASMs have a “defined therapeutic window” for effective seizure control and that concentration may decrease during pregnancy, particularly with lamotrigine and levetiracetam, the authors note.
Phenobarbital, topiramate, and valproic acid should because of the increased risk for cardiac malformations, oral clefts, and urogenital and renal malformations.
Fetal screening for major congenital malformations is recommended to enable early detection and timely intervention in patients treated with any ASM during pregnancy Patients receiving phenobarbital during pregnancy should also undergo fetal cardiac screenings.
Valproic acid and topiramate are also associated with children who are small for their gestational age. To enable early identification of fetal growth restriction, patients taking valproic acid or topiramate should be monitored. In addition, children exposed to these medications in utero should be monitored during childhood to ensure they are meeting age-appropriate developmental milestones.
Folic acid taken during pregnancy can reduce the prevalence of negative neurodevelopment outcomes, but not major congenital malformations, Dr. Pack noted.
“Due to limited available data, we were unable to define an optimal dose of folic acid supplementation beyond at least 0.4 mg/d,” Dr. Pack said. “Future studies, preferably randomized clinical trials, are needed to better define the optimal dose.”
She emphasized that epilepsy is one of the most common neurologic disorders, and 1 in 5 of those affected are people of childbearing potential. Understanding the effects of ASMs on pregnancy outcomes is critical for physicians who manage these patients.
Uncertainty Remains
Commenting for this news organization, Kimford Meador, MD, a professor in the Department of Neurology and Neurological Sciences at Stanford University School of Medicine , Stanford Neuroscience Health Center, Palo Alto, California, noted that the new guidelines reflect the gains in knowledge since 2009 and that the recommendations are “reasonable, based on available data.”
However, “one very important point is how much remains unknown,” said Dr. Meador, who was not involved in writing the current guideline. “Many ASMs have no data, and several have estimates based on small samples or a single observational study.” Thus, “the risks for the majority of ASMs are uncertain.”
Given that randomized trials “are not possible in this population, and that all observational studies are subject to residual confounding, a reliable signal across multiple studies in humans is required to be certain of findings,” he stated.
This practice guideline was developed with financial support from the American Academy of Neurology. Dr. Pack serves on the editorial board for the journal Epilepsy Currents, receives royalties from UpToDate, receives funding from the National Institutes of Health for serving as coinvestigator and site principal investigator for the Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study, and receives funding from Bayer for serving as a co-investigator on a study on women with epilepsy initiating a progestin intrauterine device. One of Dr. Pack’s immediate family members has received personal compensation for serving as an employee of REGENEXBIO. The other authors’ disclosures are listed on the original paper. Dr. Meador has received research support from the National Institutes of Health, Veterans Administration, Eisai, Inc, and Suno Medtronic Navigation, Inc, and the Epilepsy Study Consortium pays Dr. Meador’s university for his research on the Human Epilepsy Project and consultant time related to Eisai, UCB Pharma, and Xenon.
A version of this article first appeared on Medscape.com.
New expert guidance to help clinicians manage the treatment of patients with epilepsy during pregnancy has been released.
Issued by the American Academy of Neurology, the American Epilepsy Society, and the Society for Maternal-Fetal Medicine, the new practice guideline covers the use of antiseizure medications (ASMs) and folic acid supplementation before conception and during pregnancy.
“Most children born to people with epilepsy are healthy, but there is a small risk of pregnancy-related problems, partly due to seizures and partly due to the effects of antiseizure medications,” the guidelines’ lead author Alison M. Pack, MD, MPH, professor of neurology and chief of the Epilepsy and Sleep Division, Columbia University, New York City, said in a news release.
“This guideline provides recommendations regarding the effects of antiseizure medications and folic acid supplementation on malformations at birth and the development of children during pregnancy, so that doctors and people with epilepsy can determine which treatments may be best for them,” she added.
The guideline was published online in Neurology.
Why Now?
The new guideline updates the 2009 guidance on epilepsy management during pregnancy. Since then, Dr. Pack told this news organization, there has been a wealth of new data on differential effects of different ASMs — notably, lamotrigine and levetiracetam — the most commonly prescribed medications in this population.
“In this guideline, we were able to assess differential effects of different ASMs on outcomes of interest, including major congenital malformations [MCMs], perinatal outcomes, and neurodevelopmental outcomes. In addition, we looked at the effect of folic acid supplementation on each of these outcomes,” she said.
The overarching goals of care for patients are to “optimize health outcomes both for individuals and their future offspring,” the authors wrote. Shared decision-making, they add, leads to better decision-making by providing a better understanding of the available treatment options and their potential risks, resulting in enhanced decision-making that aligns with personal values.
Clinicians should recommend ASMs that optimize seizure control and fetal outcomes, in the event of a pregnancy, at the earliest possible preconception time, the guideline authors note.
“Overall, treating clinicians need to balance treating the person with epilepsy to control convulsive seizures (generalized tonic-clonic seizures and focal-to-bilateral tonic-clonic seizures) to minimize potential risks to the birth parent and the possible risks of certain ASMs on the fetus if pregnancy occurs,” they wrote.
If a patient is already pregnant, the experts recommend that clinicians “exercise caution” in removing or replacing an ASM that controls convulsive seizures, even if it’s “not an optimal choice” for the fetus.
In addition, they advise that ASM levels should be monitored throughout the pregnancy, guided by individual ASM pharmacokinetics and an individual patient’s clinical presentation. ASM dose, they note, should be adjusted during pregnancy in response to decreasing serum ASM levels or worsening seizure control.
The authors point out that there are limited data on “pregnancy-related outcomes with respect to acetazolamide, eslicarbazepine, ethosuximide, lacosamide, nitrazepam, perampanel, piracetam, pregabalin, rufinamide, stiripentol, tiagabine, and vigabatrin.”
Patients should be informed that the birth prevalence of any major congenital malformation in the general population ranges between 2.4% and 2.9%.
If Feasible, Avoid Valproic Acid
“One of the most important take-home messages is that valproic acid has the highest unadjusted birth prevalence of all major congenital malformations — 9.7% — and the highest unadjusted birth prevalence of neural tube defects at 1.4%,” Dr. Pack said. As a result, the guideline authors advise against using valproic acid, if clinically feasible.
Valproic acid also has the highest prevalence of negative neurodevelopmental outcomes, including a reduction in global IQ and an increased prevalence of autism spectrum disorder (ASD). Patients should be counseled accordingly and advised of the increased risk for ASD and decreased IQ resulting from valproic acid.
Clinicians should consider using lamotrigine, levetiracetam, or oxcarbazepine when appropriate. Serum concentrations of most ASMs have a “defined therapeutic window” for effective seizure control and that concentration may decrease during pregnancy, particularly with lamotrigine and levetiracetam, the authors note.
Phenobarbital, topiramate, and valproic acid should because of the increased risk for cardiac malformations, oral clefts, and urogenital and renal malformations.
Fetal screening for major congenital malformations is recommended to enable early detection and timely intervention in patients treated with any ASM during pregnancy Patients receiving phenobarbital during pregnancy should also undergo fetal cardiac screenings.
Valproic acid and topiramate are also associated with children who are small for their gestational age. To enable early identification of fetal growth restriction, patients taking valproic acid or topiramate should be monitored. In addition, children exposed to these medications in utero should be monitored during childhood to ensure they are meeting age-appropriate developmental milestones.
Folic acid taken during pregnancy can reduce the prevalence of negative neurodevelopment outcomes, but not major congenital malformations, Dr. Pack noted.
“Due to limited available data, we were unable to define an optimal dose of folic acid supplementation beyond at least 0.4 mg/d,” Dr. Pack said. “Future studies, preferably randomized clinical trials, are needed to better define the optimal dose.”
She emphasized that epilepsy is one of the most common neurologic disorders, and 1 in 5 of those affected are people of childbearing potential. Understanding the effects of ASMs on pregnancy outcomes is critical for physicians who manage these patients.
Uncertainty Remains
Commenting for this news organization, Kimford Meador, MD, a professor in the Department of Neurology and Neurological Sciences at Stanford University School of Medicine , Stanford Neuroscience Health Center, Palo Alto, California, noted that the new guidelines reflect the gains in knowledge since 2009 and that the recommendations are “reasonable, based on available data.”
However, “one very important point is how much remains unknown,” said Dr. Meador, who was not involved in writing the current guideline. “Many ASMs have no data, and several have estimates based on small samples or a single observational study.” Thus, “the risks for the majority of ASMs are uncertain.”
Given that randomized trials “are not possible in this population, and that all observational studies are subject to residual confounding, a reliable signal across multiple studies in humans is required to be certain of findings,” he stated.
This practice guideline was developed with financial support from the American Academy of Neurology. Dr. Pack serves on the editorial board for the journal Epilepsy Currents, receives royalties from UpToDate, receives funding from the National Institutes of Health for serving as coinvestigator and site principal investigator for the Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study, and receives funding from Bayer for serving as a co-investigator on a study on women with epilepsy initiating a progestin intrauterine device. One of Dr. Pack’s immediate family members has received personal compensation for serving as an employee of REGENEXBIO. The other authors’ disclosures are listed on the original paper. Dr. Meador has received research support from the National Institutes of Health, Veterans Administration, Eisai, Inc, and Suno Medtronic Navigation, Inc, and the Epilepsy Study Consortium pays Dr. Meador’s university for his research on the Human Epilepsy Project and consultant time related to Eisai, UCB Pharma, and Xenon.
A version of this article first appeared on Medscape.com.
FROM NEUROLOGY
Do Antipsychotic Overprescribing Warning Letters Work?
Warning letters to primary care physicians (PCPs) regarding overprescription of quetiapine were helpful in reducing overprescribing of this agent, new research suggested.
Investigators analyzed data from an earlier trial that compared prescribing patterns in 5055 PCPs who receive a placebo letter or three warning letters informing them that their prescribing of quetiapine was high and under review by Medicare. Patients in question all had dementia and were either living in nursing homes or in the community.
The intervention reduced quetiapine use among all patients with dementia, with no detectable adverse effects on cognitive function, behavioral symptoms, depression, metabolic diagnoses, hospitalization, or death.
“This study found that overprescribing warning letters to PCPs safely reduced quetiapine prescribing to their patients with dementia,” wrote investigators led by Adam Sacarny, PhD, of the Department of Health Policy and Management, Mailman School of Public Health, Columbia University, New York.
“This intervention and other[s] like it may be useful for future efforts to promote guideline-concordant care,” they added.
The study was published online in JAMA Network Open.
Off-Label Prescribing Common
The off-label use of antipsychotics in patients with dementia is fairly common, the investigators noted, affecting roughly one in seven nursing home residents and a similar number of community-dwelling older adults with dementia.
The agents are often prescribed to treat behavioral symptoms associated with dementia, including agitation and aggression. Although some evidence supports this use, antipsychotics in dementia patients can also cause an increased risk for weight gain, cognitive decline, falls and other injuries, cerebrovascular events, and mortality.
While some professional societies have called for “judicious use of antipsychotics in dementia care,” there is little evidence that reducing antipsychotic use in people with dementia might result in a benefit, investigators wrote.
The researchers analyzed data from a previous trial that focused on quetiapine, which is the most prescribed antipsychotic in the United States and is frequently used for patients with dementia.
In the original study, 2528 PCPs received a placebo letter and 2527 received three warning letters sent by the Centers for Medicare & Medicaid Services (CMS), which identified the highest-volume PCP prescribers of quetiapine.
The warning letters stated that the recipient’s quetiapine prescribing was high relative to their peers and was under review by Medicare. The placebo letter clarified an unrelated regulation.
The current secondary analysis followed the providers and a cohort of their patients from their first receipt of the letters in 2015 through April 2017. The current evaluation analyzes patients’ outcomes through December 2018, utilizing Medicare fee-for-service claims, Minimum Data Set nursing home assessment, and Medicare enrollment data.
Low-Cost, Effective Intervention
While the original study focused on total quetiapine prescribing by study PCPs, the current analysis focused on patients’ total quetiapine use per 90-day period. Additional secondary outcomes included measures of cognitive function and behavioral symptoms, indicators of depression, metabolic diagnoses, indicators of use of hospital and healthcare services, and death.
PCPs in the study had a total of 84,881 patients with dementia living in nursing homes and 261,288 living in the community. At baseline, there were 92,874 patients (mean age, 82 years; 69% female).
The warning letters were associated with reduced quetiapine use among both nursing home patients and community-dwelling patients (adjusted difference, –0.7 days; P = .02 and adjusted difference, −1.5 days; P < .001, respectively).
Among nursing home patients, there were no statistically significant adverse changes in cognitive of behavioral health measures that coincided with reduction in quetiapine use.
Although a higher percentage of treatment vs control patients reported weight loss, the difference was not significant, and rates of metabolic diagnoses were similar in both groups. There were also no significant differences between the groups in emergency department use, inpatient hospital admission, or use of restraints.
Results were similar for patients living in the community.
Additionally, no adverse effects on more severe health endpoints, including rates of hospital use or entry to nursing facilities, were detected. Importantly, the risk for death was statistically significantly lower for patients whose PCPs had received warning letters vs control patients (P = .04).
The analysis “provides evidence that a low-cost letter intervention informed by behavioral science can reduce prescribing of quetiapine to patients with dementia in nursing home and community settings,” the authors wrote.
Researchers did not directly observe the administration of the medication but instead used prescription drug fills as a proxy. Moreover, they could not observe results for patients enrolled in Medicare Advantage, and claims-based and assessment-based outcomes might have been subject to measurement errors and under-ascertainment of diagnoses.
The authors received support from the National Institute on Aging. They reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Warning letters to primary care physicians (PCPs) regarding overprescription of quetiapine were helpful in reducing overprescribing of this agent, new research suggested.
Investigators analyzed data from an earlier trial that compared prescribing patterns in 5055 PCPs who receive a placebo letter or three warning letters informing them that their prescribing of quetiapine was high and under review by Medicare. Patients in question all had dementia and were either living in nursing homes or in the community.
The intervention reduced quetiapine use among all patients with dementia, with no detectable adverse effects on cognitive function, behavioral symptoms, depression, metabolic diagnoses, hospitalization, or death.
“This study found that overprescribing warning letters to PCPs safely reduced quetiapine prescribing to their patients with dementia,” wrote investigators led by Adam Sacarny, PhD, of the Department of Health Policy and Management, Mailman School of Public Health, Columbia University, New York.
“This intervention and other[s] like it may be useful for future efforts to promote guideline-concordant care,” they added.
The study was published online in JAMA Network Open.
Off-Label Prescribing Common
The off-label use of antipsychotics in patients with dementia is fairly common, the investigators noted, affecting roughly one in seven nursing home residents and a similar number of community-dwelling older adults with dementia.
The agents are often prescribed to treat behavioral symptoms associated with dementia, including agitation and aggression. Although some evidence supports this use, antipsychotics in dementia patients can also cause an increased risk for weight gain, cognitive decline, falls and other injuries, cerebrovascular events, and mortality.
While some professional societies have called for “judicious use of antipsychotics in dementia care,” there is little evidence that reducing antipsychotic use in people with dementia might result in a benefit, investigators wrote.
The researchers analyzed data from a previous trial that focused on quetiapine, which is the most prescribed antipsychotic in the United States and is frequently used for patients with dementia.
In the original study, 2528 PCPs received a placebo letter and 2527 received three warning letters sent by the Centers for Medicare & Medicaid Services (CMS), which identified the highest-volume PCP prescribers of quetiapine.
The warning letters stated that the recipient’s quetiapine prescribing was high relative to their peers and was under review by Medicare. The placebo letter clarified an unrelated regulation.
The current secondary analysis followed the providers and a cohort of their patients from their first receipt of the letters in 2015 through April 2017. The current evaluation analyzes patients’ outcomes through December 2018, utilizing Medicare fee-for-service claims, Minimum Data Set nursing home assessment, and Medicare enrollment data.
Low-Cost, Effective Intervention
While the original study focused on total quetiapine prescribing by study PCPs, the current analysis focused on patients’ total quetiapine use per 90-day period. Additional secondary outcomes included measures of cognitive function and behavioral symptoms, indicators of depression, metabolic diagnoses, indicators of use of hospital and healthcare services, and death.
PCPs in the study had a total of 84,881 patients with dementia living in nursing homes and 261,288 living in the community. At baseline, there were 92,874 patients (mean age, 82 years; 69% female).
The warning letters were associated with reduced quetiapine use among both nursing home patients and community-dwelling patients (adjusted difference, –0.7 days; P = .02 and adjusted difference, −1.5 days; P < .001, respectively).
Among nursing home patients, there were no statistically significant adverse changes in cognitive of behavioral health measures that coincided with reduction in quetiapine use.
Although a higher percentage of treatment vs control patients reported weight loss, the difference was not significant, and rates of metabolic diagnoses were similar in both groups. There were also no significant differences between the groups in emergency department use, inpatient hospital admission, or use of restraints.
Results were similar for patients living in the community.
Additionally, no adverse effects on more severe health endpoints, including rates of hospital use or entry to nursing facilities, were detected. Importantly, the risk for death was statistically significantly lower for patients whose PCPs had received warning letters vs control patients (P = .04).
The analysis “provides evidence that a low-cost letter intervention informed by behavioral science can reduce prescribing of quetiapine to patients with dementia in nursing home and community settings,” the authors wrote.
Researchers did not directly observe the administration of the medication but instead used prescription drug fills as a proxy. Moreover, they could not observe results for patients enrolled in Medicare Advantage, and claims-based and assessment-based outcomes might have been subject to measurement errors and under-ascertainment of diagnoses.
The authors received support from the National Institute on Aging. They reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Warning letters to primary care physicians (PCPs) regarding overprescription of quetiapine were helpful in reducing overprescribing of this agent, new research suggested.
Investigators analyzed data from an earlier trial that compared prescribing patterns in 5055 PCPs who receive a placebo letter or three warning letters informing them that their prescribing of quetiapine was high and under review by Medicare. Patients in question all had dementia and were either living in nursing homes or in the community.
The intervention reduced quetiapine use among all patients with dementia, with no detectable adverse effects on cognitive function, behavioral symptoms, depression, metabolic diagnoses, hospitalization, or death.
“This study found that overprescribing warning letters to PCPs safely reduced quetiapine prescribing to their patients with dementia,” wrote investigators led by Adam Sacarny, PhD, of the Department of Health Policy and Management, Mailman School of Public Health, Columbia University, New York.
“This intervention and other[s] like it may be useful for future efforts to promote guideline-concordant care,” they added.
The study was published online in JAMA Network Open.
Off-Label Prescribing Common
The off-label use of antipsychotics in patients with dementia is fairly common, the investigators noted, affecting roughly one in seven nursing home residents and a similar number of community-dwelling older adults with dementia.
The agents are often prescribed to treat behavioral symptoms associated with dementia, including agitation and aggression. Although some evidence supports this use, antipsychotics in dementia patients can also cause an increased risk for weight gain, cognitive decline, falls and other injuries, cerebrovascular events, and mortality.
While some professional societies have called for “judicious use of antipsychotics in dementia care,” there is little evidence that reducing antipsychotic use in people with dementia might result in a benefit, investigators wrote.
The researchers analyzed data from a previous trial that focused on quetiapine, which is the most prescribed antipsychotic in the United States and is frequently used for patients with dementia.
In the original study, 2528 PCPs received a placebo letter and 2527 received three warning letters sent by the Centers for Medicare & Medicaid Services (CMS), which identified the highest-volume PCP prescribers of quetiapine.
The warning letters stated that the recipient’s quetiapine prescribing was high relative to their peers and was under review by Medicare. The placebo letter clarified an unrelated regulation.
The current secondary analysis followed the providers and a cohort of their patients from their first receipt of the letters in 2015 through April 2017. The current evaluation analyzes patients’ outcomes through December 2018, utilizing Medicare fee-for-service claims, Minimum Data Set nursing home assessment, and Medicare enrollment data.
Low-Cost, Effective Intervention
While the original study focused on total quetiapine prescribing by study PCPs, the current analysis focused on patients’ total quetiapine use per 90-day period. Additional secondary outcomes included measures of cognitive function and behavioral symptoms, indicators of depression, metabolic diagnoses, indicators of use of hospital and healthcare services, and death.
PCPs in the study had a total of 84,881 patients with dementia living in nursing homes and 261,288 living in the community. At baseline, there were 92,874 patients (mean age, 82 years; 69% female).
The warning letters were associated with reduced quetiapine use among both nursing home patients and community-dwelling patients (adjusted difference, –0.7 days; P = .02 and adjusted difference, −1.5 days; P < .001, respectively).
Among nursing home patients, there were no statistically significant adverse changes in cognitive of behavioral health measures that coincided with reduction in quetiapine use.
Although a higher percentage of treatment vs control patients reported weight loss, the difference was not significant, and rates of metabolic diagnoses were similar in both groups. There were also no significant differences between the groups in emergency department use, inpatient hospital admission, or use of restraints.
Results were similar for patients living in the community.
Additionally, no adverse effects on more severe health endpoints, including rates of hospital use or entry to nursing facilities, were detected. Importantly, the risk for death was statistically significantly lower for patients whose PCPs had received warning letters vs control patients (P = .04).
The analysis “provides evidence that a low-cost letter intervention informed by behavioral science can reduce prescribing of quetiapine to patients with dementia in nursing home and community settings,” the authors wrote.
Researchers did not directly observe the administration of the medication but instead used prescription drug fills as a proxy. Moreover, they could not observe results for patients enrolled in Medicare Advantage, and claims-based and assessment-based outcomes might have been subject to measurement errors and under-ascertainment of diagnoses.
The authors received support from the National Institute on Aging. They reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM JAMA NETWORK OPEN
Mental Health Worsens in Trans, Gender-Nonconforming Adults
TOPLINE:
Mental health distress increased disproportionately among transgender and gender-nonconforming US adults between 2014 and 2021 compared with their cisgender counterparts, a new study suggested. Investigators said the findings among an historically marginalized segment of society point to a need to address a growing inequality in mental health.
METHODOLOGY:
- Investigators drew on 2014-2021 US Behavioral Risk Factor Surveillance System (BRFSS) survey data, using logistic and ordinary least squares regression to document temporal trends in the transgender-cisgender disparity in self-reports of the number of poor mental health days in the past month and frequent mental distress.
- They included 43 states that implemented the optional sexual orientation and gender identity module in the BRFSS.
- Outcomes included the number of poor mental health days in the past month, as well as frequent mental distress (≥ 14 poor mental health days in the past month).
TAKEAWAY:
- Even in 2014, there was a discrepancy between cisgender and transgender and gender-nonconforming individuals in the reported mean of poor mental health days (3.68 vs 5.42).
- The size of this disparity, adjusted by differences in observable characteristics, increased by 2.75 days (95% CI, 0.58-4.91) over the study period.
- The inequality in mental health status between cisgender and transgender and nonconforming adults grew from 11.4% vs 18.9% in 2014, respectively, to 14.6% vs 32.9% in 2021, respectively.
IN PRACTICE:
“Our findings demonstrate sizable and worsening inequities in mental health across gender identity,” the authors wrote. “Mental health and primary care providers must be prepared to address the unique psychosocial needs of gender minority adults. Furthermore, our findings highlight the need for action to reduce these disparities.”
SOURCE:
Samuel Mann, PhD, of the RAND Corporation, was the corresponding author of the study. It was published online on April 10 in the American Journal of Public Health.
LIMITATIONS:
Measures of mental health were derived from self-reports. In addition, data from seven states were missing because these states did not include sexual orientation and gender identity in the BRFSS. And the BRFSS does not survey people who are unhoused, incarcerated, or in group living quarters.
DISCLOSURES:
No source of study funding was listed. The authors disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
TOPLINE:
Mental health distress increased disproportionately among transgender and gender-nonconforming US adults between 2014 and 2021 compared with their cisgender counterparts, a new study suggested. Investigators said the findings among an historically marginalized segment of society point to a need to address a growing inequality in mental health.
METHODOLOGY:
- Investigators drew on 2014-2021 US Behavioral Risk Factor Surveillance System (BRFSS) survey data, using logistic and ordinary least squares regression to document temporal trends in the transgender-cisgender disparity in self-reports of the number of poor mental health days in the past month and frequent mental distress.
- They included 43 states that implemented the optional sexual orientation and gender identity module in the BRFSS.
- Outcomes included the number of poor mental health days in the past month, as well as frequent mental distress (≥ 14 poor mental health days in the past month).
TAKEAWAY:
- Even in 2014, there was a discrepancy between cisgender and transgender and gender-nonconforming individuals in the reported mean of poor mental health days (3.68 vs 5.42).
- The size of this disparity, adjusted by differences in observable characteristics, increased by 2.75 days (95% CI, 0.58-4.91) over the study period.
- The inequality in mental health status between cisgender and transgender and nonconforming adults grew from 11.4% vs 18.9% in 2014, respectively, to 14.6% vs 32.9% in 2021, respectively.
IN PRACTICE:
“Our findings demonstrate sizable and worsening inequities in mental health across gender identity,” the authors wrote. “Mental health and primary care providers must be prepared to address the unique psychosocial needs of gender minority adults. Furthermore, our findings highlight the need for action to reduce these disparities.”
SOURCE:
Samuel Mann, PhD, of the RAND Corporation, was the corresponding author of the study. It was published online on April 10 in the American Journal of Public Health.
LIMITATIONS:
Measures of mental health were derived from self-reports. In addition, data from seven states were missing because these states did not include sexual orientation and gender identity in the BRFSS. And the BRFSS does not survey people who are unhoused, incarcerated, or in group living quarters.
DISCLOSURES:
No source of study funding was listed. The authors disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
TOPLINE:
Mental health distress increased disproportionately among transgender and gender-nonconforming US adults between 2014 and 2021 compared with their cisgender counterparts, a new study suggested. Investigators said the findings among an historically marginalized segment of society point to a need to address a growing inequality in mental health.
METHODOLOGY:
- Investigators drew on 2014-2021 US Behavioral Risk Factor Surveillance System (BRFSS) survey data, using logistic and ordinary least squares regression to document temporal trends in the transgender-cisgender disparity in self-reports of the number of poor mental health days in the past month and frequent mental distress.
- They included 43 states that implemented the optional sexual orientation and gender identity module in the BRFSS.
- Outcomes included the number of poor mental health days in the past month, as well as frequent mental distress (≥ 14 poor mental health days in the past month).
TAKEAWAY:
- Even in 2014, there was a discrepancy between cisgender and transgender and gender-nonconforming individuals in the reported mean of poor mental health days (3.68 vs 5.42).
- The size of this disparity, adjusted by differences in observable characteristics, increased by 2.75 days (95% CI, 0.58-4.91) over the study period.
- The inequality in mental health status between cisgender and transgender and nonconforming adults grew from 11.4% vs 18.9% in 2014, respectively, to 14.6% vs 32.9% in 2021, respectively.
IN PRACTICE:
“Our findings demonstrate sizable and worsening inequities in mental health across gender identity,” the authors wrote. “Mental health and primary care providers must be prepared to address the unique psychosocial needs of gender minority adults. Furthermore, our findings highlight the need for action to reduce these disparities.”
SOURCE:
Samuel Mann, PhD, of the RAND Corporation, was the corresponding author of the study. It was published online on April 10 in the American Journal of Public Health.
LIMITATIONS:
Measures of mental health were derived from self-reports. In addition, data from seven states were missing because these states did not include sexual orientation and gender identity in the BRFSS. And the BRFSS does not survey people who are unhoused, incarcerated, or in group living quarters.
DISCLOSURES:
No source of study funding was listed. The authors disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
High Olive Oil Intake Linked to Lower Dementia-Related Death
, a new study suggested.
Data from a prospective study of more than 92,000 people showed consuming at least 7 g of olive oil a day — about half a tablespoon — was associated with a 28% lower risk for dementia-related death.
Replacing one teaspoon of margarine and mayonnaise with the equivalent amount of olive oil was associated with an 8%-14% lower risk for dementia-related mortality.
“Opting for olive oil, a natural product, instead of more processed fats such as margarine and mayonnaise, is a safe choice and may reduce risk of fatal dementia,” said lead investigator Anne-Julie Tessier, RD, PhD, research associate, Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston.
However, “intervention studies are needed to confirm causal effect and optimal quantity of olive oil intake,” she added.
The study was published online in JAMA Network Open.
A Spoonful of Olive Oil
A growing body of evidence has shown a link between the Mediterranean diet and preserved cognitive function and lower risk for cardiovascular disease (CVD). But its association with dementia mortality was unknown.
Investigators analyzed data on over 92,000 participants (66% women; mean age, 56 years) in the Nurses’ Health Study (NHS) and Health Professionals Follow-Up Study (HPFS) who were free of CVD and cancer at baseline.
Both studies were conducted between 1990 and 2018, with olive oil intake assessed every 4 years using a food frequency questionnaire. Dementia-related mortality was ascertained from death records.
The researchers also evaluated the joint association of diet quality (particularly adherence to the Mediterranean diet and Alternative Healthy Eating Index score) and olive oil consumption with the risk for dementia-related mortality. And they estimated the difference in the risk for dementia-related mortality when other dietary fats were substituted with an equivalent amount of olive oil.
There were 4751 dementia-related deaths during the 28-year follow-up period. People with two copies of the apolipoprotein epsilon-4 (APOE epsilon-4) allele — a known risk factor for Alzheimer’s disease — had a fivefold to ninefold greater likelihood of dementia-related death.
Compared with no or rare olive oil intake, consumption of 7 g of olive oil or more per day was associated with a 28% lower risk for dementia-related mortality (adjusted hazard ratio [HR], 0.72; P < .001), after adjusting for lifestyle and socioeconomic factors. The finding remained consistent even with further adjustment for the APOE epsilon-4 allele.
Each 5-g increment in olive oil consumption had an inverse association with dementia-related death in women (HR, 0.88; 95% CI, 0.84-0.93) but not in men (HR, 0.96; 95% CI, 0.88-1.04).
No interaction by diet quality scores was found.
No Link With Diet Quality
“Typically, people who use olive oil for cooking or as a dressing have an overall better quality of their diet, but interestingly, we found the association between more olive oil and reduced risk of dementia-related death to be regardless of this factor,” Dr. Tessier said.
Replacing 5 g per day of margarine and mayonnaise with the equivalent amount of olive oil was associated with an 8%-14% lower risk for dementia mortality. Substitutions for other vegetable oils or butter were not significant.
“Some antioxidant compounds in olive oil can cross the blood-brain barrier, potentially having a direct effect on the brain,” Dr. Tessier said. “It is also possible that olive oil has an indirect effect on brain health by benefiting cardiovascular health.”
The authors noted several study limitations, including the possibility of reverse causation, due to the observational nature of the study.
It is also plausible that higher olive oil intake could be indicative of a healthier diet and higher socioeconomic status, although the results remained consistent after accounting these factors, the authors noted.
The study population included only healthcare professionals and was primarily non-Hispanic White people, which could limit generalizability.
Causality Versus Connection
Commenting on the findings, Rebecca M. Edelmayer, PhD, senior director of scientific engagement for the Alzheimer’s Association, cautioned that the study was designed to show correlation, not causation.
Other notable limitations include measuring prevalence or incidence of dementia from death records because dementia and Alzheimer’s disease are often underreported as a cause of death.
Moreover, people in the highest olive oil consumption group also had better diet quality, higher alcohol intake, were more physically active, and less likely to smoke, Dr. Edelmayer said.
“All of these factors may have an impact on risk of cognitive decline and dementia, separately from or in addition to olive oil consumption,” said Dr. Edelmayer, who was not involved with the study.
She echoed the authors’ concerns that the study was conducted in predominantly non-Hispanic White people and noted that the protective benefits of olive oil were no longer statistically significant for men after adjusting for potential confounders.
It “would be wonderful if a particular food could delay or prevent Alzheimer’s disease, but we do not have scientific evidence that these claims are true,” Dr. Edelmayer said. “We need randomized controlled clinical trials to evaluate whether any foods have a scientifically proven beneficial effect.”
This study is supported by a research grant from the National Institutes of Health to the senior author. The NHS, NHSII, and HPFS are supported by grants from the National Institutes of Health. Tessier is supported by the Canadian Institutes of Health Research Postdoctoral Fellowship Award. Senior author Guasch-Ferré is supported by a Novo Nordisk Foundation grant. Dr. Tessier reported no other relevant financial relationships. The other authors’ disclosures are listed on the original paper. Dr. Edelmayer reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
, a new study suggested.
Data from a prospective study of more than 92,000 people showed consuming at least 7 g of olive oil a day — about half a tablespoon — was associated with a 28% lower risk for dementia-related death.
Replacing one teaspoon of margarine and mayonnaise with the equivalent amount of olive oil was associated with an 8%-14% lower risk for dementia-related mortality.
“Opting for olive oil, a natural product, instead of more processed fats such as margarine and mayonnaise, is a safe choice and may reduce risk of fatal dementia,” said lead investigator Anne-Julie Tessier, RD, PhD, research associate, Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston.
However, “intervention studies are needed to confirm causal effect and optimal quantity of olive oil intake,” she added.
The study was published online in JAMA Network Open.
A Spoonful of Olive Oil
A growing body of evidence has shown a link between the Mediterranean diet and preserved cognitive function and lower risk for cardiovascular disease (CVD). But its association with dementia mortality was unknown.
Investigators analyzed data on over 92,000 participants (66% women; mean age, 56 years) in the Nurses’ Health Study (NHS) and Health Professionals Follow-Up Study (HPFS) who were free of CVD and cancer at baseline.
Both studies were conducted between 1990 and 2018, with olive oil intake assessed every 4 years using a food frequency questionnaire. Dementia-related mortality was ascertained from death records.
The researchers also evaluated the joint association of diet quality (particularly adherence to the Mediterranean diet and Alternative Healthy Eating Index score) and olive oil consumption with the risk for dementia-related mortality. And they estimated the difference in the risk for dementia-related mortality when other dietary fats were substituted with an equivalent amount of olive oil.
There were 4751 dementia-related deaths during the 28-year follow-up period. People with two copies of the apolipoprotein epsilon-4 (APOE epsilon-4) allele — a known risk factor for Alzheimer’s disease — had a fivefold to ninefold greater likelihood of dementia-related death.
Compared with no or rare olive oil intake, consumption of 7 g of olive oil or more per day was associated with a 28% lower risk for dementia-related mortality (adjusted hazard ratio [HR], 0.72; P < .001), after adjusting for lifestyle and socioeconomic factors. The finding remained consistent even with further adjustment for the APOE epsilon-4 allele.
Each 5-g increment in olive oil consumption had an inverse association with dementia-related death in women (HR, 0.88; 95% CI, 0.84-0.93) but not in men (HR, 0.96; 95% CI, 0.88-1.04).
No interaction by diet quality scores was found.
No Link With Diet Quality
“Typically, people who use olive oil for cooking or as a dressing have an overall better quality of their diet, but interestingly, we found the association between more olive oil and reduced risk of dementia-related death to be regardless of this factor,” Dr. Tessier said.
Replacing 5 g per day of margarine and mayonnaise with the equivalent amount of olive oil was associated with an 8%-14% lower risk for dementia mortality. Substitutions for other vegetable oils or butter were not significant.
“Some antioxidant compounds in olive oil can cross the blood-brain barrier, potentially having a direct effect on the brain,” Dr. Tessier said. “It is also possible that olive oil has an indirect effect on brain health by benefiting cardiovascular health.”
The authors noted several study limitations, including the possibility of reverse causation, due to the observational nature of the study.
It is also plausible that higher olive oil intake could be indicative of a healthier diet and higher socioeconomic status, although the results remained consistent after accounting these factors, the authors noted.
The study population included only healthcare professionals and was primarily non-Hispanic White people, which could limit generalizability.
Causality Versus Connection
Commenting on the findings, Rebecca M. Edelmayer, PhD, senior director of scientific engagement for the Alzheimer’s Association, cautioned that the study was designed to show correlation, not causation.
Other notable limitations include measuring prevalence or incidence of dementia from death records because dementia and Alzheimer’s disease are often underreported as a cause of death.
Moreover, people in the highest olive oil consumption group also had better diet quality, higher alcohol intake, were more physically active, and less likely to smoke, Dr. Edelmayer said.
“All of these factors may have an impact on risk of cognitive decline and dementia, separately from or in addition to olive oil consumption,” said Dr. Edelmayer, who was not involved with the study.
She echoed the authors’ concerns that the study was conducted in predominantly non-Hispanic White people and noted that the protective benefits of olive oil were no longer statistically significant for men after adjusting for potential confounders.
It “would be wonderful if a particular food could delay or prevent Alzheimer’s disease, but we do not have scientific evidence that these claims are true,” Dr. Edelmayer said. “We need randomized controlled clinical trials to evaluate whether any foods have a scientifically proven beneficial effect.”
This study is supported by a research grant from the National Institutes of Health to the senior author. The NHS, NHSII, and HPFS are supported by grants from the National Institutes of Health. Tessier is supported by the Canadian Institutes of Health Research Postdoctoral Fellowship Award. Senior author Guasch-Ferré is supported by a Novo Nordisk Foundation grant. Dr. Tessier reported no other relevant financial relationships. The other authors’ disclosures are listed on the original paper. Dr. Edelmayer reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
, a new study suggested.
Data from a prospective study of more than 92,000 people showed consuming at least 7 g of olive oil a day — about half a tablespoon — was associated with a 28% lower risk for dementia-related death.
Replacing one teaspoon of margarine and mayonnaise with the equivalent amount of olive oil was associated with an 8%-14% lower risk for dementia-related mortality.
“Opting for olive oil, a natural product, instead of more processed fats such as margarine and mayonnaise, is a safe choice and may reduce risk of fatal dementia,” said lead investigator Anne-Julie Tessier, RD, PhD, research associate, Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston.
However, “intervention studies are needed to confirm causal effect and optimal quantity of olive oil intake,” she added.
The study was published online in JAMA Network Open.
A Spoonful of Olive Oil
A growing body of evidence has shown a link between the Mediterranean diet and preserved cognitive function and lower risk for cardiovascular disease (CVD). But its association with dementia mortality was unknown.
Investigators analyzed data on over 92,000 participants (66% women; mean age, 56 years) in the Nurses’ Health Study (NHS) and Health Professionals Follow-Up Study (HPFS) who were free of CVD and cancer at baseline.
Both studies were conducted between 1990 and 2018, with olive oil intake assessed every 4 years using a food frequency questionnaire. Dementia-related mortality was ascertained from death records.
The researchers also evaluated the joint association of diet quality (particularly adherence to the Mediterranean diet and Alternative Healthy Eating Index score) and olive oil consumption with the risk for dementia-related mortality. And they estimated the difference in the risk for dementia-related mortality when other dietary fats were substituted with an equivalent amount of olive oil.
There were 4751 dementia-related deaths during the 28-year follow-up period. People with two copies of the apolipoprotein epsilon-4 (APOE epsilon-4) allele — a known risk factor for Alzheimer’s disease — had a fivefold to ninefold greater likelihood of dementia-related death.
Compared with no or rare olive oil intake, consumption of 7 g of olive oil or more per day was associated with a 28% lower risk for dementia-related mortality (adjusted hazard ratio [HR], 0.72; P < .001), after adjusting for lifestyle and socioeconomic factors. The finding remained consistent even with further adjustment for the APOE epsilon-4 allele.
Each 5-g increment in olive oil consumption had an inverse association with dementia-related death in women (HR, 0.88; 95% CI, 0.84-0.93) but not in men (HR, 0.96; 95% CI, 0.88-1.04).
No interaction by diet quality scores was found.
No Link With Diet Quality
“Typically, people who use olive oil for cooking or as a dressing have an overall better quality of their diet, but interestingly, we found the association between more olive oil and reduced risk of dementia-related death to be regardless of this factor,” Dr. Tessier said.
Replacing 5 g per day of margarine and mayonnaise with the equivalent amount of olive oil was associated with an 8%-14% lower risk for dementia mortality. Substitutions for other vegetable oils or butter were not significant.
“Some antioxidant compounds in olive oil can cross the blood-brain barrier, potentially having a direct effect on the brain,” Dr. Tessier said. “It is also possible that olive oil has an indirect effect on brain health by benefiting cardiovascular health.”
The authors noted several study limitations, including the possibility of reverse causation, due to the observational nature of the study.
It is also plausible that higher olive oil intake could be indicative of a healthier diet and higher socioeconomic status, although the results remained consistent after accounting these factors, the authors noted.
The study population included only healthcare professionals and was primarily non-Hispanic White people, which could limit generalizability.
Causality Versus Connection
Commenting on the findings, Rebecca M. Edelmayer, PhD, senior director of scientific engagement for the Alzheimer’s Association, cautioned that the study was designed to show correlation, not causation.
Other notable limitations include measuring prevalence or incidence of dementia from death records because dementia and Alzheimer’s disease are often underreported as a cause of death.
Moreover, people in the highest olive oil consumption group also had better diet quality, higher alcohol intake, were more physically active, and less likely to smoke, Dr. Edelmayer said.
“All of these factors may have an impact on risk of cognitive decline and dementia, separately from or in addition to olive oil consumption,” said Dr. Edelmayer, who was not involved with the study.
She echoed the authors’ concerns that the study was conducted in predominantly non-Hispanic White people and noted that the protective benefits of olive oil were no longer statistically significant for men after adjusting for potential confounders.
It “would be wonderful if a particular food could delay or prevent Alzheimer’s disease, but we do not have scientific evidence that these claims are true,” Dr. Edelmayer said. “We need randomized controlled clinical trials to evaluate whether any foods have a scientifically proven beneficial effect.”
This study is supported by a research grant from the National Institutes of Health to the senior author. The NHS, NHSII, and HPFS are supported by grants from the National Institutes of Health. Tessier is supported by the Canadian Institutes of Health Research Postdoctoral Fellowship Award. Senior author Guasch-Ferré is supported by a Novo Nordisk Foundation grant. Dr. Tessier reported no other relevant financial relationships. The other authors’ disclosures are listed on the original paper. Dr. Edelmayer reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
FROM JAMA NETWORK OPEN
‘Autoantibody Signature’ Flags MS Years Before Symptom Onset
, according to a new study.
Investigators screened blood samples from 250 individuals with MS drawn 5 years before and 1 year after symptom onset, profiled MS-related autoantibodies, and compared the sample with 250 matched controls.
A unique cluster of autoantibodies was found in 10% of people with MS, appearing up to 5 years before the onset of clinical symptoms and remaining higher 1 year after diagnosis.
“Our work demonstrates that a subset of MS patients has antibodies that react to a common protein motif, both before, during, and after diagnosis and symptom onset,” said lead investigator Colin R. Zamecnik, PhD, a postdoctoral researcher at UCSF School of Medicine, University of California, San Francisco.
Such a discovery could aid in early diagnosis, Dr. Zamecnik added. MS treatments “have gotten much better in the last 15-20 years and evidence shows early treatment can improve outcomes,” he said.
The study was published online in Nature Medicine.
Seeking Earlier Diagnosis
Previous research shows that nonspecific neurologic episodes occur more frequently in people who received an MS diagnosis later in life, pointing to the possibility of an MS prodrome, the authors noted.
These neurologic episodes may be indicative of ongoing neuroinflammatory processes in the preclinical period, they added. Studies in several other autoimmune diseases show that diagnostic autoantibodies can appear years before symptom onset. However, no such antibodies have previously been identified in MS patients.
To investigate, the researchers turned to data from a large, prospective incident MS cohort assembled during the Gulf War era in more than 10 million US military veterans.
Records of those with the earliest diagnosis (an average of 5 years before symptom onset) and 1 year after the first attack were analyzed, and matched controls were selected.
Investigators used a technique called phage display immunoprecipitation sequencing to screen human blood for antibodies. They conducted a whole-proteome autoantibody screen and serum neurofilament light (sNfL) measurements on these samples in both case patients and controls at the same time points.
Early Signs of Injury
In the preclinical serum samples, sNfL levels were higher nearer the date of diagnosis and significantly higher in post- versus pre-onset samples in people with MS. “Together, these data provide evidence that at least some people with MS exhibit early signs of neuroaxonal injury long before onset of symptoms,” the authors noted.
Analysis of the collection of peptides, described by the investigators as an “autoantibody signature,” was consistent over time and was present regardless of diagnosis.
Further analysis of the autoantibodies revealed a characteristic protein motif found in common viruses, including Epstein-Barr virus (EBV) and hepatitis C virus, among others.
The motif “shares remarkable similarity to those found on many pathogens that infect humans, including EBV, which is known to be a risk factor for development of MS,” Dr. Zamecnik said.
The researchers validated these findings by analyzing serum and cerebrospinal fluid samples from participants in ORIGINS, an MS cohort at the University of California, San Francisco, that enrolled patients at clinical onset. As with the other cohort, 10% of patients had the autoantibody signature.
The investigators added that the findings detail some of the first autoantigen-specific biomarkers found in preclinical MS.
“Taken together, our future work will focus on profiling these patients more closely over time to see how they differ from their counterparts and gives further evidence of viral-host crosstalk as a hallmark of this disease,” Dr. Zamecnik said.
Not Ready for Prime Time
Commenting on the findings, Bruce Bebo, PhD, executive vice president of research, National Multiple Sclerosis Society, said the study corroborates the “growing appreciation that MS has a prodrome.”
Such a discovery might “accelerate progress toward the possibility of treating MS ever-earlier in the course of the disease, or possibly even preventing MS from occurring in the first place,” he added.
Dr. Bebo, who was not involved in this research, noted that it was conducted at a single center, is only preliminary, and “has no immediate clinical applicability.”
Also, because this pattern was identified in only 10% of individuals with MS, “an additional hurdle is whether we can identify other patterns in greater numbers of people,” he added.
This work was supported by the Valhalla Foundation; the Weill Neurohub; the Westridge Foundation; the National Institute of Neurological Disorders and Stroke; the National Institute of Allergy and Infectious Diseases; National Multiple Sclerosis Society; the Department of Defense; the German Society of Multiple Sclerosis; the Water Cove Charitable Foundation; Tim and Laura O’Shaughnessy; the Littera Family; School of Medicine Dean’s Yearlong Fellowship, supported by residual funds from the Howard Hughes Medical Institute Medical Fellows at UCSF; the Chan Zuckerberg Biohub San Francisco; the John A. Watson Scholar Program at UCSF; the Hanna H. Gray Fellowship, Howard Hughes Medical Institute; the National Institutes of Health; and the University of California President’s Postdoctoral Fellowship Program. Dr. Zamecnik received funding toward this study from the National Multiple Sclerosis Society and the Water Cove Charitable Foundation. He declared no competing financial interests. The other authors’ disclosures are listed on the original paper. Dr. Bebo is the executive vice president of the National Multiple Sclerosis Society, which provided support for the study.
A version of this article appeared on Medscape.com.
, according to a new study.
Investigators screened blood samples from 250 individuals with MS drawn 5 years before and 1 year after symptom onset, profiled MS-related autoantibodies, and compared the sample with 250 matched controls.
A unique cluster of autoantibodies was found in 10% of people with MS, appearing up to 5 years before the onset of clinical symptoms and remaining higher 1 year after diagnosis.
“Our work demonstrates that a subset of MS patients has antibodies that react to a common protein motif, both before, during, and after diagnosis and symptom onset,” said lead investigator Colin R. Zamecnik, PhD, a postdoctoral researcher at UCSF School of Medicine, University of California, San Francisco.
Such a discovery could aid in early diagnosis, Dr. Zamecnik added. MS treatments “have gotten much better in the last 15-20 years and evidence shows early treatment can improve outcomes,” he said.
The study was published online in Nature Medicine.
Seeking Earlier Diagnosis
Previous research shows that nonspecific neurologic episodes occur more frequently in people who received an MS diagnosis later in life, pointing to the possibility of an MS prodrome, the authors noted.
These neurologic episodes may be indicative of ongoing neuroinflammatory processes in the preclinical period, they added. Studies in several other autoimmune diseases show that diagnostic autoantibodies can appear years before symptom onset. However, no such antibodies have previously been identified in MS patients.
To investigate, the researchers turned to data from a large, prospective incident MS cohort assembled during the Gulf War era in more than 10 million US military veterans.
Records of those with the earliest diagnosis (an average of 5 years before symptom onset) and 1 year after the first attack were analyzed, and matched controls were selected.
Investigators used a technique called phage display immunoprecipitation sequencing to screen human blood for antibodies. They conducted a whole-proteome autoantibody screen and serum neurofilament light (sNfL) measurements on these samples in both case patients and controls at the same time points.
Early Signs of Injury
In the preclinical serum samples, sNfL levels were higher nearer the date of diagnosis and significantly higher in post- versus pre-onset samples in people with MS. “Together, these data provide evidence that at least some people with MS exhibit early signs of neuroaxonal injury long before onset of symptoms,” the authors noted.
Analysis of the collection of peptides, described by the investigators as an “autoantibody signature,” was consistent over time and was present regardless of diagnosis.
Further analysis of the autoantibodies revealed a characteristic protein motif found in common viruses, including Epstein-Barr virus (EBV) and hepatitis C virus, among others.
The motif “shares remarkable similarity to those found on many pathogens that infect humans, including EBV, which is known to be a risk factor for development of MS,” Dr. Zamecnik said.
The researchers validated these findings by analyzing serum and cerebrospinal fluid samples from participants in ORIGINS, an MS cohort at the University of California, San Francisco, that enrolled patients at clinical onset. As with the other cohort, 10% of patients had the autoantibody signature.
The investigators added that the findings detail some of the first autoantigen-specific biomarkers found in preclinical MS.
“Taken together, our future work will focus on profiling these patients more closely over time to see how they differ from their counterparts and gives further evidence of viral-host crosstalk as a hallmark of this disease,” Dr. Zamecnik said.
Not Ready for Prime Time
Commenting on the findings, Bruce Bebo, PhD, executive vice president of research, National Multiple Sclerosis Society, said the study corroborates the “growing appreciation that MS has a prodrome.”
Such a discovery might “accelerate progress toward the possibility of treating MS ever-earlier in the course of the disease, or possibly even preventing MS from occurring in the first place,” he added.
Dr. Bebo, who was not involved in this research, noted that it was conducted at a single center, is only preliminary, and “has no immediate clinical applicability.”
Also, because this pattern was identified in only 10% of individuals with MS, “an additional hurdle is whether we can identify other patterns in greater numbers of people,” he added.
This work was supported by the Valhalla Foundation; the Weill Neurohub; the Westridge Foundation; the National Institute of Neurological Disorders and Stroke; the National Institute of Allergy and Infectious Diseases; National Multiple Sclerosis Society; the Department of Defense; the German Society of Multiple Sclerosis; the Water Cove Charitable Foundation; Tim and Laura O’Shaughnessy; the Littera Family; School of Medicine Dean’s Yearlong Fellowship, supported by residual funds from the Howard Hughes Medical Institute Medical Fellows at UCSF; the Chan Zuckerberg Biohub San Francisco; the John A. Watson Scholar Program at UCSF; the Hanna H. Gray Fellowship, Howard Hughes Medical Institute; the National Institutes of Health; and the University of California President’s Postdoctoral Fellowship Program. Dr. Zamecnik received funding toward this study from the National Multiple Sclerosis Society and the Water Cove Charitable Foundation. He declared no competing financial interests. The other authors’ disclosures are listed on the original paper. Dr. Bebo is the executive vice president of the National Multiple Sclerosis Society, which provided support for the study.
A version of this article appeared on Medscape.com.
, according to a new study.
Investigators screened blood samples from 250 individuals with MS drawn 5 years before and 1 year after symptom onset, profiled MS-related autoantibodies, and compared the sample with 250 matched controls.
A unique cluster of autoantibodies was found in 10% of people with MS, appearing up to 5 years before the onset of clinical symptoms and remaining higher 1 year after diagnosis.
“Our work demonstrates that a subset of MS patients has antibodies that react to a common protein motif, both before, during, and after diagnosis and symptom onset,” said lead investigator Colin R. Zamecnik, PhD, a postdoctoral researcher at UCSF School of Medicine, University of California, San Francisco.
Such a discovery could aid in early diagnosis, Dr. Zamecnik added. MS treatments “have gotten much better in the last 15-20 years and evidence shows early treatment can improve outcomes,” he said.
The study was published online in Nature Medicine.
Seeking Earlier Diagnosis
Previous research shows that nonspecific neurologic episodes occur more frequently in people who received an MS diagnosis later in life, pointing to the possibility of an MS prodrome, the authors noted.
These neurologic episodes may be indicative of ongoing neuroinflammatory processes in the preclinical period, they added. Studies in several other autoimmune diseases show that diagnostic autoantibodies can appear years before symptom onset. However, no such antibodies have previously been identified in MS patients.
To investigate, the researchers turned to data from a large, prospective incident MS cohort assembled during the Gulf War era in more than 10 million US military veterans.
Records of those with the earliest diagnosis (an average of 5 years before symptom onset) and 1 year after the first attack were analyzed, and matched controls were selected.
Investigators used a technique called phage display immunoprecipitation sequencing to screen human blood for antibodies. They conducted a whole-proteome autoantibody screen and serum neurofilament light (sNfL) measurements on these samples in both case patients and controls at the same time points.
Early Signs of Injury
In the preclinical serum samples, sNfL levels were higher nearer the date of diagnosis and significantly higher in post- versus pre-onset samples in people with MS. “Together, these data provide evidence that at least some people with MS exhibit early signs of neuroaxonal injury long before onset of symptoms,” the authors noted.
Analysis of the collection of peptides, described by the investigators as an “autoantibody signature,” was consistent over time and was present regardless of diagnosis.
Further analysis of the autoantibodies revealed a characteristic protein motif found in common viruses, including Epstein-Barr virus (EBV) and hepatitis C virus, among others.
The motif “shares remarkable similarity to those found on many pathogens that infect humans, including EBV, which is known to be a risk factor for development of MS,” Dr. Zamecnik said.
The researchers validated these findings by analyzing serum and cerebrospinal fluid samples from participants in ORIGINS, an MS cohort at the University of California, San Francisco, that enrolled patients at clinical onset. As with the other cohort, 10% of patients had the autoantibody signature.
The investigators added that the findings detail some of the first autoantigen-specific biomarkers found in preclinical MS.
“Taken together, our future work will focus on profiling these patients more closely over time to see how they differ from their counterparts and gives further evidence of viral-host crosstalk as a hallmark of this disease,” Dr. Zamecnik said.
Not Ready for Prime Time
Commenting on the findings, Bruce Bebo, PhD, executive vice president of research, National Multiple Sclerosis Society, said the study corroborates the “growing appreciation that MS has a prodrome.”
Such a discovery might “accelerate progress toward the possibility of treating MS ever-earlier in the course of the disease, or possibly even preventing MS from occurring in the first place,” he added.
Dr. Bebo, who was not involved in this research, noted that it was conducted at a single center, is only preliminary, and “has no immediate clinical applicability.”
Also, because this pattern was identified in only 10% of individuals with MS, “an additional hurdle is whether we can identify other patterns in greater numbers of people,” he added.
This work was supported by the Valhalla Foundation; the Weill Neurohub; the Westridge Foundation; the National Institute of Neurological Disorders and Stroke; the National Institute of Allergy and Infectious Diseases; National Multiple Sclerosis Society; the Department of Defense; the German Society of Multiple Sclerosis; the Water Cove Charitable Foundation; Tim and Laura O’Shaughnessy; the Littera Family; School of Medicine Dean’s Yearlong Fellowship, supported by residual funds from the Howard Hughes Medical Institute Medical Fellows at UCSF; the Chan Zuckerberg Biohub San Francisco; the John A. Watson Scholar Program at UCSF; the Hanna H. Gray Fellowship, Howard Hughes Medical Institute; the National Institutes of Health; and the University of California President’s Postdoctoral Fellowship Program. Dr. Zamecnik received funding toward this study from the National Multiple Sclerosis Society and the Water Cove Charitable Foundation. He declared no competing financial interests. The other authors’ disclosures are listed on the original paper. Dr. Bebo is the executive vice president of the National Multiple Sclerosis Society, which provided support for the study.
A version of this article appeared on Medscape.com.
FROM NATURE MEDICINE
Does ‘Brain Training’ Really Improve Cognition and Forestall Cognitive Decline?
The concept that cognitive health can be preserved or improved is often expressed as “use it or lose it.” Numerous modifiable risk factors are associated with “losing” cognitive abilities with age, and a cognitively active lifestyle may have a protective effect.
But what is a “cognitively active lifestyle” — do crosswords and Sudoku count?
One popular approach is “brain training.” While not a scientific term with an established definition, it “typically refers to tasks or drills that are designed to strengthen specific aspects of one’s cognitive function,” explained Yuko Hara, PhD, director of Aging and Alzheimer’s Prevention at the Alzheimer’s Drug Discovery Foundation.
Manuel Montero-Odasso, MD, PhD, director of the Gait and Brain Lab, Parkwood Institute, London, Ontario, Canada, elaborated: “Cognitive training involves performing a definitive task or set of tasks where you increase attentional demands to improve focus and concentration and memory. You try to execute the new things that you’ve learned and to remember them.”
In a commentary published by this news organization in 2022, neuroscientist Michael Merzenich, PhD, professor emeritus at University of California San Francisco, said that growing a person’s cognitive reserve and actively managing brain health can play an important role in preventing or delaying Alzheimer’s disease. Important components of this include brain training and physical exercise.
Brain Training: Mechanism of Action
Dr. Montero-Odasso, team leader at the Canadian Consortium on Neurodegeneration in Aging and team co-leader at the Ontario Neurodegenerative Research Initiative, explained that cognitive training creates new synapses in the brain, thus stimulating neuroplasticity.
“When we try to activate networks mainly in the frontal lobe, the prefrontal cortex, a key mechanism underlying this process is enhancement of the synaptic plasticity at excitatory synapses, which connect neurons into networks; in other words, we generate new synapses, and that’s how we enhance brain health and cognitive abilities.”
The more neural connections, the greater the processing speed of the brain, he continued. “Cognitive training creates an anatomical change in the brain.”
Executive functions, which include attention, inhibition, planning, and multitasking, are regulated predominantly by the prefrontal cortex. Damage in this region of the brain is also implicated in dementia. Alterations in the connectivity of this area are associated with cognitive impairment, independent of other structural pathological aberrations (eg, gray matter atrophy). These patterns may precede structural pathological changes associated with cognitive impairment and dementia.
Neuroplasticity changes have been corroborated through neuroimaging, which has demonstrated that after cognitive training, there is more activation in the prefrontal cortex that correlates with new synapses, Dr. Montero-Odasso said.
Henry Mahncke, PhD, CEO of the brain training company Posit Science/BrainHQ, explained that early research was conducted on rodents and monkeys, with Dr. Merzenich as one of the leading pioneers in developing the concept of brain plasticity. Dr. Merzenich cofounded Posit Science and is currently its chief scientific officer.
Dr. Mahncke recounted that as a graduate student, he had worked with Dr. Merzenich researching brain plasticity. When Dr. Merzenich founded Posit Science, he asked Dr. Mahncke to join the company to help develop approaches to enhance brain plasticity — building the brain-training exercises and running the clinical trials.
“It’s now well understood that the brain can rewire itself at any age and in almost any condition,” Dr. Mahncke said. “In kids and in younger and older adults, whether with healthy or unhealthy brains, the fundamental way the brain works is by continually rewiring and rebuilding itself, based on what we ask it to do.”
Dr. Mahncke said.
Unsubstantiated Claims and Controversy
Brain training is not without controversy, Dr. Hara pointed out. “Some manufacturers of brain games have been criticized and even fined for making unsubstantiated claims,” she said.
A 2016 review found that brain-training interventions do improve performance on specific trained tasks, but there is less evidence that they improve performance on closely related tasks and little evidence that training improves everyday cognitive performance. A 2017 review reached similar conclusions, calling evidence regarding prevention or delay of cognitive decline or dementia through brain games “insufficient,” although cognitive training could “improve cognition in the domain trained.”
“The general consensus is that for most brain-training programs, people may get better at specific tasks through practice, but these improvements don’t necessarily translate into improvement in other tasks that require other cognitive domains or prevention of dementia or age-related cognitive decline,” Dr. Hara said.
She noted that most brain-training programs “have not been rigorously tested in clinical trials” — although some, such as those featured in the ACTIVE trial, did show evidence of effectiveness.
Dr. Mahncke agreed. “Asking whether brain training works is like asking whether small molecules improve health,” he said noting that some brain-training programs are nonsense and not evidence based. He believes that his company’s product, BrainHQ, and some others are “backed by robust evidence in their ability to stave off, slow, or even reverse cognitive changes.”
BrainHQ is a web-based brain game suite that can be used independently as an app or in group settings (classes and webinars) and is covered by some Medicare Advantage insurance plans. It encompasses “dozens of individual brain-training exercises, linked by a common thread. Each one is intensively designed to make the brain faster and more accurate,” said Dr. Mahncke.
He explained that human brains “get noisy as people get older, like a radio which is wearing out, so there’s static in the background. This makes the music hard to hear, and in the case of the human brain, it makes it difficult to pay attention.” The exercises are “designed to tamp down the ‘noise,’ speed up the brain, and make information processing more accurate.”
Dr. Mahncke called this a “bottom-up” approach, in contrast to many previous cognitive-training approaches that come from the brain injury rehabilitation field. They teach “top-down” skills and strategies designed to compensate for deficits in specific domains, such as reading, concentration, or fine motor skills.
By contrast, the approach of BrainHQ is “to improve the overall processing system of the brain with speed, attention, working memory, and executive function, which will in turn impact all skills and activities.”
Supporting Evidence
Dr. Mahncke cited several supporting studies. For example, the IMPACT study randomized 487 adults (aged ≥ 65 years) to receive either a brain plasticity–based computerized cognitive training program (BrainHQ) or a novelty- and intensity-matched general cognitive stimulation treatment program (intervention and control group, respectively) for an 8-week period.
Those who underwent brain training showed significantly greater improvement in the repeatable Battery for the Assessment of Neuropsychological Status (RBANS Auditory Memory/Attention) compared with those in the control group (3.9 vs 1.8, respectively; P =.02). The intervention group also showed significant improvements on multiple secondary measures of attention and memory. The magnitude of the effect sizes suggests that the results are clinically significant, according to the authors.
The ACTIVE study tested the effects of different cognitive training programs on cognitive function and time to dementia. The researchers randomized 2802 healthy older adults (mean age, 74 years) to a control group with no cognitive training or one of three brain-training groups comprising:
1. In-person training on verbal memory skills
2. In-person training on reasoning and problem-solving
3. Computer-based speed-of-processing training on visual attention
Participants in the training groups completed 10 sessions, each lasting 60-75 minutes, over a 5- to 6-week period. A random subsample of each training group was selected to receive “booster” sessions, with four-session booster training delivered at 11 and 35 months. All study participants completed follow-up tests of cognition and function after 1, 2, 3, 5, and 10 years.
At the end of 10 years, those assigned to the speed-of-processing training, now part of BrainHQ, had a 29% lower risk for dementia than those in the control group who received no training. No reduction was found in the memory or reasoning training groups. Participants who completed the “booster” sessions had an even greater reduction: Each additional booster session was associated with a 10% lower risk for dementia.
Dr. Montero-Odasso was involved in the SYNERGIC study that randomized 175 participants with mild cognitive impairment (MCI; average age, 73 years) to one of five study arms:
1. Multidomain intervention with exercise, cognitive training, and vitamin D
2. Exercise, cognitive training, and placebo
3. Exercise, sham cognitive training, and vitamin D
4. Exercise, sham cognitive training, and placebo
5. Control group with balance-toning exercise, sham cognitive training, and placebo
“Sham” cognitive training consisted of alternating between two tasks (touristic search and video watching) performed on a tablet, with the same time exposure as the intervention training.
The researchers found that after 6 months of interventions, all active arms with aerobic-resistance exercise showed improvement in the ADAS-Cog-13, an established outcome to evaluate dementia treatments, when compared with the control group — regardless of the addition of cognitive training or vitamin D.
Compared with exercise alone (arms 3 and 4), those who did exercise plus cognitive training (arms 1 and 2) showed greater improvements in their ADAS-Cog-13l score, with a mean difference of −1.45 points (P = .02). The greatest improvement was seen in those who underwent the multidomain intervention in arm 1.
The authors noted that the mean 2.64-point improvement seen in the ADAS-Cog-13 for the multidomain intervention is actually larger than changes seen in previous pharmaceutical trials among individuals with MCI or mild dementia and “approaches” the three points considered clinically meaningful.
“We found that older adults with MCI who received aerobic-resistance exercise with sequential computerized cognitive training significantly improved cognition,” Dr. Montero-Odasso said. “The cognitive training we used was called Neuropeak, a multidomain lifestyle training delivered through a web-based platform developed by our co-leader Louis Bherer at Université de Montréal.”
He explained that the purpose “is to challenge your brain to the point where you need to make an effort to remember things, pay attention, and later to execute tasks. The evidence from clinical trials, including ours, shows this type of brain challenge is effective in slowing and even reversing cognitive decline.”
A follow-up study, SYNERGIC 2.0, is ongoing.
Puzzles, Board Games, and New Challenges
Formal brain-training programs aren’t the only way to improve brain plasticity, Dr. Hara said. Observational studies suggested an association between improved cognitive performance and/or lower dementia risk and engaging in number and word puzzles, such as crosswords, cards, or board games.
Some studies suggested that older adults who use technology might also protect their cognitive reserve. Dr. Hara cited a US longitudinal study of more than 18,000 older adults suggesting that regular Internet users had roughly half the risk for dementia compared to nonregular Internet users. Estimates of daily Internet use suggested a U-shaped relationship with dementia with 0.1-2.0 hours daily (excluding time spent watching television or movies online) associated with the lowest risk. Similar associations between Internet use and a lower risk for cognitive decline have been reported in the United Kingdom and Europe.
“Engaging in mentally stimulating activities can increase ‘cognitive reserve’ — meaning, capacity of the brain to resist the effects of age-related changes or disease-related pathology, such that one can maintain cognitive function for longer,” Dr. Hara said. “Cognitively stimulating activities, regardless of the type, may help delay the onset of cognitive decline.”
She listed several examples of activities that are stimulating to the brain, including learning a new game or puzzle, a new language, or a new dance, and learning how to play a musical instrument.
Dr. Montero-Odasso emphasized that the “newness” is key to increasing and preserving cognitive reserve. “Just surfing the Internet, playing word or board games, or doing crossword puzzles won’t be enough if you’ve been doing these things all your life,” he said. “It won’t hurt, of course, but it won’t necessarily increase your cognitive abilities.
“For example, a person who regularly engages in public speaking may not improve cognition by taking a public-speaking course, but someone who has never spoken before an audience might show cognitive improvements as a result of learning a new skill,” he said. “Or someone who knows several languages already might gain from learning a brand-new language.”
He cited research supporting the benefits of dancing, which he called “an ideal activity because it’s physical, so it provides the exercise that’s been associated with improved cognition. But it also requires learning new steps and moves, which builds the synapses in the brain. And the socialization of dance classes adds another component that can improve cognition.”
Dr. Mahncke hopes that beyond engaging in day-to-day new activities, seniors will participate in computerized brain training. “There’s no reason that evidence-based training can’t be offered in senior and community centers, as yoga and swimming are,” he said. “It doesn’t have to be simply something people do on their own virtually.”
Zoom classes and Medicare reimbursements are “good steps in the right direction, but it’s time to expand this potentially life-transformative intervention so that it reaches the ever-expanding population of seniors in the United States and beyond.”
Dr. Hara reported having no disclosures. Dr. Montero-Odasso reported having no commercial or financial interest related to this topic. He serves as the president of the Canadian Geriatrics Société and is team leader in the Canadian Consortium of Neurodegeneration in Aging. Dr. Mahncke is CEO of the brain training company Posit Science/BrainHQ.
A version of this article appeared on Medscape.com.
The concept that cognitive health can be preserved or improved is often expressed as “use it or lose it.” Numerous modifiable risk factors are associated with “losing” cognitive abilities with age, and a cognitively active lifestyle may have a protective effect.
But what is a “cognitively active lifestyle” — do crosswords and Sudoku count?
One popular approach is “brain training.” While not a scientific term with an established definition, it “typically refers to tasks or drills that are designed to strengthen specific aspects of one’s cognitive function,” explained Yuko Hara, PhD, director of Aging and Alzheimer’s Prevention at the Alzheimer’s Drug Discovery Foundation.
Manuel Montero-Odasso, MD, PhD, director of the Gait and Brain Lab, Parkwood Institute, London, Ontario, Canada, elaborated: “Cognitive training involves performing a definitive task or set of tasks where you increase attentional demands to improve focus and concentration and memory. You try to execute the new things that you’ve learned and to remember them.”
In a commentary published by this news organization in 2022, neuroscientist Michael Merzenich, PhD, professor emeritus at University of California San Francisco, said that growing a person’s cognitive reserve and actively managing brain health can play an important role in preventing or delaying Alzheimer’s disease. Important components of this include brain training and physical exercise.
Brain Training: Mechanism of Action
Dr. Montero-Odasso, team leader at the Canadian Consortium on Neurodegeneration in Aging and team co-leader at the Ontario Neurodegenerative Research Initiative, explained that cognitive training creates new synapses in the brain, thus stimulating neuroplasticity.
“When we try to activate networks mainly in the frontal lobe, the prefrontal cortex, a key mechanism underlying this process is enhancement of the synaptic plasticity at excitatory synapses, which connect neurons into networks; in other words, we generate new synapses, and that’s how we enhance brain health and cognitive abilities.”
The more neural connections, the greater the processing speed of the brain, he continued. “Cognitive training creates an anatomical change in the brain.”
Executive functions, which include attention, inhibition, planning, and multitasking, are regulated predominantly by the prefrontal cortex. Damage in this region of the brain is also implicated in dementia. Alterations in the connectivity of this area are associated with cognitive impairment, independent of other structural pathological aberrations (eg, gray matter atrophy). These patterns may precede structural pathological changes associated with cognitive impairment and dementia.
Neuroplasticity changes have been corroborated through neuroimaging, which has demonstrated that after cognitive training, there is more activation in the prefrontal cortex that correlates with new synapses, Dr. Montero-Odasso said.
Henry Mahncke, PhD, CEO of the brain training company Posit Science/BrainHQ, explained that early research was conducted on rodents and monkeys, with Dr. Merzenich as one of the leading pioneers in developing the concept of brain plasticity. Dr. Merzenich cofounded Posit Science and is currently its chief scientific officer.
Dr. Mahncke recounted that as a graduate student, he had worked with Dr. Merzenich researching brain plasticity. When Dr. Merzenich founded Posit Science, he asked Dr. Mahncke to join the company to help develop approaches to enhance brain plasticity — building the brain-training exercises and running the clinical trials.
“It’s now well understood that the brain can rewire itself at any age and in almost any condition,” Dr. Mahncke said. “In kids and in younger and older adults, whether with healthy or unhealthy brains, the fundamental way the brain works is by continually rewiring and rebuilding itself, based on what we ask it to do.”
Dr. Mahncke said.
Unsubstantiated Claims and Controversy
Brain training is not without controversy, Dr. Hara pointed out. “Some manufacturers of brain games have been criticized and even fined for making unsubstantiated claims,” she said.
A 2016 review found that brain-training interventions do improve performance on specific trained tasks, but there is less evidence that they improve performance on closely related tasks and little evidence that training improves everyday cognitive performance. A 2017 review reached similar conclusions, calling evidence regarding prevention or delay of cognitive decline or dementia through brain games “insufficient,” although cognitive training could “improve cognition in the domain trained.”
“The general consensus is that for most brain-training programs, people may get better at specific tasks through practice, but these improvements don’t necessarily translate into improvement in other tasks that require other cognitive domains or prevention of dementia or age-related cognitive decline,” Dr. Hara said.
She noted that most brain-training programs “have not been rigorously tested in clinical trials” — although some, such as those featured in the ACTIVE trial, did show evidence of effectiveness.
Dr. Mahncke agreed. “Asking whether brain training works is like asking whether small molecules improve health,” he said noting that some brain-training programs are nonsense and not evidence based. He believes that his company’s product, BrainHQ, and some others are “backed by robust evidence in their ability to stave off, slow, or even reverse cognitive changes.”
BrainHQ is a web-based brain game suite that can be used independently as an app or in group settings (classes and webinars) and is covered by some Medicare Advantage insurance plans. It encompasses “dozens of individual brain-training exercises, linked by a common thread. Each one is intensively designed to make the brain faster and more accurate,” said Dr. Mahncke.
He explained that human brains “get noisy as people get older, like a radio which is wearing out, so there’s static in the background. This makes the music hard to hear, and in the case of the human brain, it makes it difficult to pay attention.” The exercises are “designed to tamp down the ‘noise,’ speed up the brain, and make information processing more accurate.”
Dr. Mahncke called this a “bottom-up” approach, in contrast to many previous cognitive-training approaches that come from the brain injury rehabilitation field. They teach “top-down” skills and strategies designed to compensate for deficits in specific domains, such as reading, concentration, or fine motor skills.
By contrast, the approach of BrainHQ is “to improve the overall processing system of the brain with speed, attention, working memory, and executive function, which will in turn impact all skills and activities.”
Supporting Evidence
Dr. Mahncke cited several supporting studies. For example, the IMPACT study randomized 487 adults (aged ≥ 65 years) to receive either a brain plasticity–based computerized cognitive training program (BrainHQ) or a novelty- and intensity-matched general cognitive stimulation treatment program (intervention and control group, respectively) for an 8-week period.
Those who underwent brain training showed significantly greater improvement in the repeatable Battery for the Assessment of Neuropsychological Status (RBANS Auditory Memory/Attention) compared with those in the control group (3.9 vs 1.8, respectively; P =.02). The intervention group also showed significant improvements on multiple secondary measures of attention and memory. The magnitude of the effect sizes suggests that the results are clinically significant, according to the authors.
The ACTIVE study tested the effects of different cognitive training programs on cognitive function and time to dementia. The researchers randomized 2802 healthy older adults (mean age, 74 years) to a control group with no cognitive training or one of three brain-training groups comprising:
1. In-person training on verbal memory skills
2. In-person training on reasoning and problem-solving
3. Computer-based speed-of-processing training on visual attention
Participants in the training groups completed 10 sessions, each lasting 60-75 minutes, over a 5- to 6-week period. A random subsample of each training group was selected to receive “booster” sessions, with four-session booster training delivered at 11 and 35 months. All study participants completed follow-up tests of cognition and function after 1, 2, 3, 5, and 10 years.
At the end of 10 years, those assigned to the speed-of-processing training, now part of BrainHQ, had a 29% lower risk for dementia than those in the control group who received no training. No reduction was found in the memory or reasoning training groups. Participants who completed the “booster” sessions had an even greater reduction: Each additional booster session was associated with a 10% lower risk for dementia.
Dr. Montero-Odasso was involved in the SYNERGIC study that randomized 175 participants with mild cognitive impairment (MCI; average age, 73 years) to one of five study arms:
1. Multidomain intervention with exercise, cognitive training, and vitamin D
2. Exercise, cognitive training, and placebo
3. Exercise, sham cognitive training, and vitamin D
4. Exercise, sham cognitive training, and placebo
5. Control group with balance-toning exercise, sham cognitive training, and placebo
“Sham” cognitive training consisted of alternating between two tasks (touristic search and video watching) performed on a tablet, with the same time exposure as the intervention training.
The researchers found that after 6 months of interventions, all active arms with aerobic-resistance exercise showed improvement in the ADAS-Cog-13, an established outcome to evaluate dementia treatments, when compared with the control group — regardless of the addition of cognitive training or vitamin D.
Compared with exercise alone (arms 3 and 4), those who did exercise plus cognitive training (arms 1 and 2) showed greater improvements in their ADAS-Cog-13l score, with a mean difference of −1.45 points (P = .02). The greatest improvement was seen in those who underwent the multidomain intervention in arm 1.
The authors noted that the mean 2.64-point improvement seen in the ADAS-Cog-13 for the multidomain intervention is actually larger than changes seen in previous pharmaceutical trials among individuals with MCI or mild dementia and “approaches” the three points considered clinically meaningful.
“We found that older adults with MCI who received aerobic-resistance exercise with sequential computerized cognitive training significantly improved cognition,” Dr. Montero-Odasso said. “The cognitive training we used was called Neuropeak, a multidomain lifestyle training delivered through a web-based platform developed by our co-leader Louis Bherer at Université de Montréal.”
He explained that the purpose “is to challenge your brain to the point where you need to make an effort to remember things, pay attention, and later to execute tasks. The evidence from clinical trials, including ours, shows this type of brain challenge is effective in slowing and even reversing cognitive decline.”
A follow-up study, SYNERGIC 2.0, is ongoing.
Puzzles, Board Games, and New Challenges
Formal brain-training programs aren’t the only way to improve brain plasticity, Dr. Hara said. Observational studies suggested an association between improved cognitive performance and/or lower dementia risk and engaging in number and word puzzles, such as crosswords, cards, or board games.
Some studies suggested that older adults who use technology might also protect their cognitive reserve. Dr. Hara cited a US longitudinal study of more than 18,000 older adults suggesting that regular Internet users had roughly half the risk for dementia compared to nonregular Internet users. Estimates of daily Internet use suggested a U-shaped relationship with dementia with 0.1-2.0 hours daily (excluding time spent watching television or movies online) associated with the lowest risk. Similar associations between Internet use and a lower risk for cognitive decline have been reported in the United Kingdom and Europe.
“Engaging in mentally stimulating activities can increase ‘cognitive reserve’ — meaning, capacity of the brain to resist the effects of age-related changes or disease-related pathology, such that one can maintain cognitive function for longer,” Dr. Hara said. “Cognitively stimulating activities, regardless of the type, may help delay the onset of cognitive decline.”
She listed several examples of activities that are stimulating to the brain, including learning a new game or puzzle, a new language, or a new dance, and learning how to play a musical instrument.
Dr. Montero-Odasso emphasized that the “newness” is key to increasing and preserving cognitive reserve. “Just surfing the Internet, playing word or board games, or doing crossword puzzles won’t be enough if you’ve been doing these things all your life,” he said. “It won’t hurt, of course, but it won’t necessarily increase your cognitive abilities.
“For example, a person who regularly engages in public speaking may not improve cognition by taking a public-speaking course, but someone who has never spoken before an audience might show cognitive improvements as a result of learning a new skill,” he said. “Or someone who knows several languages already might gain from learning a brand-new language.”
He cited research supporting the benefits of dancing, which he called “an ideal activity because it’s physical, so it provides the exercise that’s been associated with improved cognition. But it also requires learning new steps and moves, which builds the synapses in the brain. And the socialization of dance classes adds another component that can improve cognition.”
Dr. Mahncke hopes that beyond engaging in day-to-day new activities, seniors will participate in computerized brain training. “There’s no reason that evidence-based training can’t be offered in senior and community centers, as yoga and swimming are,” he said. “It doesn’t have to be simply something people do on their own virtually.”
Zoom classes and Medicare reimbursements are “good steps in the right direction, but it’s time to expand this potentially life-transformative intervention so that it reaches the ever-expanding population of seniors in the United States and beyond.”
Dr. Hara reported having no disclosures. Dr. Montero-Odasso reported having no commercial or financial interest related to this topic. He serves as the president of the Canadian Geriatrics Société and is team leader in the Canadian Consortium of Neurodegeneration in Aging. Dr. Mahncke is CEO of the brain training company Posit Science/BrainHQ.
A version of this article appeared on Medscape.com.
The concept that cognitive health can be preserved or improved is often expressed as “use it or lose it.” Numerous modifiable risk factors are associated with “losing” cognitive abilities with age, and a cognitively active lifestyle may have a protective effect.
But what is a “cognitively active lifestyle” — do crosswords and Sudoku count?
One popular approach is “brain training.” While not a scientific term with an established definition, it “typically refers to tasks or drills that are designed to strengthen specific aspects of one’s cognitive function,” explained Yuko Hara, PhD, director of Aging and Alzheimer’s Prevention at the Alzheimer’s Drug Discovery Foundation.
Manuel Montero-Odasso, MD, PhD, director of the Gait and Brain Lab, Parkwood Institute, London, Ontario, Canada, elaborated: “Cognitive training involves performing a definitive task or set of tasks where you increase attentional demands to improve focus and concentration and memory. You try to execute the new things that you’ve learned and to remember them.”
In a commentary published by this news organization in 2022, neuroscientist Michael Merzenich, PhD, professor emeritus at University of California San Francisco, said that growing a person’s cognitive reserve and actively managing brain health can play an important role in preventing or delaying Alzheimer’s disease. Important components of this include brain training and physical exercise.
Brain Training: Mechanism of Action
Dr. Montero-Odasso, team leader at the Canadian Consortium on Neurodegeneration in Aging and team co-leader at the Ontario Neurodegenerative Research Initiative, explained that cognitive training creates new synapses in the brain, thus stimulating neuroplasticity.
“When we try to activate networks mainly in the frontal lobe, the prefrontal cortex, a key mechanism underlying this process is enhancement of the synaptic plasticity at excitatory synapses, which connect neurons into networks; in other words, we generate new synapses, and that’s how we enhance brain health and cognitive abilities.”
The more neural connections, the greater the processing speed of the brain, he continued. “Cognitive training creates an anatomical change in the brain.”
Executive functions, which include attention, inhibition, planning, and multitasking, are regulated predominantly by the prefrontal cortex. Damage in this region of the brain is also implicated in dementia. Alterations in the connectivity of this area are associated with cognitive impairment, independent of other structural pathological aberrations (eg, gray matter atrophy). These patterns may precede structural pathological changes associated with cognitive impairment and dementia.
Neuroplasticity changes have been corroborated through neuroimaging, which has demonstrated that after cognitive training, there is more activation in the prefrontal cortex that correlates with new synapses, Dr. Montero-Odasso said.
Henry Mahncke, PhD, CEO of the brain training company Posit Science/BrainHQ, explained that early research was conducted on rodents and monkeys, with Dr. Merzenich as one of the leading pioneers in developing the concept of brain plasticity. Dr. Merzenich cofounded Posit Science and is currently its chief scientific officer.
Dr. Mahncke recounted that as a graduate student, he had worked with Dr. Merzenich researching brain plasticity. When Dr. Merzenich founded Posit Science, he asked Dr. Mahncke to join the company to help develop approaches to enhance brain plasticity — building the brain-training exercises and running the clinical trials.
“It’s now well understood that the brain can rewire itself at any age and in almost any condition,” Dr. Mahncke said. “In kids and in younger and older adults, whether with healthy or unhealthy brains, the fundamental way the brain works is by continually rewiring and rebuilding itself, based on what we ask it to do.”
Dr. Mahncke said.
Unsubstantiated Claims and Controversy
Brain training is not without controversy, Dr. Hara pointed out. “Some manufacturers of brain games have been criticized and even fined for making unsubstantiated claims,” she said.
A 2016 review found that brain-training interventions do improve performance on specific trained tasks, but there is less evidence that they improve performance on closely related tasks and little evidence that training improves everyday cognitive performance. A 2017 review reached similar conclusions, calling evidence regarding prevention or delay of cognitive decline or dementia through brain games “insufficient,” although cognitive training could “improve cognition in the domain trained.”
“The general consensus is that for most brain-training programs, people may get better at specific tasks through practice, but these improvements don’t necessarily translate into improvement in other tasks that require other cognitive domains or prevention of dementia or age-related cognitive decline,” Dr. Hara said.
She noted that most brain-training programs “have not been rigorously tested in clinical trials” — although some, such as those featured in the ACTIVE trial, did show evidence of effectiveness.
Dr. Mahncke agreed. “Asking whether brain training works is like asking whether small molecules improve health,” he said noting that some brain-training programs are nonsense and not evidence based. He believes that his company’s product, BrainHQ, and some others are “backed by robust evidence in their ability to stave off, slow, or even reverse cognitive changes.”
BrainHQ is a web-based brain game suite that can be used independently as an app or in group settings (classes and webinars) and is covered by some Medicare Advantage insurance plans. It encompasses “dozens of individual brain-training exercises, linked by a common thread. Each one is intensively designed to make the brain faster and more accurate,” said Dr. Mahncke.
He explained that human brains “get noisy as people get older, like a radio which is wearing out, so there’s static in the background. This makes the music hard to hear, and in the case of the human brain, it makes it difficult to pay attention.” The exercises are “designed to tamp down the ‘noise,’ speed up the brain, and make information processing more accurate.”
Dr. Mahncke called this a “bottom-up” approach, in contrast to many previous cognitive-training approaches that come from the brain injury rehabilitation field. They teach “top-down” skills and strategies designed to compensate for deficits in specific domains, such as reading, concentration, or fine motor skills.
By contrast, the approach of BrainHQ is “to improve the overall processing system of the brain with speed, attention, working memory, and executive function, which will in turn impact all skills and activities.”
Supporting Evidence
Dr. Mahncke cited several supporting studies. For example, the IMPACT study randomized 487 adults (aged ≥ 65 years) to receive either a brain plasticity–based computerized cognitive training program (BrainHQ) or a novelty- and intensity-matched general cognitive stimulation treatment program (intervention and control group, respectively) for an 8-week period.
Those who underwent brain training showed significantly greater improvement in the repeatable Battery for the Assessment of Neuropsychological Status (RBANS Auditory Memory/Attention) compared with those in the control group (3.9 vs 1.8, respectively; P =.02). The intervention group also showed significant improvements on multiple secondary measures of attention and memory. The magnitude of the effect sizes suggests that the results are clinically significant, according to the authors.
The ACTIVE study tested the effects of different cognitive training programs on cognitive function and time to dementia. The researchers randomized 2802 healthy older adults (mean age, 74 years) to a control group with no cognitive training or one of three brain-training groups comprising:
1. In-person training on verbal memory skills
2. In-person training on reasoning and problem-solving
3. Computer-based speed-of-processing training on visual attention
Participants in the training groups completed 10 sessions, each lasting 60-75 minutes, over a 5- to 6-week period. A random subsample of each training group was selected to receive “booster” sessions, with four-session booster training delivered at 11 and 35 months. All study participants completed follow-up tests of cognition and function after 1, 2, 3, 5, and 10 years.
At the end of 10 years, those assigned to the speed-of-processing training, now part of BrainHQ, had a 29% lower risk for dementia than those in the control group who received no training. No reduction was found in the memory or reasoning training groups. Participants who completed the “booster” sessions had an even greater reduction: Each additional booster session was associated with a 10% lower risk for dementia.
Dr. Montero-Odasso was involved in the SYNERGIC study that randomized 175 participants with mild cognitive impairment (MCI; average age, 73 years) to one of five study arms:
1. Multidomain intervention with exercise, cognitive training, and vitamin D
2. Exercise, cognitive training, and placebo
3. Exercise, sham cognitive training, and vitamin D
4. Exercise, sham cognitive training, and placebo
5. Control group with balance-toning exercise, sham cognitive training, and placebo
“Sham” cognitive training consisted of alternating between two tasks (touristic search and video watching) performed on a tablet, with the same time exposure as the intervention training.
The researchers found that after 6 months of interventions, all active arms with aerobic-resistance exercise showed improvement in the ADAS-Cog-13, an established outcome to evaluate dementia treatments, when compared with the control group — regardless of the addition of cognitive training or vitamin D.
Compared with exercise alone (arms 3 and 4), those who did exercise plus cognitive training (arms 1 and 2) showed greater improvements in their ADAS-Cog-13l score, with a mean difference of −1.45 points (P = .02). The greatest improvement was seen in those who underwent the multidomain intervention in arm 1.
The authors noted that the mean 2.64-point improvement seen in the ADAS-Cog-13 for the multidomain intervention is actually larger than changes seen in previous pharmaceutical trials among individuals with MCI or mild dementia and “approaches” the three points considered clinically meaningful.
“We found that older adults with MCI who received aerobic-resistance exercise with sequential computerized cognitive training significantly improved cognition,” Dr. Montero-Odasso said. “The cognitive training we used was called Neuropeak, a multidomain lifestyle training delivered through a web-based platform developed by our co-leader Louis Bherer at Université de Montréal.”
He explained that the purpose “is to challenge your brain to the point where you need to make an effort to remember things, pay attention, and later to execute tasks. The evidence from clinical trials, including ours, shows this type of brain challenge is effective in slowing and even reversing cognitive decline.”
A follow-up study, SYNERGIC 2.0, is ongoing.
Puzzles, Board Games, and New Challenges
Formal brain-training programs aren’t the only way to improve brain plasticity, Dr. Hara said. Observational studies suggested an association between improved cognitive performance and/or lower dementia risk and engaging in number and word puzzles, such as crosswords, cards, or board games.
Some studies suggested that older adults who use technology might also protect their cognitive reserve. Dr. Hara cited a US longitudinal study of more than 18,000 older adults suggesting that regular Internet users had roughly half the risk for dementia compared to nonregular Internet users. Estimates of daily Internet use suggested a U-shaped relationship with dementia with 0.1-2.0 hours daily (excluding time spent watching television or movies online) associated with the lowest risk. Similar associations between Internet use and a lower risk for cognitive decline have been reported in the United Kingdom and Europe.
“Engaging in mentally stimulating activities can increase ‘cognitive reserve’ — meaning, capacity of the brain to resist the effects of age-related changes or disease-related pathology, such that one can maintain cognitive function for longer,” Dr. Hara said. “Cognitively stimulating activities, regardless of the type, may help delay the onset of cognitive decline.”
She listed several examples of activities that are stimulating to the brain, including learning a new game or puzzle, a new language, or a new dance, and learning how to play a musical instrument.
Dr. Montero-Odasso emphasized that the “newness” is key to increasing and preserving cognitive reserve. “Just surfing the Internet, playing word or board games, or doing crossword puzzles won’t be enough if you’ve been doing these things all your life,” he said. “It won’t hurt, of course, but it won’t necessarily increase your cognitive abilities.
“For example, a person who regularly engages in public speaking may not improve cognition by taking a public-speaking course, but someone who has never spoken before an audience might show cognitive improvements as a result of learning a new skill,” he said. “Or someone who knows several languages already might gain from learning a brand-new language.”
He cited research supporting the benefits of dancing, which he called “an ideal activity because it’s physical, so it provides the exercise that’s been associated with improved cognition. But it also requires learning new steps and moves, which builds the synapses in the brain. And the socialization of dance classes adds another component that can improve cognition.”
Dr. Mahncke hopes that beyond engaging in day-to-day new activities, seniors will participate in computerized brain training. “There’s no reason that evidence-based training can’t be offered in senior and community centers, as yoga and swimming are,” he said. “It doesn’t have to be simply something people do on their own virtually.”
Zoom classes and Medicare reimbursements are “good steps in the right direction, but it’s time to expand this potentially life-transformative intervention so that it reaches the ever-expanding population of seniors in the United States and beyond.”
Dr. Hara reported having no disclosures. Dr. Montero-Odasso reported having no commercial or financial interest related to this topic. He serves as the president of the Canadian Geriatrics Société and is team leader in the Canadian Consortium of Neurodegeneration in Aging. Dr. Mahncke is CEO of the brain training company Posit Science/BrainHQ.
A version of this article appeared on Medscape.com.
MAUD Medication at Discharge Dramatically Cuts Rehospitalization Rates
Adults with alcohol-related hospitalization who were discharged from the hospital with medication for alcohol use disorder (MAUD) were 51% less likely to be rehospitalized for an alcohol-related issue, new research suggested.
Despite the link to better outcomes, the analysis of 6500 Medicare Part D beneficiaries hospitalized for alcohol-related causes revealed that only 2% of patients were discharged with an MAUD prescription.
“Despite known efficacy, medication treatment for alcohol use disorder is underutilized and rarely initiated in the post-hospitalization setting,” lead author Eden Y. Bernstein, MD, a physician scientist in the Division of General Internal Medicine at Massachusetts General Hospital, Boston, said in a news release.
“Our findings highlight the potential clinical benefit associated with increased uptake of these medications in this setting and suggest a need to support and expand ongoing efforts to improve access to these medications upon hospital discharge,” Dr. Bernstein added.
The study was published online in JAMA Network Open.
MAUD prescribing or referral to addiction treatment at hospital discharge is widely recommended, investigators noted, making hospitalizations “important touch points” for alcohol use disorder (AUD) treatment engagement.
To study the association between discharge MAUD and 30-day rehospitalization, the researchers analyzed Medicare claims data from 2015 to 2017 in a retrospective study designed to emulate a randomized clinical trial of hospitalized patients with AUD.
The analysis included data on 6794 beneficiaries with 9834 hospitalizations for alcohol-related causes (median age, 54 years; 33% female; 72% White).
Researchers controlled for several covariates, including sociodemographic, clinical, and rehospitalization factors.
‘Sobering’ Findings
After propensity matching, discharge MAUD initiation was associated with a 42% decreased incidence of rehospitalization within 30 days of discharge (including emergency department visits and readmissions) or death within 30 days (incident rate ratio [IRR], 0.58; 95% CI, 0.45-0.76).
These findings remained consistent among secondary outcomes as well. Mortality was rare in both groups.
MAUD initiation at discharge was associated with a 51% decrease in incidence of alcohol-related return to the hospital (IRR, 0.49; 95% CI, 0.34-0.71).
Patients who received discharge MAUD were 22% more likely to have primary care or mental health follow-up visits (IRR, 1.22; 95% CI, 1.04-1.44).
Limitations noted by the authors include the observational study design and lack of information of nonpharmacologic treatment, such as 12-step facilitation or behavioral interventions.
In an accompanying editorial, Wid Yaseen, MD, of the Department of Medicine, University of Toronto, and coauthors noted that at present, most patients with AUD do not receive evidence-based treatment.
“An important first step might be reframing our mindset to consider AUD as a chronic disease,” they wrote. “We should also ask ourselves: Would we accept the status quo if only 2% of our patients with diabetes were prescribed evidence-based therapy?”
They added, “The insufficient use of MAUD is sobering and is also an enormous opportunity to do better for our patients.”
The study was funded by the Institutional National Research Service Award, Massachusetts General Hospital, the Agency for Healthcare Research and Quality, and the National Institute on Aging. Dr. Bernstein received personal fees from Alosa Health outside the submitted work, and Dr. Yaseen reported no relevant financial relationships. Full disclosures are included in the original articles.
A version of this article appeared on Medscape.com.
Adults with alcohol-related hospitalization who were discharged from the hospital with medication for alcohol use disorder (MAUD) were 51% less likely to be rehospitalized for an alcohol-related issue, new research suggested.
Despite the link to better outcomes, the analysis of 6500 Medicare Part D beneficiaries hospitalized for alcohol-related causes revealed that only 2% of patients were discharged with an MAUD prescription.
“Despite known efficacy, medication treatment for alcohol use disorder is underutilized and rarely initiated in the post-hospitalization setting,” lead author Eden Y. Bernstein, MD, a physician scientist in the Division of General Internal Medicine at Massachusetts General Hospital, Boston, said in a news release.
“Our findings highlight the potential clinical benefit associated with increased uptake of these medications in this setting and suggest a need to support and expand ongoing efforts to improve access to these medications upon hospital discharge,” Dr. Bernstein added.
The study was published online in JAMA Network Open.
MAUD prescribing or referral to addiction treatment at hospital discharge is widely recommended, investigators noted, making hospitalizations “important touch points” for alcohol use disorder (AUD) treatment engagement.
To study the association between discharge MAUD and 30-day rehospitalization, the researchers analyzed Medicare claims data from 2015 to 2017 in a retrospective study designed to emulate a randomized clinical trial of hospitalized patients with AUD.
The analysis included data on 6794 beneficiaries with 9834 hospitalizations for alcohol-related causes (median age, 54 years; 33% female; 72% White).
Researchers controlled for several covariates, including sociodemographic, clinical, and rehospitalization factors.
‘Sobering’ Findings
After propensity matching, discharge MAUD initiation was associated with a 42% decreased incidence of rehospitalization within 30 days of discharge (including emergency department visits and readmissions) or death within 30 days (incident rate ratio [IRR], 0.58; 95% CI, 0.45-0.76).
These findings remained consistent among secondary outcomes as well. Mortality was rare in both groups.
MAUD initiation at discharge was associated with a 51% decrease in incidence of alcohol-related return to the hospital (IRR, 0.49; 95% CI, 0.34-0.71).
Patients who received discharge MAUD were 22% more likely to have primary care or mental health follow-up visits (IRR, 1.22; 95% CI, 1.04-1.44).
Limitations noted by the authors include the observational study design and lack of information of nonpharmacologic treatment, such as 12-step facilitation or behavioral interventions.
In an accompanying editorial, Wid Yaseen, MD, of the Department of Medicine, University of Toronto, and coauthors noted that at present, most patients with AUD do not receive evidence-based treatment.
“An important first step might be reframing our mindset to consider AUD as a chronic disease,” they wrote. “We should also ask ourselves: Would we accept the status quo if only 2% of our patients with diabetes were prescribed evidence-based therapy?”
They added, “The insufficient use of MAUD is sobering and is also an enormous opportunity to do better for our patients.”
The study was funded by the Institutional National Research Service Award, Massachusetts General Hospital, the Agency for Healthcare Research and Quality, and the National Institute on Aging. Dr. Bernstein received personal fees from Alosa Health outside the submitted work, and Dr. Yaseen reported no relevant financial relationships. Full disclosures are included in the original articles.
A version of this article appeared on Medscape.com.
Adults with alcohol-related hospitalization who were discharged from the hospital with medication for alcohol use disorder (MAUD) were 51% less likely to be rehospitalized for an alcohol-related issue, new research suggested.
Despite the link to better outcomes, the analysis of 6500 Medicare Part D beneficiaries hospitalized for alcohol-related causes revealed that only 2% of patients were discharged with an MAUD prescription.
“Despite known efficacy, medication treatment for alcohol use disorder is underutilized and rarely initiated in the post-hospitalization setting,” lead author Eden Y. Bernstein, MD, a physician scientist in the Division of General Internal Medicine at Massachusetts General Hospital, Boston, said in a news release.
“Our findings highlight the potential clinical benefit associated with increased uptake of these medications in this setting and suggest a need to support and expand ongoing efforts to improve access to these medications upon hospital discharge,” Dr. Bernstein added.
The study was published online in JAMA Network Open.
MAUD prescribing or referral to addiction treatment at hospital discharge is widely recommended, investigators noted, making hospitalizations “important touch points” for alcohol use disorder (AUD) treatment engagement.
To study the association between discharge MAUD and 30-day rehospitalization, the researchers analyzed Medicare claims data from 2015 to 2017 in a retrospective study designed to emulate a randomized clinical trial of hospitalized patients with AUD.
The analysis included data on 6794 beneficiaries with 9834 hospitalizations for alcohol-related causes (median age, 54 years; 33% female; 72% White).
Researchers controlled for several covariates, including sociodemographic, clinical, and rehospitalization factors.
‘Sobering’ Findings
After propensity matching, discharge MAUD initiation was associated with a 42% decreased incidence of rehospitalization within 30 days of discharge (including emergency department visits and readmissions) or death within 30 days (incident rate ratio [IRR], 0.58; 95% CI, 0.45-0.76).
These findings remained consistent among secondary outcomes as well. Mortality was rare in both groups.
MAUD initiation at discharge was associated with a 51% decrease in incidence of alcohol-related return to the hospital (IRR, 0.49; 95% CI, 0.34-0.71).
Patients who received discharge MAUD were 22% more likely to have primary care or mental health follow-up visits (IRR, 1.22; 95% CI, 1.04-1.44).
Limitations noted by the authors include the observational study design and lack of information of nonpharmacologic treatment, such as 12-step facilitation or behavioral interventions.
In an accompanying editorial, Wid Yaseen, MD, of the Department of Medicine, University of Toronto, and coauthors noted that at present, most patients with AUD do not receive evidence-based treatment.
“An important first step might be reframing our mindset to consider AUD as a chronic disease,” they wrote. “We should also ask ourselves: Would we accept the status quo if only 2% of our patients with diabetes were prescribed evidence-based therapy?”
They added, “The insufficient use of MAUD is sobering and is also an enormous opportunity to do better for our patients.”
The study was funded by the Institutional National Research Service Award, Massachusetts General Hospital, the Agency for Healthcare Research and Quality, and the National Institute on Aging. Dr. Bernstein received personal fees from Alosa Health outside the submitted work, and Dr. Yaseen reported no relevant financial relationships. Full disclosures are included in the original articles.
A version of this article appeared on Medscape.com.
High-Dose Valproate Linked to Significant Weight Gain
TOPLINE:
High-dose valproate is associated with weight gain in psychiatric patients, with the greatest gain reported in those taking ≥ 1300 mg/d, new data showed.
METHODOLOGY:
- The researchers used 1-year data from two longitudinal studies conducted between 2007 and 2022.
- The study included 215 patients (median age, 48 years; 50% female) who had been diagnosed with bipolar disorder (38%), schizoaffective disorders (26%), schizophrenia (17%), or other conditions (16%).
- The researchers used linear mixed-effect models and logistic regressions to analyze the association between doses of valproate and metabolic outcomes.
TAKEAWAY:
- Each 500-mg increase in valproate dose was associated with a weight increase of 0.52% per month over a year (P < .001), an association that was evident before and after 3 months of treatment.
- Weight gain was greatest for treatment durations of < 3 months (+0.56%, P < .001) compared with ≥ 3 months (+0.12%, P = .02).
- The greatest weight gain was observed in patients receiving doses ≥ 1300 mg/d, with a 0.50% increase in weight for each dose increment of 500 mg (P = .004).
- In men, each 500-mg dose was associated with an increase of 0.59%, while the trend in women was for an increase of 0.40% (P = .09).
- The researchers did not find associations between valproate doses and blood glucose, lipid levels, or blood pressure across a treatment period of 6 months.
IN PRACTICE:
“These findings underscore the need for clinicians to closely monitor patients on [valproate] for weight gain and to prescribe the lowest effective doses,” the authors wrote.
SOURCE:
Chin B. Eap, PhD, of the Unit of Pharmacogenetics and Clinical Psychopharmacology, Centre for Psychiatric Neuroscience, Department of Psychiatry, Lausanne University Hospital, University of Lausanne, and Hôpital de Cery, Prilly-Lausanne, Switzerland, was the senior and corresponding author of the study. It was published online in the Journal of Clinical Psychiatry.
LIMITATIONS:
The study demonstrates an association, not causation. Treatment compliance could not be verified, although the daily dose administered to hospitalized patients was available. The study did not include information regarding lifestyle that could affect weight gain, such as dietary habits, physical activity, and substance use.
DISCLOSURES:
This study was funded by the Swiss National Research Foundation. Dr. Eap has received honoraria for conferences from Forum pour la formation medicale, Janssen-Cilag, Lundbeck, Otsuka, Sandoz, Servier, Sunovion, Sysmex Suisse AG, Takeda, Vifor Pharma, and Zeller in the past 3 years.
A version of this article first appeared on Medscape.com.
TOPLINE:
High-dose valproate is associated with weight gain in psychiatric patients, with the greatest gain reported in those taking ≥ 1300 mg/d, new data showed.
METHODOLOGY:
- The researchers used 1-year data from two longitudinal studies conducted between 2007 and 2022.
- The study included 215 patients (median age, 48 years; 50% female) who had been diagnosed with bipolar disorder (38%), schizoaffective disorders (26%), schizophrenia (17%), or other conditions (16%).
- The researchers used linear mixed-effect models and logistic regressions to analyze the association between doses of valproate and metabolic outcomes.
TAKEAWAY:
- Each 500-mg increase in valproate dose was associated with a weight increase of 0.52% per month over a year (P < .001), an association that was evident before and after 3 months of treatment.
- Weight gain was greatest for treatment durations of < 3 months (+0.56%, P < .001) compared with ≥ 3 months (+0.12%, P = .02).
- The greatest weight gain was observed in patients receiving doses ≥ 1300 mg/d, with a 0.50% increase in weight for each dose increment of 500 mg (P = .004).
- In men, each 500-mg dose was associated with an increase of 0.59%, while the trend in women was for an increase of 0.40% (P = .09).
- The researchers did not find associations between valproate doses and blood glucose, lipid levels, or blood pressure across a treatment period of 6 months.
IN PRACTICE:
“These findings underscore the need for clinicians to closely monitor patients on [valproate] for weight gain and to prescribe the lowest effective doses,” the authors wrote.
SOURCE:
Chin B. Eap, PhD, of the Unit of Pharmacogenetics and Clinical Psychopharmacology, Centre for Psychiatric Neuroscience, Department of Psychiatry, Lausanne University Hospital, University of Lausanne, and Hôpital de Cery, Prilly-Lausanne, Switzerland, was the senior and corresponding author of the study. It was published online in the Journal of Clinical Psychiatry.
LIMITATIONS:
The study demonstrates an association, not causation. Treatment compliance could not be verified, although the daily dose administered to hospitalized patients was available. The study did not include information regarding lifestyle that could affect weight gain, such as dietary habits, physical activity, and substance use.
DISCLOSURES:
This study was funded by the Swiss National Research Foundation. Dr. Eap has received honoraria for conferences from Forum pour la formation medicale, Janssen-Cilag, Lundbeck, Otsuka, Sandoz, Servier, Sunovion, Sysmex Suisse AG, Takeda, Vifor Pharma, and Zeller in the past 3 years.
A version of this article first appeared on Medscape.com.
TOPLINE:
High-dose valproate is associated with weight gain in psychiatric patients, with the greatest gain reported in those taking ≥ 1300 mg/d, new data showed.
METHODOLOGY:
- The researchers used 1-year data from two longitudinal studies conducted between 2007 and 2022.
- The study included 215 patients (median age, 48 years; 50% female) who had been diagnosed with bipolar disorder (38%), schizoaffective disorders (26%), schizophrenia (17%), or other conditions (16%).
- The researchers used linear mixed-effect models and logistic regressions to analyze the association between doses of valproate and metabolic outcomes.
TAKEAWAY:
- Each 500-mg increase in valproate dose was associated with a weight increase of 0.52% per month over a year (P < .001), an association that was evident before and after 3 months of treatment.
- Weight gain was greatest for treatment durations of < 3 months (+0.56%, P < .001) compared with ≥ 3 months (+0.12%, P = .02).
- The greatest weight gain was observed in patients receiving doses ≥ 1300 mg/d, with a 0.50% increase in weight for each dose increment of 500 mg (P = .004).
- In men, each 500-mg dose was associated with an increase of 0.59%, while the trend in women was for an increase of 0.40% (P = .09).
- The researchers did not find associations between valproate doses and blood glucose, lipid levels, or blood pressure across a treatment period of 6 months.
IN PRACTICE:
“These findings underscore the need for clinicians to closely monitor patients on [valproate] for weight gain and to prescribe the lowest effective doses,” the authors wrote.
SOURCE:
Chin B. Eap, PhD, of the Unit of Pharmacogenetics and Clinical Psychopharmacology, Centre for Psychiatric Neuroscience, Department of Psychiatry, Lausanne University Hospital, University of Lausanne, and Hôpital de Cery, Prilly-Lausanne, Switzerland, was the senior and corresponding author of the study. It was published online in the Journal of Clinical Psychiatry.
LIMITATIONS:
The study demonstrates an association, not causation. Treatment compliance could not be verified, although the daily dose administered to hospitalized patients was available. The study did not include information regarding lifestyle that could affect weight gain, such as dietary habits, physical activity, and substance use.
DISCLOSURES:
This study was funded by the Swiss National Research Foundation. Dr. Eap has received honoraria for conferences from Forum pour la formation medicale, Janssen-Cilag, Lundbeck, Otsuka, Sandoz, Servier, Sunovion, Sysmex Suisse AG, Takeda, Vifor Pharma, and Zeller in the past 3 years.
A version of this article first appeared on Medscape.com.