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PTSD symptoms in women tied to worse heart, brain health
TOPLINE:
METHODOLOGY:
- Researchers conducted a cross-sectional study of 274 women (mean age, 59 years) participating in the MsBrain study of menopause and brain health.
- As part of the study, the women completed the PTSD Checklist–Civilian Version and underwent physical and neuropsychological testing, as well as carotid artery ultrasonography and brain MRI.
- Outcomes of interest were associations of PTSD symptoms with carotid intima media thickness (IMT), brain white matter hyperintensity volume (WMHV), and cognition, assessed in linear regression models.
- Interactions by APOEε4 were assessed; covariates included age, race/ethnicity, education, and CVD risk factors.
TAKEAWAY:
- Higher PTSD symptoms were associated with greater carotid IMT (P = .03); associations of PTSD symptoms with neurocognitive outcomes varied significantly by APOEε4 status.
- Among APOEε4 carriers, PTSD symptoms were associated with greater whole-brain WMHV (P = .009), periventricular WMHV (P = .02), deep WMHV (P = .01), and frontal WMHV (P = .04) in multivariable models.
- APOEε4 carriers with PTSD symptoms also had poorer cognition, specifically attention and working memory (P = .02), semantic fluency (P = .01), perceptual speed (P = .002) and processing speed (P = .002), in multivariable models.
IN PRACTICE:
“This study sheds important insight on the implications of PTSD symptoms to women’s cardiovascular and neurocognitive health. Our findings indicate that the APOEε4 genotype may identify a group of women with PTSD symptoms at particular risk for poor neurocognitive health,” the authors wrote.
SOURCE:
The study, with first author Rebecca Thurston, PhD, of the department of psychiatry, University of Pittsburgh, was published online in JAMA Network Open.
LIMITATIONS:
No diagnostic clinical interviews were conducted, and PTSD treatment was not assessed. All participants identified as cisgender, and most were non-Hispanic Black or White. The study was observational and cross-sectional, precluding assertions about directionality or causality.
DISCLOSURES:
The study was funded by the National Institutes of Health, the University of Pittsburgh Clinical and Translational Science Institute, and the University of Pittsburgh Small Molecule Biomarker Core. Dr. Thurston reported receiving personal fees from Astellas Pharma, Bayer, Hello Therapeutics, Vira Health, and Happify Health outside the submitted work.
A version of this article first appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Researchers conducted a cross-sectional study of 274 women (mean age, 59 years) participating in the MsBrain study of menopause and brain health.
- As part of the study, the women completed the PTSD Checklist–Civilian Version and underwent physical and neuropsychological testing, as well as carotid artery ultrasonography and brain MRI.
- Outcomes of interest were associations of PTSD symptoms with carotid intima media thickness (IMT), brain white matter hyperintensity volume (WMHV), and cognition, assessed in linear regression models.
- Interactions by APOEε4 were assessed; covariates included age, race/ethnicity, education, and CVD risk factors.
TAKEAWAY:
- Higher PTSD symptoms were associated with greater carotid IMT (P = .03); associations of PTSD symptoms with neurocognitive outcomes varied significantly by APOEε4 status.
- Among APOEε4 carriers, PTSD symptoms were associated with greater whole-brain WMHV (P = .009), periventricular WMHV (P = .02), deep WMHV (P = .01), and frontal WMHV (P = .04) in multivariable models.
- APOEε4 carriers with PTSD symptoms also had poorer cognition, specifically attention and working memory (P = .02), semantic fluency (P = .01), perceptual speed (P = .002) and processing speed (P = .002), in multivariable models.
IN PRACTICE:
“This study sheds important insight on the implications of PTSD symptoms to women’s cardiovascular and neurocognitive health. Our findings indicate that the APOEε4 genotype may identify a group of women with PTSD symptoms at particular risk for poor neurocognitive health,” the authors wrote.
SOURCE:
The study, with first author Rebecca Thurston, PhD, of the department of psychiatry, University of Pittsburgh, was published online in JAMA Network Open.
LIMITATIONS:
No diagnostic clinical interviews were conducted, and PTSD treatment was not assessed. All participants identified as cisgender, and most were non-Hispanic Black or White. The study was observational and cross-sectional, precluding assertions about directionality or causality.
DISCLOSURES:
The study was funded by the National Institutes of Health, the University of Pittsburgh Clinical and Translational Science Institute, and the University of Pittsburgh Small Molecule Biomarker Core. Dr. Thurston reported receiving personal fees from Astellas Pharma, Bayer, Hello Therapeutics, Vira Health, and Happify Health outside the submitted work.
A version of this article first appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Researchers conducted a cross-sectional study of 274 women (mean age, 59 years) participating in the MsBrain study of menopause and brain health.
- As part of the study, the women completed the PTSD Checklist–Civilian Version and underwent physical and neuropsychological testing, as well as carotid artery ultrasonography and brain MRI.
- Outcomes of interest were associations of PTSD symptoms with carotid intima media thickness (IMT), brain white matter hyperintensity volume (WMHV), and cognition, assessed in linear regression models.
- Interactions by APOEε4 were assessed; covariates included age, race/ethnicity, education, and CVD risk factors.
TAKEAWAY:
- Higher PTSD symptoms were associated with greater carotid IMT (P = .03); associations of PTSD symptoms with neurocognitive outcomes varied significantly by APOEε4 status.
- Among APOEε4 carriers, PTSD symptoms were associated with greater whole-brain WMHV (P = .009), periventricular WMHV (P = .02), deep WMHV (P = .01), and frontal WMHV (P = .04) in multivariable models.
- APOEε4 carriers with PTSD symptoms also had poorer cognition, specifically attention and working memory (P = .02), semantic fluency (P = .01), perceptual speed (P = .002) and processing speed (P = .002), in multivariable models.
IN PRACTICE:
“This study sheds important insight on the implications of PTSD symptoms to women’s cardiovascular and neurocognitive health. Our findings indicate that the APOEε4 genotype may identify a group of women with PTSD symptoms at particular risk for poor neurocognitive health,” the authors wrote.
SOURCE:
The study, with first author Rebecca Thurston, PhD, of the department of psychiatry, University of Pittsburgh, was published online in JAMA Network Open.
LIMITATIONS:
No diagnostic clinical interviews were conducted, and PTSD treatment was not assessed. All participants identified as cisgender, and most were non-Hispanic Black or White. The study was observational and cross-sectional, precluding assertions about directionality or causality.
DISCLOSURES:
The study was funded by the National Institutes of Health, the University of Pittsburgh Clinical and Translational Science Institute, and the University of Pittsburgh Small Molecule Biomarker Core. Dr. Thurston reported receiving personal fees from Astellas Pharma, Bayer, Hello Therapeutics, Vira Health, and Happify Health outside the submitted work.
A version of this article first appeared on Medscape.com.
Not all exercise is beneficial: The physical activity paradox explained
In the pursuit of optimal health, regular physical activity (PA) is recommended to protect against dementia, cardiovascular disease (CVD), cancer, and other noncommunicable diseases. A significant body of research suggests the benefits of PA are positively correlated with higher frequency and intensity – with more often deemed better. This research has spawned a focus on increasing step counts and investing in standing desks and other interventions aimed at keeping people active.
But , but they also actually experience an increased risk for the very conditions that PA is intended to prevent.
A study published recently in The Lancet Regional Health – Europe used registry data from more than 7,000 adults in Norway, following them from age 33 to 65 years, to assess PA trajectories and risks for later-life mild cognitive impairment (MCI) and dementia at age 70 or older.
“Incorporating a life-course perspective gives a broader picture of how participants’ occupational histories relate to cognitive impairment later in life,” principal investigator Vegard Skirbekk, PhD, Columbia University Mailman School of Public Health, New York, said in an interview. Other studies typically have assessed occupational PA at a single time point, often close to the end of an individual’s career, and largely relied on self-report, he said.
Study participants worked in more than 300 different occupations. General physical activities performed on the included jobs required “considerable” use of arms and legs and moving the whole body, such as climbing, lifting, balancing, walking, stooping, and handling of materials.
Dr. Skirbekk and colleagues grouped participants into four PA trajectories over the 44-year study period: stable low, increasing then decreasing, stable intermediate, and stable high.
A total of 902 individuals were diagnosed with dementia and 2,407 with MCI at age 70 years or older. After adjustment, risks for MCI and dementia were 15.5% for those with higher occupational PA scores in the latter part of their working life and 9% for those with lower physical demands. The researchers concluded that “consistently working in an occupation with intermediate or high occupational PA was linked to an increased risk of cognitive impairment.”
The findings support those of the Copenhagen Male Study. Published in 2020, this longitudinal study compared leisure-time and occupational PA among more than 4,000 men in Denmark aged 40-59 at baseline in 1970-1971 and followed them until they turned 60. After adjustment, participants with high occupational PA had a 55% greater risk of developing dementia compared with those doing sedentary work.
Good vs. bad PA
“[T]he WHO [World Health Organization] guide to preventing dementia and disease on the whole mentions physical activity as an important factor. But our study suggests that it must be a ‘good’ form of physical activity, which hard physical work is not,” said Kirsten Nabe-Nielsen, PhD, lead author of this study
Beyond dementia, another recent study adds to a wealth of data on associations between occupational PA and cardiovascular risks. The cross-sectional analysis of U.S. data from the National Institute for Occupational Safety and Health showed that odds of CVD were higher when participants were “always” performing total occupational activity (odds ratio [OR], 1.99), occupational exertion (OR, 2.15), or occupational standing and walking around (OR, 1.84) compared with “never” engaging in these activities.
The contrasting effects of leisure-time vs. occupational PA constitute the “physical activity paradox” hypothesis. Starting in 2011, multiple studies by Andreas Holtermann, PhD, of the National Research Centre for the Working Environment lend support to the PA paradox theory, as do subsequent studies by others.
Although only “marginally considered” until a few years ago, recent large cohort studies seem to confirm the paradox, Pier Luigi Temporelli, MD wrote in a recent editorial.
In separate interviews, Dr. Skirbekk and lead author Tyler Quinn, PhD, MS, West Virginia University, Morgantown, pointed to the PA paradox as an explanation for their own recent findings, suggesting that the mechanisms that underlie it probably are responsible for the associated deleterious effects of occupational PA on the brain and heart, and even mortality.
“It’s well established that PA in your leisure time can be positive, but in the workplace, the results are quite the opposite,” Dr. Skirbekk said. “The specific mechanisms for why occupational PA is associated with elevated dementia risk are still not well understood and we need more knowledge. But we know that higher occupational physical demands have been linked to smaller hippocampal volume and poorer memory performance.”
Furthermore, he said, individuals working in jobs with high demands, both psychological and physical, combined with low job control perform more poorly on cognitive testing later in life.
“We looked mainly at professions where people have heavy workloads and you have much less autonomy, such as nursing assistants, office cleaners, childcare workers, and other personal care workers,” he said. “You cannot sit. You have somebody relying on you. It’s not all pleasure, and it can be very hard. That’s where we find the associations.”
Lack of autonomy
Specific characteristics indirectly associated with high occupational PA jobs – low cognitive stimuli, lifestyle factors, and socioeconomic influences – as well as factors directly related to high occupational PA, such as long hours, repetitive tasks, low levels of control, and stress, could also adversely affect cognitive trajectories, Dr. Skirbekk explained.
“By contrast, leisure-time physical activities tend to be of much shorter duration; are associated with socialization, play, [and] positive emotions; and [include] the opportunity to take breaks or shift to other types of activities if one prefers,” he said. “It may also be that too little or too much PA could be adversely related to cognitive outcomes – hence moderate activity levels, for example 10,000 steps a day, are still likely beneficial for cognitive functioning.”
Dr. Quinn said most of the CVD risk linked to occupational PA has to do with long periods of exertion such as lifting and carrying objects. While occupational standing and walking all day are also linked to CVD risk, they’re not as risky as lifting and carrying, he said.
Like Dr. Skirbekk, Dr. Quinn noted that individuals can take a break from leisure-time PA when they are tired, but occupational PA doesn’t have that same autonomy to allow for recovery.
“So, in many cases, individuals are not getting the recovery their body needs to actually experience PA benefits, because those benefits come during rest,” Dr. Quinn said.
“We’ve shown that PA at work raises acute cardiovascular responses, which are related to cardiovascular risk. For example, 24-hour and waking heart rate and diastolic blood pressure, as well as nonwork diastolic blood pressure, all were significantly higher on workdays versus non-workdays,” he said.
Dr. Quinn also said that psychological stress at work amplifies risk. “A person who does PA at work and is stressed is likely to be at greater risk than someone who has a physically active job but doesn’t have psychological stress combined with it.”
Research gaps
However, Dr. Skirbekk noted that there are strategies that can reduce the risk for MCI and dementia despite high levels of occupational PA. “It is often difficult to change professions, and even if you do, it won’t immediately affect cognition. But altering one’s lifestyle is likely to have effects on cognitive development across the life cycle.
“Many clinicians say they always advise lifestyle changes, but nothing happens. But it makes sense to emphasize that these changes – stopping smoking, eating well, getting proper sleep, etc. – affect not only cardiovascular risk but also cognition. And I think clinicians should also take a patient’s occupation into account during any evaluation,” Dr. Skirbekk noted.
Dr. Quinn said it isn’t realistic to expect workers to come up with solutions to the PA paradox because many don’t have the autonomy to be able to mitigate their occupational risk.
“I think administrative controls and policy changes eventually will be the levers of change. We’re not quite there yet, but those are the types of things we should do when we’re trying to reduce loads in some way, or reduce the time that people spend doing certain tasks we know are potentially bad,” he said.
However, not everyone agrees that occupational PA doesn’t confer the same benefits of leisure-time PA, at least with respect to cardiovascular risk. For example, the Prospective Urban Rural Epidemiology (PURE) study, which includes a cohort of 130,000 people from 17 high-income, middle-income, and low-income countries, concluded that both higher recreational and nonrecreational PA were associated with a lower risk for mortality and CVD events.
What additional research is needed to clarify the effects of occupational and leisure-time activity and to address conflicting findings?
“Even studies coming out now regarding the effects of occupational PA have mainly used older data,” Dr. Skirbekk noted. “Labor markets and job demands have changed over time. There are different types of tasks and skills required now than there were 20 or 40 years ago. And of course, working from home is a recent phenomenon that’s happened on a large scale and might affect daily routines, sleep patterns, and also cognition. We need a better understanding of what the consequences might be.”
Health inequity issue
More research is also necessary to understand the social determinants of cognitive decline, impairment, and dementia, he said. “Many of the studies we see today are based on self-report of what someone has done in the past, which is particularly problematic for individuals who are impaired or who give interviews with others, which can induce biases.”
Dr. Quinn suggests that PA guidelines may need to differentiate between occupational and leisure-time PA to better reflect current research findings.
Meanwhile, Dr. Skirbekk and Dr. Quinn both point to the toll that occupational PA takes on the brain and body in lower-income workers as an important health equity issue.
“Our national guidelines for PA include occupational activity,” said Dr. Quinn. “But it’s clear that a lot of people who are getting a lot of occupational PA, particularly socioeconomic and racial/ethnic minorities, are not benefiting from it.”
Dr. Holtermann, who has arguably done the most research to date on the PA paradox, noted in a recent editorial that the majority of workers with high occupational PA have a low socioeconomic position and therefore “improving our understanding of the underlying mechanisms behind the PA health paradox and identifying new intervention targets along those pathways will be an important step to reduce socioeconomic health inequalities across the globe.”
A version of this article first appeared on Medscape.com.
In the pursuit of optimal health, regular physical activity (PA) is recommended to protect against dementia, cardiovascular disease (CVD), cancer, and other noncommunicable diseases. A significant body of research suggests the benefits of PA are positively correlated with higher frequency and intensity – with more often deemed better. This research has spawned a focus on increasing step counts and investing in standing desks and other interventions aimed at keeping people active.
But , but they also actually experience an increased risk for the very conditions that PA is intended to prevent.
A study published recently in The Lancet Regional Health – Europe used registry data from more than 7,000 adults in Norway, following them from age 33 to 65 years, to assess PA trajectories and risks for later-life mild cognitive impairment (MCI) and dementia at age 70 or older.
“Incorporating a life-course perspective gives a broader picture of how participants’ occupational histories relate to cognitive impairment later in life,” principal investigator Vegard Skirbekk, PhD, Columbia University Mailman School of Public Health, New York, said in an interview. Other studies typically have assessed occupational PA at a single time point, often close to the end of an individual’s career, and largely relied on self-report, he said.
Study participants worked in more than 300 different occupations. General physical activities performed on the included jobs required “considerable” use of arms and legs and moving the whole body, such as climbing, lifting, balancing, walking, stooping, and handling of materials.
Dr. Skirbekk and colleagues grouped participants into four PA trajectories over the 44-year study period: stable low, increasing then decreasing, stable intermediate, and stable high.
A total of 902 individuals were diagnosed with dementia and 2,407 with MCI at age 70 years or older. After adjustment, risks for MCI and dementia were 15.5% for those with higher occupational PA scores in the latter part of their working life and 9% for those with lower physical demands. The researchers concluded that “consistently working in an occupation with intermediate or high occupational PA was linked to an increased risk of cognitive impairment.”
The findings support those of the Copenhagen Male Study. Published in 2020, this longitudinal study compared leisure-time and occupational PA among more than 4,000 men in Denmark aged 40-59 at baseline in 1970-1971 and followed them until they turned 60. After adjustment, participants with high occupational PA had a 55% greater risk of developing dementia compared with those doing sedentary work.
Good vs. bad PA
“[T]he WHO [World Health Organization] guide to preventing dementia and disease on the whole mentions physical activity as an important factor. But our study suggests that it must be a ‘good’ form of physical activity, which hard physical work is not,” said Kirsten Nabe-Nielsen, PhD, lead author of this study
Beyond dementia, another recent study adds to a wealth of data on associations between occupational PA and cardiovascular risks. The cross-sectional analysis of U.S. data from the National Institute for Occupational Safety and Health showed that odds of CVD were higher when participants were “always” performing total occupational activity (odds ratio [OR], 1.99), occupational exertion (OR, 2.15), or occupational standing and walking around (OR, 1.84) compared with “never” engaging in these activities.
The contrasting effects of leisure-time vs. occupational PA constitute the “physical activity paradox” hypothesis. Starting in 2011, multiple studies by Andreas Holtermann, PhD, of the National Research Centre for the Working Environment lend support to the PA paradox theory, as do subsequent studies by others.
Although only “marginally considered” until a few years ago, recent large cohort studies seem to confirm the paradox, Pier Luigi Temporelli, MD wrote in a recent editorial.
In separate interviews, Dr. Skirbekk and lead author Tyler Quinn, PhD, MS, West Virginia University, Morgantown, pointed to the PA paradox as an explanation for their own recent findings, suggesting that the mechanisms that underlie it probably are responsible for the associated deleterious effects of occupational PA on the brain and heart, and even mortality.
“It’s well established that PA in your leisure time can be positive, but in the workplace, the results are quite the opposite,” Dr. Skirbekk said. “The specific mechanisms for why occupational PA is associated with elevated dementia risk are still not well understood and we need more knowledge. But we know that higher occupational physical demands have been linked to smaller hippocampal volume and poorer memory performance.”
Furthermore, he said, individuals working in jobs with high demands, both psychological and physical, combined with low job control perform more poorly on cognitive testing later in life.
“We looked mainly at professions where people have heavy workloads and you have much less autonomy, such as nursing assistants, office cleaners, childcare workers, and other personal care workers,” he said. “You cannot sit. You have somebody relying on you. It’s not all pleasure, and it can be very hard. That’s where we find the associations.”
Lack of autonomy
Specific characteristics indirectly associated with high occupational PA jobs – low cognitive stimuli, lifestyle factors, and socioeconomic influences – as well as factors directly related to high occupational PA, such as long hours, repetitive tasks, low levels of control, and stress, could also adversely affect cognitive trajectories, Dr. Skirbekk explained.
“By contrast, leisure-time physical activities tend to be of much shorter duration; are associated with socialization, play, [and] positive emotions; and [include] the opportunity to take breaks or shift to other types of activities if one prefers,” he said. “It may also be that too little or too much PA could be adversely related to cognitive outcomes – hence moderate activity levels, for example 10,000 steps a day, are still likely beneficial for cognitive functioning.”
Dr. Quinn said most of the CVD risk linked to occupational PA has to do with long periods of exertion such as lifting and carrying objects. While occupational standing and walking all day are also linked to CVD risk, they’re not as risky as lifting and carrying, he said.
Like Dr. Skirbekk, Dr. Quinn noted that individuals can take a break from leisure-time PA when they are tired, but occupational PA doesn’t have that same autonomy to allow for recovery.
“So, in many cases, individuals are not getting the recovery their body needs to actually experience PA benefits, because those benefits come during rest,” Dr. Quinn said.
“We’ve shown that PA at work raises acute cardiovascular responses, which are related to cardiovascular risk. For example, 24-hour and waking heart rate and diastolic blood pressure, as well as nonwork diastolic blood pressure, all were significantly higher on workdays versus non-workdays,” he said.
Dr. Quinn also said that psychological stress at work amplifies risk. “A person who does PA at work and is stressed is likely to be at greater risk than someone who has a physically active job but doesn’t have psychological stress combined with it.”
Research gaps
However, Dr. Skirbekk noted that there are strategies that can reduce the risk for MCI and dementia despite high levels of occupational PA. “It is often difficult to change professions, and even if you do, it won’t immediately affect cognition. But altering one’s lifestyle is likely to have effects on cognitive development across the life cycle.
“Many clinicians say they always advise lifestyle changes, but nothing happens. But it makes sense to emphasize that these changes – stopping smoking, eating well, getting proper sleep, etc. – affect not only cardiovascular risk but also cognition. And I think clinicians should also take a patient’s occupation into account during any evaluation,” Dr. Skirbekk noted.
Dr. Quinn said it isn’t realistic to expect workers to come up with solutions to the PA paradox because many don’t have the autonomy to be able to mitigate their occupational risk.
“I think administrative controls and policy changes eventually will be the levers of change. We’re not quite there yet, but those are the types of things we should do when we’re trying to reduce loads in some way, or reduce the time that people spend doing certain tasks we know are potentially bad,” he said.
However, not everyone agrees that occupational PA doesn’t confer the same benefits of leisure-time PA, at least with respect to cardiovascular risk. For example, the Prospective Urban Rural Epidemiology (PURE) study, which includes a cohort of 130,000 people from 17 high-income, middle-income, and low-income countries, concluded that both higher recreational and nonrecreational PA were associated with a lower risk for mortality and CVD events.
What additional research is needed to clarify the effects of occupational and leisure-time activity and to address conflicting findings?
“Even studies coming out now regarding the effects of occupational PA have mainly used older data,” Dr. Skirbekk noted. “Labor markets and job demands have changed over time. There are different types of tasks and skills required now than there were 20 or 40 years ago. And of course, working from home is a recent phenomenon that’s happened on a large scale and might affect daily routines, sleep patterns, and also cognition. We need a better understanding of what the consequences might be.”
Health inequity issue
More research is also necessary to understand the social determinants of cognitive decline, impairment, and dementia, he said. “Many of the studies we see today are based on self-report of what someone has done in the past, which is particularly problematic for individuals who are impaired or who give interviews with others, which can induce biases.”
Dr. Quinn suggests that PA guidelines may need to differentiate between occupational and leisure-time PA to better reflect current research findings.
Meanwhile, Dr. Skirbekk and Dr. Quinn both point to the toll that occupational PA takes on the brain and body in lower-income workers as an important health equity issue.
“Our national guidelines for PA include occupational activity,” said Dr. Quinn. “But it’s clear that a lot of people who are getting a lot of occupational PA, particularly socioeconomic and racial/ethnic minorities, are not benefiting from it.”
Dr. Holtermann, who has arguably done the most research to date on the PA paradox, noted in a recent editorial that the majority of workers with high occupational PA have a low socioeconomic position and therefore “improving our understanding of the underlying mechanisms behind the PA health paradox and identifying new intervention targets along those pathways will be an important step to reduce socioeconomic health inequalities across the globe.”
A version of this article first appeared on Medscape.com.
In the pursuit of optimal health, regular physical activity (PA) is recommended to protect against dementia, cardiovascular disease (CVD), cancer, and other noncommunicable diseases. A significant body of research suggests the benefits of PA are positively correlated with higher frequency and intensity – with more often deemed better. This research has spawned a focus on increasing step counts and investing in standing desks and other interventions aimed at keeping people active.
But , but they also actually experience an increased risk for the very conditions that PA is intended to prevent.
A study published recently in The Lancet Regional Health – Europe used registry data from more than 7,000 adults in Norway, following them from age 33 to 65 years, to assess PA trajectories and risks for later-life mild cognitive impairment (MCI) and dementia at age 70 or older.
“Incorporating a life-course perspective gives a broader picture of how participants’ occupational histories relate to cognitive impairment later in life,” principal investigator Vegard Skirbekk, PhD, Columbia University Mailman School of Public Health, New York, said in an interview. Other studies typically have assessed occupational PA at a single time point, often close to the end of an individual’s career, and largely relied on self-report, he said.
Study participants worked in more than 300 different occupations. General physical activities performed on the included jobs required “considerable” use of arms and legs and moving the whole body, such as climbing, lifting, balancing, walking, stooping, and handling of materials.
Dr. Skirbekk and colleagues grouped participants into four PA trajectories over the 44-year study period: stable low, increasing then decreasing, stable intermediate, and stable high.
A total of 902 individuals were diagnosed with dementia and 2,407 with MCI at age 70 years or older. After adjustment, risks for MCI and dementia were 15.5% for those with higher occupational PA scores in the latter part of their working life and 9% for those with lower physical demands. The researchers concluded that “consistently working in an occupation with intermediate or high occupational PA was linked to an increased risk of cognitive impairment.”
The findings support those of the Copenhagen Male Study. Published in 2020, this longitudinal study compared leisure-time and occupational PA among more than 4,000 men in Denmark aged 40-59 at baseline in 1970-1971 and followed them until they turned 60. After adjustment, participants with high occupational PA had a 55% greater risk of developing dementia compared with those doing sedentary work.
Good vs. bad PA
“[T]he WHO [World Health Organization] guide to preventing dementia and disease on the whole mentions physical activity as an important factor. But our study suggests that it must be a ‘good’ form of physical activity, which hard physical work is not,” said Kirsten Nabe-Nielsen, PhD, lead author of this study
Beyond dementia, another recent study adds to a wealth of data on associations between occupational PA and cardiovascular risks. The cross-sectional analysis of U.S. data from the National Institute for Occupational Safety and Health showed that odds of CVD were higher when participants were “always” performing total occupational activity (odds ratio [OR], 1.99), occupational exertion (OR, 2.15), or occupational standing and walking around (OR, 1.84) compared with “never” engaging in these activities.
The contrasting effects of leisure-time vs. occupational PA constitute the “physical activity paradox” hypothesis. Starting in 2011, multiple studies by Andreas Holtermann, PhD, of the National Research Centre for the Working Environment lend support to the PA paradox theory, as do subsequent studies by others.
Although only “marginally considered” until a few years ago, recent large cohort studies seem to confirm the paradox, Pier Luigi Temporelli, MD wrote in a recent editorial.
In separate interviews, Dr. Skirbekk and lead author Tyler Quinn, PhD, MS, West Virginia University, Morgantown, pointed to the PA paradox as an explanation for their own recent findings, suggesting that the mechanisms that underlie it probably are responsible for the associated deleterious effects of occupational PA on the brain and heart, and even mortality.
“It’s well established that PA in your leisure time can be positive, but in the workplace, the results are quite the opposite,” Dr. Skirbekk said. “The specific mechanisms for why occupational PA is associated with elevated dementia risk are still not well understood and we need more knowledge. But we know that higher occupational physical demands have been linked to smaller hippocampal volume and poorer memory performance.”
Furthermore, he said, individuals working in jobs with high demands, both psychological and physical, combined with low job control perform more poorly on cognitive testing later in life.
“We looked mainly at professions where people have heavy workloads and you have much less autonomy, such as nursing assistants, office cleaners, childcare workers, and other personal care workers,” he said. “You cannot sit. You have somebody relying on you. It’s not all pleasure, and it can be very hard. That’s where we find the associations.”
Lack of autonomy
Specific characteristics indirectly associated with high occupational PA jobs – low cognitive stimuli, lifestyle factors, and socioeconomic influences – as well as factors directly related to high occupational PA, such as long hours, repetitive tasks, low levels of control, and stress, could also adversely affect cognitive trajectories, Dr. Skirbekk explained.
“By contrast, leisure-time physical activities tend to be of much shorter duration; are associated with socialization, play, [and] positive emotions; and [include] the opportunity to take breaks or shift to other types of activities if one prefers,” he said. “It may also be that too little or too much PA could be adversely related to cognitive outcomes – hence moderate activity levels, for example 10,000 steps a day, are still likely beneficial for cognitive functioning.”
Dr. Quinn said most of the CVD risk linked to occupational PA has to do with long periods of exertion such as lifting and carrying objects. While occupational standing and walking all day are also linked to CVD risk, they’re not as risky as lifting and carrying, he said.
Like Dr. Skirbekk, Dr. Quinn noted that individuals can take a break from leisure-time PA when they are tired, but occupational PA doesn’t have that same autonomy to allow for recovery.
“So, in many cases, individuals are not getting the recovery their body needs to actually experience PA benefits, because those benefits come during rest,” Dr. Quinn said.
“We’ve shown that PA at work raises acute cardiovascular responses, which are related to cardiovascular risk. For example, 24-hour and waking heart rate and diastolic blood pressure, as well as nonwork diastolic blood pressure, all were significantly higher on workdays versus non-workdays,” he said.
Dr. Quinn also said that psychological stress at work amplifies risk. “A person who does PA at work and is stressed is likely to be at greater risk than someone who has a physically active job but doesn’t have psychological stress combined with it.”
Research gaps
However, Dr. Skirbekk noted that there are strategies that can reduce the risk for MCI and dementia despite high levels of occupational PA. “It is often difficult to change professions, and even if you do, it won’t immediately affect cognition. But altering one’s lifestyle is likely to have effects on cognitive development across the life cycle.
“Many clinicians say they always advise lifestyle changes, but nothing happens. But it makes sense to emphasize that these changes – stopping smoking, eating well, getting proper sleep, etc. – affect not only cardiovascular risk but also cognition. And I think clinicians should also take a patient’s occupation into account during any evaluation,” Dr. Skirbekk noted.
Dr. Quinn said it isn’t realistic to expect workers to come up with solutions to the PA paradox because many don’t have the autonomy to be able to mitigate their occupational risk.
“I think administrative controls and policy changes eventually will be the levers of change. We’re not quite there yet, but those are the types of things we should do when we’re trying to reduce loads in some way, or reduce the time that people spend doing certain tasks we know are potentially bad,” he said.
However, not everyone agrees that occupational PA doesn’t confer the same benefits of leisure-time PA, at least with respect to cardiovascular risk. For example, the Prospective Urban Rural Epidemiology (PURE) study, which includes a cohort of 130,000 people from 17 high-income, middle-income, and low-income countries, concluded that both higher recreational and nonrecreational PA were associated with a lower risk for mortality and CVD events.
What additional research is needed to clarify the effects of occupational and leisure-time activity and to address conflicting findings?
“Even studies coming out now regarding the effects of occupational PA have mainly used older data,” Dr. Skirbekk noted. “Labor markets and job demands have changed over time. There are different types of tasks and skills required now than there were 20 or 40 years ago. And of course, working from home is a recent phenomenon that’s happened on a large scale and might affect daily routines, sleep patterns, and also cognition. We need a better understanding of what the consequences might be.”
Health inequity issue
More research is also necessary to understand the social determinants of cognitive decline, impairment, and dementia, he said. “Many of the studies we see today are based on self-report of what someone has done in the past, which is particularly problematic for individuals who are impaired or who give interviews with others, which can induce biases.”
Dr. Quinn suggests that PA guidelines may need to differentiate between occupational and leisure-time PA to better reflect current research findings.
Meanwhile, Dr. Skirbekk and Dr. Quinn both point to the toll that occupational PA takes on the brain and body in lower-income workers as an important health equity issue.
“Our national guidelines for PA include occupational activity,” said Dr. Quinn. “But it’s clear that a lot of people who are getting a lot of occupational PA, particularly socioeconomic and racial/ethnic minorities, are not benefiting from it.”
Dr. Holtermann, who has arguably done the most research to date on the PA paradox, noted in a recent editorial that the majority of workers with high occupational PA have a low socioeconomic position and therefore “improving our understanding of the underlying mechanisms behind the PA health paradox and identifying new intervention targets along those pathways will be an important step to reduce socioeconomic health inequalities across the globe.”
A version of this article first appeared on Medscape.com.
The Lancet Regional Health – Europe
Alzheimer’s blood test coming within 5 years, UK group pledges
Alzheimer’s Research UK, the Alzheimer’s Society, and the National Institute for Health and Care Research (NIHR) are collaborating and leading AD researchers to bring a diagnostic blood test to the UK’s National Health Service (NHS).
“Dementia affects around 900,000 people in the UK today, and that number is expected to rise to 1.4 million by 2040. It is the UK’s biggest killer,” Fiona Carragher, with the Alzheimer’s Society, said during a media briefing announcing the project.
Yet, many people face a very long wait of up to 2-4 years to get a dementia diagnosis, and many cases remain undiagnosed, she noted.
A chief reason is lack of access to specialized diagnostic testing. Currently, only 2% of people in the United Kingdom have access to advanced diagnostic tests such as PET scans and lumbar punctures owing to limited availability.
“Getting an early and accurate diagnosis is the pivotal first step to getting help today and unlocking hope for the future” and blood biomarkers provide a “real opportunity to disrupt the diagnostic paradigm,” Ms. Carragher said. It also offers greater opportunities to participate in research and clinical trials, she added.
Attitude shift
Susan Kohlhaas, PhD, with Alzheimer’s Research UK, noted that attitudes toward dementia diagnosis have changed in the past few years. The days when people may have not wanted to know if they have dementia are gone.
Data from the latest wave of the Alzheimer’s Research UK Dementia Attitudes Monitor survey show that 9 in 10 people would seek a diagnosis from their provider. “That’s been driven by awareness of treatments and things that people can proactively do to try and slow disease progression,” Dr. Kohlhaas said.
“As new treatments for dementia become available there will to be a surge in people seeking a diagnosis. At the moment, we don’t have adequate infrastructure to cope with that demand,” Dr. Kohlhaas added.
She noted that blood tests are starting to show their potential as an effective part of the diagnosis and are widely used in research.
“In some cases, they are similar in sensitivity to gold-standard PET scans and lumbar punctures, and they’re less expensive and potentially more scalable on the NHS. What we need to do over the next several years is to understand how they fit into the clinical pathway,” Dr. Kohlhaas said.
The project will involve working with leading dementia researchers to pilot the implementation of potential blood tests in the NHS that can give an early and accurate diagnose of dementia.
The project, which kicks off in January 2024, will receive £5 million ($6.13 million) awarded by the UK Postcode Dream Fund. Specific details regarding the leadership team, participating centers, and specific blood biomarker tests to be trialed will be announced then.
Ms. Carragher and Dr. Kohlhaas reported no relevant financial conflicts of interest.
A version of this article appeared on Medscape.com.
Alzheimer’s Research UK, the Alzheimer’s Society, and the National Institute for Health and Care Research (NIHR) are collaborating and leading AD researchers to bring a diagnostic blood test to the UK’s National Health Service (NHS).
“Dementia affects around 900,000 people in the UK today, and that number is expected to rise to 1.4 million by 2040. It is the UK’s biggest killer,” Fiona Carragher, with the Alzheimer’s Society, said during a media briefing announcing the project.
Yet, many people face a very long wait of up to 2-4 years to get a dementia diagnosis, and many cases remain undiagnosed, she noted.
A chief reason is lack of access to specialized diagnostic testing. Currently, only 2% of people in the United Kingdom have access to advanced diagnostic tests such as PET scans and lumbar punctures owing to limited availability.
“Getting an early and accurate diagnosis is the pivotal first step to getting help today and unlocking hope for the future” and blood biomarkers provide a “real opportunity to disrupt the diagnostic paradigm,” Ms. Carragher said. It also offers greater opportunities to participate in research and clinical trials, she added.
Attitude shift
Susan Kohlhaas, PhD, with Alzheimer’s Research UK, noted that attitudes toward dementia diagnosis have changed in the past few years. The days when people may have not wanted to know if they have dementia are gone.
Data from the latest wave of the Alzheimer’s Research UK Dementia Attitudes Monitor survey show that 9 in 10 people would seek a diagnosis from their provider. “That’s been driven by awareness of treatments and things that people can proactively do to try and slow disease progression,” Dr. Kohlhaas said.
“As new treatments for dementia become available there will to be a surge in people seeking a diagnosis. At the moment, we don’t have adequate infrastructure to cope with that demand,” Dr. Kohlhaas added.
She noted that blood tests are starting to show their potential as an effective part of the diagnosis and are widely used in research.
“In some cases, they are similar in sensitivity to gold-standard PET scans and lumbar punctures, and they’re less expensive and potentially more scalable on the NHS. What we need to do over the next several years is to understand how they fit into the clinical pathway,” Dr. Kohlhaas said.
The project will involve working with leading dementia researchers to pilot the implementation of potential blood tests in the NHS that can give an early and accurate diagnose of dementia.
The project, which kicks off in January 2024, will receive £5 million ($6.13 million) awarded by the UK Postcode Dream Fund. Specific details regarding the leadership team, participating centers, and specific blood biomarker tests to be trialed will be announced then.
Ms. Carragher and Dr. Kohlhaas reported no relevant financial conflicts of interest.
A version of this article appeared on Medscape.com.
Alzheimer’s Research UK, the Alzheimer’s Society, and the National Institute for Health and Care Research (NIHR) are collaborating and leading AD researchers to bring a diagnostic blood test to the UK’s National Health Service (NHS).
“Dementia affects around 900,000 people in the UK today, and that number is expected to rise to 1.4 million by 2040. It is the UK’s biggest killer,” Fiona Carragher, with the Alzheimer’s Society, said during a media briefing announcing the project.
Yet, many people face a very long wait of up to 2-4 years to get a dementia diagnosis, and many cases remain undiagnosed, she noted.
A chief reason is lack of access to specialized diagnostic testing. Currently, only 2% of people in the United Kingdom have access to advanced diagnostic tests such as PET scans and lumbar punctures owing to limited availability.
“Getting an early and accurate diagnosis is the pivotal first step to getting help today and unlocking hope for the future” and blood biomarkers provide a “real opportunity to disrupt the diagnostic paradigm,” Ms. Carragher said. It also offers greater opportunities to participate in research and clinical trials, she added.
Attitude shift
Susan Kohlhaas, PhD, with Alzheimer’s Research UK, noted that attitudes toward dementia diagnosis have changed in the past few years. The days when people may have not wanted to know if they have dementia are gone.
Data from the latest wave of the Alzheimer’s Research UK Dementia Attitudes Monitor survey show that 9 in 10 people would seek a diagnosis from their provider. “That’s been driven by awareness of treatments and things that people can proactively do to try and slow disease progression,” Dr. Kohlhaas said.
“As new treatments for dementia become available there will to be a surge in people seeking a diagnosis. At the moment, we don’t have adequate infrastructure to cope with that demand,” Dr. Kohlhaas added.
She noted that blood tests are starting to show their potential as an effective part of the diagnosis and are widely used in research.
“In some cases, they are similar in sensitivity to gold-standard PET scans and lumbar punctures, and they’re less expensive and potentially more scalable on the NHS. What we need to do over the next several years is to understand how they fit into the clinical pathway,” Dr. Kohlhaas said.
The project will involve working with leading dementia researchers to pilot the implementation of potential blood tests in the NHS that can give an early and accurate diagnose of dementia.
The project, which kicks off in January 2024, will receive £5 million ($6.13 million) awarded by the UK Postcode Dream Fund. Specific details regarding the leadership team, participating centers, and specific blood biomarker tests to be trialed will be announced then.
Ms. Carragher and Dr. Kohlhaas reported no relevant financial conflicts of interest.
A version of this article appeared on Medscape.com.
Military service linked to Alzheimer’s neuropathology
TOPLINE:
METHODOLOGY:
- The study included 597 male decedents who donated their brains to one of two Alzheimer’s Disease Research Center (ADRC) brain bank programs between 1986 and 2018.
- Researchers conducted public data tracing for historical information on military history, which included searching online commercial genealogical databases and paper archives.
- They evaluated tau tangles (using a B score of neurofibrillary tangle deposition in four stages: B0 [not present], B1 [transentorhinal stages], B2 [limbic stages], and B3 [isocortical stages]) and amyloid plaque pathology (using a C score that classifies neuritic amyloid plaque into four categories: no plaques, sparse, moderate, or frequent).
- The study involved three B score comparisons (1, 2, 3 vs. 0; 2, 3 vs. 0, 1; and 3 vs. 0, 1, 2) and two C score comparisons (sparse, moderate, or frequent vs. no plaques, and moderate or frequent vs. no plaque or sparse).
TAKEAWAY:
- Public record tracing determined that 60% of the sample of male decedents had a history of military service; the median year of birth was 1923 and the median year of death was 2007.
- After adjustment for age and year of death, those with a military service history had a 26% increased risk for a higher neuritic amyloid plaque C score compared with those without such history (odds ratio [OR], 1.26; 95% confidence interval [CI], 1.06-1.49), an increase that applied for both relevant comparisons.
- A history of military service was also associated with a 10% greater adjusted odds of a higher neurofibrillary tangle B score (OR, 1.10; 95% CI, 1.08-1.12), with the increase applying to all three comparisons.
- A sensitivity analysis that included both the male decedents and 556 female decedents (increasing the overall sample to 1,153) and was adjusted for sex in addition to age and year of death showed similar results to the male-only sample estimations for both B and C score comparisons.
IN PRACTICE:
Understanding how military service affects AD biological processes is “essential” from a research perspective, the investigators noted. These new findings “emphasize that targeted AD therapies in the veteran population are urgently needed.”
SOURCE:
The study was conducted by W. Ryan Powell, Center for Health Disparities Research and Department of Medicine, Geriatrics Division, University of Wisconsin School of Medicine and Public Health, and colleagues. It was published online in Alzheimer’s & Dementia.
LIMITATIONS:
Selection bias in brain donation is likely because ADRC cohorts are recruitment based. The study was unable to rigorously identify factors that may explain why individuals with military service are at greater risk of having amyloid and tau neuropathology (including the interplay between environmental and genetic risk factors such as apolipoprotein E status).
DISCLOSURES:
The study was supported by the National Institute on Aging. The authors reported no disclosures.
A version of this article appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- The study included 597 male decedents who donated their brains to one of two Alzheimer’s Disease Research Center (ADRC) brain bank programs between 1986 and 2018.
- Researchers conducted public data tracing for historical information on military history, which included searching online commercial genealogical databases and paper archives.
- They evaluated tau tangles (using a B score of neurofibrillary tangle deposition in four stages: B0 [not present], B1 [transentorhinal stages], B2 [limbic stages], and B3 [isocortical stages]) and amyloid plaque pathology (using a C score that classifies neuritic amyloid plaque into four categories: no plaques, sparse, moderate, or frequent).
- The study involved three B score comparisons (1, 2, 3 vs. 0; 2, 3 vs. 0, 1; and 3 vs. 0, 1, 2) and two C score comparisons (sparse, moderate, or frequent vs. no plaques, and moderate or frequent vs. no plaque or sparse).
TAKEAWAY:
- Public record tracing determined that 60% of the sample of male decedents had a history of military service; the median year of birth was 1923 and the median year of death was 2007.
- After adjustment for age and year of death, those with a military service history had a 26% increased risk for a higher neuritic amyloid plaque C score compared with those without such history (odds ratio [OR], 1.26; 95% confidence interval [CI], 1.06-1.49), an increase that applied for both relevant comparisons.
- A history of military service was also associated with a 10% greater adjusted odds of a higher neurofibrillary tangle B score (OR, 1.10; 95% CI, 1.08-1.12), with the increase applying to all three comparisons.
- A sensitivity analysis that included both the male decedents and 556 female decedents (increasing the overall sample to 1,153) and was adjusted for sex in addition to age and year of death showed similar results to the male-only sample estimations for both B and C score comparisons.
IN PRACTICE:
Understanding how military service affects AD biological processes is “essential” from a research perspective, the investigators noted. These new findings “emphasize that targeted AD therapies in the veteran population are urgently needed.”
SOURCE:
The study was conducted by W. Ryan Powell, Center for Health Disparities Research and Department of Medicine, Geriatrics Division, University of Wisconsin School of Medicine and Public Health, and colleagues. It was published online in Alzheimer’s & Dementia.
LIMITATIONS:
Selection bias in brain donation is likely because ADRC cohorts are recruitment based. The study was unable to rigorously identify factors that may explain why individuals with military service are at greater risk of having amyloid and tau neuropathology (including the interplay between environmental and genetic risk factors such as apolipoprotein E status).
DISCLOSURES:
The study was supported by the National Institute on Aging. The authors reported no disclosures.
A version of this article appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- The study included 597 male decedents who donated their brains to one of two Alzheimer’s Disease Research Center (ADRC) brain bank programs between 1986 and 2018.
- Researchers conducted public data tracing for historical information on military history, which included searching online commercial genealogical databases and paper archives.
- They evaluated tau tangles (using a B score of neurofibrillary tangle deposition in four stages: B0 [not present], B1 [transentorhinal stages], B2 [limbic stages], and B3 [isocortical stages]) and amyloid plaque pathology (using a C score that classifies neuritic amyloid plaque into four categories: no plaques, sparse, moderate, or frequent).
- The study involved three B score comparisons (1, 2, 3 vs. 0; 2, 3 vs. 0, 1; and 3 vs. 0, 1, 2) and two C score comparisons (sparse, moderate, or frequent vs. no plaques, and moderate or frequent vs. no plaque or sparse).
TAKEAWAY:
- Public record tracing determined that 60% of the sample of male decedents had a history of military service; the median year of birth was 1923 and the median year of death was 2007.
- After adjustment for age and year of death, those with a military service history had a 26% increased risk for a higher neuritic amyloid plaque C score compared with those without such history (odds ratio [OR], 1.26; 95% confidence interval [CI], 1.06-1.49), an increase that applied for both relevant comparisons.
- A history of military service was also associated with a 10% greater adjusted odds of a higher neurofibrillary tangle B score (OR, 1.10; 95% CI, 1.08-1.12), with the increase applying to all three comparisons.
- A sensitivity analysis that included both the male decedents and 556 female decedents (increasing the overall sample to 1,153) and was adjusted for sex in addition to age and year of death showed similar results to the male-only sample estimations for both B and C score comparisons.
IN PRACTICE:
Understanding how military service affects AD biological processes is “essential” from a research perspective, the investigators noted. These new findings “emphasize that targeted AD therapies in the veteran population are urgently needed.”
SOURCE:
The study was conducted by W. Ryan Powell, Center for Health Disparities Research and Department of Medicine, Geriatrics Division, University of Wisconsin School of Medicine and Public Health, and colleagues. It was published online in Alzheimer’s & Dementia.
LIMITATIONS:
Selection bias in brain donation is likely because ADRC cohorts are recruitment based. The study was unable to rigorously identify factors that may explain why individuals with military service are at greater risk of having amyloid and tau neuropathology (including the interplay between environmental and genetic risk factors such as apolipoprotein E status).
DISCLOSURES:
The study was supported by the National Institute on Aging. The authors reported no disclosures.
A version of this article appeared on Medscape.com.
Pandemic tied to a 50% drop in memory, executive function in older adults
TOPLINE:
This was attributed to an increase in known dementia risk factors, including increased alcohol use and a more sedentary lifestyle. This trend persisted into the second year of the pandemic, after social restrictions had eased.
METHODOLOGY:
- In total, 3,140 participants (54% women; mean age, 68 years) in the PROTECT study, a longitudinal aging study in the United Kingdom, completed annual cognitive assessments and self-reported questionnaires related to mental health and lifestyle.
- Investigators analyzed cognition across three time periods: during the year before the pandemic (March 2019 to February 2020), during pandemic year 1 (March 2020 to February 2021), and pandemic year 2 (March 2021 to February 2022).
- Investigators conducted a subanalysis on those with mild cognitive impairment and those with a history of COVID-19 (n = 752).
TAKEAWAY:
- During the first year of the pandemic, when there were societal lockdowns totaling 6 months, significant worsening of executive function and working memory was seen across the entire cohort (effect sizes, 0.15 and 0.51, respectively), in people with mild cognitive impairment (effect sizes, 0.13 and 0.40, respectively), and in those with a previous history of COVID-19 (effect sizes, 0.24 and 0.46, respectively).
- Worsening of working memory was sustained across the whole cohort in the second year of the pandemic after lockdowns were lifted (effect size, 0.47).
- Even after investigators removed data on people with mild cognitive impairment and COVID-19, the decline in executive function (effect size, 0.15; P < .0001) and working memory (effect size, 0.53; P < .0001) persisted.
- Cognitive decline was significantly associated with known risk factors for dementia, such as reduced exercise (P = .0049) and increased alcohol use (P = .049), across the whole cohort, as well as depression (P = .011) in those with a history of COVID-19 and loneliness (P = .0038) in those with mild cognitive impairment.
IN PRACTICE:
Investigators noted that these data add to existing knowledge of long-standing health consequences of COVID-19, especially for older people with memory problems. “On the positive note, there is evidence that lifestyle changes and improved health management can positively influence mental functioning,” study coauthor Dag Aarsland, MD, PhD, professor of old age psychiatry at the Institute of Psychiatry, Psychology & Neuroscience of King’s College London, said in a press release. “The current study underlines the importance of careful monitoring of people at risk during major events such as the pandemic.”
SOURCE:
The study was led by Anne Corbett, PhD, of University of Exeter, and was published online in The Lancet Healthy Longevity. The research was funded by the National Institute for Health and Care Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London and the NIHR Exeter Biomedical Research Centre.
LIMITATIONS:
The study relied on self-reported data. In addition, the PROTECT cohort is self-selected and may skew toward participants with higher education levels.
DISCLOSURES:
Dr. Corbett reported receiving funding from the NIHR and grants from Synexus, reMYND, and Novo Nordisk. Other disclosures are noted in the original article.
A version of this article appeared on Medscape.com.
TOPLINE:
This was attributed to an increase in known dementia risk factors, including increased alcohol use and a more sedentary lifestyle. This trend persisted into the second year of the pandemic, after social restrictions had eased.
METHODOLOGY:
- In total, 3,140 participants (54% women; mean age, 68 years) in the PROTECT study, a longitudinal aging study in the United Kingdom, completed annual cognitive assessments and self-reported questionnaires related to mental health and lifestyle.
- Investigators analyzed cognition across three time periods: during the year before the pandemic (March 2019 to February 2020), during pandemic year 1 (March 2020 to February 2021), and pandemic year 2 (March 2021 to February 2022).
- Investigators conducted a subanalysis on those with mild cognitive impairment and those with a history of COVID-19 (n = 752).
TAKEAWAY:
- During the first year of the pandemic, when there were societal lockdowns totaling 6 months, significant worsening of executive function and working memory was seen across the entire cohort (effect sizes, 0.15 and 0.51, respectively), in people with mild cognitive impairment (effect sizes, 0.13 and 0.40, respectively), and in those with a previous history of COVID-19 (effect sizes, 0.24 and 0.46, respectively).
- Worsening of working memory was sustained across the whole cohort in the second year of the pandemic after lockdowns were lifted (effect size, 0.47).
- Even after investigators removed data on people with mild cognitive impairment and COVID-19, the decline in executive function (effect size, 0.15; P < .0001) and working memory (effect size, 0.53; P < .0001) persisted.
- Cognitive decline was significantly associated with known risk factors for dementia, such as reduced exercise (P = .0049) and increased alcohol use (P = .049), across the whole cohort, as well as depression (P = .011) in those with a history of COVID-19 and loneliness (P = .0038) in those with mild cognitive impairment.
IN PRACTICE:
Investigators noted that these data add to existing knowledge of long-standing health consequences of COVID-19, especially for older people with memory problems. “On the positive note, there is evidence that lifestyle changes and improved health management can positively influence mental functioning,” study coauthor Dag Aarsland, MD, PhD, professor of old age psychiatry at the Institute of Psychiatry, Psychology & Neuroscience of King’s College London, said in a press release. “The current study underlines the importance of careful monitoring of people at risk during major events such as the pandemic.”
SOURCE:
The study was led by Anne Corbett, PhD, of University of Exeter, and was published online in The Lancet Healthy Longevity. The research was funded by the National Institute for Health and Care Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London and the NIHR Exeter Biomedical Research Centre.
LIMITATIONS:
The study relied on self-reported data. In addition, the PROTECT cohort is self-selected and may skew toward participants with higher education levels.
DISCLOSURES:
Dr. Corbett reported receiving funding from the NIHR and grants from Synexus, reMYND, and Novo Nordisk. Other disclosures are noted in the original article.
A version of this article appeared on Medscape.com.
TOPLINE:
This was attributed to an increase in known dementia risk factors, including increased alcohol use and a more sedentary lifestyle. This trend persisted into the second year of the pandemic, after social restrictions had eased.
METHODOLOGY:
- In total, 3,140 participants (54% women; mean age, 68 years) in the PROTECT study, a longitudinal aging study in the United Kingdom, completed annual cognitive assessments and self-reported questionnaires related to mental health and lifestyle.
- Investigators analyzed cognition across three time periods: during the year before the pandemic (March 2019 to February 2020), during pandemic year 1 (March 2020 to February 2021), and pandemic year 2 (March 2021 to February 2022).
- Investigators conducted a subanalysis on those with mild cognitive impairment and those with a history of COVID-19 (n = 752).
TAKEAWAY:
- During the first year of the pandemic, when there were societal lockdowns totaling 6 months, significant worsening of executive function and working memory was seen across the entire cohort (effect sizes, 0.15 and 0.51, respectively), in people with mild cognitive impairment (effect sizes, 0.13 and 0.40, respectively), and in those with a previous history of COVID-19 (effect sizes, 0.24 and 0.46, respectively).
- Worsening of working memory was sustained across the whole cohort in the second year of the pandemic after lockdowns were lifted (effect size, 0.47).
- Even after investigators removed data on people with mild cognitive impairment and COVID-19, the decline in executive function (effect size, 0.15; P < .0001) and working memory (effect size, 0.53; P < .0001) persisted.
- Cognitive decline was significantly associated with known risk factors for dementia, such as reduced exercise (P = .0049) and increased alcohol use (P = .049), across the whole cohort, as well as depression (P = .011) in those with a history of COVID-19 and loneliness (P = .0038) in those with mild cognitive impairment.
IN PRACTICE:
Investigators noted that these data add to existing knowledge of long-standing health consequences of COVID-19, especially for older people with memory problems. “On the positive note, there is evidence that lifestyle changes and improved health management can positively influence mental functioning,” study coauthor Dag Aarsland, MD, PhD, professor of old age psychiatry at the Institute of Psychiatry, Psychology & Neuroscience of King’s College London, said in a press release. “The current study underlines the importance of careful monitoring of people at risk during major events such as the pandemic.”
SOURCE:
The study was led by Anne Corbett, PhD, of University of Exeter, and was published online in The Lancet Healthy Longevity. The research was funded by the National Institute for Health and Care Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London and the NIHR Exeter Biomedical Research Centre.
LIMITATIONS:
The study relied on self-reported data. In addition, the PROTECT cohort is self-selected and may skew toward participants with higher education levels.
DISCLOSURES:
Dr. Corbett reported receiving funding from the NIHR and grants from Synexus, reMYND, and Novo Nordisk. Other disclosures are noted in the original article.
A version of this article appeared on Medscape.com.
Alzheimer’s Disease: Differential Diagnosis
What to tell your patients about anti-amyloids for Alzheimer’s disease
Recorded October 13, 2023. This transcript has been edited for clarity.
Kathrin LaFaver, MD: I’ll be talking today with Dr. Meredith Wicklund, senior associate consultant and behavioral neurologist specialist at Mayo Clinic in Arizona. Welcome, Meredith.
Meredith Wicklund, MD: Thank you.
Lecanemab data
Dr. LaFaver: I’m very excited about our topic. Could you give us a brief overview of why there has been so much research interest in this topic of anti-amyloid antibodies?
Dr. Wicklund: The pathologic component of what defines something as Alzheimer’s disease is, by definition, presence of amyloid plaques and tau tangles. When it was first discovered in the 1980s that the component of the plaques was actually the amyloid protein – beta amyloid specifically – interest went right from there to developing therapies to directly target the pathology that is Alzheimer’s disease.
Dr. LaFaver: Lecanemab is the first FDA-approved disease-modifying antibody in that realm. Could you review the study data, especially as it applies to both of us in daily neurology clinic?
Dr. Wicklund: The study data from a phase 3 trial did show, for the primary outcome, that there was a 27% slowing of decline compared with individuals on placebo. It’s important to point out that this was slowing of decline. It was not stabilizing decline. It was not improving decline.
I think it’s important that we inform our patients that really, even with this therapy, there’s no prospect of stabilizing or restoring cognition or function. We do progress at a slower rate compared with individuals not on this treatment, which, given that this medication is for individuals in mild disease who have relatively preserved functional status, that can be potentially very meaningful to families.
The overall benefit was small. It essentially amounts to half a point on an 18-point scale, which is statistically significant. How much clinical meaningfulness that actually leads to is unclear. Finding clinical meaningfulness cannot be defined by a particular test. It really can only be defined on the individual level, what is meaningful to them.
Recommended tests
Dr. LaFaver: It is my understanding that, to qualify for lecanemab use, one needs to have a biomarker-supported diagnosis of Alzheimer’s disease, either via an amyloid PET scan or CSF biomarkers. What would your recommendation be for a neurologist in practice to go about these requirements?
Dr. Wicklund: Since this medication is directly targeting the amyloid pathology, and it does convey a potential risk, we want to make sure that the actual pathology is present in the individuals before we treat them and potentially expose them to risk. The best way of doing that is through either an amyloid PET scan or spinal fluid testing of beta amyloid and tau.
There are several plasma-based biomarkers in development. However, I would avoid using those currently. There are still many unknowns in terms of what exactly is the right species of tau that we should be looking at, the right mechanism of the lab test, how minority status may influence it, and how different comorbidities may influence it.
I would recommend, at this time, sticking with amyloid PET or CSF testing. Given that amyloid PET is not widely available in many community practices, generally only available at academic centers, and is quite costly, many insurances do not cover it – although Medicare has a proposal to potentially start covering it – I generally go with spinal fluid testing, which is more widely available. There are several labs across the country that can process that testing in a reliable way.
Amyloid-related imaging abnormalities
Dr. LaFaver: That’s very helpful to know. There’s been a large amount of buzz just these past couple of weeks about the blood biomarker coming up. I think, as you point out, this wasn’t the marker used in the clinical studies and there are still unknowns. Maybe it’s not quite time for clinical use, unfortunately.
We also have learned that there are significant potential risks involved. One issue that’s really been a focus is ARIA – amyloid-related imaging abnormalities. Could you speak a bit about that and requirements for monitoring?
Dr. Wicklund: ARIA essentially amounts to either vasogenic edema, microhemorrhages, or superficial siderosis that develops as a result of treatment. It relates to activation of the immune system with these passive monoclonal antibodies that’s going to occur with targeting against the plaques. In the parenchyma, it will cause edema. If you have amyloid in the walls of the blood vessels, it can cause microhemorrhages.
While the term “ARIA” implies an imaging-related abnormality, and it largely is purely an imaging finding, it’s not solely an imaging-related finding. It can cause symptoms, including very serious symptoms.
Overall, with lecanemab, the incidence of ARIA within the treatment group in the phase 3 study, combined between both ARIA-E (edema/effusion) and ARIA-H (hemorrhage), was 21.5%, with about 17% being ARIA-H and about 12.5% being ARIA-E. Of course, they can occur at the same time.
Overall, in terms of people in the clinical trials, for most it was purely an imaging-related finding. About 3% developed symptomatic ARIA. Some of those were very serious symptoms, including things like seizures and need to be hospitalized. A couple of deaths have been attributed to ARIA as well.
Patients on anticoagulation
Dr. LaFaver: Along those lines, any additional words to say for people who might be on anticoagulation or might require medications for a stroke, for example?
Dr. Wicklund: While individuals on anticoagulation were allowed in the clinical trials, the current, published appropriate-use guideline is recommending against its use, as several of the serious adverse effects, including the deaths, were for the most part attributed to anticoagulation use.
When it comes to acute stroke treatment, one must carefully consider use of tPA, as two of the three deaths were tPA associated in the clinical trials. It shouldn’t necessarily be an absolute contraindication, but it can make the clinical picture very muddy. If an individual is on lecanemab and comes to the ER with acute stroke-like symptoms, it’s more likely that they’re going to be having an ARIA side effect rather than an acute stroke.
A general recommendation would be to obtain an acute head CT with a CTA, and if there is a large vessel occlusion, proceed to thrombectomy. However, if there isn’t a large vessel occlusion, if you have the ability to get a rapid MRI with diffusion-weighted imaging to screen for acute stroke changes or tissue flair with acute edema changes suggestive of ARIA, that would be preferred before proceeding with thrombolysis. These are all relative contraindications and are going to depend on what’s available near you.
Donanemab approval pending
Dr. LaFaver: This will be an issue because the population we’re talking about is definitely at risk for stroke as well as Alzheimer’s disease. Where do you see this field going as far as amyloid antibody therapy is concerned, with another agent, donanemab, possibly getting FDA approval later this year as well?
Dr. Wicklund: We’re anticipating that donanemab will get FDA approval in the next coming months. Donanemab also targets the amyloid in the brain, although lecanemab and donanemab target different aspects of the production of the amyloid plaque. They were both shown to have roughly equal efficacy in their phase 3 clinical trials. Donanemab has the benefit of being a once-monthly infusion as opposed to twice-monthly infusions with lecanemab. It does have a slightly higher risk for ARIA compared with lecanemab.
Those are just some things to take into consideration when talking with your patients. In terms of where we’re going from here, we’re moving even earlier in terms of disease state. The lecanemab and donanemab phase 3 trials were done in individuals with mild cognitive impairment or mild dementia due to Alzheimer’s disease. They should not be used in individuals with moderate or more advanced Alzheimer’s disease.
There are ongoing, large, national, multicenter clinical trials of both lecanemab and donanemab in a preclinical state of Alzheimer’s disease. These individuals have evidence of amyloidosis, either through PET imaging or through CSF, but are clinically asymptomatic and do not yet have any signs of cognitive impairment or functional decline. We look forward to those results in the next few years. Hopefully, they’ll be able to show even greater benefit when moving into these early disease states in terms of delaying or even preventing cognitive decline.
Dr. LaFaver: That’s definitely very interesting to hear about. Where can people go for more information?
Dr. Wicklund: There’s a guideline on the use of lecanemab through the American Academy of Neurology. I encourage you to look at that. Also, look at the appropriate-use recommendations that were published this year in The Journal of Prevention of Alzheimer’s Disease.
Dr. LaFaver: Wonderful. With that being said, thank you so much for talking to me. I learned a lot. Thanks, everyone, for listening.
Dr. LaFaver is a neurologist at Saratoga Hospital Medical Group, Saratoga Springs, N.Y. She disclosed having no relevant financial relationships. Dr. Wicklund is senior associate consultant in the department of Neurology at Mayo Clinic, Phoenix, Ariz. She disclosed having no relevant financial relationships.
A version of this article appeared on Medscape.com.
Recorded October 13, 2023. This transcript has been edited for clarity.
Kathrin LaFaver, MD: I’ll be talking today with Dr. Meredith Wicklund, senior associate consultant and behavioral neurologist specialist at Mayo Clinic in Arizona. Welcome, Meredith.
Meredith Wicklund, MD: Thank you.
Lecanemab data
Dr. LaFaver: I’m very excited about our topic. Could you give us a brief overview of why there has been so much research interest in this topic of anti-amyloid antibodies?
Dr. Wicklund: The pathologic component of what defines something as Alzheimer’s disease is, by definition, presence of amyloid plaques and tau tangles. When it was first discovered in the 1980s that the component of the plaques was actually the amyloid protein – beta amyloid specifically – interest went right from there to developing therapies to directly target the pathology that is Alzheimer’s disease.
Dr. LaFaver: Lecanemab is the first FDA-approved disease-modifying antibody in that realm. Could you review the study data, especially as it applies to both of us in daily neurology clinic?
Dr. Wicklund: The study data from a phase 3 trial did show, for the primary outcome, that there was a 27% slowing of decline compared with individuals on placebo. It’s important to point out that this was slowing of decline. It was not stabilizing decline. It was not improving decline.
I think it’s important that we inform our patients that really, even with this therapy, there’s no prospect of stabilizing or restoring cognition or function. We do progress at a slower rate compared with individuals not on this treatment, which, given that this medication is for individuals in mild disease who have relatively preserved functional status, that can be potentially very meaningful to families.
The overall benefit was small. It essentially amounts to half a point on an 18-point scale, which is statistically significant. How much clinical meaningfulness that actually leads to is unclear. Finding clinical meaningfulness cannot be defined by a particular test. It really can only be defined on the individual level, what is meaningful to them.
Recommended tests
Dr. LaFaver: It is my understanding that, to qualify for lecanemab use, one needs to have a biomarker-supported diagnosis of Alzheimer’s disease, either via an amyloid PET scan or CSF biomarkers. What would your recommendation be for a neurologist in practice to go about these requirements?
Dr. Wicklund: Since this medication is directly targeting the amyloid pathology, and it does convey a potential risk, we want to make sure that the actual pathology is present in the individuals before we treat them and potentially expose them to risk. The best way of doing that is through either an amyloid PET scan or spinal fluid testing of beta amyloid and tau.
There are several plasma-based biomarkers in development. However, I would avoid using those currently. There are still many unknowns in terms of what exactly is the right species of tau that we should be looking at, the right mechanism of the lab test, how minority status may influence it, and how different comorbidities may influence it.
I would recommend, at this time, sticking with amyloid PET or CSF testing. Given that amyloid PET is not widely available in many community practices, generally only available at academic centers, and is quite costly, many insurances do not cover it – although Medicare has a proposal to potentially start covering it – I generally go with spinal fluid testing, which is more widely available. There are several labs across the country that can process that testing in a reliable way.
Amyloid-related imaging abnormalities
Dr. LaFaver: That’s very helpful to know. There’s been a large amount of buzz just these past couple of weeks about the blood biomarker coming up. I think, as you point out, this wasn’t the marker used in the clinical studies and there are still unknowns. Maybe it’s not quite time for clinical use, unfortunately.
We also have learned that there are significant potential risks involved. One issue that’s really been a focus is ARIA – amyloid-related imaging abnormalities. Could you speak a bit about that and requirements for monitoring?
Dr. Wicklund: ARIA essentially amounts to either vasogenic edema, microhemorrhages, or superficial siderosis that develops as a result of treatment. It relates to activation of the immune system with these passive monoclonal antibodies that’s going to occur with targeting against the plaques. In the parenchyma, it will cause edema. If you have amyloid in the walls of the blood vessels, it can cause microhemorrhages.
While the term “ARIA” implies an imaging-related abnormality, and it largely is purely an imaging finding, it’s not solely an imaging-related finding. It can cause symptoms, including very serious symptoms.
Overall, with lecanemab, the incidence of ARIA within the treatment group in the phase 3 study, combined between both ARIA-E (edema/effusion) and ARIA-H (hemorrhage), was 21.5%, with about 17% being ARIA-H and about 12.5% being ARIA-E. Of course, they can occur at the same time.
Overall, in terms of people in the clinical trials, for most it was purely an imaging-related finding. About 3% developed symptomatic ARIA. Some of those were very serious symptoms, including things like seizures and need to be hospitalized. A couple of deaths have been attributed to ARIA as well.
Patients on anticoagulation
Dr. LaFaver: Along those lines, any additional words to say for people who might be on anticoagulation or might require medications for a stroke, for example?
Dr. Wicklund: While individuals on anticoagulation were allowed in the clinical trials, the current, published appropriate-use guideline is recommending against its use, as several of the serious adverse effects, including the deaths, were for the most part attributed to anticoagulation use.
When it comes to acute stroke treatment, one must carefully consider use of tPA, as two of the three deaths were tPA associated in the clinical trials. It shouldn’t necessarily be an absolute contraindication, but it can make the clinical picture very muddy. If an individual is on lecanemab and comes to the ER with acute stroke-like symptoms, it’s more likely that they’re going to be having an ARIA side effect rather than an acute stroke.
A general recommendation would be to obtain an acute head CT with a CTA, and if there is a large vessel occlusion, proceed to thrombectomy. However, if there isn’t a large vessel occlusion, if you have the ability to get a rapid MRI with diffusion-weighted imaging to screen for acute stroke changes or tissue flair with acute edema changes suggestive of ARIA, that would be preferred before proceeding with thrombolysis. These are all relative contraindications and are going to depend on what’s available near you.
Donanemab approval pending
Dr. LaFaver: This will be an issue because the population we’re talking about is definitely at risk for stroke as well as Alzheimer’s disease. Where do you see this field going as far as amyloid antibody therapy is concerned, with another agent, donanemab, possibly getting FDA approval later this year as well?
Dr. Wicklund: We’re anticipating that donanemab will get FDA approval in the next coming months. Donanemab also targets the amyloid in the brain, although lecanemab and donanemab target different aspects of the production of the amyloid plaque. They were both shown to have roughly equal efficacy in their phase 3 clinical trials. Donanemab has the benefit of being a once-monthly infusion as opposed to twice-monthly infusions with lecanemab. It does have a slightly higher risk for ARIA compared with lecanemab.
Those are just some things to take into consideration when talking with your patients. In terms of where we’re going from here, we’re moving even earlier in terms of disease state. The lecanemab and donanemab phase 3 trials were done in individuals with mild cognitive impairment or mild dementia due to Alzheimer’s disease. They should not be used in individuals with moderate or more advanced Alzheimer’s disease.
There are ongoing, large, national, multicenter clinical trials of both lecanemab and donanemab in a preclinical state of Alzheimer’s disease. These individuals have evidence of amyloidosis, either through PET imaging or through CSF, but are clinically asymptomatic and do not yet have any signs of cognitive impairment or functional decline. We look forward to those results in the next few years. Hopefully, they’ll be able to show even greater benefit when moving into these early disease states in terms of delaying or even preventing cognitive decline.
Dr. LaFaver: That’s definitely very interesting to hear about. Where can people go for more information?
Dr. Wicklund: There’s a guideline on the use of lecanemab through the American Academy of Neurology. I encourage you to look at that. Also, look at the appropriate-use recommendations that were published this year in The Journal of Prevention of Alzheimer’s Disease.
Dr. LaFaver: Wonderful. With that being said, thank you so much for talking to me. I learned a lot. Thanks, everyone, for listening.
Dr. LaFaver is a neurologist at Saratoga Hospital Medical Group, Saratoga Springs, N.Y. She disclosed having no relevant financial relationships. Dr. Wicklund is senior associate consultant in the department of Neurology at Mayo Clinic, Phoenix, Ariz. She disclosed having no relevant financial relationships.
A version of this article appeared on Medscape.com.
Recorded October 13, 2023. This transcript has been edited for clarity.
Kathrin LaFaver, MD: I’ll be talking today with Dr. Meredith Wicklund, senior associate consultant and behavioral neurologist specialist at Mayo Clinic in Arizona. Welcome, Meredith.
Meredith Wicklund, MD: Thank you.
Lecanemab data
Dr. LaFaver: I’m very excited about our topic. Could you give us a brief overview of why there has been so much research interest in this topic of anti-amyloid antibodies?
Dr. Wicklund: The pathologic component of what defines something as Alzheimer’s disease is, by definition, presence of amyloid plaques and tau tangles. When it was first discovered in the 1980s that the component of the plaques was actually the amyloid protein – beta amyloid specifically – interest went right from there to developing therapies to directly target the pathology that is Alzheimer’s disease.
Dr. LaFaver: Lecanemab is the first FDA-approved disease-modifying antibody in that realm. Could you review the study data, especially as it applies to both of us in daily neurology clinic?
Dr. Wicklund: The study data from a phase 3 trial did show, for the primary outcome, that there was a 27% slowing of decline compared with individuals on placebo. It’s important to point out that this was slowing of decline. It was not stabilizing decline. It was not improving decline.
I think it’s important that we inform our patients that really, even with this therapy, there’s no prospect of stabilizing or restoring cognition or function. We do progress at a slower rate compared with individuals not on this treatment, which, given that this medication is for individuals in mild disease who have relatively preserved functional status, that can be potentially very meaningful to families.
The overall benefit was small. It essentially amounts to half a point on an 18-point scale, which is statistically significant. How much clinical meaningfulness that actually leads to is unclear. Finding clinical meaningfulness cannot be defined by a particular test. It really can only be defined on the individual level, what is meaningful to them.
Recommended tests
Dr. LaFaver: It is my understanding that, to qualify for lecanemab use, one needs to have a biomarker-supported diagnosis of Alzheimer’s disease, either via an amyloid PET scan or CSF biomarkers. What would your recommendation be for a neurologist in practice to go about these requirements?
Dr. Wicklund: Since this medication is directly targeting the amyloid pathology, and it does convey a potential risk, we want to make sure that the actual pathology is present in the individuals before we treat them and potentially expose them to risk. The best way of doing that is through either an amyloid PET scan or spinal fluid testing of beta amyloid and tau.
There are several plasma-based biomarkers in development. However, I would avoid using those currently. There are still many unknowns in terms of what exactly is the right species of tau that we should be looking at, the right mechanism of the lab test, how minority status may influence it, and how different comorbidities may influence it.
I would recommend, at this time, sticking with amyloid PET or CSF testing. Given that amyloid PET is not widely available in many community practices, generally only available at academic centers, and is quite costly, many insurances do not cover it – although Medicare has a proposal to potentially start covering it – I generally go with spinal fluid testing, which is more widely available. There are several labs across the country that can process that testing in a reliable way.
Amyloid-related imaging abnormalities
Dr. LaFaver: That’s very helpful to know. There’s been a large amount of buzz just these past couple of weeks about the blood biomarker coming up. I think, as you point out, this wasn’t the marker used in the clinical studies and there are still unknowns. Maybe it’s not quite time for clinical use, unfortunately.
We also have learned that there are significant potential risks involved. One issue that’s really been a focus is ARIA – amyloid-related imaging abnormalities. Could you speak a bit about that and requirements for monitoring?
Dr. Wicklund: ARIA essentially amounts to either vasogenic edema, microhemorrhages, or superficial siderosis that develops as a result of treatment. It relates to activation of the immune system with these passive monoclonal antibodies that’s going to occur with targeting against the plaques. In the parenchyma, it will cause edema. If you have amyloid in the walls of the blood vessels, it can cause microhemorrhages.
While the term “ARIA” implies an imaging-related abnormality, and it largely is purely an imaging finding, it’s not solely an imaging-related finding. It can cause symptoms, including very serious symptoms.
Overall, with lecanemab, the incidence of ARIA within the treatment group in the phase 3 study, combined between both ARIA-E (edema/effusion) and ARIA-H (hemorrhage), was 21.5%, with about 17% being ARIA-H and about 12.5% being ARIA-E. Of course, they can occur at the same time.
Overall, in terms of people in the clinical trials, for most it was purely an imaging-related finding. About 3% developed symptomatic ARIA. Some of those were very serious symptoms, including things like seizures and need to be hospitalized. A couple of deaths have been attributed to ARIA as well.
Patients on anticoagulation
Dr. LaFaver: Along those lines, any additional words to say for people who might be on anticoagulation or might require medications for a stroke, for example?
Dr. Wicklund: While individuals on anticoagulation were allowed in the clinical trials, the current, published appropriate-use guideline is recommending against its use, as several of the serious adverse effects, including the deaths, were for the most part attributed to anticoagulation use.
When it comes to acute stroke treatment, one must carefully consider use of tPA, as two of the three deaths were tPA associated in the clinical trials. It shouldn’t necessarily be an absolute contraindication, but it can make the clinical picture very muddy. If an individual is on lecanemab and comes to the ER with acute stroke-like symptoms, it’s more likely that they’re going to be having an ARIA side effect rather than an acute stroke.
A general recommendation would be to obtain an acute head CT with a CTA, and if there is a large vessel occlusion, proceed to thrombectomy. However, if there isn’t a large vessel occlusion, if you have the ability to get a rapid MRI with diffusion-weighted imaging to screen for acute stroke changes or tissue flair with acute edema changes suggestive of ARIA, that would be preferred before proceeding with thrombolysis. These are all relative contraindications and are going to depend on what’s available near you.
Donanemab approval pending
Dr. LaFaver: This will be an issue because the population we’re talking about is definitely at risk for stroke as well as Alzheimer’s disease. Where do you see this field going as far as amyloid antibody therapy is concerned, with another agent, donanemab, possibly getting FDA approval later this year as well?
Dr. Wicklund: We’re anticipating that donanemab will get FDA approval in the next coming months. Donanemab also targets the amyloid in the brain, although lecanemab and donanemab target different aspects of the production of the amyloid plaque. They were both shown to have roughly equal efficacy in their phase 3 clinical trials. Donanemab has the benefit of being a once-monthly infusion as opposed to twice-monthly infusions with lecanemab. It does have a slightly higher risk for ARIA compared with lecanemab.
Those are just some things to take into consideration when talking with your patients. In terms of where we’re going from here, we’re moving even earlier in terms of disease state. The lecanemab and donanemab phase 3 trials were done in individuals with mild cognitive impairment or mild dementia due to Alzheimer’s disease. They should not be used in individuals with moderate or more advanced Alzheimer’s disease.
There are ongoing, large, national, multicenter clinical trials of both lecanemab and donanemab in a preclinical state of Alzheimer’s disease. These individuals have evidence of amyloidosis, either through PET imaging or through CSF, but are clinically asymptomatic and do not yet have any signs of cognitive impairment or functional decline. We look forward to those results in the next few years. Hopefully, they’ll be able to show even greater benefit when moving into these early disease states in terms of delaying or even preventing cognitive decline.
Dr. LaFaver: That’s definitely very interesting to hear about. Where can people go for more information?
Dr. Wicklund: There’s a guideline on the use of lecanemab through the American Academy of Neurology. I encourage you to look at that. Also, look at the appropriate-use recommendations that were published this year in The Journal of Prevention of Alzheimer’s Disease.
Dr. LaFaver: Wonderful. With that being said, thank you so much for talking to me. I learned a lot. Thanks, everyone, for listening.
Dr. LaFaver is a neurologist at Saratoga Hospital Medical Group, Saratoga Springs, N.Y. She disclosed having no relevant financial relationships. Dr. Wicklund is senior associate consultant in the department of Neurology at Mayo Clinic, Phoenix, Ariz. She disclosed having no relevant financial relationships.
A version of this article appeared on Medscape.com.
Memory-enhancing intervention may help boost confidence, not necessarily memory, in older adults, study suggests
A novel approach aimed at enhancing everyday memory may lead older adults to feel more confident that they can accurately recollect phone numbers, names, and other information, according to findings from a small randomized controlled trial that were presented at the annual meeting of the Gerontological Society of America.
The tool, called Everyday Memory and Metacognitive Intervention (EMMI), trains people to be more mindful of memories, like where they parked their car, by repeating information at increasing intervals and self-testing.
EMMI “is a very important approach, focused on everyday memory,” said George W. Rebok, PhD, professor emeritus in the department of mental health at Johns Hopkins University, Baltimore, who was not involved with the study. “Many times, when we do memory interventions, we only focus on improving objective memories,” such as recalling major life events or one-time occurrences.
Everyday memory was defined as recalling basic facts including names, phone numbers, and daily appointments. The research, led by Ann Pearman, MD, associate director of adult psychology at Case Western Reserve University School of Medicine at MetroHealth Medical Center, Cleveland, Ohio, expanded on previous work she conducted with colleagues. That study found that EMMI may help improve confidence in the ability to recollect information and functional independence among older adults.
The current study was of 62 of the same participants in the earlier research, with one group that received EMMI (n = 30) and another that underwent traditional memory strategy training ([MSC]; n = 32). Both groups underwent four 3-hour virtual training sessions in their designated intervention over 2 weeks.
“One of the most important parts of the study is the [training] period,” when participants build new habits to help recall their everyday memories, Dr. Pearman said.
For 7 weeks, participants reported errors in everyday memories on a smartphone and submitted diary entries for each. Dr. Rebok that said tracking can help identify patterns or circumstances under which a person is likely to experience a memory lapse.
The study found mixed results when comparing EMMI with MSC, with the latter group demonstrating greater improvements in associative memory, such as pairing of a name to a face, highlighting the effectiveness of traditional MCS.
However, participants who underwent EMMI reported an increase in self-confidence that they were able to remember things, compared with those in the MSC group (4.92, confidence interval 95%, P = .30).
The EMMI intervention also was not uniformly effective in reducing memory errors across all participants in the group, which is to be expected, experts note. “In memory training, as with any kind of cognitive training, one size doesn’t fit all,” Dr. Rebok said.
“The mixed findings may highlight the need for a holistic approach to memory improvement and brain health, especially in older adults,” said Krystal L. Culler, DBH, founder of the Virtual Brain Health Center in Cleveland, who was not involved with the study.
EMMI could potentially be part of a broader strategy that includes lifestyle factors like sleep hygiene, physical exercise, diet, and social engagement to support optimal memory care, Dr. Culler said.
Patients who noticed some change in their memory and who are interested in making some positive changes in their daily cognitive functioning may benefit most from EMMI, according to Dr. Pearman.
“Making proactive decisions about memory challenges [patients] in their thinking and doing in everyday life,” she said.
Dr. Pearman shared that she and her colleagues are now looking into a combined EMMI and traditional memory strategy training to maximize the benefits of both interventions.
The study was supported by the Retirement Research Foundation (2018-2019); and the National Institute of Diabetes and Digestive and Kidney Diseases (P30DK111024) from the Georgia Center for Diabetes Translation Research. The study authors report no relevant conflicts. Dr. Culler and Dr. Rebok report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
A novel approach aimed at enhancing everyday memory may lead older adults to feel more confident that they can accurately recollect phone numbers, names, and other information, according to findings from a small randomized controlled trial that were presented at the annual meeting of the Gerontological Society of America.
The tool, called Everyday Memory and Metacognitive Intervention (EMMI), trains people to be more mindful of memories, like where they parked their car, by repeating information at increasing intervals and self-testing.
EMMI “is a very important approach, focused on everyday memory,” said George W. Rebok, PhD, professor emeritus in the department of mental health at Johns Hopkins University, Baltimore, who was not involved with the study. “Many times, when we do memory interventions, we only focus on improving objective memories,” such as recalling major life events or one-time occurrences.
Everyday memory was defined as recalling basic facts including names, phone numbers, and daily appointments. The research, led by Ann Pearman, MD, associate director of adult psychology at Case Western Reserve University School of Medicine at MetroHealth Medical Center, Cleveland, Ohio, expanded on previous work she conducted with colleagues. That study found that EMMI may help improve confidence in the ability to recollect information and functional independence among older adults.
The current study was of 62 of the same participants in the earlier research, with one group that received EMMI (n = 30) and another that underwent traditional memory strategy training ([MSC]; n = 32). Both groups underwent four 3-hour virtual training sessions in their designated intervention over 2 weeks.
“One of the most important parts of the study is the [training] period,” when participants build new habits to help recall their everyday memories, Dr. Pearman said.
For 7 weeks, participants reported errors in everyday memories on a smartphone and submitted diary entries for each. Dr. Rebok that said tracking can help identify patterns or circumstances under which a person is likely to experience a memory lapse.
The study found mixed results when comparing EMMI with MSC, with the latter group demonstrating greater improvements in associative memory, such as pairing of a name to a face, highlighting the effectiveness of traditional MCS.
However, participants who underwent EMMI reported an increase in self-confidence that they were able to remember things, compared with those in the MSC group (4.92, confidence interval 95%, P = .30).
The EMMI intervention also was not uniformly effective in reducing memory errors across all participants in the group, which is to be expected, experts note. “In memory training, as with any kind of cognitive training, one size doesn’t fit all,” Dr. Rebok said.
“The mixed findings may highlight the need for a holistic approach to memory improvement and brain health, especially in older adults,” said Krystal L. Culler, DBH, founder of the Virtual Brain Health Center in Cleveland, who was not involved with the study.
EMMI could potentially be part of a broader strategy that includes lifestyle factors like sleep hygiene, physical exercise, diet, and social engagement to support optimal memory care, Dr. Culler said.
Patients who noticed some change in their memory and who are interested in making some positive changes in their daily cognitive functioning may benefit most from EMMI, according to Dr. Pearman.
“Making proactive decisions about memory challenges [patients] in their thinking and doing in everyday life,” she said.
Dr. Pearman shared that she and her colleagues are now looking into a combined EMMI and traditional memory strategy training to maximize the benefits of both interventions.
The study was supported by the Retirement Research Foundation (2018-2019); and the National Institute of Diabetes and Digestive and Kidney Diseases (P30DK111024) from the Georgia Center for Diabetes Translation Research. The study authors report no relevant conflicts. Dr. Culler and Dr. Rebok report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
A novel approach aimed at enhancing everyday memory may lead older adults to feel more confident that they can accurately recollect phone numbers, names, and other information, according to findings from a small randomized controlled trial that were presented at the annual meeting of the Gerontological Society of America.
The tool, called Everyday Memory and Metacognitive Intervention (EMMI), trains people to be more mindful of memories, like where they parked their car, by repeating information at increasing intervals and self-testing.
EMMI “is a very important approach, focused on everyday memory,” said George W. Rebok, PhD, professor emeritus in the department of mental health at Johns Hopkins University, Baltimore, who was not involved with the study. “Many times, when we do memory interventions, we only focus on improving objective memories,” such as recalling major life events or one-time occurrences.
Everyday memory was defined as recalling basic facts including names, phone numbers, and daily appointments. The research, led by Ann Pearman, MD, associate director of adult psychology at Case Western Reserve University School of Medicine at MetroHealth Medical Center, Cleveland, Ohio, expanded on previous work she conducted with colleagues. That study found that EMMI may help improve confidence in the ability to recollect information and functional independence among older adults.
The current study was of 62 of the same participants in the earlier research, with one group that received EMMI (n = 30) and another that underwent traditional memory strategy training ([MSC]; n = 32). Both groups underwent four 3-hour virtual training sessions in their designated intervention over 2 weeks.
“One of the most important parts of the study is the [training] period,” when participants build new habits to help recall their everyday memories, Dr. Pearman said.
For 7 weeks, participants reported errors in everyday memories on a smartphone and submitted diary entries for each. Dr. Rebok that said tracking can help identify patterns or circumstances under which a person is likely to experience a memory lapse.
The study found mixed results when comparing EMMI with MSC, with the latter group demonstrating greater improvements in associative memory, such as pairing of a name to a face, highlighting the effectiveness of traditional MCS.
However, participants who underwent EMMI reported an increase in self-confidence that they were able to remember things, compared with those in the MSC group (4.92, confidence interval 95%, P = .30).
The EMMI intervention also was not uniformly effective in reducing memory errors across all participants in the group, which is to be expected, experts note. “In memory training, as with any kind of cognitive training, one size doesn’t fit all,” Dr. Rebok said.
“The mixed findings may highlight the need for a holistic approach to memory improvement and brain health, especially in older adults,” said Krystal L. Culler, DBH, founder of the Virtual Brain Health Center in Cleveland, who was not involved with the study.
EMMI could potentially be part of a broader strategy that includes lifestyle factors like sleep hygiene, physical exercise, diet, and social engagement to support optimal memory care, Dr. Culler said.
Patients who noticed some change in their memory and who are interested in making some positive changes in their daily cognitive functioning may benefit most from EMMI, according to Dr. Pearman.
“Making proactive decisions about memory challenges [patients] in their thinking and doing in everyday life,” she said.
Dr. Pearman shared that she and her colleagues are now looking into a combined EMMI and traditional memory strategy training to maximize the benefits of both interventions.
The study was supported by the Retirement Research Foundation (2018-2019); and the National Institute of Diabetes and Digestive and Kidney Diseases (P30DK111024) from the Georgia Center for Diabetes Translation Research. The study authors report no relevant conflicts. Dr. Culler and Dr. Rebok report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM GSA 2023
Atrial fibrillation linked to dementia, especially when diagnosed before age 65 years
TOPLINE:
Adults with atrial fibrillation (AFib) are at increased risk for dementia, especially when AFib occurs before age 65 years, new research shows. Investigators note the findings highlight the importance of monitoring cognitive function in adults with AF.
METHODOLOGY:
- This prospective, population-based cohort study leveraged data from 433,746 UK Biobank participants (55% women), including 30,601 with AFib, who were followed for a median of 12.6 years
- Incident cases of dementia were determined through linkage from multiple databases.
- Cox proportional hazards models and propensity score matching were used to estimate the association between age at onset of AFib and incident dementia.
TAKEAWAY:
- During follow-up, new-onset dementia occurred in 5,898 participants (2,546 with Alzheimer’s disease [AD] and 1,211 with vascular dementia [VD]), of which, 1,031 had AFib (350 with AD; 320 with VD).
- Compared with participants without AFib, those with AFib had a 42% higher risk for all-cause dementia (adjusted hazard ratio, 1.42; P < .001) and more than double the risk for VD (aHR, 2.06; P < .001), but no significantly higher risk for AD.
- Younger age at AFib onset was associated with higher risks for all-cause dementia, AD and VD, with aHRs per 10-year decrease of 1.23, 1.27, and 1.35, respectively (P < .001 for all).
- After propensity score matching, AFib onset before age 65 years had the highest risk for all-cause dementia (aHR, 1.82; P < .001), followed by AF onset at age 65-74 years (aHR, 1.47; P < .001). Similar results were seen in AD and VD.
IN PRACTICE:
“The findings indicate that careful monitoring of cognitive function for patients with a younger [AFib] onset age, particularly those diagnosed with [AFib] before age 65 years, is important to attenuate the risk of subsequent dementia,” the authors write.
SOURCE:
The study, with first author Wenya Zhang, with the Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, was published online in JAMA Network Open.
LIMITATIONS:
Because the study was observational, a cause-effect relationship cannot be established. Despite the adjustment for many underlying confounders, residual unidentified confounders may still exist. The vast majority of participants were White. The analyses did not consider the potential impact of effective treatment of AFib on dementia risk.
DISCLOSURES:
The study had no commercial funding. The authors have declared no conflicts of interest.
A version of this article appeared on Medscape.com.
TOPLINE:
Adults with atrial fibrillation (AFib) are at increased risk for dementia, especially when AFib occurs before age 65 years, new research shows. Investigators note the findings highlight the importance of monitoring cognitive function in adults with AF.
METHODOLOGY:
- This prospective, population-based cohort study leveraged data from 433,746 UK Biobank participants (55% women), including 30,601 with AFib, who were followed for a median of 12.6 years
- Incident cases of dementia were determined through linkage from multiple databases.
- Cox proportional hazards models and propensity score matching were used to estimate the association between age at onset of AFib and incident dementia.
TAKEAWAY:
- During follow-up, new-onset dementia occurred in 5,898 participants (2,546 with Alzheimer’s disease [AD] and 1,211 with vascular dementia [VD]), of which, 1,031 had AFib (350 with AD; 320 with VD).
- Compared with participants without AFib, those with AFib had a 42% higher risk for all-cause dementia (adjusted hazard ratio, 1.42; P < .001) and more than double the risk for VD (aHR, 2.06; P < .001), but no significantly higher risk for AD.
- Younger age at AFib onset was associated with higher risks for all-cause dementia, AD and VD, with aHRs per 10-year decrease of 1.23, 1.27, and 1.35, respectively (P < .001 for all).
- After propensity score matching, AFib onset before age 65 years had the highest risk for all-cause dementia (aHR, 1.82; P < .001), followed by AF onset at age 65-74 years (aHR, 1.47; P < .001). Similar results were seen in AD and VD.
IN PRACTICE:
“The findings indicate that careful monitoring of cognitive function for patients with a younger [AFib] onset age, particularly those diagnosed with [AFib] before age 65 years, is important to attenuate the risk of subsequent dementia,” the authors write.
SOURCE:
The study, with first author Wenya Zhang, with the Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, was published online in JAMA Network Open.
LIMITATIONS:
Because the study was observational, a cause-effect relationship cannot be established. Despite the adjustment for many underlying confounders, residual unidentified confounders may still exist. The vast majority of participants were White. The analyses did not consider the potential impact of effective treatment of AFib on dementia risk.
DISCLOSURES:
The study had no commercial funding. The authors have declared no conflicts of interest.
A version of this article appeared on Medscape.com.
TOPLINE:
Adults with atrial fibrillation (AFib) are at increased risk for dementia, especially when AFib occurs before age 65 years, new research shows. Investigators note the findings highlight the importance of monitoring cognitive function in adults with AF.
METHODOLOGY:
- This prospective, population-based cohort study leveraged data from 433,746 UK Biobank participants (55% women), including 30,601 with AFib, who were followed for a median of 12.6 years
- Incident cases of dementia were determined through linkage from multiple databases.
- Cox proportional hazards models and propensity score matching were used to estimate the association between age at onset of AFib and incident dementia.
TAKEAWAY:
- During follow-up, new-onset dementia occurred in 5,898 participants (2,546 with Alzheimer’s disease [AD] and 1,211 with vascular dementia [VD]), of which, 1,031 had AFib (350 with AD; 320 with VD).
- Compared with participants without AFib, those with AFib had a 42% higher risk for all-cause dementia (adjusted hazard ratio, 1.42; P < .001) and more than double the risk for VD (aHR, 2.06; P < .001), but no significantly higher risk for AD.
- Younger age at AFib onset was associated with higher risks for all-cause dementia, AD and VD, with aHRs per 10-year decrease of 1.23, 1.27, and 1.35, respectively (P < .001 for all).
- After propensity score matching, AFib onset before age 65 years had the highest risk for all-cause dementia (aHR, 1.82; P < .001), followed by AF onset at age 65-74 years (aHR, 1.47; P < .001). Similar results were seen in AD and VD.
IN PRACTICE:
“The findings indicate that careful monitoring of cognitive function for patients with a younger [AFib] onset age, particularly those diagnosed with [AFib] before age 65 years, is important to attenuate the risk of subsequent dementia,” the authors write.
SOURCE:
The study, with first author Wenya Zhang, with the Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, was published online in JAMA Network Open.
LIMITATIONS:
Because the study was observational, a cause-effect relationship cannot be established. Despite the adjustment for many underlying confounders, residual unidentified confounders may still exist. The vast majority of participants were White. The analyses did not consider the potential impact of effective treatment of AFib on dementia risk.
DISCLOSURES:
The study had no commercial funding. The authors have declared no conflicts of interest.
A version of this article appeared on Medscape.com.
Artificial intelligence presents opportunities, challenges in neurologic practice
PHOENIX – and it presents opportunities for increased production and automation of some tasks. However, it is prone to error and ‘hallucinations’ despite an authoritative tone, so its conclusions must be verified.
Those were some of the messages from a talk by John Morren, MD, an associate professor of neurology at Case Western Reserve University, Cleveland, who spoke about AI at the 2023 annual meeting of the American Association for Neuromuscular and Electrodiagnostic Medicine (AANEM).
He encouraged attendees to get involved in the conversation of AI, because it is here to stay and will have a big impact on health care. “If we’re not around the table making decisions, decisions will be made for us in our absence and won’t be in our favor,” said Dr. Morren.
He started out his talk by asking if anyone in the room had used AI. After about half raised their hands, he countered that nearly everyone likely had. Voice assistants like SIRI and Alexa, social media with curated feeds, online shopping tools that provide product suggestions, and content recommendations from streaming services like Netflix all rely on AI technology.
Within medicine, AI is already playing a role in various fields, including medical imaging, disease diagnosis, drug discovery and development, predictive analytics, personalized medicine, telemedicine, and health care management.
It also has potential to be used on the job. For example, ChatGPT can generate and refine conversations towards a specific length, format, style, and level of detail. Alternatives include Bing AI from Microsoft, Bard AI from Google, Writesonic, Copy.ai, SpinBot, HIX.AI, and Chatsonic.
Specific to medicine, Consensus is a search engine that uses AI to search for, summarize, and synthesize studies from peer-reviewed literature.
Trust, but verify
Dr. Morren presented some specific use cases, including patient education and responses to patient inquiries, as well as generating letters to insurance companies appealing denial of coverage claims. He also showed an example where he asked Bing AI to explain to a patient, at a sixth- to seventh-grade reading level, the red-flag symptoms of myasthenic crisis.
AI can generate summaries of clinical evidence of previous studies. Asked by this reporter how to trust the accuracies of the summaries if the user hasn’t thoroughly read the papers, he acknowledged the imperfection of AI. “I would say that if you’re going to make a decision that you would not have made normally based on the summary that it’s giving, if you can find the fact that you’re anchoring the decision on, go into the article yourself and make sure that it’s well vetted. The AI is just good to tap you on your shoulder and say, ‘hey, just consider this.’ That’s all it is. You should always trust, but verify. If the AI is forcing you to say something new that you would not say, maybe don’t do it – or at least research it to know that it’s the truth and then you elevate yourself and get yourself to the next level.”
Limitations
The need to verify can create its own burden, according to one attendee. “I often find I end up spending more time verifying [what ChatGPT has provided]. This seems to take more time than a traditional way of going to PubMed or UpToDate or any of the other human generated consensus way,” he said.
Dr. Morren replied that he wouldn’t recommend using ChatGPT to query medical literature. Instead he recommended Consensus, which only searches the peer-reviewed medical literature.
Another key limitation is that most AI programs are date limited: For example, ChatGPT doesn’t include information after September 2021, though this may change with paid subscriptions. He also starkly warned the audience to never enter sensitive information, including patient identifiers.
There are legal and ethical considerations to AI. Dr. Morren warned against overreliance on AI, as this could undermine compassion and lead to erosion of trust, which makes it important to disclose any use of AI-generated content.
Another attendee raised concerns that AI may be generating research content, including slides for presentations, abstracts, titles, or article text. Dr. Morren said that some organizations, such as the International Committee of Medical Journal Editors, have incorporated AI in their recommendations, stating that authors should disclose any contributions of AI to their publications. However, there is little that can be done to identify AI-generated content, leaving it up to the honor code.
Asked to make predictions about how AI will evolve in the clinic over the next 2-3 years, Dr. Morren suggested that it will likely be embedded in electronic medical records. He anticipated that it will save physicians time so that they can spend more time interacting directly with patients. He quoted Eric Topol, MD, professor of medicine at Scripps Research Translational Institute, La Jolla, Calif., as saying that AI could save 20% of a physician’s time, which could be spent with patients. Dr. Morren saw it differently. “I know where that 20% of time liberated is going to go. I’m going to see 20% more patients. I’m a realist,” he said, to audience laughter.
He also predicted that AI will be found in wearables and devices, allowing health care to expand into the patient’s home in real time. “A lot of what we’re wearing is going to be an extension of the doctor’s office,” he said.
For those hoping for more guidance, Dr. Morren noted that he is the chairman of the professional practice committee of AANEM, and the group will be putting out a position statement within the next couple of months. “It will be a little bit of a blueprint for the path going forward. There are specific things that need to be done. In research, for example, you have to ensure that datasets are diverse enough. To do that we need to have inter-institutional collaboration. We have to ensure patient privacy. Consent for this needs to be a little more explicit because this is a novel area. Those are things that need to be stipulated and ratified through a task force.”
Dr. Morren has no relevant financial disclosures.
PHOENIX – and it presents opportunities for increased production and automation of some tasks. However, it is prone to error and ‘hallucinations’ despite an authoritative tone, so its conclusions must be verified.
Those were some of the messages from a talk by John Morren, MD, an associate professor of neurology at Case Western Reserve University, Cleveland, who spoke about AI at the 2023 annual meeting of the American Association for Neuromuscular and Electrodiagnostic Medicine (AANEM).
He encouraged attendees to get involved in the conversation of AI, because it is here to stay and will have a big impact on health care. “If we’re not around the table making decisions, decisions will be made for us in our absence and won’t be in our favor,” said Dr. Morren.
He started out his talk by asking if anyone in the room had used AI. After about half raised their hands, he countered that nearly everyone likely had. Voice assistants like SIRI and Alexa, social media with curated feeds, online shopping tools that provide product suggestions, and content recommendations from streaming services like Netflix all rely on AI technology.
Within medicine, AI is already playing a role in various fields, including medical imaging, disease diagnosis, drug discovery and development, predictive analytics, personalized medicine, telemedicine, and health care management.
It also has potential to be used on the job. For example, ChatGPT can generate and refine conversations towards a specific length, format, style, and level of detail. Alternatives include Bing AI from Microsoft, Bard AI from Google, Writesonic, Copy.ai, SpinBot, HIX.AI, and Chatsonic.
Specific to medicine, Consensus is a search engine that uses AI to search for, summarize, and synthesize studies from peer-reviewed literature.
Trust, but verify
Dr. Morren presented some specific use cases, including patient education and responses to patient inquiries, as well as generating letters to insurance companies appealing denial of coverage claims. He also showed an example where he asked Bing AI to explain to a patient, at a sixth- to seventh-grade reading level, the red-flag symptoms of myasthenic crisis.
AI can generate summaries of clinical evidence of previous studies. Asked by this reporter how to trust the accuracies of the summaries if the user hasn’t thoroughly read the papers, he acknowledged the imperfection of AI. “I would say that if you’re going to make a decision that you would not have made normally based on the summary that it’s giving, if you can find the fact that you’re anchoring the decision on, go into the article yourself and make sure that it’s well vetted. The AI is just good to tap you on your shoulder and say, ‘hey, just consider this.’ That’s all it is. You should always trust, but verify. If the AI is forcing you to say something new that you would not say, maybe don’t do it – or at least research it to know that it’s the truth and then you elevate yourself and get yourself to the next level.”
Limitations
The need to verify can create its own burden, according to one attendee. “I often find I end up spending more time verifying [what ChatGPT has provided]. This seems to take more time than a traditional way of going to PubMed or UpToDate or any of the other human generated consensus way,” he said.
Dr. Morren replied that he wouldn’t recommend using ChatGPT to query medical literature. Instead he recommended Consensus, which only searches the peer-reviewed medical literature.
Another key limitation is that most AI programs are date limited: For example, ChatGPT doesn’t include information after September 2021, though this may change with paid subscriptions. He also starkly warned the audience to never enter sensitive information, including patient identifiers.
There are legal and ethical considerations to AI. Dr. Morren warned against overreliance on AI, as this could undermine compassion and lead to erosion of trust, which makes it important to disclose any use of AI-generated content.
Another attendee raised concerns that AI may be generating research content, including slides for presentations, abstracts, titles, or article text. Dr. Morren said that some organizations, such as the International Committee of Medical Journal Editors, have incorporated AI in their recommendations, stating that authors should disclose any contributions of AI to their publications. However, there is little that can be done to identify AI-generated content, leaving it up to the honor code.
Asked to make predictions about how AI will evolve in the clinic over the next 2-3 years, Dr. Morren suggested that it will likely be embedded in electronic medical records. He anticipated that it will save physicians time so that they can spend more time interacting directly with patients. He quoted Eric Topol, MD, professor of medicine at Scripps Research Translational Institute, La Jolla, Calif., as saying that AI could save 20% of a physician’s time, which could be spent with patients. Dr. Morren saw it differently. “I know where that 20% of time liberated is going to go. I’m going to see 20% more patients. I’m a realist,” he said, to audience laughter.
He also predicted that AI will be found in wearables and devices, allowing health care to expand into the patient’s home in real time. “A lot of what we’re wearing is going to be an extension of the doctor’s office,” he said.
For those hoping for more guidance, Dr. Morren noted that he is the chairman of the professional practice committee of AANEM, and the group will be putting out a position statement within the next couple of months. “It will be a little bit of a blueprint for the path going forward. There are specific things that need to be done. In research, for example, you have to ensure that datasets are diverse enough. To do that we need to have inter-institutional collaboration. We have to ensure patient privacy. Consent for this needs to be a little more explicit because this is a novel area. Those are things that need to be stipulated and ratified through a task force.”
Dr. Morren has no relevant financial disclosures.
PHOENIX – and it presents opportunities for increased production and automation of some tasks. However, it is prone to error and ‘hallucinations’ despite an authoritative tone, so its conclusions must be verified.
Those were some of the messages from a talk by John Morren, MD, an associate professor of neurology at Case Western Reserve University, Cleveland, who spoke about AI at the 2023 annual meeting of the American Association for Neuromuscular and Electrodiagnostic Medicine (AANEM).
He encouraged attendees to get involved in the conversation of AI, because it is here to stay and will have a big impact on health care. “If we’re not around the table making decisions, decisions will be made for us in our absence and won’t be in our favor,” said Dr. Morren.
He started out his talk by asking if anyone in the room had used AI. After about half raised their hands, he countered that nearly everyone likely had. Voice assistants like SIRI and Alexa, social media with curated feeds, online shopping tools that provide product suggestions, and content recommendations from streaming services like Netflix all rely on AI technology.
Within medicine, AI is already playing a role in various fields, including medical imaging, disease diagnosis, drug discovery and development, predictive analytics, personalized medicine, telemedicine, and health care management.
It also has potential to be used on the job. For example, ChatGPT can generate and refine conversations towards a specific length, format, style, and level of detail. Alternatives include Bing AI from Microsoft, Bard AI from Google, Writesonic, Copy.ai, SpinBot, HIX.AI, and Chatsonic.
Specific to medicine, Consensus is a search engine that uses AI to search for, summarize, and synthesize studies from peer-reviewed literature.
Trust, but verify
Dr. Morren presented some specific use cases, including patient education and responses to patient inquiries, as well as generating letters to insurance companies appealing denial of coverage claims. He also showed an example where he asked Bing AI to explain to a patient, at a sixth- to seventh-grade reading level, the red-flag symptoms of myasthenic crisis.
AI can generate summaries of clinical evidence of previous studies. Asked by this reporter how to trust the accuracies of the summaries if the user hasn’t thoroughly read the papers, he acknowledged the imperfection of AI. “I would say that if you’re going to make a decision that you would not have made normally based on the summary that it’s giving, if you can find the fact that you’re anchoring the decision on, go into the article yourself and make sure that it’s well vetted. The AI is just good to tap you on your shoulder and say, ‘hey, just consider this.’ That’s all it is. You should always trust, but verify. If the AI is forcing you to say something new that you would not say, maybe don’t do it – or at least research it to know that it’s the truth and then you elevate yourself and get yourself to the next level.”
Limitations
The need to verify can create its own burden, according to one attendee. “I often find I end up spending more time verifying [what ChatGPT has provided]. This seems to take more time than a traditional way of going to PubMed or UpToDate or any of the other human generated consensus way,” he said.
Dr. Morren replied that he wouldn’t recommend using ChatGPT to query medical literature. Instead he recommended Consensus, which only searches the peer-reviewed medical literature.
Another key limitation is that most AI programs are date limited: For example, ChatGPT doesn’t include information after September 2021, though this may change with paid subscriptions. He also starkly warned the audience to never enter sensitive information, including patient identifiers.
There are legal and ethical considerations to AI. Dr. Morren warned against overreliance on AI, as this could undermine compassion and lead to erosion of trust, which makes it important to disclose any use of AI-generated content.
Another attendee raised concerns that AI may be generating research content, including slides for presentations, abstracts, titles, or article text. Dr. Morren said that some organizations, such as the International Committee of Medical Journal Editors, have incorporated AI in their recommendations, stating that authors should disclose any contributions of AI to their publications. However, there is little that can be done to identify AI-generated content, leaving it up to the honor code.
Asked to make predictions about how AI will evolve in the clinic over the next 2-3 years, Dr. Morren suggested that it will likely be embedded in electronic medical records. He anticipated that it will save physicians time so that they can spend more time interacting directly with patients. He quoted Eric Topol, MD, professor of medicine at Scripps Research Translational Institute, La Jolla, Calif., as saying that AI could save 20% of a physician’s time, which could be spent with patients. Dr. Morren saw it differently. “I know where that 20% of time liberated is going to go. I’m going to see 20% more patients. I’m a realist,” he said, to audience laughter.
He also predicted that AI will be found in wearables and devices, allowing health care to expand into the patient’s home in real time. “A lot of what we’re wearing is going to be an extension of the doctor’s office,” he said.
For those hoping for more guidance, Dr. Morren noted that he is the chairman of the professional practice committee of AANEM, and the group will be putting out a position statement within the next couple of months. “It will be a little bit of a blueprint for the path going forward. There are specific things that need to be done. In research, for example, you have to ensure that datasets are diverse enough. To do that we need to have inter-institutional collaboration. We have to ensure patient privacy. Consent for this needs to be a little more explicit because this is a novel area. Those are things that need to be stipulated and ratified through a task force.”
Dr. Morren has no relevant financial disclosures.
AT AANEM 2023