Literature Review

TOPLINE:

Mindfulness-based interventions (MBIs) via telehealth improves pain-related function and biopsychosocial outcomes in veterans with chronic pain as compared with usual care.

METHODOLOGY:

• Researchers conducted a randomized clinical trial of 811 veterans who had moderate to severe chronic pain and were recruited from three Veterans Affairs facilities in the United States.
• Participants were divided into three groups: Group MBI (270), self-paced MBI (271), and usual care (270), with interventions lasting 8 weeks.
• The primary outcome was pain-related function measured using a scale on interference from pain in areas like mood, walking, work, relationships, and sleep at 10 weeks, 6 months, and 1 year.
• Secondary outcomes included pain intensity, anxiety, fatigue, sleep disturbance, participation in social roles and activities, depression, and posttraumatic stress disorder (PTSD).

TAKEAWAY:

• Pain-related function significantly improved in participants in both the MBI groups versus usual care group, with a mean difference of −0.4 (95% CI, −0.7 to −0.2) for group MBI and −0.7 (95% CI, −1.0 to −0.4) for self-paced MBI (P < .001).
• Compared with the usual care group, both the MBI groups had significantly improved secondary outcomes, including pain intensity, depression, and PTSD.
• The probability of achieving 30% improvement in pain-related function was higher for group MBI at 10 weeks and 6 months and for self-paced MBI at all three timepoints.
• No significant differences were found between the MBI groups for primary and secondary outcomes.

IN PRACTICE:

“The viability and similarity of both these approaches for delivering MBIs increase patient options for meeting their individual needs and could help accelerate and improve the implementation of nonpharmacological pain treatment in health care systems,” the study authors wrote.

SOURCE:

The study was led by Diana J. Burgess, PhD, of the Center for Care Delivery and Outcomes Research, VA Health Systems Research in Minneapolis, Minnesota, and published online in JAMA Internal Medicine. 

LIMITATIONS:

The trial was not designed to compare less resource-intensive MBIs with more intensive mindfulness-based stress reduction programs or in-person MBIs. The study did not address cost-effectiveness or control for time, attention, and other contextual factors. The high nonresponse rate (81%) to initial recruitment may have affected the generalizability of the findings.

DISCLOSURES:

The study was supported by the Pain Management Collaboratory–Pragmatic Clinical Trials Demonstration. Various authors reported grants from the National Center for Complementary and Integrative Health and the National Institute of Nursing Research.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Mindfulness-based interventions (MBIs) via telehealth improves pain-related function and biopsychosocial outcomes in veterans with chronic pain as compared with usual care.

METHODOLOGY:

• Researchers conducted a randomized clinical trial of 811 veterans who had moderate to severe chronic pain and were recruited from three Veterans Affairs facilities in the United States.
• Participants were divided into three groups: Group MBI (270), self-paced MBI (271), and usual care (270), with interventions lasting 8 weeks.
• The primary outcome was pain-related function measured using a scale on interference from pain in areas like mood, walking, work, relationships, and sleep at 10 weeks, 6 months, and 1 year.
• Secondary outcomes included pain intensity, anxiety, fatigue, sleep disturbance, participation in social roles and activities, depression, and posttraumatic stress disorder (PTSD).

TAKEAWAY:

• Pain-related function significantly improved in participants in both the MBI groups versus usual care group, with a mean difference of −0.4 (95% CI, −0.7 to −0.2) for group MBI and −0.7 (95% CI, −1.0 to −0.4) for self-paced MBI (P < .001).
• Compared with the usual care group, both the MBI groups had significantly improved secondary outcomes, including pain intensity, depression, and PTSD.
• The probability of achieving 30% improvement in pain-related function was higher for group MBI at 10 weeks and 6 months and for self-paced MBI at all three timepoints.
• No significant differences were found between the MBI groups for primary and secondary outcomes.

IN PRACTICE:

“The viability and similarity of both these approaches for delivering MBIs increase patient options for meeting their individual needs and could help accelerate and improve the implementation of nonpharmacological pain treatment in health care systems,” the study authors wrote.

SOURCE:

The study was led by Diana J. Burgess, PhD, of the Center for Care Delivery and Outcomes Research, VA Health Systems Research in Minneapolis, Minnesota, and published online in JAMA Internal Medicine. 

LIMITATIONS:

The trial was not designed to compare less resource-intensive MBIs with more intensive mindfulness-based stress reduction programs or in-person MBIs. The study did not address cost-effectiveness or control for time, attention, and other contextual factors. The high nonresponse rate (81%) to initial recruitment may have affected the generalizability of the findings.

DISCLOSURES:

The study was supported by the Pain Management Collaboratory–Pragmatic Clinical Trials Demonstration. Various authors reported grants from the National Center for Complementary and Integrative Health and the National Institute of Nursing Research.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Mindfulness-based interventions (MBIs) via telehealth improves pain-related function and biopsychosocial outcomes in veterans with chronic pain as compared with usual care.

METHODOLOGY:

• Researchers conducted a randomized clinical trial of 811 veterans who had moderate to severe chronic pain and were recruited from three Veterans Affairs facilities in the United States.
• Participants were divided into three groups: Group MBI (270), self-paced MBI (271), and usual care (270), with interventions lasting 8 weeks.
• The primary outcome was pain-related function measured using a scale on interference from pain in areas like mood, walking, work, relationships, and sleep at 10 weeks, 6 months, and 1 year.
• Secondary outcomes included pain intensity, anxiety, fatigue, sleep disturbance, participation in social roles and activities, depression, and posttraumatic stress disorder (PTSD).

TAKEAWAY:

• Pain-related function significantly improved in participants in both the MBI groups versus usual care group, with a mean difference of −0.4 (95% CI, −0.7 to −0.2) for group MBI and −0.7 (95% CI, −1.0 to −0.4) for self-paced MBI (P < .001).
• Compared with the usual care group, both the MBI groups had significantly improved secondary outcomes, including pain intensity, depression, and PTSD.
• The probability of achieving 30% improvement in pain-related function was higher for group MBI at 10 weeks and 6 months and for self-paced MBI at all three timepoints.
• No significant differences were found between the MBI groups for primary and secondary outcomes.

IN PRACTICE:

“The viability and similarity of both these approaches for delivering MBIs increase patient options for meeting their individual needs and could help accelerate and improve the implementation of nonpharmacological pain treatment in health care systems,” the study authors wrote.

SOURCE:

The study was led by Diana J. Burgess, PhD, of the Center for Care Delivery and Outcomes Research, VA Health Systems Research in Minneapolis, Minnesota, and published online in JAMA Internal Medicine. 

LIMITATIONS:

The trial was not designed to compare less resource-intensive MBIs with more intensive mindfulness-based stress reduction programs or in-person MBIs. The study did not address cost-effectiveness or control for time, attention, and other contextual factors. The high nonresponse rate (81%) to initial recruitment may have affected the generalizability of the findings.

DISCLOSURES:

The study was supported by the Pain Management Collaboratory–Pragmatic Clinical Trials Demonstration. Various authors reported grants from the National Center for Complementary and Integrative Health and the National Institute of Nursing Research.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Age-related hearing loss and peripheral neuropathy in older adults reduce longevity both directly and indirectly by affecting balance and gait.

METHODOLOGY:

• Researchers analyzed 793 older adults recruited from primary care practices participating in the OKLAHOMA Studies in 1999.
• Participants completed a questionnaire and underwent a physical examination; timed gait assessments (50 ft); and tests for peripheral nerve function, balance, and hearing.
• Hearing thresholds were tested at 20, 25, and 40 dB, respectively, and at sound frequencies of 500, 1000, 2000, and 4000 Hz.
• Researchers tracked mortality data over 22 years.

TAKEAWAY:

• Overall, 83% participants experienced hearing loss. Regular use of hearing aids was low, reported in 19% and 55% of those with moderate and severe hearing loss, respectively.
• Hearing loss was linked to impaired balance (P = .0014), slower walking (P = .0024), and reduced survival time (P = .0001). Moderate to severe hearing loss was strongly associated with reduced survival time (odds ratio, 1.36; P = .001), independent of the use of hearing aids.
• Peripheral neuropathy was present in 32% participants. The condition also increased the risk for death over the study period (hazard ratio [HR], 1.32; P = .003). Participants with both hearing loss and peripheral neuropathy showed reduced balance and survival time compared with people with either condition alone (HR, 1.55; P < .0001).

IN PRACTICE:

“Like peripheral neuropathy, advanced-age hearing loss is associated with reduced life expectancy, probably mediated in part through an adverse impact on balance,” the authors wrote. “Greater appreciation for the serious impacts of hearing loss and peripheral neuropathy could lead to further efforts to understand their causes and improve prevention and treatment strategies.”

SOURCE:

The study was led by James W. Mold, MD, MPH, of the University of Oklahoma Health Sciences Center, Oklahoma City. It was published online in the Journal of the American Geriatrics Society.

LIMITATIONS:

The dataset was collected in 1999 and may not entirely represent the current cohorts of older primary care patients. The absence of soundproof rooms and the exclusion of some components of the standard audiometric evaluation may have affected low-frequency sound measurements. Furthermore, physical examination was a less accurate measure of peripheral neuropathy. Information on the duration or severity of predictors and causes of death was not available.

DISCLOSURES:

The study was funded by the Presbyterian Health Foundation. The authors did not disclose any competing interests.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Age-related hearing loss and peripheral neuropathy in older adults reduce longevity both directly and indirectly by affecting balance and gait.

METHODOLOGY:

• Researchers analyzed 793 older adults recruited from primary care practices participating in the OKLAHOMA Studies in 1999.
• Participants completed a questionnaire and underwent a physical examination; timed gait assessments (50 ft); and tests for peripheral nerve function, balance, and hearing.
• Hearing thresholds were tested at 20, 25, and 40 dB, respectively, and at sound frequencies of 500, 1000, 2000, and 4000 Hz.
• Researchers tracked mortality data over 22 years.

TAKEAWAY:

• Overall, 83% participants experienced hearing loss. Regular use of hearing aids was low, reported in 19% and 55% of those with moderate and severe hearing loss, respectively.
• Hearing loss was linked to impaired balance (P = .0014), slower walking (P = .0024), and reduced survival time (P = .0001). Moderate to severe hearing loss was strongly associated with reduced survival time (odds ratio, 1.36; P = .001), independent of the use of hearing aids.
• Peripheral neuropathy was present in 32% participants. The condition also increased the risk for death over the study period (hazard ratio [HR], 1.32; P = .003). Participants with both hearing loss and peripheral neuropathy showed reduced balance and survival time compared with people with either condition alone (HR, 1.55; P < .0001).

IN PRACTICE:

“Like peripheral neuropathy, advanced-age hearing loss is associated with reduced life expectancy, probably mediated in part through an adverse impact on balance,” the authors wrote. “Greater appreciation for the serious impacts of hearing loss and peripheral neuropathy could lead to further efforts to understand their causes and improve prevention and treatment strategies.”

SOURCE:

The study was led by James W. Mold, MD, MPH, of the University of Oklahoma Health Sciences Center, Oklahoma City. It was published online in the Journal of the American Geriatrics Society.

LIMITATIONS:

The dataset was collected in 1999 and may not entirely represent the current cohorts of older primary care patients. The absence of soundproof rooms and the exclusion of some components of the standard audiometric evaluation may have affected low-frequency sound measurements. Furthermore, physical examination was a less accurate measure of peripheral neuropathy. Information on the duration or severity of predictors and causes of death was not available.

DISCLOSURES:

The study was funded by the Presbyterian Health Foundation. The authors did not disclose any competing interests.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Age-related hearing loss and peripheral neuropathy in older adults reduce longevity both directly and indirectly by affecting balance and gait.

METHODOLOGY:

• Researchers analyzed 793 older adults recruited from primary care practices participating in the OKLAHOMA Studies in 1999.
• Participants completed a questionnaire and underwent a physical examination; timed gait assessments (50 ft); and tests for peripheral nerve function, balance, and hearing.
• Hearing thresholds were tested at 20, 25, and 40 dB, respectively, and at sound frequencies of 500, 1000, 2000, and 4000 Hz.
• Researchers tracked mortality data over 22 years.

TAKEAWAY:

• Overall, 83% participants experienced hearing loss. Regular use of hearing aids was low, reported in 19% and 55% of those with moderate and severe hearing loss, respectively.
• Hearing loss was linked to impaired balance (P = .0014), slower walking (P = .0024), and reduced survival time (P = .0001). Moderate to severe hearing loss was strongly associated with reduced survival time (odds ratio, 1.36; P = .001), independent of the use of hearing aids.
• Peripheral neuropathy was present in 32% participants. The condition also increased the risk for death over the study period (hazard ratio [HR], 1.32; P = .003). Participants with both hearing loss and peripheral neuropathy showed reduced balance and survival time compared with people with either condition alone (HR, 1.55; P < .0001).

IN PRACTICE:

“Like peripheral neuropathy, advanced-age hearing loss is associated with reduced life expectancy, probably mediated in part through an adverse impact on balance,” the authors wrote. “Greater appreciation for the serious impacts of hearing loss and peripheral neuropathy could lead to further efforts to understand their causes and improve prevention and treatment strategies.”

SOURCE:

The study was led by James W. Mold, MD, MPH, of the University of Oklahoma Health Sciences Center, Oklahoma City. It was published online in the Journal of the American Geriatrics Society.

LIMITATIONS:

The dataset was collected in 1999 and may not entirely represent the current cohorts of older primary care patients. The absence of soundproof rooms and the exclusion of some components of the standard audiometric evaluation may have affected low-frequency sound measurements. Furthermore, physical examination was a less accurate measure of peripheral neuropathy. Information on the duration or severity of predictors and causes of death was not available.

DISCLOSURES:

The study was funded by the Presbyterian Health Foundation. The authors did not disclose any competing interests.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Artificial intelligence (AI) can accurately interpret routine clinical EEGs across a diverse population of patients, equipment types, and recording settings, according to investigators.

These findings suggest that SCORE-AI, the model tested, can reliably interpret common EEGs in real-world practice, supporting its recent FDA approval, reported lead author Daniel Mansilla, MD, a neurologist at Montreal Neurological Institute and Hospital, and colleagues.

“Overinterpretation of clinical EEG is the most common cause of misdiagnosing epilepsy,” the investigators wrote in Epilepsia. “AI tools may be a solution for this challenge, both as an additional resource for confirmation and classification of epilepsy, and as an aid for the interpretation of EEG in critical care medicine.”

To date, however, AI tools have struggled with the variability encountered in real-world neurology practice.“When tested on external data from different centers and diverse patient populations, and using equipment distinct from the initial study, medical AI models frequently exhibit modest performance, and only a few AI tools have successfully transitioned into medical practice,” the investigators wrote.
 

SCORE-AI Matches Expert Interpretation of Routine EEGs

The present study put SCORE-AI to the test with EEGs from 104 patients between 16 and 91 years. These individuals hailed from “geographically distinct” regions, while recording equipment and conditions also varied widely, according to Dr. Mansilla and colleagues.

To set an external gold-standard for comparison, EEGs were first interpreted by three human expert raters, who were blinded to all case information except the EEGs themselves. The dataset comprised 50% normal and 50% abnormal EEGs. Four major classes of EEG abnormalities were included: focal epileptiform, generalized epileptiform, focal nonepileptiform, and diffuse nonepileptiform.

Comparing SCORE-AI interpretations with the experts’ interpretations revealed no significant difference in any metric or category. The AI tool had an overall accuracy of 92%, compared with 94% for the human experts. Of note, SCORE-AI maintained this level of performance regardless of vigilance state or normal variants.

“SCORE-AI has obtained FDA approval for routine clinical EEGs and is presently being integrated into broadly available EEG software (Natus NeuroWorks),” the investigators wrote.
 

Further Validation May Be Needed

Wesley T. Kerr, MD, PhD, functional (nonepileptic) seizures clinic lead epileptologist at the University of Pittsburgh Medical Center, and handling associate editor for this study in Epilepsia, said the present findings are important because they show that SCORE-AI can perform in scenarios beyond the one in which it was developed.

Still, it may be premature for broad commercial rollout.

University of Pittsburgh

NYU Langone

AI-Assisted EEG Interpretation Is Here to Stay

When asked about the long-term future of AI-assisted EEG interpretation, Dr. Friedman predicted that it will be “critical” for helping improve the accuracy of epilepsy diagnoses, particularly because most EEGs worldwide are interpreted by non-experts, leading to the known issue with epilepsy misdiagnosis.

“However,” he added, “it is important to note that epilepsy is a clinical diagnosis ... [EEG] is only one piece of evidence in neurologic decision making. History and accurate eyewitness description of the events of concern are extremely critical to the diagnosis and cannot be replaced by AI yet.”

Dr. Kerr offered a similar view, highlighting the potential for SCORE-AI to raise the game of non-epileptologists.

“My anticipation is that neurologists who don’t use SCORE-AI will be replaced by neurologists who use SCORE-AI well,” he said. “Neurologists who use it well will be able to read more EEGs in less time without sacrificing quality. This will allow the neurologist to spend more time talking with the patient about the interpretation of the tests and how that impacts clinical care.”

Then again, that time spent talking with the patient may also one day be delegated to a machine.

“It is certainly imaginable that AI chatbots using large language models to interact with patients and family could be developed to extract consistent epilepsy histories for diagnostic support,” Dr. Wesley said.

This work was supported by a project grant from the Canadian Institutes of Health Research and Duke Neurology start-up funding. The investigators and interviewees reported no relevant conflicts of interest.

Artificial intelligence (AI) can accurately interpret routine clinical EEGs across a diverse population of patients, equipment types, and recording settings, according to investigators.

These findings suggest that SCORE-AI, the model tested, can reliably interpret common EEGs in real-world practice, supporting its recent FDA approval, reported lead author Daniel Mansilla, MD, a neurologist at Montreal Neurological Institute and Hospital, and colleagues.

“Overinterpretation of clinical EEG is the most common cause of misdiagnosing epilepsy,” the investigators wrote in Epilepsia. “AI tools may be a solution for this challenge, both as an additional resource for confirmation and classification of epilepsy, and as an aid for the interpretation of EEG in critical care medicine.”

To date, however, AI tools have struggled with the variability encountered in real-world neurology practice.“When tested on external data from different centers and diverse patient populations, and using equipment distinct from the initial study, medical AI models frequently exhibit modest performance, and only a few AI tools have successfully transitioned into medical practice,” the investigators wrote.
 

SCORE-AI Matches Expert Interpretation of Routine EEGs

The present study put SCORE-AI to the test with EEGs from 104 patients between 16 and 91 years. These individuals hailed from “geographically distinct” regions, while recording equipment and conditions also varied widely, according to Dr. Mansilla and colleagues.

To set an external gold-standard for comparison, EEGs were first interpreted by three human expert raters, who were blinded to all case information except the EEGs themselves. The dataset comprised 50% normal and 50% abnormal EEGs. Four major classes of EEG abnormalities were included: focal epileptiform, generalized epileptiform, focal nonepileptiform, and diffuse nonepileptiform.

Comparing SCORE-AI interpretations with the experts’ interpretations revealed no significant difference in any metric or category. The AI tool had an overall accuracy of 92%, compared with 94% for the human experts. Of note, SCORE-AI maintained this level of performance regardless of vigilance state or normal variants.

“SCORE-AI has obtained FDA approval for routine clinical EEGs and is presently being integrated into broadly available EEG software (Natus NeuroWorks),” the investigators wrote.
 

Further Validation May Be Needed

Wesley T. Kerr, MD, PhD, functional (nonepileptic) seizures clinic lead epileptologist at the University of Pittsburgh Medical Center, and handling associate editor for this study in Epilepsia, said the present findings are important because they show that SCORE-AI can perform in scenarios beyond the one in which it was developed.

Still, it may be premature for broad commercial rollout.

University of Pittsburgh

NYU Langone

AI-Assisted EEG Interpretation Is Here to Stay

When asked about the long-term future of AI-assisted EEG interpretation, Dr. Friedman predicted that it will be “critical” for helping improve the accuracy of epilepsy diagnoses, particularly because most EEGs worldwide are interpreted by non-experts, leading to the known issue with epilepsy misdiagnosis.

“However,” he added, “it is important to note that epilepsy is a clinical diagnosis ... [EEG] is only one piece of evidence in neurologic decision making. History and accurate eyewitness description of the events of concern are extremely critical to the diagnosis and cannot be replaced by AI yet.”

Dr. Kerr offered a similar view, highlighting the potential for SCORE-AI to raise the game of non-epileptologists.

“My anticipation is that neurologists who don’t use SCORE-AI will be replaced by neurologists who use SCORE-AI well,” he said. “Neurologists who use it well will be able to read more EEGs in less time without sacrificing quality. This will allow the neurologist to spend more time talking with the patient about the interpretation of the tests and how that impacts clinical care.”

Then again, that time spent talking with the patient may also one day be delegated to a machine.

“It is certainly imaginable that AI chatbots using large language models to interact with patients and family could be developed to extract consistent epilepsy histories for diagnostic support,” Dr. Wesley said.

This work was supported by a project grant from the Canadian Institutes of Health Research and Duke Neurology start-up funding. The investigators and interviewees reported no relevant conflicts of interest.

Artificial intelligence (AI) can accurately interpret routine clinical EEGs across a diverse population of patients, equipment types, and recording settings, according to investigators.

These findings suggest that SCORE-AI, the model tested, can reliably interpret common EEGs in real-world practice, supporting its recent FDA approval, reported lead author Daniel Mansilla, MD, a neurologist at Montreal Neurological Institute and Hospital, and colleagues.

“Overinterpretation of clinical EEG is the most common cause of misdiagnosing epilepsy,” the investigators wrote in Epilepsia. “AI tools may be a solution for this challenge, both as an additional resource for confirmation and classification of epilepsy, and as an aid for the interpretation of EEG in critical care medicine.”

To date, however, AI tools have struggled with the variability encountered in real-world neurology practice.“When tested on external data from different centers and diverse patient populations, and using equipment distinct from the initial study, medical AI models frequently exhibit modest performance, and only a few AI tools have successfully transitioned into medical practice,” the investigators wrote.
 

SCORE-AI Matches Expert Interpretation of Routine EEGs

The present study put SCORE-AI to the test with EEGs from 104 patients between 16 and 91 years. These individuals hailed from “geographically distinct” regions, while recording equipment and conditions also varied widely, according to Dr. Mansilla and colleagues.

To set an external gold-standard for comparison, EEGs were first interpreted by three human expert raters, who were blinded to all case information except the EEGs themselves. The dataset comprised 50% normal and 50% abnormal EEGs. Four major classes of EEG abnormalities were included: focal epileptiform, generalized epileptiform, focal nonepileptiform, and diffuse nonepileptiform.

Comparing SCORE-AI interpretations with the experts’ interpretations revealed no significant difference in any metric or category. The AI tool had an overall accuracy of 92%, compared with 94% for the human experts. Of note, SCORE-AI maintained this level of performance regardless of vigilance state or normal variants.

“SCORE-AI has obtained FDA approval for routine clinical EEGs and is presently being integrated into broadly available EEG software (Natus NeuroWorks),” the investigators wrote.
 

Further Validation May Be Needed

Wesley T. Kerr, MD, PhD, functional (nonepileptic) seizures clinic lead epileptologist at the University of Pittsburgh Medical Center, and handling associate editor for this study in Epilepsia, said the present findings are important because they show that SCORE-AI can perform in scenarios beyond the one in which it was developed.

Still, it may be premature for broad commercial rollout.

University of Pittsburgh

NYU Langone

AI-Assisted EEG Interpretation Is Here to Stay

When asked about the long-term future of AI-assisted EEG interpretation, Dr. Friedman predicted that it will be “critical” for helping improve the accuracy of epilepsy diagnoses, particularly because most EEGs worldwide are interpreted by non-experts, leading to the known issue with epilepsy misdiagnosis.

“However,” he added, “it is important to note that epilepsy is a clinical diagnosis ... [EEG] is only one piece of evidence in neurologic decision making. History and accurate eyewitness description of the events of concern are extremely critical to the diagnosis and cannot be replaced by AI yet.”

Dr. Kerr offered a similar view, highlighting the potential for SCORE-AI to raise the game of non-epileptologists.

“My anticipation is that neurologists who don’t use SCORE-AI will be replaced by neurologists who use SCORE-AI well,” he said. “Neurologists who use it well will be able to read more EEGs in less time without sacrificing quality. This will allow the neurologist to spend more time talking with the patient about the interpretation of the tests and how that impacts clinical care.”

Then again, that time spent talking with the patient may also one day be delegated to a machine.

“It is certainly imaginable that AI chatbots using large language models to interact with patients and family could be developed to extract consistent epilepsy histories for diagnostic support,” Dr. Wesley said.

This work was supported by a project grant from the Canadian Institutes of Health Research and Duke Neurology start-up funding. The investigators and interviewees reported no relevant conflicts of interest.

In 2019, 57 million people worldwide were living with dementia, a figure expected to soar to 153 million by 2050. A recent Lancet Commission report suggests that nearly half of dementia cases could be prevented or delayed by addressing 14 modifiable risk factors, including impaired vision. 

The report’s authors recommend that vision-loss screening and treatment be universally available. But are these recommendations warranted? What is the evidence? What is the potential mechanism? And what are the potential implications for clinical practice? 

Worldwide, the prevalence of avoidable vision loss and blindness in adults aged 50 years or older is estimated to hover around 13%.

“There is now overwhelming evidence that vision impairment in later life is associated with more rapid cognitive decline and an increased risk of dementia,” said Joshua Ehrlich, MD, MPH, associate professor in ophthalmology and visual sciences, the Institute for Social Research at the University of Michigan, Ann Arbor. 

The evidence includes a meta-analysis of 14 prospective cohort studies with roughly 6.2 million older adults who were cognitively intact at baseline. Over the course of up to 14 years, 171,888 developed dementia. Vision loss was associated with a pooled relative risk (RR) for dementia of 1.47. 

A separate meta-analysis also identified an increased risk for dementia (RR, 1.38) with visual loss. When broken down into different eye conditions, an increased dementia risk was associated with cataracts and diabetic retinopathy but not with glaucoma or age-related macular degeneration.

A US study that followed roughly 3000 older adults with cataracts and normal cognition at baseline for more than 20 years found that those who had cataract extraction had significantly reduced risk for dementia compared with those who did not have cataract extraction (hazard ratio, 0.71), after controlling for age, race, APOE genotype, education, smoking, and an extensive list of comorbidities. 
 

Causation or Coincidence?

The mechanisms behind these associations might be related to underlying illness, such as diabetes, which is a risk factor for dementia; vision loss itself, as might be suggested by a possible effect of cataract surgery; or shared neuropathologic processes in the retina and the brain. 

A longitudinal study from Korea that included roughly 6 million adults showed that dementia risk increased with severity of visual loss, which supports the hypothesis that vision loss in itself might be causal or that there is a dose-response effect to a shared causal factor. 

“Work is still needed to sort out” exactly how visual deficits may raise dementia risk, although several hypotheses exist, Dr. Ehrlich said. 

For example, “decreased input to the brain via the visual pathways may directly induce brain changes. Also, consequences of vision loss, like social isolation, physical inactivity, and depression, are themselves risk factors for dementia and may explain the pathways through which vision impairment increases risk,” he said. 

Is the link causal? “We’ll never know definitively because we can’t randomize people to not get cataract surgery versus getting cataract surgery, because we know that improving vision improves quality of life, so we’d never want to do that. But the new evidence that’s come in over the last 5 years or so is pretty promising,” said Esme Fuller-Thomson, PhD, director of the Institute for Life Course and Aging and professor, Department of Family and Community Medicine and Faculty of Nursing, at the University of Toronto, Ontario, Canada.

She noted that results of two studies that have looked at this “seem to indicate that those who have cataract surgery are not nearly at as high risk of dementia as those who have cataracts but don’t have the surgery. That’s leaning towards causality.”

A study published in July suggests that cataracts increase dementia risk through vascular and non–Alzheimer’s disease mechanisms. 
 

Clear Clinical Implications 

Dr. Ehrlich said that evidence for an association between untreated vision loss and dementia risk and potential modification by treatment has clear implications for care. 

“Loss of vision impacts so many aspects of people’s lives beyond just how they see the world and losing vision in later life is not a normal part of aging. Thus, when older adults experience vision loss, this should be a cause for concern and prompt an immediate referral to an eye care professional,” he noted. 

Dr. Fuller-Thomson agrees. “Addressing vision loss will certainly help people see better and function at a higher level and improve quality of life, and it seems probable that it might decrease dementia risk so it’s a win-win,” she said.

In her own research, Dr. Fuller-Thomson has found that the combination of hearing loss and vision loss is linked to an eightfold increased risk for cognitive impairment.

“The idea is that vision and/or hearing loss makes it harder for you to be physically active, to be socially engaged, to be mentally stimulated. They are equally important in terms of social isolation, which could lead to loneliness, and we know that loneliness is not good for dementia,” she said.

“With dual sensory impairment, you don’t have as much information coming in — your brain is not engaged as much — and having an engaged brain, doing hobbies, having intellectually stimulating conversation, all of those are factors are associated with lowering risk of dementia,” Dr. Fuller-Thomson said.

The latest Lancet Commission report noted that treatment for visual loss is “effective and cost-effective” for an estimated 90% of people. However, across the world, particularly in low- and middle-income countries, visual loss often goes untreated. 

“A clear opportunity for dementia prevention exists with treatment of visual loss,” the report concluded.

Dr. Ehrlich and Dr. Fuller-Thomson have no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

In 2019, 57 million people worldwide were living with dementia, a figure expected to soar to 153 million by 2050. A recent Lancet Commission report suggests that nearly half of dementia cases could be prevented or delayed by addressing 14 modifiable risk factors, including impaired vision. 

The report’s authors recommend that vision-loss screening and treatment be universally available. But are these recommendations warranted? What is the evidence? What is the potential mechanism? And what are the potential implications for clinical practice? 

Worldwide, the prevalence of avoidable vision loss and blindness in adults aged 50 years or older is estimated to hover around 13%.

“There is now overwhelming evidence that vision impairment in later life is associated with more rapid cognitive decline and an increased risk of dementia,” said Joshua Ehrlich, MD, MPH, associate professor in ophthalmology and visual sciences, the Institute for Social Research at the University of Michigan, Ann Arbor. 

The evidence includes a meta-analysis of 14 prospective cohort studies with roughly 6.2 million older adults who were cognitively intact at baseline. Over the course of up to 14 years, 171,888 developed dementia. Vision loss was associated with a pooled relative risk (RR) for dementia of 1.47. 

A separate meta-analysis also identified an increased risk for dementia (RR, 1.38) with visual loss. When broken down into different eye conditions, an increased dementia risk was associated with cataracts and diabetic retinopathy but not with glaucoma or age-related macular degeneration.

A US study that followed roughly 3000 older adults with cataracts and normal cognition at baseline for more than 20 years found that those who had cataract extraction had significantly reduced risk for dementia compared with those who did not have cataract extraction (hazard ratio, 0.71), after controlling for age, race, APOE genotype, education, smoking, and an extensive list of comorbidities. 
 

Causation or Coincidence?

The mechanisms behind these associations might be related to underlying illness, such as diabetes, which is a risk factor for dementia; vision loss itself, as might be suggested by a possible effect of cataract surgery; or shared neuropathologic processes in the retina and the brain. 

A longitudinal study from Korea that included roughly 6 million adults showed that dementia risk increased with severity of visual loss, which supports the hypothesis that vision loss in itself might be causal or that there is a dose-response effect to a shared causal factor. 

“Work is still needed to sort out” exactly how visual deficits may raise dementia risk, although several hypotheses exist, Dr. Ehrlich said. 

For example, “decreased input to the brain via the visual pathways may directly induce brain changes. Also, consequences of vision loss, like social isolation, physical inactivity, and depression, are themselves risk factors for dementia and may explain the pathways through which vision impairment increases risk,” he said. 

Is the link causal? “We’ll never know definitively because we can’t randomize people to not get cataract surgery versus getting cataract surgery, because we know that improving vision improves quality of life, so we’d never want to do that. But the new evidence that’s come in over the last 5 years or so is pretty promising,” said Esme Fuller-Thomson, PhD, director of the Institute for Life Course and Aging and professor, Department of Family and Community Medicine and Faculty of Nursing, at the University of Toronto, Ontario, Canada.

She noted that results of two studies that have looked at this “seem to indicate that those who have cataract surgery are not nearly at as high risk of dementia as those who have cataracts but don’t have the surgery. That’s leaning towards causality.”

A study published in July suggests that cataracts increase dementia risk through vascular and non–Alzheimer’s disease mechanisms. 
 

Clear Clinical Implications 

Dr. Ehrlich said that evidence for an association between untreated vision loss and dementia risk and potential modification by treatment has clear implications for care. 

“Loss of vision impacts so many aspects of people’s lives beyond just how they see the world and losing vision in later life is not a normal part of aging. Thus, when older adults experience vision loss, this should be a cause for concern and prompt an immediate referral to an eye care professional,” he noted. 

Dr. Fuller-Thomson agrees. “Addressing vision loss will certainly help people see better and function at a higher level and improve quality of life, and it seems probable that it might decrease dementia risk so it’s a win-win,” she said.

In her own research, Dr. Fuller-Thomson has found that the combination of hearing loss and vision loss is linked to an eightfold increased risk for cognitive impairment.

“The idea is that vision and/or hearing loss makes it harder for you to be physically active, to be socially engaged, to be mentally stimulated. They are equally important in terms of social isolation, which could lead to loneliness, and we know that loneliness is not good for dementia,” she said.

“With dual sensory impairment, you don’t have as much information coming in — your brain is not engaged as much — and having an engaged brain, doing hobbies, having intellectually stimulating conversation, all of those are factors are associated with lowering risk of dementia,” Dr. Fuller-Thomson said.

The latest Lancet Commission report noted that treatment for visual loss is “effective and cost-effective” for an estimated 90% of people. However, across the world, particularly in low- and middle-income countries, visual loss often goes untreated. 

“A clear opportunity for dementia prevention exists with treatment of visual loss,” the report concluded.

Dr. Ehrlich and Dr. Fuller-Thomson have no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

In 2019, 57 million people worldwide were living with dementia, a figure expected to soar to 153 million by 2050. A recent Lancet Commission report suggests that nearly half of dementia cases could be prevented or delayed by addressing 14 modifiable risk factors, including impaired vision. 

The report’s authors recommend that vision-loss screening and treatment be universally available. But are these recommendations warranted? What is the evidence? What is the potential mechanism? And what are the potential implications for clinical practice? 

Worldwide, the prevalence of avoidable vision loss and blindness in adults aged 50 years or older is estimated to hover around 13%.

“There is now overwhelming evidence that vision impairment in later life is associated with more rapid cognitive decline and an increased risk of dementia,” said Joshua Ehrlich, MD, MPH, associate professor in ophthalmology and visual sciences, the Institute for Social Research at the University of Michigan, Ann Arbor. 

The evidence includes a meta-analysis of 14 prospective cohort studies with roughly 6.2 million older adults who were cognitively intact at baseline. Over the course of up to 14 years, 171,888 developed dementia. Vision loss was associated with a pooled relative risk (RR) for dementia of 1.47. 

A separate meta-analysis also identified an increased risk for dementia (RR, 1.38) with visual loss. When broken down into different eye conditions, an increased dementia risk was associated with cataracts and diabetic retinopathy but not with glaucoma or age-related macular degeneration.

A US study that followed roughly 3000 older adults with cataracts and normal cognition at baseline for more than 20 years found that those who had cataract extraction had significantly reduced risk for dementia compared with those who did not have cataract extraction (hazard ratio, 0.71), after controlling for age, race, APOE genotype, education, smoking, and an extensive list of comorbidities. 
 

Causation or Coincidence?

The mechanisms behind these associations might be related to underlying illness, such as diabetes, which is a risk factor for dementia; vision loss itself, as might be suggested by a possible effect of cataract surgery; or shared neuropathologic processes in the retina and the brain. 

A longitudinal study from Korea that included roughly 6 million adults showed that dementia risk increased with severity of visual loss, which supports the hypothesis that vision loss in itself might be causal or that there is a dose-response effect to a shared causal factor. 

“Work is still needed to sort out” exactly how visual deficits may raise dementia risk, although several hypotheses exist, Dr. Ehrlich said. 

For example, “decreased input to the brain via the visual pathways may directly induce brain changes. Also, consequences of vision loss, like social isolation, physical inactivity, and depression, are themselves risk factors for dementia and may explain the pathways through which vision impairment increases risk,” he said. 

Is the link causal? “We’ll never know definitively because we can’t randomize people to not get cataract surgery versus getting cataract surgery, because we know that improving vision improves quality of life, so we’d never want to do that. But the new evidence that’s come in over the last 5 years or so is pretty promising,” said Esme Fuller-Thomson, PhD, director of the Institute for Life Course and Aging and professor, Department of Family and Community Medicine and Faculty of Nursing, at the University of Toronto, Ontario, Canada.

She noted that results of two studies that have looked at this “seem to indicate that those who have cataract surgery are not nearly at as high risk of dementia as those who have cataracts but don’t have the surgery. That’s leaning towards causality.”

A study published in July suggests that cataracts increase dementia risk through vascular and non–Alzheimer’s disease mechanisms. 
 

Clear Clinical Implications 

Dr. Ehrlich said that evidence for an association between untreated vision loss and dementia risk and potential modification by treatment has clear implications for care. 

“Loss of vision impacts so many aspects of people’s lives beyond just how they see the world and losing vision in later life is not a normal part of aging. Thus, when older adults experience vision loss, this should be a cause for concern and prompt an immediate referral to an eye care professional,” he noted. 

Dr. Fuller-Thomson agrees. “Addressing vision loss will certainly help people see better and function at a higher level and improve quality of life, and it seems probable that it might decrease dementia risk so it’s a win-win,” she said.

In her own research, Dr. Fuller-Thomson has found that the combination of hearing loss and vision loss is linked to an eightfold increased risk for cognitive impairment.

“The idea is that vision and/or hearing loss makes it harder for you to be physically active, to be socially engaged, to be mentally stimulated. They are equally important in terms of social isolation, which could lead to loneliness, and we know that loneliness is not good for dementia,” she said.

“With dual sensory impairment, you don’t have as much information coming in — your brain is not engaged as much — and having an engaged brain, doing hobbies, having intellectually stimulating conversation, all of those are factors are associated with lowering risk of dementia,” Dr. Fuller-Thomson said.

The latest Lancet Commission report noted that treatment for visual loss is “effective and cost-effective” for an estimated 90% of people. However, across the world, particularly in low- and middle-income countries, visual loss often goes untreated. 

“A clear opportunity for dementia prevention exists with treatment of visual loss,” the report concluded.

Dr. Ehrlich and Dr. Fuller-Thomson have no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

A new report on the preventability of dementia is both exciting and paradigm-shifting. The new study, published in The Lancet by the Lancet Commission on Dementia, estimates that close to 50% of cases of dementia worldwide can be prevented or delayed by improving 14 modifiable risk factors. 

This is paradigm-shifting because dementia is often perceived as an inevitable consequence of the aging process, with a major genetic component. But this study suggests that modifying these risk factors can benefit everyone, irrespective of genetic risk, and that it’s important to have a life-course approach. It’s never too early or too late to start to modify these factors. 

We’ve known for a long time that many chronic diseases are highly preventable and modifiable. Some that come to mind are type 2 diabetes, coronary heart disease, and even certain forms of cancer. Modifiable risk factors include cigarette smoking, diet, physical activity, and maintaining a healthy weight. This study suggests that many of the same risk factors and more are relevant to reducing risk for dementia. 

Let’s go through the risk factors, many of which are behavioral. These risk factors include lifestyle factors such as lack of physical activity, cigarette smoking, excessive alcohol consumption, and obesity. The cardiovascular or vascular-specific risk factors include not only those behavioral factors but also hypertension, high LDL cholesterol, and diabetes. Cognitive engagement–specific risk factors include social isolation, which is a major risk factor for dementia, as well as untreated hearing or vision loss, which can exacerbate social isolation and depression, and low educational attainment, which can be related to less cognitive engagement.

They also mention traumatic brain injury from an accident or contact sports without head protection as a risk factor, and the environmental risk factor of air pollution or poor air quality. 

Two of these risk factors are new since the previous report in 2020: elevated LDL cholesterol and untreated vision loss, both of which are quite treatable. Overall, these findings suggest that a lot can be done to lower dementia risk, but it requires individual behavior modifications as well as a comprehensive approach with involvement of the healthcare system for improved screening, access, and public policy to reduce air pollution.

Some of these risk factors are more relevant to women, especially the social isolation that is so common later in life in women. In the United States, close to two out of three patients with dementia are women.

So, informing our patients about these risk factors and what can be done in terms of behavior modification, increased screening, and treatment for these conditions can go a long way in helping our patients reduce their risk for dementia.
 

Dr. Manson is professor of medicine and the Michael and Lee Bell Professor of Women’s Health, Harvard Medical School, chief, Division of Preventive Medicine, Brigham and Women’s Hospital, Boston, and past president, North American Menopause Society, 2011-2012. She disclosed receiving study pill donation and infrastructure support from Mars Symbioscience (for the COSMOS trial).

A version of this article appeared on Medscape.com.

A new report on the preventability of dementia is both exciting and paradigm-shifting. The new study, published in The Lancet by the Lancet Commission on Dementia, estimates that close to 50% of cases of dementia worldwide can be prevented or delayed by improving 14 modifiable risk factors. 

This is paradigm-shifting because dementia is often perceived as an inevitable consequence of the aging process, with a major genetic component. But this study suggests that modifying these risk factors can benefit everyone, irrespective of genetic risk, and that it’s important to have a life-course approach. It’s never too early or too late to start to modify these factors. 

We’ve known for a long time that many chronic diseases are highly preventable and modifiable. Some that come to mind are type 2 diabetes, coronary heart disease, and even certain forms of cancer. Modifiable risk factors include cigarette smoking, diet, physical activity, and maintaining a healthy weight. This study suggests that many of the same risk factors and more are relevant to reducing risk for dementia. 

Let’s go through the risk factors, many of which are behavioral. These risk factors include lifestyle factors such as lack of physical activity, cigarette smoking, excessive alcohol consumption, and obesity. The cardiovascular or vascular-specific risk factors include not only those behavioral factors but also hypertension, high LDL cholesterol, and diabetes. Cognitive engagement–specific risk factors include social isolation, which is a major risk factor for dementia, as well as untreated hearing or vision loss, which can exacerbate social isolation and depression, and low educational attainment, which can be related to less cognitive engagement.

They also mention traumatic brain injury from an accident or contact sports without head protection as a risk factor, and the environmental risk factor of air pollution or poor air quality. 

Two of these risk factors are new since the previous report in 2020: elevated LDL cholesterol and untreated vision loss, both of which are quite treatable. Overall, these findings suggest that a lot can be done to lower dementia risk, but it requires individual behavior modifications as well as a comprehensive approach with involvement of the healthcare system for improved screening, access, and public policy to reduce air pollution.

Some of these risk factors are more relevant to women, especially the social isolation that is so common later in life in women. In the United States, close to two out of three patients with dementia are women.

So, informing our patients about these risk factors and what can be done in terms of behavior modification, increased screening, and treatment for these conditions can go a long way in helping our patients reduce their risk for dementia.
 

Dr. Manson is professor of medicine and the Michael and Lee Bell Professor of Women’s Health, Harvard Medical School, chief, Division of Preventive Medicine, Brigham and Women’s Hospital, Boston, and past president, North American Menopause Society, 2011-2012. She disclosed receiving study pill donation and infrastructure support from Mars Symbioscience (for the COSMOS trial).

A version of this article appeared on Medscape.com.

A new report on the preventability of dementia is both exciting and paradigm-shifting. The new study, published in The Lancet by the Lancet Commission on Dementia, estimates that close to 50% of cases of dementia worldwide can be prevented or delayed by improving 14 modifiable risk factors. 

This is paradigm-shifting because dementia is often perceived as an inevitable consequence of the aging process, with a major genetic component. But this study suggests that modifying these risk factors can benefit everyone, irrespective of genetic risk, and that it’s important to have a life-course approach. It’s never too early or too late to start to modify these factors. 

We’ve known for a long time that many chronic diseases are highly preventable and modifiable. Some that come to mind are type 2 diabetes, coronary heart disease, and even certain forms of cancer. Modifiable risk factors include cigarette smoking, diet, physical activity, and maintaining a healthy weight. This study suggests that many of the same risk factors and more are relevant to reducing risk for dementia. 

Let’s go through the risk factors, many of which are behavioral. These risk factors include lifestyle factors such as lack of physical activity, cigarette smoking, excessive alcohol consumption, and obesity. The cardiovascular or vascular-specific risk factors include not only those behavioral factors but also hypertension, high LDL cholesterol, and diabetes. Cognitive engagement–specific risk factors include social isolation, which is a major risk factor for dementia, as well as untreated hearing or vision loss, which can exacerbate social isolation and depression, and low educational attainment, which can be related to less cognitive engagement.

They also mention traumatic brain injury from an accident or contact sports without head protection as a risk factor, and the environmental risk factor of air pollution or poor air quality. 

Two of these risk factors are new since the previous report in 2020: elevated LDL cholesterol and untreated vision loss, both of which are quite treatable. Overall, these findings suggest that a lot can be done to lower dementia risk, but it requires individual behavior modifications as well as a comprehensive approach with involvement of the healthcare system for improved screening, access, and public policy to reduce air pollution.

Some of these risk factors are more relevant to women, especially the social isolation that is so common later in life in women. In the United States, close to two out of three patients with dementia are women.

So, informing our patients about these risk factors and what can be done in terms of behavior modification, increased screening, and treatment for these conditions can go a long way in helping our patients reduce their risk for dementia.
 

Dr. Manson is professor of medicine and the Michael and Lee Bell Professor of Women’s Health, Harvard Medical School, chief, Division of Preventive Medicine, Brigham and Women’s Hospital, Boston, and past president, North American Menopause Society, 2011-2012. She disclosed receiving study pill donation and infrastructure support from Mars Symbioscience (for the COSMOS trial).

A version of this article appeared on Medscape.com.

The American Headache Society (AHS) has published a white paper guiding the treatment of posttraumatic headache caused by concussion in youth.

The guidance document, the first of its kind, covers risk factors for prolonged recovery, along with pharmacologic and nonpharmacologic management strategies, and supports an emphasis on multidisciplinary care, lead author Carlyn Patterson Gentile, MD, PhD, attending physician in the Division of Neurology at Children’s Hospital of Philadelphia in Pennsylvania, and colleagues reported.

“There are no guidelines to inform the management of posttraumatic headache in youth, but multiple studies have been conducted over the past 2 decades,” the authors wrote in Headache. “This white paper aims to provide a thorough review of the current literature, identify gaps in knowledge, and provide a road map for [posttraumatic headache] management in youth based on available evidence and expert opinion.”
 

Clarity for an Underrecognized Issue

According to Russell Lonser, MD, professor and chair of neurological surgery at Ohio State University, Columbus, the white paper is important because it offers concrete guidance for health care providers who may be less familiar with posttraumatic headache in youth.

courtesy Ohio State College of Medicine

“It brings together all of the previous literature ... in a very well-written way,” Dr. Lonser said in an interview. “More than anything, it could reassure [providers] that they shouldn’t be hunting down potentially magical cures, and reassure them in symptomatic management.”

Meeryo C. Choe, MD, associate clinical professor of pediatric neurology at UCLA Health in Calabasas, California, said the paper also helps shine a light on what may be a more common condition than the public suspects.

“While the media focuses on the effects of concussion in professional sports athletes, the biggest population of athletes is in our youth population,” Dr. Choe said in a written comment. “Almost 25 million children participate in sports throughout the country, and yet we lack guidelines on how to treat posttraumatic headache which can often develop into persistent postconcussive symptoms.”

This white paper, she noted, builds on Dr. Gentile’s 2021 systematic review, introduces new management recommendations, and aligns with the latest consensus statement from the Concussion in Sport Group.

Risk Factors

The white paper first emphasizes the importance of early identification of youth at high risk for prolonged recovery from posttraumatic headache. Risk factors include female sex, adolescent age, a high number of acute symptoms following the initial injury, and social determinants of health.

courtesy UCLA Health

“I agree that it is important to identify these patients early to improve the recovery trajectory,” Dr. Choe said.

Identifying these individuals quickly allows for timely intervention with both pharmacologic and nonpharmacologic therapies, Dr. Gentile and colleagues noted, potentially mitigating persistent symptoms. Clinicians are encouraged to perform thorough initial assessments to identify these risk factors and initiate early, personalized management plans.

Initial Management of Acute Posttraumatic Headache

For the initial management of acute posttraumatic headache, the white paper recommends a scheduled dosing regimen of simple analgesics. Ibuprofen at a dosage of 10 mg/kg every 6-8 hours (up to a maximum of 600 mg per dose) combined with acetaminophen has shown the best evidence for efficacy. Provided the patient is clinically stable, this regimen should be initiated within 48 hours of the injury and maintained with scheduled dosing for 3-10 days.

If effective, these medications can subsequently be used on an as-needed basis. Careful usage of analgesics is crucial, the white paper cautions, as overadministration can lead to medication-overuse headaches, complicating the recovery process.

Secondary Treatment Options

In cases where first-line oral medications are ineffective, the AHS white paper outlines several secondary treatment options. These include acute intravenous therapies such as ketorolac, dopamine receptor antagonists, and intravenous fluids. Nerve blocks and oral corticosteroid bridges may also be considered.

The white paper stresses the importance of individualized treatment plans that consider the specific needs and responses of each patient, noting that the evidence supporting these approaches is primarily derived from retrospective studies and case reports.

courtesy Nationwide Children&#039;s Hospital

“Patient preferences should be factored in,” said Sean Rose, MD, pediatric neurologist and codirector of the Complex Concussion Clinic at Nationwide Children’s Hospital, Columbus, Ohio.

Supplements and Preventive Measures

For adolescents and young adults at high risk of prolonged posttraumatic headache, the white paper suggests the use of riboflavin and magnesium supplements. Small randomized clinical trials suggest that these supplements may aid in speeding recovery when administered for 1-2 weeks within 48 hours of injury.

If significant headache persists after 2 weeks, a regimen of riboflavin 400 mg daily and magnesium 400-500 mg nightly can be trialed for 6-8 weeks, in line with recommendations for migraine prevention. Additionally, melatonin at a dose of 3-5 mg nightly for an 8-week course may be considered for patients experiencing comorbid sleep disturbances.

Targeted Preventative Therapy

The white paper emphasizes the importance of targeting preventative therapy to the primary headache phenotype.

For instance, patients presenting with a migraine phenotype, or those with a personal or family history of migraines, may be most likely to respond to medications proven effective in migraine prevention, such as amitriptyline, topiramate, and propranolol.

“Most research evidence [for treating posttraumatic headache in youth] is still based on the treatment of migraine,” Dr. Rose pointed out in a written comment.

Dr. Gentile and colleagues recommend initiating preventive therapies 4-6 weeks post injury if headaches are not improving, occur more than 1-2 days per week, or significantly impact daily functioning.

Specialist Referrals and Physical Activity

Referral to a headache specialist is advised for patients who do not respond to first-line acute and preventive therapies. Specialists can offer advanced diagnostic and therapeutic options, the authors noted, ensuring a comprehensive approach to managing posttraumatic headache.

The white paper also recommends noncontact, sub–symptom threshold aerobic physical activity and activities of daily living after an initial 24-48 hour period of symptom-limited cognitive and physical rest. Engaging in these activities may promote faster recovery and help patients gradually return to their normal routines.

“This has been a shift in the concussion treatment approach over the last decade, and is one of the most important interventions we can recommend as physicians,” Dr. Choe noted. “This is where pediatricians and emergency department physicians seeing children acutely can really make a difference in the recovery trajectory for a child after a concussion. ‘Cocoon therapy’ has been proven not only to not work, but be detrimental to recovery.”
 

Nonpharmacologic Interventions

Based on clinical assessment, nonpharmacologic interventions may also be considered, according to the white paper. These interventions include cervico-vestibular therapy, which addresses neck and balance issues, and cognitive-behavioral therapy, which helps manage the psychological aspects of chronic headache. Dr. Gentile and colleagues highlighted the potential benefits of a collaborative care model that incorporates these nonpharmacologic interventions alongside pharmacologic treatments, providing a holistic approach to posttraumatic headache management.

“Persisting headaches after concussion are often driven by multiple factors,” Dr. Rose said. “Multidisciplinary concussion clinics can offer multiple treatment approaches such as behavioral, physical therapy, exercise, and medication options.”
 

Unmet Needs

The white paper concludes by calling for high-quality prospective cohort studies and placebo-controlled, randomized, controlled trials to further advance the understanding and treatment of posttraumatic headache in children.

Dr. Lonser, Dr. Choe, and Dr. Rose all agreed.

“More focused treatment trials are needed to gauge efficacy in children with headache after concussion,” Dr. Rose said.

Specifically, Dr. Gentile and colleagues underscored the need to standardize data collection via common elements, which could improve the ability to compare results across studies and develop more effective treatments. In addition, research into the underlying pathophysiology of posttraumatic headache is crucial for identifying new therapeutic targets and clinical and biological markers that can personalize patient care.

They also stressed the importance of exploring the impact of health disparities and social determinants on posttraumatic headache outcomes, aiming to develop interventions that are equitable and accessible to all patient populations.The white paper was approved by the AHS, and supported by the National Institutes of Health/National Institute of Neurological Disorders and Stroke K23 NS124986. The authors disclosed relationships with Eli Lilly, Pfizer, Amgen, and others. The interviewees disclosed no conflicts of interest.

The American Headache Society (AHS) has published a white paper guiding the treatment of posttraumatic headache caused by concussion in youth.

The guidance document, the first of its kind, covers risk factors for prolonged recovery, along with pharmacologic and nonpharmacologic management strategies, and supports an emphasis on multidisciplinary care, lead author Carlyn Patterson Gentile, MD, PhD, attending physician in the Division of Neurology at Children’s Hospital of Philadelphia in Pennsylvania, and colleagues reported.

“There are no guidelines to inform the management of posttraumatic headache in youth, but multiple studies have been conducted over the past 2 decades,” the authors wrote in Headache. “This white paper aims to provide a thorough review of the current literature, identify gaps in knowledge, and provide a road map for [posttraumatic headache] management in youth based on available evidence and expert opinion.”
 

Clarity for an Underrecognized Issue

According to Russell Lonser, MD, professor and chair of neurological surgery at Ohio State University, Columbus, the white paper is important because it offers concrete guidance for health care providers who may be less familiar with posttraumatic headache in youth.

courtesy Ohio State College of Medicine

“It brings together all of the previous literature ... in a very well-written way,” Dr. Lonser said in an interview. “More than anything, it could reassure [providers] that they shouldn’t be hunting down potentially magical cures, and reassure them in symptomatic management.”

Meeryo C. Choe, MD, associate clinical professor of pediatric neurology at UCLA Health in Calabasas, California, said the paper also helps shine a light on what may be a more common condition than the public suspects.

“While the media focuses on the effects of concussion in professional sports athletes, the biggest population of athletes is in our youth population,” Dr. Choe said in a written comment. “Almost 25 million children participate in sports throughout the country, and yet we lack guidelines on how to treat posttraumatic headache which can often develop into persistent postconcussive symptoms.”

This white paper, she noted, builds on Dr. Gentile’s 2021 systematic review, introduces new management recommendations, and aligns with the latest consensus statement from the Concussion in Sport Group.

Risk Factors

The white paper first emphasizes the importance of early identification of youth at high risk for prolonged recovery from posttraumatic headache. Risk factors include female sex, adolescent age, a high number of acute symptoms following the initial injury, and social determinants of health.

courtesy UCLA Health

“I agree that it is important to identify these patients early to improve the recovery trajectory,” Dr. Choe said.

Identifying these individuals quickly allows for timely intervention with both pharmacologic and nonpharmacologic therapies, Dr. Gentile and colleagues noted, potentially mitigating persistent symptoms. Clinicians are encouraged to perform thorough initial assessments to identify these risk factors and initiate early, personalized management plans.

Initial Management of Acute Posttraumatic Headache

For the initial management of acute posttraumatic headache, the white paper recommends a scheduled dosing regimen of simple analgesics. Ibuprofen at a dosage of 10 mg/kg every 6-8 hours (up to a maximum of 600 mg per dose) combined with acetaminophen has shown the best evidence for efficacy. Provided the patient is clinically stable, this regimen should be initiated within 48 hours of the injury and maintained with scheduled dosing for 3-10 days.

If effective, these medications can subsequently be used on an as-needed basis. Careful usage of analgesics is crucial, the white paper cautions, as overadministration can lead to medication-overuse headaches, complicating the recovery process.

Secondary Treatment Options

In cases where first-line oral medications are ineffective, the AHS white paper outlines several secondary treatment options. These include acute intravenous therapies such as ketorolac, dopamine receptor antagonists, and intravenous fluids. Nerve blocks and oral corticosteroid bridges may also be considered.

The white paper stresses the importance of individualized treatment plans that consider the specific needs and responses of each patient, noting that the evidence supporting these approaches is primarily derived from retrospective studies and case reports.

courtesy Nationwide Children&#039;s Hospital

“Patient preferences should be factored in,” said Sean Rose, MD, pediatric neurologist and codirector of the Complex Concussion Clinic at Nationwide Children’s Hospital, Columbus, Ohio.

Supplements and Preventive Measures

For adolescents and young adults at high risk of prolonged posttraumatic headache, the white paper suggests the use of riboflavin and magnesium supplements. Small randomized clinical trials suggest that these supplements may aid in speeding recovery when administered for 1-2 weeks within 48 hours of injury.

If significant headache persists after 2 weeks, a regimen of riboflavin 400 mg daily and magnesium 400-500 mg nightly can be trialed for 6-8 weeks, in line with recommendations for migraine prevention. Additionally, melatonin at a dose of 3-5 mg nightly for an 8-week course may be considered for patients experiencing comorbid sleep disturbances.

Targeted Preventative Therapy

The white paper emphasizes the importance of targeting preventative therapy to the primary headache phenotype.

For instance, patients presenting with a migraine phenotype, or those with a personal or family history of migraines, may be most likely to respond to medications proven effective in migraine prevention, such as amitriptyline, topiramate, and propranolol.

“Most research evidence [for treating posttraumatic headache in youth] is still based on the treatment of migraine,” Dr. Rose pointed out in a written comment.

Dr. Gentile and colleagues recommend initiating preventive therapies 4-6 weeks post injury if headaches are not improving, occur more than 1-2 days per week, or significantly impact daily functioning.

Specialist Referrals and Physical Activity

Referral to a headache specialist is advised for patients who do not respond to first-line acute and preventive therapies. Specialists can offer advanced diagnostic and therapeutic options, the authors noted, ensuring a comprehensive approach to managing posttraumatic headache.

The white paper also recommends noncontact, sub–symptom threshold aerobic physical activity and activities of daily living after an initial 24-48 hour period of symptom-limited cognitive and physical rest. Engaging in these activities may promote faster recovery and help patients gradually return to their normal routines.

“This has been a shift in the concussion treatment approach over the last decade, and is one of the most important interventions we can recommend as physicians,” Dr. Choe noted. “This is where pediatricians and emergency department physicians seeing children acutely can really make a difference in the recovery trajectory for a child after a concussion. ‘Cocoon therapy’ has been proven not only to not work, but be detrimental to recovery.”
 

Nonpharmacologic Interventions

Based on clinical assessment, nonpharmacologic interventions may also be considered, according to the white paper. These interventions include cervico-vestibular therapy, which addresses neck and balance issues, and cognitive-behavioral therapy, which helps manage the psychological aspects of chronic headache. Dr. Gentile and colleagues highlighted the potential benefits of a collaborative care model that incorporates these nonpharmacologic interventions alongside pharmacologic treatments, providing a holistic approach to posttraumatic headache management.

“Persisting headaches after concussion are often driven by multiple factors,” Dr. Rose said. “Multidisciplinary concussion clinics can offer multiple treatment approaches such as behavioral, physical therapy, exercise, and medication options.”
 

Unmet Needs

The white paper concludes by calling for high-quality prospective cohort studies and placebo-controlled, randomized, controlled trials to further advance the understanding and treatment of posttraumatic headache in children.

Dr. Lonser, Dr. Choe, and Dr. Rose all agreed.

“More focused treatment trials are needed to gauge efficacy in children with headache after concussion,” Dr. Rose said.

Specifically, Dr. Gentile and colleagues underscored the need to standardize data collection via common elements, which could improve the ability to compare results across studies and develop more effective treatments. In addition, research into the underlying pathophysiology of posttraumatic headache is crucial for identifying new therapeutic targets and clinical and biological markers that can personalize patient care.

They also stressed the importance of exploring the impact of health disparities and social determinants on posttraumatic headache outcomes, aiming to develop interventions that are equitable and accessible to all patient populations.The white paper was approved by the AHS, and supported by the National Institutes of Health/National Institute of Neurological Disorders and Stroke K23 NS124986. The authors disclosed relationships with Eli Lilly, Pfizer, Amgen, and others. The interviewees disclosed no conflicts of interest.

The American Headache Society (AHS) has published a white paper guiding the treatment of posttraumatic headache caused by concussion in youth.

The guidance document, the first of its kind, covers risk factors for prolonged recovery, along with pharmacologic and nonpharmacologic management strategies, and supports an emphasis on multidisciplinary care, lead author Carlyn Patterson Gentile, MD, PhD, attending physician in the Division of Neurology at Children’s Hospital of Philadelphia in Pennsylvania, and colleagues reported.

“There are no guidelines to inform the management of posttraumatic headache in youth, but multiple studies have been conducted over the past 2 decades,” the authors wrote in Headache. “This white paper aims to provide a thorough review of the current literature, identify gaps in knowledge, and provide a road map for [posttraumatic headache] management in youth based on available evidence and expert opinion.”
 

Clarity for an Underrecognized Issue

According to Russell Lonser, MD, professor and chair of neurological surgery at Ohio State University, Columbus, the white paper is important because it offers concrete guidance for health care providers who may be less familiar with posttraumatic headache in youth.

courtesy Ohio State College of Medicine

“It brings together all of the previous literature ... in a very well-written way,” Dr. Lonser said in an interview. “More than anything, it could reassure [providers] that they shouldn’t be hunting down potentially magical cures, and reassure them in symptomatic management.”

Meeryo C. Choe, MD, associate clinical professor of pediatric neurology at UCLA Health in Calabasas, California, said the paper also helps shine a light on what may be a more common condition than the public suspects.

“While the media focuses on the effects of concussion in professional sports athletes, the biggest population of athletes is in our youth population,” Dr. Choe said in a written comment. “Almost 25 million children participate in sports throughout the country, and yet we lack guidelines on how to treat posttraumatic headache which can often develop into persistent postconcussive symptoms.”

This white paper, she noted, builds on Dr. Gentile’s 2021 systematic review, introduces new management recommendations, and aligns with the latest consensus statement from the Concussion in Sport Group.

Risk Factors

The white paper first emphasizes the importance of early identification of youth at high risk for prolonged recovery from posttraumatic headache. Risk factors include female sex, adolescent age, a high number of acute symptoms following the initial injury, and social determinants of health.

courtesy UCLA Health

“I agree that it is important to identify these patients early to improve the recovery trajectory,” Dr. Choe said.

Identifying these individuals quickly allows for timely intervention with both pharmacologic and nonpharmacologic therapies, Dr. Gentile and colleagues noted, potentially mitigating persistent symptoms. Clinicians are encouraged to perform thorough initial assessments to identify these risk factors and initiate early, personalized management plans.

Initial Management of Acute Posttraumatic Headache

For the initial management of acute posttraumatic headache, the white paper recommends a scheduled dosing regimen of simple analgesics. Ibuprofen at a dosage of 10 mg/kg every 6-8 hours (up to a maximum of 600 mg per dose) combined with acetaminophen has shown the best evidence for efficacy. Provided the patient is clinically stable, this regimen should be initiated within 48 hours of the injury and maintained with scheduled dosing for 3-10 days.

If effective, these medications can subsequently be used on an as-needed basis. Careful usage of analgesics is crucial, the white paper cautions, as overadministration can lead to medication-overuse headaches, complicating the recovery process.

Secondary Treatment Options

In cases where first-line oral medications are ineffective, the AHS white paper outlines several secondary treatment options. These include acute intravenous therapies such as ketorolac, dopamine receptor antagonists, and intravenous fluids. Nerve blocks and oral corticosteroid bridges may also be considered.

The white paper stresses the importance of individualized treatment plans that consider the specific needs and responses of each patient, noting that the evidence supporting these approaches is primarily derived from retrospective studies and case reports.

courtesy Nationwide Children&#039;s Hospital

“Patient preferences should be factored in,” said Sean Rose, MD, pediatric neurologist and codirector of the Complex Concussion Clinic at Nationwide Children’s Hospital, Columbus, Ohio.

Supplements and Preventive Measures

For adolescents and young adults at high risk of prolonged posttraumatic headache, the white paper suggests the use of riboflavin and magnesium supplements. Small randomized clinical trials suggest that these supplements may aid in speeding recovery when administered for 1-2 weeks within 48 hours of injury.

If significant headache persists after 2 weeks, a regimen of riboflavin 400 mg daily and magnesium 400-500 mg nightly can be trialed for 6-8 weeks, in line with recommendations for migraine prevention. Additionally, melatonin at a dose of 3-5 mg nightly for an 8-week course may be considered for patients experiencing comorbid sleep disturbances.

Targeted Preventative Therapy

The white paper emphasizes the importance of targeting preventative therapy to the primary headache phenotype.

For instance, patients presenting with a migraine phenotype, or those with a personal or family history of migraines, may be most likely to respond to medications proven effective in migraine prevention, such as amitriptyline, topiramate, and propranolol.

“Most research evidence [for treating posttraumatic headache in youth] is still based on the treatment of migraine,” Dr. Rose pointed out in a written comment.

Dr. Gentile and colleagues recommend initiating preventive therapies 4-6 weeks post injury if headaches are not improving, occur more than 1-2 days per week, or significantly impact daily functioning.

Specialist Referrals and Physical Activity

Referral to a headache specialist is advised for patients who do not respond to first-line acute and preventive therapies. Specialists can offer advanced diagnostic and therapeutic options, the authors noted, ensuring a comprehensive approach to managing posttraumatic headache.

The white paper also recommends noncontact, sub–symptom threshold aerobic physical activity and activities of daily living after an initial 24-48 hour period of symptom-limited cognitive and physical rest. Engaging in these activities may promote faster recovery and help patients gradually return to their normal routines.

“This has been a shift in the concussion treatment approach over the last decade, and is one of the most important interventions we can recommend as physicians,” Dr. Choe noted. “This is where pediatricians and emergency department physicians seeing children acutely can really make a difference in the recovery trajectory for a child after a concussion. ‘Cocoon therapy’ has been proven not only to not work, but be detrimental to recovery.”
 

Nonpharmacologic Interventions

Based on clinical assessment, nonpharmacologic interventions may also be considered, according to the white paper. These interventions include cervico-vestibular therapy, which addresses neck and balance issues, and cognitive-behavioral therapy, which helps manage the psychological aspects of chronic headache. Dr. Gentile and colleagues highlighted the potential benefits of a collaborative care model that incorporates these nonpharmacologic interventions alongside pharmacologic treatments, providing a holistic approach to posttraumatic headache management.

“Persisting headaches after concussion are often driven by multiple factors,” Dr. Rose said. “Multidisciplinary concussion clinics can offer multiple treatment approaches such as behavioral, physical therapy, exercise, and medication options.”
 

Unmet Needs

The white paper concludes by calling for high-quality prospective cohort studies and placebo-controlled, randomized, controlled trials to further advance the understanding and treatment of posttraumatic headache in children.

Dr. Lonser, Dr. Choe, and Dr. Rose all agreed.

“More focused treatment trials are needed to gauge efficacy in children with headache after concussion,” Dr. Rose said.

Specifically, Dr. Gentile and colleagues underscored the need to standardize data collection via common elements, which could improve the ability to compare results across studies and develop more effective treatments. In addition, research into the underlying pathophysiology of posttraumatic headache is crucial for identifying new therapeutic targets and clinical and biological markers that can personalize patient care.

They also stressed the importance of exploring the impact of health disparities and social determinants on posttraumatic headache outcomes, aiming to develop interventions that are equitable and accessible to all patient populations.The white paper was approved by the AHS, and supported by the National Institutes of Health/National Institute of Neurological Disorders and Stroke K23 NS124986. The authors disclosed relationships with Eli Lilly, Pfizer, Amgen, and others. The interviewees disclosed no conflicts of interest.

TOPLINE:

Both chronic and new-onset anxiety are linked to a threefold increased risk for dementia onset in later life, new research shows.

METHODOLOGY:

• A total of 2132 participants aged 55-85 years (mean age, 76 years) were recruited from the Hunter Community Study. Of these, 53% were women.
• Participants were assessed over three different waves, 5 years apart. Demographic and health-related data were captured at wave 1.
• Researchers used the Kessler Psychological Distress Scale (K10) to measure anxiety at two points: Baseline (wave 1) and first follow-up (wave 2), with a 5-year interval between them. Anxiety was classified as chronic if present during both waves, resolved if only present at wave 1, and new if only appearing at wave 2.
• The primary outcome, incident all-cause dementia, during the follow-up period (maximum 13 years after baseline) was identified using the International Classification of Disease-10 codes.

TAKEAWAY:

• Out of 2132 cognitively healthy participants, 64 developed dementia, with an average time to diagnosis of 10 years. Chronic anxiety was linked to a 2.8-fold increased risk for dementia, while new-onset anxiety was associated with a 3.2-fold increased risk (P = .01).
• Participants younger than 70 years with chronic anxiety had a 4.6-fold increased risk for dementia (P = .03), and those with new-onset anxiety had a 7.2 times higher risk for dementia (P = .004).
• There was no significant risk for dementia in participants with anxiety that had resolved.
• Investigators speculated that individuals with anxiety were more likely to engage in unhealthy lifestyle behaviors, such as poor diet and smoking, which can lead to cardiovascular disease — a condition strongly associated with dementia.

IN PRACTICE: 

“This prospective cohort study used causal inference methods to explore the role of anxiety in promoting the development of dementia,” lead author Kay Khaing, MMed, The University of Newcastle, Australia, wrote in a press release. “The findings suggest that anxiety may be a new risk factor to target in the prevention of dementia and also indicate that treating anxiety may reduce this risk.”

SOURCE: 

Kay Khaing, MMed, of The University of Newcastle, Australia, led the study, which was published online in the Journal of the American Geriatrics Society.

LIMITATIONS: 

Anxiety was measured using K10, which assessed symptoms experienced in the most recent 4 weeks, raising concerns about its accuracy over the entire observation period. The authors acknowledged that despite using a combination of the total K10 score and the anxiety subscale, the overlap of anxiety and depression might not be fully disentangled, leading to residual confounding by depression. Additionally, 33% of participants were lost to follow-up, and those lost had higher anxiety rates at baseline, potentially leading to missing cases of dementia and affecting the effect estimate.

DISCLOSURES: 

This study did not report any funding or conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article appeared on Medscape.com.

TOPLINE:

Both chronic and new-onset anxiety are linked to a threefold increased risk for dementia onset in later life, new research shows.

METHODOLOGY:

• A total of 2132 participants aged 55-85 years (mean age, 76 years) were recruited from the Hunter Community Study. Of these, 53% were women.
• Participants were assessed over three different waves, 5 years apart. Demographic and health-related data were captured at wave 1.
• Researchers used the Kessler Psychological Distress Scale (K10) to measure anxiety at two points: Baseline (wave 1) and first follow-up (wave 2), with a 5-year interval between them. Anxiety was classified as chronic if present during both waves, resolved if only present at wave 1, and new if only appearing at wave 2.
• The primary outcome, incident all-cause dementia, during the follow-up period (maximum 13 years after baseline) was identified using the International Classification of Disease-10 codes.

TAKEAWAY:

• Out of 2132 cognitively healthy participants, 64 developed dementia, with an average time to diagnosis of 10 years. Chronic anxiety was linked to a 2.8-fold increased risk for dementia, while new-onset anxiety was associated with a 3.2-fold increased risk (P = .01).
• Participants younger than 70 years with chronic anxiety had a 4.6-fold increased risk for dementia (P = .03), and those with new-onset anxiety had a 7.2 times higher risk for dementia (P = .004).
• There was no significant risk for dementia in participants with anxiety that had resolved.
• Investigators speculated that individuals with anxiety were more likely to engage in unhealthy lifestyle behaviors, such as poor diet and smoking, which can lead to cardiovascular disease — a condition strongly associated with dementia.

IN PRACTICE: 

“This prospective cohort study used causal inference methods to explore the role of anxiety in promoting the development of dementia,” lead author Kay Khaing, MMed, The University of Newcastle, Australia, wrote in a press release. “The findings suggest that anxiety may be a new risk factor to target in the prevention of dementia and also indicate that treating anxiety may reduce this risk.”

SOURCE: 

Kay Khaing, MMed, of The University of Newcastle, Australia, led the study, which was published online in the Journal of the American Geriatrics Society.

LIMITATIONS: 

Anxiety was measured using K10, which assessed symptoms experienced in the most recent 4 weeks, raising concerns about its accuracy over the entire observation period. The authors acknowledged that despite using a combination of the total K10 score and the anxiety subscale, the overlap of anxiety and depression might not be fully disentangled, leading to residual confounding by depression. Additionally, 33% of participants were lost to follow-up, and those lost had higher anxiety rates at baseline, potentially leading to missing cases of dementia and affecting the effect estimate.

DISCLOSURES: 

This study did not report any funding or conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article appeared on Medscape.com.

TOPLINE:

Both chronic and new-onset anxiety are linked to a threefold increased risk for dementia onset in later life, new research shows.

METHODOLOGY:

• A total of 2132 participants aged 55-85 years (mean age, 76 years) were recruited from the Hunter Community Study. Of these, 53% were women.
• Participants were assessed over three different waves, 5 years apart. Demographic and health-related data were captured at wave 1.
• Researchers used the Kessler Psychological Distress Scale (K10) to measure anxiety at two points: Baseline (wave 1) and first follow-up (wave 2), with a 5-year interval between them. Anxiety was classified as chronic if present during both waves, resolved if only present at wave 1, and new if only appearing at wave 2.
• The primary outcome, incident all-cause dementia, during the follow-up period (maximum 13 years after baseline) was identified using the International Classification of Disease-10 codes.

TAKEAWAY:

• Out of 2132 cognitively healthy participants, 64 developed dementia, with an average time to diagnosis of 10 years. Chronic anxiety was linked to a 2.8-fold increased risk for dementia, while new-onset anxiety was associated with a 3.2-fold increased risk (P = .01).
• Participants younger than 70 years with chronic anxiety had a 4.6-fold increased risk for dementia (P = .03), and those with new-onset anxiety had a 7.2 times higher risk for dementia (P = .004).
• There was no significant risk for dementia in participants with anxiety that had resolved.
• Investigators speculated that individuals with anxiety were more likely to engage in unhealthy lifestyle behaviors, such as poor diet and smoking, which can lead to cardiovascular disease — a condition strongly associated with dementia.

IN PRACTICE: 

“This prospective cohort study used causal inference methods to explore the role of anxiety in promoting the development of dementia,” lead author Kay Khaing, MMed, The University of Newcastle, Australia, wrote in a press release. “The findings suggest that anxiety may be a new risk factor to target in the prevention of dementia and also indicate that treating anxiety may reduce this risk.”

SOURCE: 

Kay Khaing, MMed, of The University of Newcastle, Australia, led the study, which was published online in the Journal of the American Geriatrics Society.

LIMITATIONS: 

Anxiety was measured using K10, which assessed symptoms experienced in the most recent 4 weeks, raising concerns about its accuracy over the entire observation period. The authors acknowledged that despite using a combination of the total K10 score and the anxiety subscale, the overlap of anxiety and depression might not be fully disentangled, leading to residual confounding by depression. Additionally, 33% of participants were lost to follow-up, and those lost had higher anxiety rates at baseline, potentially leading to missing cases of dementia and affecting the effect estimate.

DISCLOSURES: 

This study did not report any funding or conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article appeared on Medscape.com.

The ability of advanced diffusion MRI (dMRI) techniques to detect microstructural neurological changes in military patients with remote mild traumatic brain injury (mTBI) supports wider adoption of these techniques, according to authors of a recent study. In particular, they said, using neurite orientation dispersion and density imaging (NODDI) to monitor long-term mTBI impact on brain regions related to cognitive and emotional processing can help clinicians assess recovery, predict progression, and optimize treatment.

“Currently,” said co-senior study author Ping-Hong Yeh, PhD, “there is a lack of minimally invasive, quantitative diagnostic biomarkers for monitoring progression or recovery after mild TBI. However, mild TBI can be quite disabling, with many patients reporting symptoms months or even years after injury. This is the most difficult part to diagnose.” Dr. Yeh is a researcher at the National Intrepid Center of Excellence (NICoE) at Walter Reed National Military Medical Center, Bethesda, Maryland.

The NICoE, a Department of Defense organization and the senior member of Defense Intrepid Network for Traumatic Brain Injury and Brain Health, is among several centers charged with improving support for injured service members’ recovery, rehabilitation, and reintegration into their communities. The overarching goal, said Dr. Yeh, is to enable community neurologists to refer service members and veterans to these centers for treatment and advanced imaging when needed.
 

Invisible Wounds

Limitations of conventional MRI and CT make it tough to discern which patients with mTBI will return to baseline functioning, and which will develop long-term complications. Addressing the silent or invisible wounds of mTBI will require improved diagnostic, prognostic, and therapeutic tools, he said.

For their study, published in JAMA Network Open, Dr. Yeh and colleagues compared diffusion tensor imaging (DTI) and NODDI data from 65 male service members with remote (more than 2 years old) mTBI against scans of 33 noninjured controls matched for age, sex, and active-duty status.

“Although DTI is very sensitive in detecting microstructural changes in mild TBI,” he said, “it is not specific to the underlying pathophysiological changes.”

Conversely, NODDI uses biophysical modeling of intracellular diffusion, extracellular diffusion, and free water to help physicians to understand subtle pathophysiological changes with greater sensitivity and specificity than does DTI. “This will allow us to correlate symptoms with brain structural changes, making the invisible wound visible.”

In the study, the greatest differences between injured and control patients appeared in the following NODDI metrics (P <.001 in all analyses):

• Intracellular volume fraction (ICVF) of the right corticospinal tract (CST)
• Orientation dispersion index (ODI) of the left posterior thalamic radiation (PTR)
• ODI of the left uncinate fasciculus (UNC)

Regarding patient-reported neurobehavioral symptoms, Neurobehavioral Symptom Inventory cognitive subscores were associated with fractional anisotropy of the left UNC. In addition, PTSD Checklist–Civilian version total scores and avoidance subscores corresponded, respectively, with isotropic volume fraction (ISOVF) of the genu of corpus callosum and with ODI of the left fornix and stria terminalis.
 

Next Steps

Presently, Dr. Yeh said, conventional MRI and CT usually cannot differentiate between axonal injury, axonal inflammation (which develops during the chronic phase of mTBI), and demyelination. “But newer biophysical modeling, such as NODDI, will allow us to tell the difference.” Along with providing prognostic information, he said, such technology can guide appropriate treatment, such as anti-inflammatory agents for chronic inflammation.

Most community neurologists refer patients with persistent mTBI symptoms in the absence of red flags using CT and conventional MRI for advanced neuroimaging, said Dr. Yeh. But because few community neurologists are familiar with NODDI, he said, broadening its reach will require educating these providers. Additional steps that Dr. Yeh said could occur over the next decade or more include boosting advanced dMRI sensitivity levels through improved hardware, software, and diagnostic tools.

“We need to make these techniques clinically feasible,” he added. Currently, protocols that allow advanced dMRI scans in about 10 minutes can be achievable.

The investments required to implement advanced dMRI techniques will be substantial. A state-of-the-art 3T MRI scanner that can support NODDI and DTI can easily cost $1 million, said Dr. Yeh. Factor in additional equipment options and construction costs, he added, and the total price tag can easily exceed $2 million. But rather than replacing all existing MRI systems, said Dr. Yeh, AI one day may help translate high-gradient capability even to widely used lower-field MRI scanners operating at 0.5T.

Streamlining systems that incorporate disparate scanners with different acquisition parameters will require standardized data acquisition and sharing parameters. Along with helping to evaluate new techniques as they become available, data harmonization and sharing can facilitate a shift from research comparisons between large groups to comparing a single patient against many others — a move that Dr. Yeh said must occur for advanced dMRI techniques to achieve clinical relevance.

In addition, experts will need to revise clinical guidelines for use of new technologies as their availability grows. “Improper use of these techniques will not only increase health costs, but also probably result in adverse health results.” Such guidelines could be very useful in evaluating the suitability and quality of referrals for diagnostic images, Dr. Yeh said.

Dr. Yeh reports no relevant financial interests. The project was partially funded by the US Army Medical Research and Materiel Command.

The ability of advanced diffusion MRI (dMRI) techniques to detect microstructural neurological changes in military patients with remote mild traumatic brain injury (mTBI) supports wider adoption of these techniques, according to authors of a recent study. In particular, they said, using neurite orientation dispersion and density imaging (NODDI) to monitor long-term mTBI impact on brain regions related to cognitive and emotional processing can help clinicians assess recovery, predict progression, and optimize treatment.

“Currently,” said co-senior study author Ping-Hong Yeh, PhD, “there is a lack of minimally invasive, quantitative diagnostic biomarkers for monitoring progression or recovery after mild TBI. However, mild TBI can be quite disabling, with many patients reporting symptoms months or even years after injury. This is the most difficult part to diagnose.” Dr. Yeh is a researcher at the National Intrepid Center of Excellence (NICoE) at Walter Reed National Military Medical Center, Bethesda, Maryland.

The NICoE, a Department of Defense organization and the senior member of Defense Intrepid Network for Traumatic Brain Injury and Brain Health, is among several centers charged with improving support for injured service members’ recovery, rehabilitation, and reintegration into their communities. The overarching goal, said Dr. Yeh, is to enable community neurologists to refer service members and veterans to these centers for treatment and advanced imaging when needed.
 

Invisible Wounds

Limitations of conventional MRI and CT make it tough to discern which patients with mTBI will return to baseline functioning, and which will develop long-term complications. Addressing the silent or invisible wounds of mTBI will require improved diagnostic, prognostic, and therapeutic tools, he said.

For their study, published in JAMA Network Open, Dr. Yeh and colleagues compared diffusion tensor imaging (DTI) and NODDI data from 65 male service members with remote (more than 2 years old) mTBI against scans of 33 noninjured controls matched for age, sex, and active-duty status.

“Although DTI is very sensitive in detecting microstructural changes in mild TBI,” he said, “it is not specific to the underlying pathophysiological changes.”

Conversely, NODDI uses biophysical modeling of intracellular diffusion, extracellular diffusion, and free water to help physicians to understand subtle pathophysiological changes with greater sensitivity and specificity than does DTI. “This will allow us to correlate symptoms with brain structural changes, making the invisible wound visible.”

In the study, the greatest differences between injured and control patients appeared in the following NODDI metrics (P <.001 in all analyses):

• Intracellular volume fraction (ICVF) of the right corticospinal tract (CST)
• Orientation dispersion index (ODI) of the left posterior thalamic radiation (PTR)
• ODI of the left uncinate fasciculus (UNC)

Regarding patient-reported neurobehavioral symptoms, Neurobehavioral Symptom Inventory cognitive subscores were associated with fractional anisotropy of the left UNC. In addition, PTSD Checklist–Civilian version total scores and avoidance subscores corresponded, respectively, with isotropic volume fraction (ISOVF) of the genu of corpus callosum and with ODI of the left fornix and stria terminalis.
 

Next Steps

Presently, Dr. Yeh said, conventional MRI and CT usually cannot differentiate between axonal injury, axonal inflammation (which develops during the chronic phase of mTBI), and demyelination. “But newer biophysical modeling, such as NODDI, will allow us to tell the difference.” Along with providing prognostic information, he said, such technology can guide appropriate treatment, such as anti-inflammatory agents for chronic inflammation.

Most community neurologists refer patients with persistent mTBI symptoms in the absence of red flags using CT and conventional MRI for advanced neuroimaging, said Dr. Yeh. But because few community neurologists are familiar with NODDI, he said, broadening its reach will require educating these providers. Additional steps that Dr. Yeh said could occur over the next decade or more include boosting advanced dMRI sensitivity levels through improved hardware, software, and diagnostic tools.

“We need to make these techniques clinically feasible,” he added. Currently, protocols that allow advanced dMRI scans in about 10 minutes can be achievable.

The investments required to implement advanced dMRI techniques will be substantial. A state-of-the-art 3T MRI scanner that can support NODDI and DTI can easily cost $1 million, said Dr. Yeh. Factor in additional equipment options and construction costs, he added, and the total price tag can easily exceed $2 million. But rather than replacing all existing MRI systems, said Dr. Yeh, AI one day may help translate high-gradient capability even to widely used lower-field MRI scanners operating at 0.5T.

Streamlining systems that incorporate disparate scanners with different acquisition parameters will require standardized data acquisition and sharing parameters. Along with helping to evaluate new techniques as they become available, data harmonization and sharing can facilitate a shift from research comparisons between large groups to comparing a single patient against many others — a move that Dr. Yeh said must occur for advanced dMRI techniques to achieve clinical relevance.

In addition, experts will need to revise clinical guidelines for use of new technologies as their availability grows. “Improper use of these techniques will not only increase health costs, but also probably result in adverse health results.” Such guidelines could be very useful in evaluating the suitability and quality of referrals for diagnostic images, Dr. Yeh said.

Dr. Yeh reports no relevant financial interests. The project was partially funded by the US Army Medical Research and Materiel Command.

The ability of advanced diffusion MRI (dMRI) techniques to detect microstructural neurological changes in military patients with remote mild traumatic brain injury (mTBI) supports wider adoption of these techniques, according to authors of a recent study. In particular, they said, using neurite orientation dispersion and density imaging (NODDI) to monitor long-term mTBI impact on brain regions related to cognitive and emotional processing can help clinicians assess recovery, predict progression, and optimize treatment.

“Currently,” said co-senior study author Ping-Hong Yeh, PhD, “there is a lack of minimally invasive, quantitative diagnostic biomarkers for monitoring progression or recovery after mild TBI. However, mild TBI can be quite disabling, with many patients reporting symptoms months or even years after injury. This is the most difficult part to diagnose.” Dr. Yeh is a researcher at the National Intrepid Center of Excellence (NICoE) at Walter Reed National Military Medical Center, Bethesda, Maryland.

The NICoE, a Department of Defense organization and the senior member of Defense Intrepid Network for Traumatic Brain Injury and Brain Health, is among several centers charged with improving support for injured service members’ recovery, rehabilitation, and reintegration into their communities. The overarching goal, said Dr. Yeh, is to enable community neurologists to refer service members and veterans to these centers for treatment and advanced imaging when needed.
 

Invisible Wounds

Limitations of conventional MRI and CT make it tough to discern which patients with mTBI will return to baseline functioning, and which will develop long-term complications. Addressing the silent or invisible wounds of mTBI will require improved diagnostic, prognostic, and therapeutic tools, he said.

For their study, published in JAMA Network Open, Dr. Yeh and colleagues compared diffusion tensor imaging (DTI) and NODDI data from 65 male service members with remote (more than 2 years old) mTBI against scans of 33 noninjured controls matched for age, sex, and active-duty status.

“Although DTI is very sensitive in detecting microstructural changes in mild TBI,” he said, “it is not specific to the underlying pathophysiological changes.”

Conversely, NODDI uses biophysical modeling of intracellular diffusion, extracellular diffusion, and free water to help physicians to understand subtle pathophysiological changes with greater sensitivity and specificity than does DTI. “This will allow us to correlate symptoms with brain structural changes, making the invisible wound visible.”

In the study, the greatest differences between injured and control patients appeared in the following NODDI metrics (P <.001 in all analyses):

• Intracellular volume fraction (ICVF) of the right corticospinal tract (CST)
• Orientation dispersion index (ODI) of the left posterior thalamic radiation (PTR)
• ODI of the left uncinate fasciculus (UNC)

Regarding patient-reported neurobehavioral symptoms, Neurobehavioral Symptom Inventory cognitive subscores were associated with fractional anisotropy of the left UNC. In addition, PTSD Checklist–Civilian version total scores and avoidance subscores corresponded, respectively, with isotropic volume fraction (ISOVF) of the genu of corpus callosum and with ODI of the left fornix and stria terminalis.
 

Next Steps

Presently, Dr. Yeh said, conventional MRI and CT usually cannot differentiate between axonal injury, axonal inflammation (which develops during the chronic phase of mTBI), and demyelination. “But newer biophysical modeling, such as NODDI, will allow us to tell the difference.” Along with providing prognostic information, he said, such technology can guide appropriate treatment, such as anti-inflammatory agents for chronic inflammation.

Most community neurologists refer patients with persistent mTBI symptoms in the absence of red flags using CT and conventional MRI for advanced neuroimaging, said Dr. Yeh. But because few community neurologists are familiar with NODDI, he said, broadening its reach will require educating these providers. Additional steps that Dr. Yeh said could occur over the next decade or more include boosting advanced dMRI sensitivity levels through improved hardware, software, and diagnostic tools.

“We need to make these techniques clinically feasible,” he added. Currently, protocols that allow advanced dMRI scans in about 10 minutes can be achievable.

The investments required to implement advanced dMRI techniques will be substantial. A state-of-the-art 3T MRI scanner that can support NODDI and DTI can easily cost $1 million, said Dr. Yeh. Factor in additional equipment options and construction costs, he added, and the total price tag can easily exceed $2 million. But rather than replacing all existing MRI systems, said Dr. Yeh, AI one day may help translate high-gradient capability even to widely used lower-field MRI scanners operating at 0.5T.

Streamlining systems that incorporate disparate scanners with different acquisition parameters will require standardized data acquisition and sharing parameters. Along with helping to evaluate new techniques as they become available, data harmonization and sharing can facilitate a shift from research comparisons between large groups to comparing a single patient against many others — a move that Dr. Yeh said must occur for advanced dMRI techniques to achieve clinical relevance.

In addition, experts will need to revise clinical guidelines for use of new technologies as their availability grows. “Improper use of these techniques will not only increase health costs, but also probably result in adverse health results.” Such guidelines could be very useful in evaluating the suitability and quality of referrals for diagnostic images, Dr. Yeh said.

Dr. Yeh reports no relevant financial interests. The project was partially funded by the US Army Medical Research and Materiel Command.

Fecal microbiota transplantation (FMT) for Parkinson’s disease is safe but does not offer clinically meaningful improvement in symptoms, results of a new, randomized placebo-controlled trial show.

However, investigators discovered some interesting insights from the study, which they believe may help in designing future “improved, and hopefully successful, trials” with the intervention.

“Further studies — for example, through modified fecal microbiota transplantation approaches or bowel cleansing — are warranted,” they concluded. 

The study was published online in JAMA Neurology. 
 

Gut Dysfunction: An Early Symptom

Investigators led by Filip Scheperjans, MD, Helsinki University Hospital, Finland, explained that gut dysfunction is a prevalent, early symptom in Parkinson’s disease and is associated with more rapid disease progression. 

Interventions targeting gut microbiota, such as FMT, have shown promising symptomatic, and potentially neuroprotective, effects in animal models of Parkinson’s disease. 

Although several randomized clinical trials suggest efficacy of probiotics for Parkinson’s disease-related constipation, only limited clinical information on FMT is available.

In the current trial, 48 patients with Parkinson’s disease aged 35-75 years with mild to moderate symptoms and dysbiosis of fecal microbiota were randomized in a 2:1 ratio to receive FMT or placebo infused into the cecum via colonoscopy.  

All patients had whole-bowel lavage starting the day before the colonoscopy. Fecal microbiota transplantation was administered as a single-dose and without antibiotic pretreatment. 

Active treatment was a freeze-stored preparation of 30 g of feces from one of two donors who were healthy individuals without dysbiosis. The preparation was mixed with 150 mL of sterile physiologic saline and 20 mL of 85% glycerol for cryoprotection to improve viability of microbes. Placebo was the carrier solution alone, consisting of 180 mL of sterile physiologic saline and 20 mL of 85% glycerol.

The primary endpoint, a change in Parkinson’s disease symptoms as assessed on the Unified Parkinson’s Disease Rating Scale (UPDRS) at 6 months, did not differ between the two study groups.

Gastrointestinal adverse events were more frequent in the FMT group, occurring in 16 patients (53%) versus one patient (7%) in the placebo group. But no major safety concerns were observed.

Secondary outcomes and post hoc analyses showed a greater increase in dopaminergic medication, which may indicate faster disease progression, but also improvement in certain motor and nonmotor outcomes in the placebo group. 

Microbiota changes were more pronounced after FMT, but dysbiosis status was reversed more frequently in the placebo group. 

The researchers noted that the apparent futility in this trial is in contrast to several previous small clinical studies of fecal transplant that have suggested the potential for improvement of Parkinson’s disease symptoms. 

In addition, encouraging results from the probiotics field suggest that an impact on motor and nonmotor Parkinson’s disease symptoms through gut microbiota manipulation is possible. 

The researchers raised the possibility that the placebo procedure was not an inert comparator, given the relatively strong and sustained gut microbiota alteration and dysbiosis conversion observed in the placebo group, and suggested that the colonic cleansing procedure may also have had some beneficial effect. 

“It seems possible that, after cleansing of a dysbiotic gut microbiota, recolonization leads to a more physiologic gut microbiota composition with symptom improvement in the placebo group. This warrants further exploration of modified fecal microbiota transplantation approaches and bowel cleansing in Parkinson’s disease,” they concluded. 
 

Distinct Gut Microbiome 

In an accompanying editorial, Timothy R. Sampson, PhD, assistant professor, Department of Cell Biology, Emory University School of Medicine, Atlanta, pointed out that dozens of independent studies have now demonstrated a distinct gut microbiome composition associated with Parkinson’s disease, and experimental data suggest that this has the capacity to incite inflammatory responses; degrade intestinal mucosa; and dysregulate a number of neuroactive and amyloidogenic molecules, which could contribute to the disease. 

He noted that three other small placebo-controlled studies of fecal transplantation in Parkinson’s disease showed slightly more robust responses in the active treatment group, including improvements in UPDRS scores and gastrointestinal symptoms.

However, these studies tested different FMT procedures, including lyophilized oral capsules given at different dosing frequencies and either nasojejunal or colonic transfusion following a standard bowel preparation.

In addition, there is no consensus on pretransplant procedures, such as antibiotics or bowel clearance, and the choice of donor microbiome is probably essential, because there may be certain microbes required to shift the entire community, Dr. Sampson wrote. 

Understanding how microbial contributions directly relate to Parkinson’s disease would identify individuals more likely to respond to peripheral interventions, and further exploration is needed to shed light on particular microbes that warrant targeting for either enrichment or depletion, he added. 

“Despite a lack of primary end point efficacy in this latest study, in-depth comparison across these studies may reveal opportunities to refine fecal microbiota transplantation approaches. Together, these studies will continue to refine the hypothesis of a microbial contribution to Parkinson’s disease and reveal new therapeutic avenues,” Dr. Sampson concluded.
 

‘Planting Grass in a Yard Full of Weeds’

Commenting on the research, James Beck, PhD, chief scientific officer of the Parkinson’s Foundation, New York, said that whether FMT are helpful remains to be determined. 

“The key question that needs to be solved is how to best perform these transplants. One issue is that you cannot plant grass when the yard is full of weeds. However, if you take too hard an approach killing the weeds — that is, with powerful antibiotics — you jeopardize the new grass, or in this case, the bacteria in the transplant. Solving that issue will be important as we consider whether this is effective or not.”

Dr. Beck added that there is still much to be learned from research into the gut microbiota. “I am hopeful with additional effort we will have answers soon.”
 

A version of this article appeared on Medscape.com.

Fecal microbiota transplantation (FMT) for Parkinson’s disease is safe but does not offer clinically meaningful improvement in symptoms, results of a new, randomized placebo-controlled trial show.

However, investigators discovered some interesting insights from the study, which they believe may help in designing future “improved, and hopefully successful, trials” with the intervention.

“Further studies — for example, through modified fecal microbiota transplantation approaches or bowel cleansing — are warranted,” they concluded. 

The study was published online in JAMA Neurology. 
 

Gut Dysfunction: An Early Symptom

Investigators led by Filip Scheperjans, MD, Helsinki University Hospital, Finland, explained that gut dysfunction is a prevalent, early symptom in Parkinson’s disease and is associated with more rapid disease progression. 

Interventions targeting gut microbiota, such as FMT, have shown promising symptomatic, and potentially neuroprotective, effects in animal models of Parkinson’s disease. 

Although several randomized clinical trials suggest efficacy of probiotics for Parkinson’s disease-related constipation, only limited clinical information on FMT is available.

In the current trial, 48 patients with Parkinson’s disease aged 35-75 years with mild to moderate symptoms and dysbiosis of fecal microbiota were randomized in a 2:1 ratio to receive FMT or placebo infused into the cecum via colonoscopy.  

All patients had whole-bowel lavage starting the day before the colonoscopy. Fecal microbiota transplantation was administered as a single-dose and without antibiotic pretreatment. 

Active treatment was a freeze-stored preparation of 30 g of feces from one of two donors who were healthy individuals without dysbiosis. The preparation was mixed with 150 mL of sterile physiologic saline and 20 mL of 85% glycerol for cryoprotection to improve viability of microbes. Placebo was the carrier solution alone, consisting of 180 mL of sterile physiologic saline and 20 mL of 85% glycerol.

The primary endpoint, a change in Parkinson’s disease symptoms as assessed on the Unified Parkinson’s Disease Rating Scale (UPDRS) at 6 months, did not differ between the two study groups.

Gastrointestinal adverse events were more frequent in the FMT group, occurring in 16 patients (53%) versus one patient (7%) in the placebo group. But no major safety concerns were observed.

Secondary outcomes and post hoc analyses showed a greater increase in dopaminergic medication, which may indicate faster disease progression, but also improvement in certain motor and nonmotor outcomes in the placebo group. 

Microbiota changes were more pronounced after FMT, but dysbiosis status was reversed more frequently in the placebo group. 

The researchers noted that the apparent futility in this trial is in contrast to several previous small clinical studies of fecal transplant that have suggested the potential for improvement of Parkinson’s disease symptoms. 

In addition, encouraging results from the probiotics field suggest that an impact on motor and nonmotor Parkinson’s disease symptoms through gut microbiota manipulation is possible. 

The researchers raised the possibility that the placebo procedure was not an inert comparator, given the relatively strong and sustained gut microbiota alteration and dysbiosis conversion observed in the placebo group, and suggested that the colonic cleansing procedure may also have had some beneficial effect. 

“It seems possible that, after cleansing of a dysbiotic gut microbiota, recolonization leads to a more physiologic gut microbiota composition with symptom improvement in the placebo group. This warrants further exploration of modified fecal microbiota transplantation approaches and bowel cleansing in Parkinson’s disease,” they concluded. 
 

Distinct Gut Microbiome 

In an accompanying editorial, Timothy R. Sampson, PhD, assistant professor, Department of Cell Biology, Emory University School of Medicine, Atlanta, pointed out that dozens of independent studies have now demonstrated a distinct gut microbiome composition associated with Parkinson’s disease, and experimental data suggest that this has the capacity to incite inflammatory responses; degrade intestinal mucosa; and dysregulate a number of neuroactive and amyloidogenic molecules, which could contribute to the disease. 

He noted that three other small placebo-controlled studies of fecal transplantation in Parkinson’s disease showed slightly more robust responses in the active treatment group, including improvements in UPDRS scores and gastrointestinal symptoms.

However, these studies tested different FMT procedures, including lyophilized oral capsules given at different dosing frequencies and either nasojejunal or colonic transfusion following a standard bowel preparation.

In addition, there is no consensus on pretransplant procedures, such as antibiotics or bowel clearance, and the choice of donor microbiome is probably essential, because there may be certain microbes required to shift the entire community, Dr. Sampson wrote. 

Understanding how microbial contributions directly relate to Parkinson’s disease would identify individuals more likely to respond to peripheral interventions, and further exploration is needed to shed light on particular microbes that warrant targeting for either enrichment or depletion, he added. 

“Despite a lack of primary end point efficacy in this latest study, in-depth comparison across these studies may reveal opportunities to refine fecal microbiota transplantation approaches. Together, these studies will continue to refine the hypothesis of a microbial contribution to Parkinson’s disease and reveal new therapeutic avenues,” Dr. Sampson concluded.
 

‘Planting Grass in a Yard Full of Weeds’

Commenting on the research, James Beck, PhD, chief scientific officer of the Parkinson’s Foundation, New York, said that whether FMT are helpful remains to be determined. 

“The key question that needs to be solved is how to best perform these transplants. One issue is that you cannot plant grass when the yard is full of weeds. However, if you take too hard an approach killing the weeds — that is, with powerful antibiotics — you jeopardize the new grass, or in this case, the bacteria in the transplant. Solving that issue will be important as we consider whether this is effective or not.”

Dr. Beck added that there is still much to be learned from research into the gut microbiota. “I am hopeful with additional effort we will have answers soon.”
 

A version of this article appeared on Medscape.com.

Fecal microbiota transplantation (FMT) for Parkinson’s disease is safe but does not offer clinically meaningful improvement in symptoms, results of a new, randomized placebo-controlled trial show.

However, investigators discovered some interesting insights from the study, which they believe may help in designing future “improved, and hopefully successful, trials” with the intervention.

“Further studies — for example, through modified fecal microbiota transplantation approaches or bowel cleansing — are warranted,” they concluded. 

The study was published online in JAMA Neurology. 
 

Gut Dysfunction: An Early Symptom

Investigators led by Filip Scheperjans, MD, Helsinki University Hospital, Finland, explained that gut dysfunction is a prevalent, early symptom in Parkinson’s disease and is associated with more rapid disease progression. 

Interventions targeting gut microbiota, such as FMT, have shown promising symptomatic, and potentially neuroprotective, effects in animal models of Parkinson’s disease. 

Although several randomized clinical trials suggest efficacy of probiotics for Parkinson’s disease-related constipation, only limited clinical information on FMT is available.

In the current trial, 48 patients with Parkinson’s disease aged 35-75 years with mild to moderate symptoms and dysbiosis of fecal microbiota were randomized in a 2:1 ratio to receive FMT or placebo infused into the cecum via colonoscopy.  

All patients had whole-bowel lavage starting the day before the colonoscopy. Fecal microbiota transplantation was administered as a single-dose and without antibiotic pretreatment. 

Active treatment was a freeze-stored preparation of 30 g of feces from one of two donors who were healthy individuals without dysbiosis. The preparation was mixed with 150 mL of sterile physiologic saline and 20 mL of 85% glycerol for cryoprotection to improve viability of microbes. Placebo was the carrier solution alone, consisting of 180 mL of sterile physiologic saline and 20 mL of 85% glycerol.

The primary endpoint, a change in Parkinson’s disease symptoms as assessed on the Unified Parkinson’s Disease Rating Scale (UPDRS) at 6 months, did not differ between the two study groups.

Gastrointestinal adverse events were more frequent in the FMT group, occurring in 16 patients (53%) versus one patient (7%) in the placebo group. But no major safety concerns were observed.

Secondary outcomes and post hoc analyses showed a greater increase in dopaminergic medication, which may indicate faster disease progression, but also improvement in certain motor and nonmotor outcomes in the placebo group. 

Microbiota changes were more pronounced after FMT, but dysbiosis status was reversed more frequently in the placebo group. 

The researchers noted that the apparent futility in this trial is in contrast to several previous small clinical studies of fecal transplant that have suggested the potential for improvement of Parkinson’s disease symptoms. 

In addition, encouraging results from the probiotics field suggest that an impact on motor and nonmotor Parkinson’s disease symptoms through gut microbiota manipulation is possible. 

The researchers raised the possibility that the placebo procedure was not an inert comparator, given the relatively strong and sustained gut microbiota alteration and dysbiosis conversion observed in the placebo group, and suggested that the colonic cleansing procedure may also have had some beneficial effect. 

“It seems possible that, after cleansing of a dysbiotic gut microbiota, recolonization leads to a more physiologic gut microbiota composition with symptom improvement in the placebo group. This warrants further exploration of modified fecal microbiota transplantation approaches and bowel cleansing in Parkinson’s disease,” they concluded. 
 

Distinct Gut Microbiome 

In an accompanying editorial, Timothy R. Sampson, PhD, assistant professor, Department of Cell Biology, Emory University School of Medicine, Atlanta, pointed out that dozens of independent studies have now demonstrated a distinct gut microbiome composition associated with Parkinson’s disease, and experimental data suggest that this has the capacity to incite inflammatory responses; degrade intestinal mucosa; and dysregulate a number of neuroactive and amyloidogenic molecules, which could contribute to the disease. 

He noted that three other small placebo-controlled studies of fecal transplantation in Parkinson’s disease showed slightly more robust responses in the active treatment group, including improvements in UPDRS scores and gastrointestinal symptoms.

However, these studies tested different FMT procedures, including lyophilized oral capsules given at different dosing frequencies and either nasojejunal or colonic transfusion following a standard bowel preparation.

In addition, there is no consensus on pretransplant procedures, such as antibiotics or bowel clearance, and the choice of donor microbiome is probably essential, because there may be certain microbes required to shift the entire community, Dr. Sampson wrote. 

Understanding how microbial contributions directly relate to Parkinson’s disease would identify individuals more likely to respond to peripheral interventions, and further exploration is needed to shed light on particular microbes that warrant targeting for either enrichment or depletion, he added. 

“Despite a lack of primary end point efficacy in this latest study, in-depth comparison across these studies may reveal opportunities to refine fecal microbiota transplantation approaches. Together, these studies will continue to refine the hypothesis of a microbial contribution to Parkinson’s disease and reveal new therapeutic avenues,” Dr. Sampson concluded.
 

‘Planting Grass in a Yard Full of Weeds’

Commenting on the research, James Beck, PhD, chief scientific officer of the Parkinson’s Foundation, New York, said that whether FMT are helpful remains to be determined. 

“The key question that needs to be solved is how to best perform these transplants. One issue is that you cannot plant grass when the yard is full of weeds. However, if you take too hard an approach killing the weeds — that is, with powerful antibiotics — you jeopardize the new grass, or in this case, the bacteria in the transplant. Solving that issue will be important as we consider whether this is effective or not.”

Dr. Beck added that there is still much to be learned from research into the gut microbiota. “I am hopeful with additional effort we will have answers soon.”
 

A version of this article appeared on Medscape.com.

Patients with dementia may instead have hepatic encephalopathy and should be screened with the Fibrosis-4 (FIB-4) index for cirrhosis, one of the main causes of the condition, new research suggests.

The study of more than 68,000 individuals in the general population diagnosed with dementia between 2009 and 2019 found that almost 13% had FIB-4 scores indicative of cirrhosis and potential hepatic encephalopathy.

The findings, recently published online in The American Journal of Medicine, corroborate and extend the researchers’ previous work, which showed that about 10% of US veterans with a dementia diagnosis may in fact have hepatic encephalopathy.

“We need to increase awareness that cirrhosis and related brain complications are common, silent, but treatable when found,” said corresponding author Jasmohan Bajaj, MD, of Virginia Commonwealth University and Richmond VA Medical Center, Richmond, Virginia. “Moreover, these are being increasingly diagnosed in older individuals.”

“Cirrhosis can also predispose patients to liver cancer and other complications, so diagnosing it in all patients is important, regardless of the hepatic encephalopathy-dementia connection,” he said.
 

FIB-4 Is Key

Dr. Bajaj and colleagues analyzed data from 72 healthcare centers on 68,807 nonveteran patients diagnosed with dementia at two or more physician visits between 2009 and 2019. Patients had no prior cirrhosis diagnosis, the mean age was 73 years, 44.7% were men, and 78% were White.

The team measured the prevalence of two high FIB-4 scores (> 2.67 and > 3.25), selected for their strong predictive value for advanced cirrhosis. Researchers also examined associations between high scores and multiple comorbidities and demographic factors.

Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and platelet labs were collected up to 2 years after the index dementia diagnosis because they are used to calculate FIB-4.

The mean FIB-4 score was 1.78, mean ALT was 23.72 U/L, mean AST was 27.42 U/L, and mean platelets were 243.51 × 109/µL.

A total of 8683 participants (12.8%) had a FIB-4 score greater than 2.67 and 5185 (7.6%) had a score greater than 3.25.

In multivariable logistic regression models, FIB-4 greater than 3.25 was associated with viral hepatitis (odds ratio [OR], 2.23), congestive heart failure (OR,1.73), HIV (OR, 1.72), male gender (OR, 1.42), alcohol use disorder (OR, 1.39), and chronic kidney disease (OR, 1.38).

FIB-4 greater than 3.25 was inversely associated with White race (OR, 0.76) and diabetes (OR, 0.82).

The associations were similar when using a threshold score of greater than 2.67.

“With the aging population, including those with cirrhosis, the potential for overlap between hepatic encephalopathy and dementia has risen and should be considered in the differential diagnosis,” the authors wrote. “Undiagnosed cirrhosis and potential hepatic encephalopathy can be a treatable cause of or contributor towards cognitive impairment in patients diagnosed with dementia.”

Providers should use the FIB-4 index as a screening tool to detect cirrhosis in patients with dementia, they concluded.

The team’s next steps will include investigating barriers to the use of FIB-4 among practitioners, Dr. Bajaj said.

Incorporating use of the FIB-4 index into screening guidelines “with input from all stakeholders, including geriatricians, primary care providers, and neurologists … would greatly expand the diagnosis of cirrhosis and potentially hepatic encephalopathy in dementia patients,” Dr. Bajaj said.

The study had a few limitations, including the selected centers in the cohort database, lack of chart review to confirm diagnoses in individual cases, and the use of a modified FIB-4, with age capped at 65 years.
 

‘Easy to Miss’

Commenting on the research, Nancy Reau, MD, section chief of hepatology at Rush University Medical Center in Chicago, said that it is easy for physicians to miss asymptomatic liver disease that could progress and lead to cognitive decline.

“Most of my patients are already labeled with liver disease; however, it is not uncommon to receive a patient from another specialist who felt their presentation was more consistent with liver disease than the issue they were referred for,” she said.

Still, even in metabolic dysfunction–associated steatotic liver disease, which affects nearly one third of the population, the condition isn’t advanced enough in most patients to cause symptoms similar to those of dementia, said Dr. Reau, who was not associated with the study.

“It is more important for specialists in neurology to exclude liver disease and for hepatologists or gastroenterologists to be equipped with tools to exclude alternative explanations for neurocognitive presentations,” she said. “It is important to not label a patient as having HE and then miss alternative explanations.”

“Every presentation has a differential diagnosis. Using easy tools like FIB-4 can make sure you don’t miss liver disease as a contributing factor in a patient that presents with neurocognitive symptoms,” Dr. Reau said.

This work was partly supported by grants from Department of Veterans Affairs merit review program and the National Institutes of Health’s National Center for Advancing Translational Science. Dr. Bajaj and Dr. Reau reported no conflicts of interest.
 

A version of this article appeared on Medscape.com.

Patients with dementia may instead have hepatic encephalopathy and should be screened with the Fibrosis-4 (FIB-4) index for cirrhosis, one of the main causes of the condition, new research suggests.

The study of more than 68,000 individuals in the general population diagnosed with dementia between 2009 and 2019 found that almost 13% had FIB-4 scores indicative of cirrhosis and potential hepatic encephalopathy.

The findings, recently published online in The American Journal of Medicine, corroborate and extend the researchers’ previous work, which showed that about 10% of US veterans with a dementia diagnosis may in fact have hepatic encephalopathy.

“We need to increase awareness that cirrhosis and related brain complications are common, silent, but treatable when found,” said corresponding author Jasmohan Bajaj, MD, of Virginia Commonwealth University and Richmond VA Medical Center, Richmond, Virginia. “Moreover, these are being increasingly diagnosed in older individuals.”

“Cirrhosis can also predispose patients to liver cancer and other complications, so diagnosing it in all patients is important, regardless of the hepatic encephalopathy-dementia connection,” he said.
 

FIB-4 Is Key

Dr. Bajaj and colleagues analyzed data from 72 healthcare centers on 68,807 nonveteran patients diagnosed with dementia at two or more physician visits between 2009 and 2019. Patients had no prior cirrhosis diagnosis, the mean age was 73 years, 44.7% were men, and 78% were White.

The team measured the prevalence of two high FIB-4 scores (> 2.67 and > 3.25), selected for their strong predictive value for advanced cirrhosis. Researchers also examined associations between high scores and multiple comorbidities and demographic factors.

Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and platelet labs were collected up to 2 years after the index dementia diagnosis because they are used to calculate FIB-4.

The mean FIB-4 score was 1.78, mean ALT was 23.72 U/L, mean AST was 27.42 U/L, and mean platelets were 243.51 × 109/µL.

A total of 8683 participants (12.8%) had a FIB-4 score greater than 2.67 and 5185 (7.6%) had a score greater than 3.25.

In multivariable logistic regression models, FIB-4 greater than 3.25 was associated with viral hepatitis (odds ratio [OR], 2.23), congestive heart failure (OR,1.73), HIV (OR, 1.72), male gender (OR, 1.42), alcohol use disorder (OR, 1.39), and chronic kidney disease (OR, 1.38).

FIB-4 greater than 3.25 was inversely associated with White race (OR, 0.76) and diabetes (OR, 0.82).

The associations were similar when using a threshold score of greater than 2.67.

“With the aging population, including those with cirrhosis, the potential for overlap between hepatic encephalopathy and dementia has risen and should be considered in the differential diagnosis,” the authors wrote. “Undiagnosed cirrhosis and potential hepatic encephalopathy can be a treatable cause of or contributor towards cognitive impairment in patients diagnosed with dementia.”

Providers should use the FIB-4 index as a screening tool to detect cirrhosis in patients with dementia, they concluded.

The team’s next steps will include investigating barriers to the use of FIB-4 among practitioners, Dr. Bajaj said.

Incorporating use of the FIB-4 index into screening guidelines “with input from all stakeholders, including geriatricians, primary care providers, and neurologists … would greatly expand the diagnosis of cirrhosis and potentially hepatic encephalopathy in dementia patients,” Dr. Bajaj said.

The study had a few limitations, including the selected centers in the cohort database, lack of chart review to confirm diagnoses in individual cases, and the use of a modified FIB-4, with age capped at 65 years.
 

‘Easy to Miss’

Commenting on the research, Nancy Reau, MD, section chief of hepatology at Rush University Medical Center in Chicago, said that it is easy for physicians to miss asymptomatic liver disease that could progress and lead to cognitive decline.

“Most of my patients are already labeled with liver disease; however, it is not uncommon to receive a patient from another specialist who felt their presentation was more consistent with liver disease than the issue they were referred for,” she said.

Still, even in metabolic dysfunction–associated steatotic liver disease, which affects nearly one third of the population, the condition isn’t advanced enough in most patients to cause symptoms similar to those of dementia, said Dr. Reau, who was not associated with the study.

“It is more important for specialists in neurology to exclude liver disease and for hepatologists or gastroenterologists to be equipped with tools to exclude alternative explanations for neurocognitive presentations,” she said. “It is important to not label a patient as having HE and then miss alternative explanations.”

“Every presentation has a differential diagnosis. Using easy tools like FIB-4 can make sure you don’t miss liver disease as a contributing factor in a patient that presents with neurocognitive symptoms,” Dr. Reau said.

This work was partly supported by grants from Department of Veterans Affairs merit review program and the National Institutes of Health’s National Center for Advancing Translational Science. Dr. Bajaj and Dr. Reau reported no conflicts of interest.
 

A version of this article appeared on Medscape.com.

Patients with dementia may instead have hepatic encephalopathy and should be screened with the Fibrosis-4 (FIB-4) index for cirrhosis, one of the main causes of the condition, new research suggests.

The study of more than 68,000 individuals in the general population diagnosed with dementia between 2009 and 2019 found that almost 13% had FIB-4 scores indicative of cirrhosis and potential hepatic encephalopathy.

The findings, recently published online in The American Journal of Medicine, corroborate and extend the researchers’ previous work, which showed that about 10% of US veterans with a dementia diagnosis may in fact have hepatic encephalopathy.

“We need to increase awareness that cirrhosis and related brain complications are common, silent, but treatable when found,” said corresponding author Jasmohan Bajaj, MD, of Virginia Commonwealth University and Richmond VA Medical Center, Richmond, Virginia. “Moreover, these are being increasingly diagnosed in older individuals.”

“Cirrhosis can also predispose patients to liver cancer and other complications, so diagnosing it in all patients is important, regardless of the hepatic encephalopathy-dementia connection,” he said.
 

FIB-4 Is Key

Dr. Bajaj and colleagues analyzed data from 72 healthcare centers on 68,807 nonveteran patients diagnosed with dementia at two or more physician visits between 2009 and 2019. Patients had no prior cirrhosis diagnosis, the mean age was 73 years, 44.7% were men, and 78% were White.

The team measured the prevalence of two high FIB-4 scores (> 2.67 and > 3.25), selected for their strong predictive value for advanced cirrhosis. Researchers also examined associations between high scores and multiple comorbidities and demographic factors.

Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and platelet labs were collected up to 2 years after the index dementia diagnosis because they are used to calculate FIB-4.

The mean FIB-4 score was 1.78, mean ALT was 23.72 U/L, mean AST was 27.42 U/L, and mean platelets were 243.51 × 109/µL.

A total of 8683 participants (12.8%) had a FIB-4 score greater than 2.67 and 5185 (7.6%) had a score greater than 3.25.

In multivariable logistic regression models, FIB-4 greater than 3.25 was associated with viral hepatitis (odds ratio [OR], 2.23), congestive heart failure (OR,1.73), HIV (OR, 1.72), male gender (OR, 1.42), alcohol use disorder (OR, 1.39), and chronic kidney disease (OR, 1.38).

FIB-4 greater than 3.25 was inversely associated with White race (OR, 0.76) and diabetes (OR, 0.82).

The associations were similar when using a threshold score of greater than 2.67.

“With the aging population, including those with cirrhosis, the potential for overlap between hepatic encephalopathy and dementia has risen and should be considered in the differential diagnosis,” the authors wrote. “Undiagnosed cirrhosis and potential hepatic encephalopathy can be a treatable cause of or contributor towards cognitive impairment in patients diagnosed with dementia.”

Providers should use the FIB-4 index as a screening tool to detect cirrhosis in patients with dementia, they concluded.

The team’s next steps will include investigating barriers to the use of FIB-4 among practitioners, Dr. Bajaj said.

Incorporating use of the FIB-4 index into screening guidelines “with input from all stakeholders, including geriatricians, primary care providers, and neurologists … would greatly expand the diagnosis of cirrhosis and potentially hepatic encephalopathy in dementia patients,” Dr. Bajaj said.

The study had a few limitations, including the selected centers in the cohort database, lack of chart review to confirm diagnoses in individual cases, and the use of a modified FIB-4, with age capped at 65 years.
 

‘Easy to Miss’

Commenting on the research, Nancy Reau, MD, section chief of hepatology at Rush University Medical Center in Chicago, said that it is easy for physicians to miss asymptomatic liver disease that could progress and lead to cognitive decline.

“Most of my patients are already labeled with liver disease; however, it is not uncommon to receive a patient from another specialist who felt their presentation was more consistent with liver disease than the issue they were referred for,” she said.

Still, even in metabolic dysfunction–associated steatotic liver disease, which affects nearly one third of the population, the condition isn’t advanced enough in most patients to cause symptoms similar to those of dementia, said Dr. Reau, who was not associated with the study.

“It is more important for specialists in neurology to exclude liver disease and for hepatologists or gastroenterologists to be equipped with tools to exclude alternative explanations for neurocognitive presentations,” she said. “It is important to not label a patient as having HE and then miss alternative explanations.”

“Every presentation has a differential diagnosis. Using easy tools like FIB-4 can make sure you don’t miss liver disease as a contributing factor in a patient that presents with neurocognitive symptoms,” Dr. Reau said.

This work was partly supported by grants from Department of Veterans Affairs merit review program and the National Institutes of Health’s National Center for Advancing Translational Science. Dr. Bajaj and Dr. Reau reported no conflicts of interest.
 

A version of this article appeared on Medscape.com.