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Unexpected link between light drinking and dementia risk
new research suggests.
Investigators assessed dementia risk using changes in alcohol consumption over a 2-year period in nearly 4 million people in South Korea. After about 7 years, dementia was 21% less likely in mild drinkers and 17% less likely in moderate drinkers. Heavy drinking was linked to an 8% increased risk.
Other studies of the relationship between alcohol and dementia have yielded mixed results, and this study does little to clear those murky waters. Nor do the results mean that drinking is recommended, the investigators note.
But the study does offer new information on how risk changes over time as people change their drinking habits, lead investigator Keun Hye Jeon, MD, assistant professor of family medicine at Cha Gumi Medical Center at Cha University, Gumi, South Korea, told this news organization.
“Although numerous studies have shown a relationship between alcohol consumption and dementia, there is a paucity of understanding as to how the incidence of dementia changes with changes in drinking habits,” Dr. Jeon said.
“By measuring alcohol consumption at two time points, we were able to study the relationship between reducing, ceasing, maintaining, and increasing alcohol consumption and incident dementia,” he added.
The findings were published online in JAMA Network Open.
Tracking drinking habits
Researchers analyzed data from nearly 4 million individuals aged 40 years and older in the Korean National Health Insurance Service who completed questionnaires and underwent physical exams in 2009 and 2011.
Study participants completed questionnaires on their drinking habits and were assigned to one of five groups according to change in alcohol consumption during the study period. These groups consisted of sustained nondrinkers; those who stopped drinking (quitters); those who reduced their consumption of alcohol but did not stop drinking (reducers); those who maintained the same level of consumption (sustainers); and those who increased their level of consumption (increasers).
A standard drink in the United States contains 14 g of alcohol. For this study, mild drinking was defined as less than 15 g/day, or one drink; moderate consumption as 15-29.9 g/day, or one to two drinks; and heavy drinking as 30 g/day or more, or three or more drinks.
At baseline, 54.8% of participants were nondrinkers, 26.7% were mild drinkers, 11.0% were moderate drinkers, and 7.5% were heavy drinkers.
From 2009 to 2011, 24.2% of mild drinkers, 8.4% of moderate drinkers, and 7.6% of heavy drinkers became quitters. In the same period, 13.9% of nondrinkers, 16.1% of mild drinkers, and 17.4% of moderate drinkers increased their drinking level.
After a mean follow-up of 6.3 years, 2.5% of participants were diagnosed with dementia, 2.0% with Alzheimer’s disease, and 0.3% with vascular dementia.
Unexpected finding
Compared with consistently not drinking, mild and moderate alcohol consumption was associated with a 21% (adjust hazard ratio, 0.79; 95% confidence interval, 0.77-0.81) and 17% (aHR, 0.83; 95% CI, 0.79-0.88) decreased risk for dementia, respectively.
Heavy drinking was linked to an 8% increased risk (aHR, 1.08; 95% CI, 1.03-1.12).
Similar associations were found between alcohol consumption and risk for Alzheimer’s disease and vascular dementia.
Reducing drinking habits from heavy to moderate led to a reduction in risk for dementia and Alzheimer’s, and increasing drinking levels led to an increase in risk for both conditions.
But when the researchers analyzed dementia risk for nondrinkers who began drinking at mild levels during the study period, they found something unexpected – the risk in this group decreased by 7% for dementia (aHR, 0.93; 95% CI, 0.90-0.96) and by 8% for Alzheimer’s (aHR, 0.92; 95% CI, 0.89-0.95), compared with sustained mild drinkers.
“Our study showed that initiation of mild alcohol consumption leads to a reduced risk of all-cause dementia and Alzheimer’s disease, which has never been reported in previous studies,” Dr. Jeon said.
However, Dr. Jeon was quick to point out that this doesn’t mean that people who don’t drink should start.
Previous studies have shown that heavy alcohol use can triple an individual’s dementia risk, while other studies have shown that no amount of alcohol consumption is good for the brain.
“None of the existing health guidelines recommend starting alcohol drinking,” Dr. Jeon said. “Our findings regarding an initiation of mild alcohol consumption cannot be directly translated into clinical recommendations,” but the findings do warrant additional study, he added.
Risks persist
Commenting on the findings, Percy Griffin, PhD, director of scientific engagement for the Alzheimer’s Association in Chicago, agrees.
“While this study is interesting, and this topic deserves further study, no one should drink alcohol as a method of reducing risk of Alzheimer’s disease or other dementia based on this study,” said Dr. Griffin, who was not part of the study.
The exact tipping point in alcohol consumption that can lead to problems with cognition or increased dementia risk is unknown, Dr. Griffin said. Nor do researchers understand why mild drinking may have a protective effect.
“We do know, however, that excessive alcohol consumption has negative effects on heart health and general health, which can lead to problems with brain function,” he said. “Clinicians should have discussions with their patients around their alcohol consumption patterns and the risks associated with drinking in excess, including potential damage to their cognition.”
Funding for the study was not disclosed. Dr. Jeon and Dr. Griffin report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
new research suggests.
Investigators assessed dementia risk using changes in alcohol consumption over a 2-year period in nearly 4 million people in South Korea. After about 7 years, dementia was 21% less likely in mild drinkers and 17% less likely in moderate drinkers. Heavy drinking was linked to an 8% increased risk.
Other studies of the relationship between alcohol and dementia have yielded mixed results, and this study does little to clear those murky waters. Nor do the results mean that drinking is recommended, the investigators note.
But the study does offer new information on how risk changes over time as people change their drinking habits, lead investigator Keun Hye Jeon, MD, assistant professor of family medicine at Cha Gumi Medical Center at Cha University, Gumi, South Korea, told this news organization.
“Although numerous studies have shown a relationship between alcohol consumption and dementia, there is a paucity of understanding as to how the incidence of dementia changes with changes in drinking habits,” Dr. Jeon said.
“By measuring alcohol consumption at two time points, we were able to study the relationship between reducing, ceasing, maintaining, and increasing alcohol consumption and incident dementia,” he added.
The findings were published online in JAMA Network Open.
Tracking drinking habits
Researchers analyzed data from nearly 4 million individuals aged 40 years and older in the Korean National Health Insurance Service who completed questionnaires and underwent physical exams in 2009 and 2011.
Study participants completed questionnaires on their drinking habits and were assigned to one of five groups according to change in alcohol consumption during the study period. These groups consisted of sustained nondrinkers; those who stopped drinking (quitters); those who reduced their consumption of alcohol but did not stop drinking (reducers); those who maintained the same level of consumption (sustainers); and those who increased their level of consumption (increasers).
A standard drink in the United States contains 14 g of alcohol. For this study, mild drinking was defined as less than 15 g/day, or one drink; moderate consumption as 15-29.9 g/day, or one to two drinks; and heavy drinking as 30 g/day or more, or three or more drinks.
At baseline, 54.8% of participants were nondrinkers, 26.7% were mild drinkers, 11.0% were moderate drinkers, and 7.5% were heavy drinkers.
From 2009 to 2011, 24.2% of mild drinkers, 8.4% of moderate drinkers, and 7.6% of heavy drinkers became quitters. In the same period, 13.9% of nondrinkers, 16.1% of mild drinkers, and 17.4% of moderate drinkers increased their drinking level.
After a mean follow-up of 6.3 years, 2.5% of participants were diagnosed with dementia, 2.0% with Alzheimer’s disease, and 0.3% with vascular dementia.
Unexpected finding
Compared with consistently not drinking, mild and moderate alcohol consumption was associated with a 21% (adjust hazard ratio, 0.79; 95% confidence interval, 0.77-0.81) and 17% (aHR, 0.83; 95% CI, 0.79-0.88) decreased risk for dementia, respectively.
Heavy drinking was linked to an 8% increased risk (aHR, 1.08; 95% CI, 1.03-1.12).
Similar associations were found between alcohol consumption and risk for Alzheimer’s disease and vascular dementia.
Reducing drinking habits from heavy to moderate led to a reduction in risk for dementia and Alzheimer’s, and increasing drinking levels led to an increase in risk for both conditions.
But when the researchers analyzed dementia risk for nondrinkers who began drinking at mild levels during the study period, they found something unexpected – the risk in this group decreased by 7% for dementia (aHR, 0.93; 95% CI, 0.90-0.96) and by 8% for Alzheimer’s (aHR, 0.92; 95% CI, 0.89-0.95), compared with sustained mild drinkers.
“Our study showed that initiation of mild alcohol consumption leads to a reduced risk of all-cause dementia and Alzheimer’s disease, which has never been reported in previous studies,” Dr. Jeon said.
However, Dr. Jeon was quick to point out that this doesn’t mean that people who don’t drink should start.
Previous studies have shown that heavy alcohol use can triple an individual’s dementia risk, while other studies have shown that no amount of alcohol consumption is good for the brain.
“None of the existing health guidelines recommend starting alcohol drinking,” Dr. Jeon said. “Our findings regarding an initiation of mild alcohol consumption cannot be directly translated into clinical recommendations,” but the findings do warrant additional study, he added.
Risks persist
Commenting on the findings, Percy Griffin, PhD, director of scientific engagement for the Alzheimer’s Association in Chicago, agrees.
“While this study is interesting, and this topic deserves further study, no one should drink alcohol as a method of reducing risk of Alzheimer’s disease or other dementia based on this study,” said Dr. Griffin, who was not part of the study.
The exact tipping point in alcohol consumption that can lead to problems with cognition or increased dementia risk is unknown, Dr. Griffin said. Nor do researchers understand why mild drinking may have a protective effect.
“We do know, however, that excessive alcohol consumption has negative effects on heart health and general health, which can lead to problems with brain function,” he said. “Clinicians should have discussions with their patients around their alcohol consumption patterns and the risks associated with drinking in excess, including potential damage to their cognition.”
Funding for the study was not disclosed. Dr. Jeon and Dr. Griffin report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
new research suggests.
Investigators assessed dementia risk using changes in alcohol consumption over a 2-year period in nearly 4 million people in South Korea. After about 7 years, dementia was 21% less likely in mild drinkers and 17% less likely in moderate drinkers. Heavy drinking was linked to an 8% increased risk.
Other studies of the relationship between alcohol and dementia have yielded mixed results, and this study does little to clear those murky waters. Nor do the results mean that drinking is recommended, the investigators note.
But the study does offer new information on how risk changes over time as people change their drinking habits, lead investigator Keun Hye Jeon, MD, assistant professor of family medicine at Cha Gumi Medical Center at Cha University, Gumi, South Korea, told this news organization.
“Although numerous studies have shown a relationship between alcohol consumption and dementia, there is a paucity of understanding as to how the incidence of dementia changes with changes in drinking habits,” Dr. Jeon said.
“By measuring alcohol consumption at two time points, we were able to study the relationship between reducing, ceasing, maintaining, and increasing alcohol consumption and incident dementia,” he added.
The findings were published online in JAMA Network Open.
Tracking drinking habits
Researchers analyzed data from nearly 4 million individuals aged 40 years and older in the Korean National Health Insurance Service who completed questionnaires and underwent physical exams in 2009 and 2011.
Study participants completed questionnaires on their drinking habits and were assigned to one of five groups according to change in alcohol consumption during the study period. These groups consisted of sustained nondrinkers; those who stopped drinking (quitters); those who reduced their consumption of alcohol but did not stop drinking (reducers); those who maintained the same level of consumption (sustainers); and those who increased their level of consumption (increasers).
A standard drink in the United States contains 14 g of alcohol. For this study, mild drinking was defined as less than 15 g/day, or one drink; moderate consumption as 15-29.9 g/day, or one to two drinks; and heavy drinking as 30 g/day or more, or three or more drinks.
At baseline, 54.8% of participants were nondrinkers, 26.7% were mild drinkers, 11.0% were moderate drinkers, and 7.5% were heavy drinkers.
From 2009 to 2011, 24.2% of mild drinkers, 8.4% of moderate drinkers, and 7.6% of heavy drinkers became quitters. In the same period, 13.9% of nondrinkers, 16.1% of mild drinkers, and 17.4% of moderate drinkers increased their drinking level.
After a mean follow-up of 6.3 years, 2.5% of participants were diagnosed with dementia, 2.0% with Alzheimer’s disease, and 0.3% with vascular dementia.
Unexpected finding
Compared with consistently not drinking, mild and moderate alcohol consumption was associated with a 21% (adjust hazard ratio, 0.79; 95% confidence interval, 0.77-0.81) and 17% (aHR, 0.83; 95% CI, 0.79-0.88) decreased risk for dementia, respectively.
Heavy drinking was linked to an 8% increased risk (aHR, 1.08; 95% CI, 1.03-1.12).
Similar associations were found between alcohol consumption and risk for Alzheimer’s disease and vascular dementia.
Reducing drinking habits from heavy to moderate led to a reduction in risk for dementia and Alzheimer’s, and increasing drinking levels led to an increase in risk for both conditions.
But when the researchers analyzed dementia risk for nondrinkers who began drinking at mild levels during the study period, they found something unexpected – the risk in this group decreased by 7% for dementia (aHR, 0.93; 95% CI, 0.90-0.96) and by 8% for Alzheimer’s (aHR, 0.92; 95% CI, 0.89-0.95), compared with sustained mild drinkers.
“Our study showed that initiation of mild alcohol consumption leads to a reduced risk of all-cause dementia and Alzheimer’s disease, which has never been reported in previous studies,” Dr. Jeon said.
However, Dr. Jeon was quick to point out that this doesn’t mean that people who don’t drink should start.
Previous studies have shown that heavy alcohol use can triple an individual’s dementia risk, while other studies have shown that no amount of alcohol consumption is good for the brain.
“None of the existing health guidelines recommend starting alcohol drinking,” Dr. Jeon said. “Our findings regarding an initiation of mild alcohol consumption cannot be directly translated into clinical recommendations,” but the findings do warrant additional study, he added.
Risks persist
Commenting on the findings, Percy Griffin, PhD, director of scientific engagement for the Alzheimer’s Association in Chicago, agrees.
“While this study is interesting, and this topic deserves further study, no one should drink alcohol as a method of reducing risk of Alzheimer’s disease or other dementia based on this study,” said Dr. Griffin, who was not part of the study.
The exact tipping point in alcohol consumption that can lead to problems with cognition or increased dementia risk is unknown, Dr. Griffin said. Nor do researchers understand why mild drinking may have a protective effect.
“We do know, however, that excessive alcohol consumption has negative effects on heart health and general health, which can lead to problems with brain function,” he said. “Clinicians should have discussions with their patients around their alcohol consumption patterns and the risks associated with drinking in excess, including potential damage to their cognition.”
Funding for the study was not disclosed. Dr. Jeon and Dr. Griffin report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM JAMA NETWORK OPEN
We don’t lose our keys (or other things) as much as we think
Can’t find your keys? Misplaced your glasses? No clue where you parked your car?
We all lose things from time to time. And we’ve all heard the standard-issue advice: Picture when you had the object last. Despite this common experience,
“It is well known that we have massive recognition memory for objects,” says study coauthor Jeremy Wolfe, PhD, a professor of ophthalmology and radiology at Harvard Medical School, Boston. In other words, we’re good at recognizing objects we’ve seen before. “For example, after viewing 100 objects for 2-3 seconds each, observers can discriminate those 100 old images from 100 new ones with well over 80% accuracy.”
But remembering what your keys look like won’t necessarily help you find them. “We often want to know when and where we saw [an object],” Dr. Wolfe says. “So our goal was to measure these spatial and temporal memories.”
In a series of experiments, reported in Current Biology, Wolfe and colleagues asked people in the study to remember objects placed on a grid. They viewed 300 objects (pictures of things like a vase, a wedding dress, camo pants, a wet suit) and were asked to recall each one and where it had been located on the grid.
About a third of the people remembered 100 or more locations, by choosing either the correct square on the grid or one directly next to it. Another third remembered between 50 and 100, and the rest remembered less than 50.
Results would likely be even better in the real world “because no one gives up and decides ‘I can’t remember where anything is. I will just guess in this silly experiment,’ ” Dr. Wolfe says.
Later, they were shown items one at a time and asked to click on a time line to indicate when they had seen them. Between 60% and 80% of the time, they identified when they had seen an object within 10% of the correct time. That’s a lot better than the 40% they would have achieved by guessing.
The findings build on previous research and expand our understanding of memory, Dr. Wolfe says. “We knew that people could remember where some things were located. However, no one had tried to quantify that memory,” he says.
But wait: If we’re so good at remembering the where and when, why do we struggle to locate lost objects so much? Chances are, we don’t. We just feel that way because we tend to focus on the fails and overlook the many wins.
“This [study] is showing us something about how we come to know where hundreds of things are in our world,” Dr. Wolfe says. “We tend to notice when this fails – ‘where are my keys?’ – but on a normal day, you are successfully tapping a massive memory on a regular basis.”
Next, the researchers plan to investigate whether spatial and temporal memories are correlated – if you’re good at one, are you good at the other? So far, “that correlation looks rather weak,” Dr. Wolfe says.
A version of this article first appeared on WebMD.com.
Can’t find your keys? Misplaced your glasses? No clue where you parked your car?
We all lose things from time to time. And we’ve all heard the standard-issue advice: Picture when you had the object last. Despite this common experience,
“It is well known that we have massive recognition memory for objects,” says study coauthor Jeremy Wolfe, PhD, a professor of ophthalmology and radiology at Harvard Medical School, Boston. In other words, we’re good at recognizing objects we’ve seen before. “For example, after viewing 100 objects for 2-3 seconds each, observers can discriminate those 100 old images from 100 new ones with well over 80% accuracy.”
But remembering what your keys look like won’t necessarily help you find them. “We often want to know when and where we saw [an object],” Dr. Wolfe says. “So our goal was to measure these spatial and temporal memories.”
In a series of experiments, reported in Current Biology, Wolfe and colleagues asked people in the study to remember objects placed on a grid. They viewed 300 objects (pictures of things like a vase, a wedding dress, camo pants, a wet suit) and were asked to recall each one and where it had been located on the grid.
About a third of the people remembered 100 or more locations, by choosing either the correct square on the grid or one directly next to it. Another third remembered between 50 and 100, and the rest remembered less than 50.
Results would likely be even better in the real world “because no one gives up and decides ‘I can’t remember where anything is. I will just guess in this silly experiment,’ ” Dr. Wolfe says.
Later, they were shown items one at a time and asked to click on a time line to indicate when they had seen them. Between 60% and 80% of the time, they identified when they had seen an object within 10% of the correct time. That’s a lot better than the 40% they would have achieved by guessing.
The findings build on previous research and expand our understanding of memory, Dr. Wolfe says. “We knew that people could remember where some things were located. However, no one had tried to quantify that memory,” he says.
But wait: If we’re so good at remembering the where and when, why do we struggle to locate lost objects so much? Chances are, we don’t. We just feel that way because we tend to focus on the fails and overlook the many wins.
“This [study] is showing us something about how we come to know where hundreds of things are in our world,” Dr. Wolfe says. “We tend to notice when this fails – ‘where are my keys?’ – but on a normal day, you are successfully tapping a massive memory on a regular basis.”
Next, the researchers plan to investigate whether spatial and temporal memories are correlated – if you’re good at one, are you good at the other? So far, “that correlation looks rather weak,” Dr. Wolfe says.
A version of this article first appeared on WebMD.com.
Can’t find your keys? Misplaced your glasses? No clue where you parked your car?
We all lose things from time to time. And we’ve all heard the standard-issue advice: Picture when you had the object last. Despite this common experience,
“It is well known that we have massive recognition memory for objects,” says study coauthor Jeremy Wolfe, PhD, a professor of ophthalmology and radiology at Harvard Medical School, Boston. In other words, we’re good at recognizing objects we’ve seen before. “For example, after viewing 100 objects for 2-3 seconds each, observers can discriminate those 100 old images from 100 new ones with well over 80% accuracy.”
But remembering what your keys look like won’t necessarily help you find them. “We often want to know when and where we saw [an object],” Dr. Wolfe says. “So our goal was to measure these spatial and temporal memories.”
In a series of experiments, reported in Current Biology, Wolfe and colleagues asked people in the study to remember objects placed on a grid. They viewed 300 objects (pictures of things like a vase, a wedding dress, camo pants, a wet suit) and were asked to recall each one and where it had been located on the grid.
About a third of the people remembered 100 or more locations, by choosing either the correct square on the grid or one directly next to it. Another third remembered between 50 and 100, and the rest remembered less than 50.
Results would likely be even better in the real world “because no one gives up and decides ‘I can’t remember where anything is. I will just guess in this silly experiment,’ ” Dr. Wolfe says.
Later, they were shown items one at a time and asked to click on a time line to indicate when they had seen them. Between 60% and 80% of the time, they identified when they had seen an object within 10% of the correct time. That’s a lot better than the 40% they would have achieved by guessing.
The findings build on previous research and expand our understanding of memory, Dr. Wolfe says. “We knew that people could remember where some things were located. However, no one had tried to quantify that memory,” he says.
But wait: If we’re so good at remembering the where and when, why do we struggle to locate lost objects so much? Chances are, we don’t. We just feel that way because we tend to focus on the fails and overlook the many wins.
“This [study] is showing us something about how we come to know where hundreds of things are in our world,” Dr. Wolfe says. “We tend to notice when this fails – ‘where are my keys?’ – but on a normal day, you are successfully tapping a massive memory on a regular basis.”
Next, the researchers plan to investigate whether spatial and temporal memories are correlated – if you’re good at one, are you good at the other? So far, “that correlation looks rather weak,” Dr. Wolfe says.
A version of this article first appeared on WebMD.com.
FROM CURRENT BIOLOGY
Long-term depression may hasten brain aging in midlife
Previous research suggests a possible link between depression and increased risk of dementia in older adults, but the association between depression and brain health in early adulthood and midlife has not been well studied, wrote Christina S. Dintica, PhD, of the University of California, San Francisco, and colleagues.
In a study published in the Journal of Affective Disorders, the researchers identified 649 individuals aged 23-36 at baseline who were part of the Coronary Artery Risk Development in Young Adults (CARDIA) study. All participants underwent brain MRI and cognitive testing. Depressive symptoms were assessed six times over a 25-year period using the Center for Epidemiological Studies Depression scale (CES–D), and the scores were analyzed as time-weighted averages (TWA). Elevated depressive symptoms were defined as CES-D scores of 16 or higher. Brain age was assessed via high-dimensional neuroimaging. Approximately half of the participants were female, and half were Black.
Overall, each 5-point increment in TWA depression symptoms over 25 years was associated with a 1-year increase in brain age, and individuals with elevated TWA depression averaged a 3-year increase in brain age compared with those with lower levels of depression after controlling for factors including chronological age, sex, education, race, MRI scanning site, and intracranial volume, they said. The association was attenuated in a model controlling for antidepressant use, and further attenuated after adjusting for smoking, alcohol consumption, income, body mass index, diabetes, and physical exercise.
The researchers also investigated the impact of the age period of elevated depressive symptoms on brain age. Compared with low depressive symptoms, elevated TWA CES-D at ages 30-39 years, 40-49 years, and 50-59 years was associated with increased brain ages of 2.43, 3.19, and 1.82.
In addition, elevated depressive symptoms were associated with a threefold increase in the odds of poor cognitive function at midlife (odds ratio, 3.30), although these odds were reduced after adjusting for use of antidepressants (OR, 1.47).
The mechanisms of action for the link between depression and accelerated brain aging remains uncertain, the researchers wrote in their discussion. “Studies over the last 20 years have demonstrated that increased inflammation and hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis are two of the most consistent biological findings in major depression, which have been linked to premature aging,” they noted. “Alternative explanations for the link between depression and adverse brain health could be underlying factors that explain both outcomes rather independently, such as low socioeconomic status, childhood maltreatment, or shared genetic effects,” they added.
Adjustment for antidepressant use had little effect overall on the association between depressive symptom severity and brain age, they said.
The current study findings were limited by the single assessment of brain age, which prevented evaluation of the temporality of the association between brain aging and depression, the researchers noted.
However, the results were strengthened by the large and diverse cohort, long-term follow-up, and use of high-dimensional neuroimaging, they said. Longitudinal studies are needed to explore mechanisms of action and the potential benefits of antidepressants, they added.
In the meantime, monitoring and treating depressive symptoms in young adults may help promote brain health in midlife and older age, they concluded.
The CARDIA study was supported by the National Heart, Lung, and Blood Institute, the National Institute on Aging, and the Alzheimer’s Association. The researchers had no financial conflicts to disclose.
Previous research suggests a possible link between depression and increased risk of dementia in older adults, but the association between depression and brain health in early adulthood and midlife has not been well studied, wrote Christina S. Dintica, PhD, of the University of California, San Francisco, and colleagues.
In a study published in the Journal of Affective Disorders, the researchers identified 649 individuals aged 23-36 at baseline who were part of the Coronary Artery Risk Development in Young Adults (CARDIA) study. All participants underwent brain MRI and cognitive testing. Depressive symptoms were assessed six times over a 25-year period using the Center for Epidemiological Studies Depression scale (CES–D), and the scores were analyzed as time-weighted averages (TWA). Elevated depressive symptoms were defined as CES-D scores of 16 or higher. Brain age was assessed via high-dimensional neuroimaging. Approximately half of the participants were female, and half were Black.
Overall, each 5-point increment in TWA depression symptoms over 25 years was associated with a 1-year increase in brain age, and individuals with elevated TWA depression averaged a 3-year increase in brain age compared with those with lower levels of depression after controlling for factors including chronological age, sex, education, race, MRI scanning site, and intracranial volume, they said. The association was attenuated in a model controlling for antidepressant use, and further attenuated after adjusting for smoking, alcohol consumption, income, body mass index, diabetes, and physical exercise.
The researchers also investigated the impact of the age period of elevated depressive symptoms on brain age. Compared with low depressive symptoms, elevated TWA CES-D at ages 30-39 years, 40-49 years, and 50-59 years was associated with increased brain ages of 2.43, 3.19, and 1.82.
In addition, elevated depressive symptoms were associated with a threefold increase in the odds of poor cognitive function at midlife (odds ratio, 3.30), although these odds were reduced after adjusting for use of antidepressants (OR, 1.47).
The mechanisms of action for the link between depression and accelerated brain aging remains uncertain, the researchers wrote in their discussion. “Studies over the last 20 years have demonstrated that increased inflammation and hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis are two of the most consistent biological findings in major depression, which have been linked to premature aging,” they noted. “Alternative explanations for the link between depression and adverse brain health could be underlying factors that explain both outcomes rather independently, such as low socioeconomic status, childhood maltreatment, or shared genetic effects,” they added.
Adjustment for antidepressant use had little effect overall on the association between depressive symptom severity and brain age, they said.
The current study findings were limited by the single assessment of brain age, which prevented evaluation of the temporality of the association between brain aging and depression, the researchers noted.
However, the results were strengthened by the large and diverse cohort, long-term follow-up, and use of high-dimensional neuroimaging, they said. Longitudinal studies are needed to explore mechanisms of action and the potential benefits of antidepressants, they added.
In the meantime, monitoring and treating depressive symptoms in young adults may help promote brain health in midlife and older age, they concluded.
The CARDIA study was supported by the National Heart, Lung, and Blood Institute, the National Institute on Aging, and the Alzheimer’s Association. The researchers had no financial conflicts to disclose.
Previous research suggests a possible link between depression and increased risk of dementia in older adults, but the association between depression and brain health in early adulthood and midlife has not been well studied, wrote Christina S. Dintica, PhD, of the University of California, San Francisco, and colleagues.
In a study published in the Journal of Affective Disorders, the researchers identified 649 individuals aged 23-36 at baseline who were part of the Coronary Artery Risk Development in Young Adults (CARDIA) study. All participants underwent brain MRI and cognitive testing. Depressive symptoms were assessed six times over a 25-year period using the Center for Epidemiological Studies Depression scale (CES–D), and the scores were analyzed as time-weighted averages (TWA). Elevated depressive symptoms were defined as CES-D scores of 16 or higher. Brain age was assessed via high-dimensional neuroimaging. Approximately half of the participants were female, and half were Black.
Overall, each 5-point increment in TWA depression symptoms over 25 years was associated with a 1-year increase in brain age, and individuals with elevated TWA depression averaged a 3-year increase in brain age compared with those with lower levels of depression after controlling for factors including chronological age, sex, education, race, MRI scanning site, and intracranial volume, they said. The association was attenuated in a model controlling for antidepressant use, and further attenuated after adjusting for smoking, alcohol consumption, income, body mass index, diabetes, and physical exercise.
The researchers also investigated the impact of the age period of elevated depressive symptoms on brain age. Compared with low depressive symptoms, elevated TWA CES-D at ages 30-39 years, 40-49 years, and 50-59 years was associated with increased brain ages of 2.43, 3.19, and 1.82.
In addition, elevated depressive symptoms were associated with a threefold increase in the odds of poor cognitive function at midlife (odds ratio, 3.30), although these odds were reduced after adjusting for use of antidepressants (OR, 1.47).
The mechanisms of action for the link between depression and accelerated brain aging remains uncertain, the researchers wrote in their discussion. “Studies over the last 20 years have demonstrated that increased inflammation and hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis are two of the most consistent biological findings in major depression, which have been linked to premature aging,” they noted. “Alternative explanations for the link between depression and adverse brain health could be underlying factors that explain both outcomes rather independently, such as low socioeconomic status, childhood maltreatment, or shared genetic effects,” they added.
Adjustment for antidepressant use had little effect overall on the association between depressive symptom severity and brain age, they said.
The current study findings were limited by the single assessment of brain age, which prevented evaluation of the temporality of the association between brain aging and depression, the researchers noted.
However, the results were strengthened by the large and diverse cohort, long-term follow-up, and use of high-dimensional neuroimaging, they said. Longitudinal studies are needed to explore mechanisms of action and the potential benefits of antidepressants, they added.
In the meantime, monitoring and treating depressive symptoms in young adults may help promote brain health in midlife and older age, they concluded.
The CARDIA study was supported by the National Heart, Lung, and Blood Institute, the National Institute on Aging, and the Alzheimer’s Association. The researchers had no financial conflicts to disclose.
FROM THE JOURNAL OF AFFECTIVE DISORDERS
Cognitive testing for older drivers: Is there a benefit?
, according to results from a large population-based study using data from Japan.
But the same study, published in the Journal of the American Geriatrics Society, also reported a concurrent increase in pedestrian and cycling injuries, possibly because more older former drivers were getting around by alternative means. That finding echoed a 2012 study from Denmark, which also looked at the effects of an age-based cognitive screening policy for older drivers, and saw more fatal road injuries among older people who were not driving.
While some governments, including those of Denmark, Taiwan, and Japan, have implemented age-based cognitive screening for older drivers, there has been little evidence to date that such policies improve road safety. Guidelines issued in 2010 by the American Academy of Neurology discourage age-based screening, advising instead that people diagnosed with cognitive disorders be carefully evaluated for driving fitness and recommending one widely used scale, the Clinical Dementia Rating, as useful in identifying potentially unsafe drivers.
Japan’s national screening policy: Did it work?
The new study, led by Haruhiko Inada, MD, PhD, an epidemiologist at Johns Hopkins University in Baltimore, used national crash data from Japan, where since 2017 all drivers 75 and older not only must take cognitive tests measuring temporal orientation and memory at license renewal, but are also referred for medical evaluation if they fail them. People receiving a subsequent dementia diagnosis can have their licenses suspended or revoked.
Dr. Inada and his colleagues looked at national data from nearly 603,000 police-reported vehicle collisions and nearly 197,000 pedestrian or cyclist road injuries between March 2012 and December 2019, all involving people aged 70 and older. To assess the screening policy’s impact, the researchers calculated estimated monthly collision or injury incidence rates per 100,000 person-years. This way, they could “control for secular trends that were unaffected by the policy, such as the decreasing incidence of motor vehicle collisions year by year,” the researchers explained.
After the screening was implemented, cumulative estimated collisions among drivers 75 or older decreased by 3,670 (95% confidence interval, 5,125-2,104), while reported pedestrian or cyclist injuries increased by an estimated 959 (95% CI, 24-1,834). Dr. Inada and colleagues found that crashes declined among men but not women, noting also that more older men than women are licensed to drive in Japan. Pedestrian and cyclist injuries were highest among men aged 80-84, and women aged 80 and older.
“Cognitively screening older drivers at license renewal and promoting voluntary surrender of licenses may prevent motor vehicle collisions,” Dr. Inada and his colleagues concluded. “However, they are associated with an increase in road injuries for older pedestrians and cyclists. Future studies should examine the effectiveness of mitigation measures, such as alternative, safe transportation, and accommodations for pedestrians and cyclists.”
No definitive answers
Two investigators who have studied cognitive screening related to road safety were contacted for commentary on the study findings.
Anu Siren, PhD, professor of gerontology at Tampere (Finland) University, who in 2012 reported higher injuries after implementation of older-driver cognitive screening in Denmark, commented that the new study, while benefiting from a much larger data set than earlier studies, still “fails to show that decrease in collisions is because ‘unfit’ drivers were removed from the road. But it does confirm previous findings about how strict screening policies make people shift from cars to unprotected modes of transportation,” which are riskier.
In studies measuring driving safety, the usual definition of risk is incidents per exposure, Dr. Siren noted. In Dr. Inada and colleagues’ study, “the incident measure, or numerator, is the number of collisions. The exposure measure or denominator is population. Because the study uses population and not driver licenses (or distance traveled) as an exposure measure, the observed decrease in collisions does not say much about how the collision risk develops after the implementation of screening.”
Older driver screening “is likely to cause some older persons to cease from driving and probably continue to travel as unprotected road users,” Dr. Siren continued. “Similar to what we found [in 2012], the injury rates for pedestrians and cyclists went up after the introduction of screening, which suggests that screening indirectly causes increasing number of injuries among older unprotected road users.”
Matthew Rizzo, MD, professor and chair of the department of neurological sciences at the University of Nebraska Medical Center and codirector of the Nebraska Neuroscience Alliance in Omaha, Neb., and the lead author of the 2010 AAN guidelines on cognitive impairment and driving risk, cautioned against ageism in designing policies meant to protect motorists.
“We find some erratic/weak effects of age here and there, but the big effects we consistently find are from cognitive and visual decline – which is somewhat correlated with age, but with huge variance,” Dr. Rizzo said. “It is hard to say what an optimal age threshold for risk would be, and if 75 is it.”
U.S. crash data from the last decade points to drivers 80 and older as significantly more accident-prone than those in their 70s, or even late 70s, Dr. Rizzo noted. Moreover, “willingness to get on the road, number of miles driven, type of road (urban, rural, highway, commercial, residential), type of vehicle driven, traffic, and environment (day, night, weather), et cetera, are all factors to consider in driving risk and restriction,” he said.
Dr. Rizzo added that the 2010 AAN guidelines might need to be revisited in light of newer vehicle safety systems and automation.
Dr. Inada and colleagues’ study was funded by Japanese government grants, and Dr. Inada and his coauthors reported no financial conflicts of interest. Dr. Siren and Dr. Rizzo reported no financial conflicts of interest.
, according to results from a large population-based study using data from Japan.
But the same study, published in the Journal of the American Geriatrics Society, also reported a concurrent increase in pedestrian and cycling injuries, possibly because more older former drivers were getting around by alternative means. That finding echoed a 2012 study from Denmark, which also looked at the effects of an age-based cognitive screening policy for older drivers, and saw more fatal road injuries among older people who were not driving.
While some governments, including those of Denmark, Taiwan, and Japan, have implemented age-based cognitive screening for older drivers, there has been little evidence to date that such policies improve road safety. Guidelines issued in 2010 by the American Academy of Neurology discourage age-based screening, advising instead that people diagnosed with cognitive disorders be carefully evaluated for driving fitness and recommending one widely used scale, the Clinical Dementia Rating, as useful in identifying potentially unsafe drivers.
Japan’s national screening policy: Did it work?
The new study, led by Haruhiko Inada, MD, PhD, an epidemiologist at Johns Hopkins University in Baltimore, used national crash data from Japan, where since 2017 all drivers 75 and older not only must take cognitive tests measuring temporal orientation and memory at license renewal, but are also referred for medical evaluation if they fail them. People receiving a subsequent dementia diagnosis can have their licenses suspended or revoked.
Dr. Inada and his colleagues looked at national data from nearly 603,000 police-reported vehicle collisions and nearly 197,000 pedestrian or cyclist road injuries between March 2012 and December 2019, all involving people aged 70 and older. To assess the screening policy’s impact, the researchers calculated estimated monthly collision or injury incidence rates per 100,000 person-years. This way, they could “control for secular trends that were unaffected by the policy, such as the decreasing incidence of motor vehicle collisions year by year,” the researchers explained.
After the screening was implemented, cumulative estimated collisions among drivers 75 or older decreased by 3,670 (95% confidence interval, 5,125-2,104), while reported pedestrian or cyclist injuries increased by an estimated 959 (95% CI, 24-1,834). Dr. Inada and colleagues found that crashes declined among men but not women, noting also that more older men than women are licensed to drive in Japan. Pedestrian and cyclist injuries were highest among men aged 80-84, and women aged 80 and older.
“Cognitively screening older drivers at license renewal and promoting voluntary surrender of licenses may prevent motor vehicle collisions,” Dr. Inada and his colleagues concluded. “However, they are associated with an increase in road injuries for older pedestrians and cyclists. Future studies should examine the effectiveness of mitigation measures, such as alternative, safe transportation, and accommodations for pedestrians and cyclists.”
No definitive answers
Two investigators who have studied cognitive screening related to road safety were contacted for commentary on the study findings.
Anu Siren, PhD, professor of gerontology at Tampere (Finland) University, who in 2012 reported higher injuries after implementation of older-driver cognitive screening in Denmark, commented that the new study, while benefiting from a much larger data set than earlier studies, still “fails to show that decrease in collisions is because ‘unfit’ drivers were removed from the road. But it does confirm previous findings about how strict screening policies make people shift from cars to unprotected modes of transportation,” which are riskier.
In studies measuring driving safety, the usual definition of risk is incidents per exposure, Dr. Siren noted. In Dr. Inada and colleagues’ study, “the incident measure, or numerator, is the number of collisions. The exposure measure or denominator is population. Because the study uses population and not driver licenses (or distance traveled) as an exposure measure, the observed decrease in collisions does not say much about how the collision risk develops after the implementation of screening.”
Older driver screening “is likely to cause some older persons to cease from driving and probably continue to travel as unprotected road users,” Dr. Siren continued. “Similar to what we found [in 2012], the injury rates for pedestrians and cyclists went up after the introduction of screening, which suggests that screening indirectly causes increasing number of injuries among older unprotected road users.”
Matthew Rizzo, MD, professor and chair of the department of neurological sciences at the University of Nebraska Medical Center and codirector of the Nebraska Neuroscience Alliance in Omaha, Neb., and the lead author of the 2010 AAN guidelines on cognitive impairment and driving risk, cautioned against ageism in designing policies meant to protect motorists.
“We find some erratic/weak effects of age here and there, but the big effects we consistently find are from cognitive and visual decline – which is somewhat correlated with age, but with huge variance,” Dr. Rizzo said. “It is hard to say what an optimal age threshold for risk would be, and if 75 is it.”
U.S. crash data from the last decade points to drivers 80 and older as significantly more accident-prone than those in their 70s, or even late 70s, Dr. Rizzo noted. Moreover, “willingness to get on the road, number of miles driven, type of road (urban, rural, highway, commercial, residential), type of vehicle driven, traffic, and environment (day, night, weather), et cetera, are all factors to consider in driving risk and restriction,” he said.
Dr. Rizzo added that the 2010 AAN guidelines might need to be revisited in light of newer vehicle safety systems and automation.
Dr. Inada and colleagues’ study was funded by Japanese government grants, and Dr. Inada and his coauthors reported no financial conflicts of interest. Dr. Siren and Dr. Rizzo reported no financial conflicts of interest.
, according to results from a large population-based study using data from Japan.
But the same study, published in the Journal of the American Geriatrics Society, also reported a concurrent increase in pedestrian and cycling injuries, possibly because more older former drivers were getting around by alternative means. That finding echoed a 2012 study from Denmark, which also looked at the effects of an age-based cognitive screening policy for older drivers, and saw more fatal road injuries among older people who were not driving.
While some governments, including those of Denmark, Taiwan, and Japan, have implemented age-based cognitive screening for older drivers, there has been little evidence to date that such policies improve road safety. Guidelines issued in 2010 by the American Academy of Neurology discourage age-based screening, advising instead that people diagnosed with cognitive disorders be carefully evaluated for driving fitness and recommending one widely used scale, the Clinical Dementia Rating, as useful in identifying potentially unsafe drivers.
Japan’s national screening policy: Did it work?
The new study, led by Haruhiko Inada, MD, PhD, an epidemiologist at Johns Hopkins University in Baltimore, used national crash data from Japan, where since 2017 all drivers 75 and older not only must take cognitive tests measuring temporal orientation and memory at license renewal, but are also referred for medical evaluation if they fail them. People receiving a subsequent dementia diagnosis can have their licenses suspended or revoked.
Dr. Inada and his colleagues looked at national data from nearly 603,000 police-reported vehicle collisions and nearly 197,000 pedestrian or cyclist road injuries between March 2012 and December 2019, all involving people aged 70 and older. To assess the screening policy’s impact, the researchers calculated estimated monthly collision or injury incidence rates per 100,000 person-years. This way, they could “control for secular trends that were unaffected by the policy, such as the decreasing incidence of motor vehicle collisions year by year,” the researchers explained.
After the screening was implemented, cumulative estimated collisions among drivers 75 or older decreased by 3,670 (95% confidence interval, 5,125-2,104), while reported pedestrian or cyclist injuries increased by an estimated 959 (95% CI, 24-1,834). Dr. Inada and colleagues found that crashes declined among men but not women, noting also that more older men than women are licensed to drive in Japan. Pedestrian and cyclist injuries were highest among men aged 80-84, and women aged 80 and older.
“Cognitively screening older drivers at license renewal and promoting voluntary surrender of licenses may prevent motor vehicle collisions,” Dr. Inada and his colleagues concluded. “However, they are associated with an increase in road injuries for older pedestrians and cyclists. Future studies should examine the effectiveness of mitigation measures, such as alternative, safe transportation, and accommodations for pedestrians and cyclists.”
No definitive answers
Two investigators who have studied cognitive screening related to road safety were contacted for commentary on the study findings.
Anu Siren, PhD, professor of gerontology at Tampere (Finland) University, who in 2012 reported higher injuries after implementation of older-driver cognitive screening in Denmark, commented that the new study, while benefiting from a much larger data set than earlier studies, still “fails to show that decrease in collisions is because ‘unfit’ drivers were removed from the road. But it does confirm previous findings about how strict screening policies make people shift from cars to unprotected modes of transportation,” which are riskier.
In studies measuring driving safety, the usual definition of risk is incidents per exposure, Dr. Siren noted. In Dr. Inada and colleagues’ study, “the incident measure, or numerator, is the number of collisions. The exposure measure or denominator is population. Because the study uses population and not driver licenses (or distance traveled) as an exposure measure, the observed decrease in collisions does not say much about how the collision risk develops after the implementation of screening.”
Older driver screening “is likely to cause some older persons to cease from driving and probably continue to travel as unprotected road users,” Dr. Siren continued. “Similar to what we found [in 2012], the injury rates for pedestrians and cyclists went up after the introduction of screening, which suggests that screening indirectly causes increasing number of injuries among older unprotected road users.”
Matthew Rizzo, MD, professor and chair of the department of neurological sciences at the University of Nebraska Medical Center and codirector of the Nebraska Neuroscience Alliance in Omaha, Neb., and the lead author of the 2010 AAN guidelines on cognitive impairment and driving risk, cautioned against ageism in designing policies meant to protect motorists.
“We find some erratic/weak effects of age here and there, but the big effects we consistently find are from cognitive and visual decline – which is somewhat correlated with age, but with huge variance,” Dr. Rizzo said. “It is hard to say what an optimal age threshold for risk would be, and if 75 is it.”
U.S. crash data from the last decade points to drivers 80 and older as significantly more accident-prone than those in their 70s, or even late 70s, Dr. Rizzo noted. Moreover, “willingness to get on the road, number of miles driven, type of road (urban, rural, highway, commercial, residential), type of vehicle driven, traffic, and environment (day, night, weather), et cetera, are all factors to consider in driving risk and restriction,” he said.
Dr. Rizzo added that the 2010 AAN guidelines might need to be revisited in light of newer vehicle safety systems and automation.
Dr. Inada and colleagues’ study was funded by Japanese government grants, and Dr. Inada and his coauthors reported no financial conflicts of interest. Dr. Siren and Dr. Rizzo reported no financial conflicts of interest.
FROM THE JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
Similar brain atrophy in obesity and Alzheimer’s disease
Comparisons of MRI scans for more than 1,000 participants indicate correlations between the two conditions, especially in areas of gray matter thinning, suggesting that managing excess weight might slow cognitive decline and lower the risk for AD, according to the researchers.
However, brain maps of obesity did not correlate with maps of amyloid or tau protein accumulation.
“The fact that obesity-related brain atrophy did not correlate with the distribution of amyloid and tau proteins in AD was not what we expected,” study author Filip Morys, PhD, a postdoctoral researcher at McGill University, Montreal, said in an interview. “But it might just show that the specific mechanisms underpinning obesity- and Alzheimer’s disease–related neurodegeneration are different. This remains to be confirmed.”
The study was published in the Journal of Alzheimer’s Disease.
Cortical Thinning
The current study was prompted by the team’s earlier study, which showed that obesity-related neurodegeneration patterns were visually similar to those of AD, said Dr. Morys. “It was known previously that obesity is a risk factor for AD, but we wanted to directly compare brain atrophy patterns in both, which is what we did in this new study.”
The researchers analyzed data from a pooled sample of more than 1,300 participants. From the ADNI database, the researchers selected participants with AD and age- and sex-matched cognitively healthy controls. From the UK Biobank, the researchers drew a sample of lean, overweight, and obese participants without neurologic disease.
To determine how the weight status of patients with AD affects the correspondence between AD and obesity maps, they categorized participants with AD and healthy controls from the ADNI database into lean, overweight, and obese subgroups.
Then, to investigate mechanisms that might drive the similarities between obesity-related brain atrophy and AD-related amyloid-beta accumulation, they looked for overlapping areas in PET brain maps between patients with these outcomes.
The investigations showed that obesity maps were highly correlated with AD maps, but not with amyloid-beta or tau protein maps. The researchers also found significant correlations between obesity and the lean individuals with AD.
Brain regions with the highest similarities between obesity and AD were located mainly in the left temporal and bilateral prefrontal cortices.
“Our research confirms that obesity-related gray matter atrophy resembles that of AD,” the authors concluded. “Excess weight management could lead to improved health outcomes, slow down cognitive decline in aging, and lower the risk for AD.”
Upcoming research “will focus on investigating how weight loss can affect the risk for AD, other dementias, and cognitive decline in general,” said Dr. Morys. “At this point, our study suggests that obesity prevention, weight loss, but also decreasing other metabolic risk factors related to obesity, such as type-2 diabetes or hypertension, might reduce the risk for AD and have beneficial effects on cognition.”
Lifestyle habits
Commenting on the findings, Claire Sexton, DPhil, vice president of scientific programs and outreach at the Alzheimer’s Association, cautioned that a single cross-sectional study isn’t conclusive. “Previous studies have illustrated that the relationship between obesity and dementia is complex. Growing evidence indicates that people can reduce their risk of cognitive decline by adopting key lifestyle habits, like regular exercise, a heart-healthy diet and staying socially and cognitively engaged.”
The Alzheimer’s Association is leading a 2-year clinical trial, U.S. Pointer, to study how targeting these risk factors in combination may reduce risk for cognitive decline in older adults.
The work was supported by a Foundation Scheme award from the Canadian Institutes of Health Research. Dr. Morys received a postdoctoral fellowship from Fonds de Recherche du Quebec – Santé. Data collection and sharing were funded by the Alzheimer’s Disease Neuroimaging Initiative, the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and multiple pharmaceutical companies and other private sector organizations. Dr. Morys and Dr. Sexton reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Comparisons of MRI scans for more than 1,000 participants indicate correlations between the two conditions, especially in areas of gray matter thinning, suggesting that managing excess weight might slow cognitive decline and lower the risk for AD, according to the researchers.
However, brain maps of obesity did not correlate with maps of amyloid or tau protein accumulation.
“The fact that obesity-related brain atrophy did not correlate with the distribution of amyloid and tau proteins in AD was not what we expected,” study author Filip Morys, PhD, a postdoctoral researcher at McGill University, Montreal, said in an interview. “But it might just show that the specific mechanisms underpinning obesity- and Alzheimer’s disease–related neurodegeneration are different. This remains to be confirmed.”
The study was published in the Journal of Alzheimer’s Disease.
Cortical Thinning
The current study was prompted by the team’s earlier study, which showed that obesity-related neurodegeneration patterns were visually similar to those of AD, said Dr. Morys. “It was known previously that obesity is a risk factor for AD, but we wanted to directly compare brain atrophy patterns in both, which is what we did in this new study.”
The researchers analyzed data from a pooled sample of more than 1,300 participants. From the ADNI database, the researchers selected participants with AD and age- and sex-matched cognitively healthy controls. From the UK Biobank, the researchers drew a sample of lean, overweight, and obese participants without neurologic disease.
To determine how the weight status of patients with AD affects the correspondence between AD and obesity maps, they categorized participants with AD and healthy controls from the ADNI database into lean, overweight, and obese subgroups.
Then, to investigate mechanisms that might drive the similarities between obesity-related brain atrophy and AD-related amyloid-beta accumulation, they looked for overlapping areas in PET brain maps between patients with these outcomes.
The investigations showed that obesity maps were highly correlated with AD maps, but not with amyloid-beta or tau protein maps. The researchers also found significant correlations between obesity and the lean individuals with AD.
Brain regions with the highest similarities between obesity and AD were located mainly in the left temporal and bilateral prefrontal cortices.
“Our research confirms that obesity-related gray matter atrophy resembles that of AD,” the authors concluded. “Excess weight management could lead to improved health outcomes, slow down cognitive decline in aging, and lower the risk for AD.”
Upcoming research “will focus on investigating how weight loss can affect the risk for AD, other dementias, and cognitive decline in general,” said Dr. Morys. “At this point, our study suggests that obesity prevention, weight loss, but also decreasing other metabolic risk factors related to obesity, such as type-2 diabetes or hypertension, might reduce the risk for AD and have beneficial effects on cognition.”
Lifestyle habits
Commenting on the findings, Claire Sexton, DPhil, vice president of scientific programs and outreach at the Alzheimer’s Association, cautioned that a single cross-sectional study isn’t conclusive. “Previous studies have illustrated that the relationship between obesity and dementia is complex. Growing evidence indicates that people can reduce their risk of cognitive decline by adopting key lifestyle habits, like regular exercise, a heart-healthy diet and staying socially and cognitively engaged.”
The Alzheimer’s Association is leading a 2-year clinical trial, U.S. Pointer, to study how targeting these risk factors in combination may reduce risk for cognitive decline in older adults.
The work was supported by a Foundation Scheme award from the Canadian Institutes of Health Research. Dr. Morys received a postdoctoral fellowship from Fonds de Recherche du Quebec – Santé. Data collection and sharing were funded by the Alzheimer’s Disease Neuroimaging Initiative, the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and multiple pharmaceutical companies and other private sector organizations. Dr. Morys and Dr. Sexton reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Comparisons of MRI scans for more than 1,000 participants indicate correlations between the two conditions, especially in areas of gray matter thinning, suggesting that managing excess weight might slow cognitive decline and lower the risk for AD, according to the researchers.
However, brain maps of obesity did not correlate with maps of amyloid or tau protein accumulation.
“The fact that obesity-related brain atrophy did not correlate with the distribution of amyloid and tau proteins in AD was not what we expected,” study author Filip Morys, PhD, a postdoctoral researcher at McGill University, Montreal, said in an interview. “But it might just show that the specific mechanisms underpinning obesity- and Alzheimer’s disease–related neurodegeneration are different. This remains to be confirmed.”
The study was published in the Journal of Alzheimer’s Disease.
Cortical Thinning
The current study was prompted by the team’s earlier study, which showed that obesity-related neurodegeneration patterns were visually similar to those of AD, said Dr. Morys. “It was known previously that obesity is a risk factor for AD, but we wanted to directly compare brain atrophy patterns in both, which is what we did in this new study.”
The researchers analyzed data from a pooled sample of more than 1,300 participants. From the ADNI database, the researchers selected participants with AD and age- and sex-matched cognitively healthy controls. From the UK Biobank, the researchers drew a sample of lean, overweight, and obese participants without neurologic disease.
To determine how the weight status of patients with AD affects the correspondence between AD and obesity maps, they categorized participants with AD and healthy controls from the ADNI database into lean, overweight, and obese subgroups.
Then, to investigate mechanisms that might drive the similarities between obesity-related brain atrophy and AD-related amyloid-beta accumulation, they looked for overlapping areas in PET brain maps between patients with these outcomes.
The investigations showed that obesity maps were highly correlated with AD maps, but not with amyloid-beta or tau protein maps. The researchers also found significant correlations between obesity and the lean individuals with AD.
Brain regions with the highest similarities between obesity and AD were located mainly in the left temporal and bilateral prefrontal cortices.
“Our research confirms that obesity-related gray matter atrophy resembles that of AD,” the authors concluded. “Excess weight management could lead to improved health outcomes, slow down cognitive decline in aging, and lower the risk for AD.”
Upcoming research “will focus on investigating how weight loss can affect the risk for AD, other dementias, and cognitive decline in general,” said Dr. Morys. “At this point, our study suggests that obesity prevention, weight loss, but also decreasing other metabolic risk factors related to obesity, such as type-2 diabetes or hypertension, might reduce the risk for AD and have beneficial effects on cognition.”
Lifestyle habits
Commenting on the findings, Claire Sexton, DPhil, vice president of scientific programs and outreach at the Alzheimer’s Association, cautioned that a single cross-sectional study isn’t conclusive. “Previous studies have illustrated that the relationship between obesity and dementia is complex. Growing evidence indicates that people can reduce their risk of cognitive decline by adopting key lifestyle habits, like regular exercise, a heart-healthy diet and staying socially and cognitively engaged.”
The Alzheimer’s Association is leading a 2-year clinical trial, U.S. Pointer, to study how targeting these risk factors in combination may reduce risk for cognitive decline in older adults.
The work was supported by a Foundation Scheme award from the Canadian Institutes of Health Research. Dr. Morys received a postdoctoral fellowship from Fonds de Recherche du Quebec – Santé. Data collection and sharing were funded by the Alzheimer’s Disease Neuroimaging Initiative, the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and multiple pharmaceutical companies and other private sector organizations. Dr. Morys and Dr. Sexton reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM THE JOURNAL OF ALZHEIMER’S DISEASE
Can a ‘smart’ skin patch detect early neurodegenerative diseases?
A new “smart patch” composed of microneedles that can detect proinflammatory markers via simulated skin interstitial fluid (ISF) may help diagnose neurodegenerative disorders such as Alzheimer’s disease and Parkinson’s disease very early on.
Originally developed to deliver medications and vaccines via the skin in a minimally invasive manner, the microneedle arrays were fitted with molecular sensors that, when placed on the skin, detect neuroinflammatory biomarkers such as interleukin-6 in as little as 6 minutes.
The literature suggests that these biomarkers of neurodegenerative disease are present years before patients become symptomatic, said study investigator Sanjiv Sharma, PhD.
“Neurodegenerative disorders such as Parkinson’s disease and Alzheimer’s disease are [characterized by] progressive loss in nerve cell and brain cells, which leads to memory problems and a loss of mental ability. That is why early diagnosis is key to preventing the loss of brain tissue in dementia, which can go undetected for years,” added Dr. Sharma, who is a lecturer in medical engineering at Swansea (Wales) University.
Dr. Sharma developed the patch with scientists at the Polytechnic of Porto (Portugal) School of Engineering in Portugal. In 2022, they designed, and are currently testing, a microneedle patch that will deliver the COVID vaccine.
The investigators describe their research on the patch’s ability to detect IL-6 in an article published in ACS Omega.
At-home diagnosis?
“The skin is the largest organ in the body – it contains more skin interstitial fluid than the total blood volume,” Dr. Sharma noted. “This fluid is an ultrafiltrate of blood and holds biomarkers that complement other biofluids, such as sweat, saliva, and urine. It can be sampled in a minimally invasive manner and used either for point-of-care testing or real-time using microneedle devices.”
Dr. Sharma and associates tested the microneedle patch in artificial ISF that contained the inflammatory cytokine IL-6. They found that the patch accurately detected IL-6 concentrations as low as 1 pg/mL in the fabricated ISF solution.
“In general, the transdermal sensor presented here showed simplicity in designing, short measuring time, high accuracy, and low detection limit. This approach seems a successful tool for the screening of inflammatory biomarkers in point of care testing wherein the skin acts as a window to the body,” the investigators reported.
Dr. Sharma noted that early detection of neurodegenerative diseases is crucial, as once symptoms appear, the disease may have already progressed significantly, and meaningful intervention is challenging.
The device has yet to be tested in humans, which is the next step, said Dr. Sharma.
“We will have to test the hypothesis through extensive preclinical and clinical studies to determine if bloodless, transdermal (skin) diagnostics can offer a cost-effective device that could allow testing in simpler settings such as a clinician’s practice or even home settings,” he noted.
Early days
Commenting on the research, David K. Simon, MD, PhD, professor of neurology at Harvard Medical School, Boston, said it is “a promising step regarding validation of a potentially beneficial method for rapidly and accurately measuring IL-6.”
However, he added, “many additional steps are needed to validate the method in actual human skin and to determine whether or not measuring these biomarkers in skin will be useful in studies of neurodegenerative diseases.”
He noted that one study limitation is that inflammatory cytokines such as IL-6 are highly nonspecific, and levels are elevated in various diseases associated with inflammation.
“It is highly unlikely that measuring IL-6 will be useful as a diagnostic tool. However, it does have potential as a biomarker for measuring the impact of treatments aimed at reducing inflammation. As the authors point out, it’s more likely that clinicians will require a panel of biomarkers rather than only measuring IL-6,” he said.
The study was funded by Fundação para a Ciência e Tecnologia. The investigators disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
A new “smart patch” composed of microneedles that can detect proinflammatory markers via simulated skin interstitial fluid (ISF) may help diagnose neurodegenerative disorders such as Alzheimer’s disease and Parkinson’s disease very early on.
Originally developed to deliver medications and vaccines via the skin in a minimally invasive manner, the microneedle arrays were fitted with molecular sensors that, when placed on the skin, detect neuroinflammatory biomarkers such as interleukin-6 in as little as 6 minutes.
The literature suggests that these biomarkers of neurodegenerative disease are present years before patients become symptomatic, said study investigator Sanjiv Sharma, PhD.
“Neurodegenerative disorders such as Parkinson’s disease and Alzheimer’s disease are [characterized by] progressive loss in nerve cell and brain cells, which leads to memory problems and a loss of mental ability. That is why early diagnosis is key to preventing the loss of brain tissue in dementia, which can go undetected for years,” added Dr. Sharma, who is a lecturer in medical engineering at Swansea (Wales) University.
Dr. Sharma developed the patch with scientists at the Polytechnic of Porto (Portugal) School of Engineering in Portugal. In 2022, they designed, and are currently testing, a microneedle patch that will deliver the COVID vaccine.
The investigators describe their research on the patch’s ability to detect IL-6 in an article published in ACS Omega.
At-home diagnosis?
“The skin is the largest organ in the body – it contains more skin interstitial fluid than the total blood volume,” Dr. Sharma noted. “This fluid is an ultrafiltrate of blood and holds biomarkers that complement other biofluids, such as sweat, saliva, and urine. It can be sampled in a minimally invasive manner and used either for point-of-care testing or real-time using microneedle devices.”
Dr. Sharma and associates tested the microneedle patch in artificial ISF that contained the inflammatory cytokine IL-6. They found that the patch accurately detected IL-6 concentrations as low as 1 pg/mL in the fabricated ISF solution.
“In general, the transdermal sensor presented here showed simplicity in designing, short measuring time, high accuracy, and low detection limit. This approach seems a successful tool for the screening of inflammatory biomarkers in point of care testing wherein the skin acts as a window to the body,” the investigators reported.
Dr. Sharma noted that early detection of neurodegenerative diseases is crucial, as once symptoms appear, the disease may have already progressed significantly, and meaningful intervention is challenging.
The device has yet to be tested in humans, which is the next step, said Dr. Sharma.
“We will have to test the hypothesis through extensive preclinical and clinical studies to determine if bloodless, transdermal (skin) diagnostics can offer a cost-effective device that could allow testing in simpler settings such as a clinician’s practice or even home settings,” he noted.
Early days
Commenting on the research, David K. Simon, MD, PhD, professor of neurology at Harvard Medical School, Boston, said it is “a promising step regarding validation of a potentially beneficial method for rapidly and accurately measuring IL-6.”
However, he added, “many additional steps are needed to validate the method in actual human skin and to determine whether or not measuring these biomarkers in skin will be useful in studies of neurodegenerative diseases.”
He noted that one study limitation is that inflammatory cytokines such as IL-6 are highly nonspecific, and levels are elevated in various diseases associated with inflammation.
“It is highly unlikely that measuring IL-6 will be useful as a diagnostic tool. However, it does have potential as a biomarker for measuring the impact of treatments aimed at reducing inflammation. As the authors point out, it’s more likely that clinicians will require a panel of biomarkers rather than only measuring IL-6,” he said.
The study was funded by Fundação para a Ciência e Tecnologia. The investigators disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
A new “smart patch” composed of microneedles that can detect proinflammatory markers via simulated skin interstitial fluid (ISF) may help diagnose neurodegenerative disorders such as Alzheimer’s disease and Parkinson’s disease very early on.
Originally developed to deliver medications and vaccines via the skin in a minimally invasive manner, the microneedle arrays were fitted with molecular sensors that, when placed on the skin, detect neuroinflammatory biomarkers such as interleukin-6 in as little as 6 minutes.
The literature suggests that these biomarkers of neurodegenerative disease are present years before patients become symptomatic, said study investigator Sanjiv Sharma, PhD.
“Neurodegenerative disorders such as Parkinson’s disease and Alzheimer’s disease are [characterized by] progressive loss in nerve cell and brain cells, which leads to memory problems and a loss of mental ability. That is why early diagnosis is key to preventing the loss of brain tissue in dementia, which can go undetected for years,” added Dr. Sharma, who is a lecturer in medical engineering at Swansea (Wales) University.
Dr. Sharma developed the patch with scientists at the Polytechnic of Porto (Portugal) School of Engineering in Portugal. In 2022, they designed, and are currently testing, a microneedle patch that will deliver the COVID vaccine.
The investigators describe their research on the patch’s ability to detect IL-6 in an article published in ACS Omega.
At-home diagnosis?
“The skin is the largest organ in the body – it contains more skin interstitial fluid than the total blood volume,” Dr. Sharma noted. “This fluid is an ultrafiltrate of blood and holds biomarkers that complement other biofluids, such as sweat, saliva, and urine. It can be sampled in a minimally invasive manner and used either for point-of-care testing or real-time using microneedle devices.”
Dr. Sharma and associates tested the microneedle patch in artificial ISF that contained the inflammatory cytokine IL-6. They found that the patch accurately detected IL-6 concentrations as low as 1 pg/mL in the fabricated ISF solution.
“In general, the transdermal sensor presented here showed simplicity in designing, short measuring time, high accuracy, and low detection limit. This approach seems a successful tool for the screening of inflammatory biomarkers in point of care testing wherein the skin acts as a window to the body,” the investigators reported.
Dr. Sharma noted that early detection of neurodegenerative diseases is crucial, as once symptoms appear, the disease may have already progressed significantly, and meaningful intervention is challenging.
The device has yet to be tested in humans, which is the next step, said Dr. Sharma.
“We will have to test the hypothesis through extensive preclinical and clinical studies to determine if bloodless, transdermal (skin) diagnostics can offer a cost-effective device that could allow testing in simpler settings such as a clinician’s practice or even home settings,” he noted.
Early days
Commenting on the research, David K. Simon, MD, PhD, professor of neurology at Harvard Medical School, Boston, said it is “a promising step regarding validation of a potentially beneficial method for rapidly and accurately measuring IL-6.”
However, he added, “many additional steps are needed to validate the method in actual human skin and to determine whether or not measuring these biomarkers in skin will be useful in studies of neurodegenerative diseases.”
He noted that one study limitation is that inflammatory cytokines such as IL-6 are highly nonspecific, and levels are elevated in various diseases associated with inflammation.
“It is highly unlikely that measuring IL-6 will be useful as a diagnostic tool. However, it does have potential as a biomarker for measuring the impact of treatments aimed at reducing inflammation. As the authors point out, it’s more likely that clinicians will require a panel of biomarkers rather than only measuring IL-6,” he said.
The study was funded by Fundação para a Ciência e Tecnologia. The investigators disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM ACS OMEGA
Six healthy lifestyle habits linked to slowed memory decline
Investigators found that a healthy diet, cognitive activity, regular physical exercise, not smoking, and abstaining from alcohol were significantly linked to slowed cognitive decline irrespective of APOE4 status.
After adjusting for health and socioeconomic factors, investigators found that each individual healthy behavior was associated with a slower-than-average decline in memory over a decade. A healthy diet emerged as the strongest deterrent, followed by cognitive activity and physical exercise.
“A healthy lifestyle is associated with slower memory decline, even in the presence of the APOE4 allele,” study investigators led by Jianping Jia, MD, PhD, of the Innovation Center for Neurological Disorders and the department of neurology, Xuan Wu Hospital, Capital Medical University, Beijing, write.
“This study might offer important information to protect older adults against memory decline,” they add.
The study was published online in the BMJ.
Preventing memory decline
Memory “continuously declines as people age,” but age-related memory decline is not necessarily a prodrome of dementia and can “merely be senescent forgetfulness,” the investigators note. This can be “reversed or [can] become stable,” instead of progressing to a pathologic state.
Factors affecting memory include aging, APOE4 genotype, chronic diseases, and lifestyle patterns, with lifestyle “receiving increasing attention as a modifiable behavior.”
Nevertheless, few studies have focused on the impact of lifestyle on memory, and those that have are mostly cross-sectional and also “did not consider the interaction between a healthy lifestyle and genetic risk,” the researchers note.
To investigate, the researchers conducted a longitudinal study, known as the China Cognition and Aging Study, that considered genetic risk as well as lifestyle factors.
The study began in 2009 and concluded in 2019. Participants were evaluated and underwent neuropsychological testing in 2012, 2014, 2016, and at the study’s conclusion.
Participants (n = 29,072; mean [SD] age, 72.23 [6.61] years; 48.54% women; 20.43% APOE4 carriers) were required to have normal cognitive function at baseline. Data on those whose condition progressed to mild cognitive impairment (MCI) or dementia during the follow-up period were excluded after their diagnosis.
The Mini–Mental State Examination was used to assess global cognitive function. Memory function was assessed using the World Health Organization/University of California, Los Angeles Auditory Verbal Learning Test.
“Lifestyle” consisted of six modifiable factors: physical exercise (weekly frequency and total time), smoking (current, former, or never-smokers), alcohol consumption (never drank, drank occasionally, low to excess drinking, and heavy drinking), diet (daily intake of 12 food items: fruits, vegetables, fish, meat, dairy products, salt, oil, eggs, cereals, legumes, nuts, tea), cognitive activity (writing, reading, playing cards, mahjong, other games), and social contact (participating in meetings, attending parties, visiting friends/relatives, traveling, chatting online).
Participants’ lifestyles were scored on the basis of the number of healthy factors they engaged in.
Participants were also stratified by APOE genotype into APOE4 carriers and noncarriers.
Demographic and other items of health information, including the presence of medical illness, were used as covariates. The researchers also included the “learning effect of each participant as a covariate, due to repeated cognitive assessments.”
Important for public health
During the 10-year period, 7,164 participants died, and 3,567 stopped participating.
Participants in the favorable and average groups showed slower memory decline per increased year of age (0.007 [0.005-0.009], P < .001; and 0.002 [0 .000-0.003], P = .033 points higher, respectively), compared with those in the unfavorable group.
Healthy diet had the strongest protective effect on memory.
Memory decline occurred faster in APOE4 vesus non-APOE4 carriers (0.002 points/year [95% confidence interval, 0.001-0.003]; P = .007).
But APOE4 carriers with favorable and average lifestyles showed slower memory decline (0.027 [0.023-0.031] and 0.014 [0.010-0.019], respectively), compared with those with unfavorable lifestyles. Similar findings were obtained in non-APOE4 carriers.
Those with favorable or average lifestyle were respectively almost 90% and 30% less likely to develop dementia or MCI, compared with those with an unfavorable lifestyle.
The authors acknowledge the study’s limitations, including its observational design and the potential for measurement errors, owing to self-reporting of lifestyle factors. Additionally, some participants did not return for follow-up evaluations, leading to potential selection bias.
Nevertheless, the findings “might offer important information for public health to protect older [people] against memory decline,” they note – especially since the study “provides evidence that these effects also include individuals with the APOE4 allele.”
‘Important, encouraging’ research
In a comment, Severine Sabia, PhD, a senior researcher at the Université Paris Cité, INSERM Institut National de la Santé et de la Recherche Medicalé, France, called the findings “important and encouraging.”
However, said Dr. Sabia, who was not involved with the study, “there remain important research questions that need to be investigated in order to identify key behaviors: which combination, the cutoff of risk, and when to intervene.”
Future research on prevention “should examine a wider range of possible risk factors” and should also “identify specific exposures associated with the greatest risk, while also considering the risk threshold and age at exposure for each one.”
In an accompanying editorial, Dr. Sabia and co-author Archana Singh-Manoux, PhD, note that the risk of cognitive decline and dementia are probably determined by multiple factors.
They liken it to the “multifactorial risk paradigm introduced by the Framingham study,” which has “led to a substantial reduction in cardiovascular disease.” A similar approach could be used with dementia prevention, they suggest.
The authors received support from the Xuanwu Hospital of Capital Medical University for the submitted work. One of the authors received a grant from the French National Research Agency. The other authors have disclosed no relevant financial relationships. Dr. Sabia received grant funding from the French National Research Agency. Dr. Singh-Manoux received grants from the National Institute on Aging of the National Institutes of Health.
A version of this article first appeared on Medscape.com.
Investigators found that a healthy diet, cognitive activity, regular physical exercise, not smoking, and abstaining from alcohol were significantly linked to slowed cognitive decline irrespective of APOE4 status.
After adjusting for health and socioeconomic factors, investigators found that each individual healthy behavior was associated with a slower-than-average decline in memory over a decade. A healthy diet emerged as the strongest deterrent, followed by cognitive activity and physical exercise.
“A healthy lifestyle is associated with slower memory decline, even in the presence of the APOE4 allele,” study investigators led by Jianping Jia, MD, PhD, of the Innovation Center for Neurological Disorders and the department of neurology, Xuan Wu Hospital, Capital Medical University, Beijing, write.
“This study might offer important information to protect older adults against memory decline,” they add.
The study was published online in the BMJ.
Preventing memory decline
Memory “continuously declines as people age,” but age-related memory decline is not necessarily a prodrome of dementia and can “merely be senescent forgetfulness,” the investigators note. This can be “reversed or [can] become stable,” instead of progressing to a pathologic state.
Factors affecting memory include aging, APOE4 genotype, chronic diseases, and lifestyle patterns, with lifestyle “receiving increasing attention as a modifiable behavior.”
Nevertheless, few studies have focused on the impact of lifestyle on memory, and those that have are mostly cross-sectional and also “did not consider the interaction between a healthy lifestyle and genetic risk,” the researchers note.
To investigate, the researchers conducted a longitudinal study, known as the China Cognition and Aging Study, that considered genetic risk as well as lifestyle factors.
The study began in 2009 and concluded in 2019. Participants were evaluated and underwent neuropsychological testing in 2012, 2014, 2016, and at the study’s conclusion.
Participants (n = 29,072; mean [SD] age, 72.23 [6.61] years; 48.54% women; 20.43% APOE4 carriers) were required to have normal cognitive function at baseline. Data on those whose condition progressed to mild cognitive impairment (MCI) or dementia during the follow-up period were excluded after their diagnosis.
The Mini–Mental State Examination was used to assess global cognitive function. Memory function was assessed using the World Health Organization/University of California, Los Angeles Auditory Verbal Learning Test.
“Lifestyle” consisted of six modifiable factors: physical exercise (weekly frequency and total time), smoking (current, former, or never-smokers), alcohol consumption (never drank, drank occasionally, low to excess drinking, and heavy drinking), diet (daily intake of 12 food items: fruits, vegetables, fish, meat, dairy products, salt, oil, eggs, cereals, legumes, nuts, tea), cognitive activity (writing, reading, playing cards, mahjong, other games), and social contact (participating in meetings, attending parties, visiting friends/relatives, traveling, chatting online).
Participants’ lifestyles were scored on the basis of the number of healthy factors they engaged in.
Participants were also stratified by APOE genotype into APOE4 carriers and noncarriers.
Demographic and other items of health information, including the presence of medical illness, were used as covariates. The researchers also included the “learning effect of each participant as a covariate, due to repeated cognitive assessments.”
Important for public health
During the 10-year period, 7,164 participants died, and 3,567 stopped participating.
Participants in the favorable and average groups showed slower memory decline per increased year of age (0.007 [0.005-0.009], P < .001; and 0.002 [0 .000-0.003], P = .033 points higher, respectively), compared with those in the unfavorable group.
Healthy diet had the strongest protective effect on memory.
Memory decline occurred faster in APOE4 vesus non-APOE4 carriers (0.002 points/year [95% confidence interval, 0.001-0.003]; P = .007).
But APOE4 carriers with favorable and average lifestyles showed slower memory decline (0.027 [0.023-0.031] and 0.014 [0.010-0.019], respectively), compared with those with unfavorable lifestyles. Similar findings were obtained in non-APOE4 carriers.
Those with favorable or average lifestyle were respectively almost 90% and 30% less likely to develop dementia or MCI, compared with those with an unfavorable lifestyle.
The authors acknowledge the study’s limitations, including its observational design and the potential for measurement errors, owing to self-reporting of lifestyle factors. Additionally, some participants did not return for follow-up evaluations, leading to potential selection bias.
Nevertheless, the findings “might offer important information for public health to protect older [people] against memory decline,” they note – especially since the study “provides evidence that these effects also include individuals with the APOE4 allele.”
‘Important, encouraging’ research
In a comment, Severine Sabia, PhD, a senior researcher at the Université Paris Cité, INSERM Institut National de la Santé et de la Recherche Medicalé, France, called the findings “important and encouraging.”
However, said Dr. Sabia, who was not involved with the study, “there remain important research questions that need to be investigated in order to identify key behaviors: which combination, the cutoff of risk, and when to intervene.”
Future research on prevention “should examine a wider range of possible risk factors” and should also “identify specific exposures associated with the greatest risk, while also considering the risk threshold and age at exposure for each one.”
In an accompanying editorial, Dr. Sabia and co-author Archana Singh-Manoux, PhD, note that the risk of cognitive decline and dementia are probably determined by multiple factors.
They liken it to the “multifactorial risk paradigm introduced by the Framingham study,” which has “led to a substantial reduction in cardiovascular disease.” A similar approach could be used with dementia prevention, they suggest.
The authors received support from the Xuanwu Hospital of Capital Medical University for the submitted work. One of the authors received a grant from the French National Research Agency. The other authors have disclosed no relevant financial relationships. Dr. Sabia received grant funding from the French National Research Agency. Dr. Singh-Manoux received grants from the National Institute on Aging of the National Institutes of Health.
A version of this article first appeared on Medscape.com.
Investigators found that a healthy diet, cognitive activity, regular physical exercise, not smoking, and abstaining from alcohol were significantly linked to slowed cognitive decline irrespective of APOE4 status.
After adjusting for health and socioeconomic factors, investigators found that each individual healthy behavior was associated with a slower-than-average decline in memory over a decade. A healthy diet emerged as the strongest deterrent, followed by cognitive activity and physical exercise.
“A healthy lifestyle is associated with slower memory decline, even in the presence of the APOE4 allele,” study investigators led by Jianping Jia, MD, PhD, of the Innovation Center for Neurological Disorders and the department of neurology, Xuan Wu Hospital, Capital Medical University, Beijing, write.
“This study might offer important information to protect older adults against memory decline,” they add.
The study was published online in the BMJ.
Preventing memory decline
Memory “continuously declines as people age,” but age-related memory decline is not necessarily a prodrome of dementia and can “merely be senescent forgetfulness,” the investigators note. This can be “reversed or [can] become stable,” instead of progressing to a pathologic state.
Factors affecting memory include aging, APOE4 genotype, chronic diseases, and lifestyle patterns, with lifestyle “receiving increasing attention as a modifiable behavior.”
Nevertheless, few studies have focused on the impact of lifestyle on memory, and those that have are mostly cross-sectional and also “did not consider the interaction between a healthy lifestyle and genetic risk,” the researchers note.
To investigate, the researchers conducted a longitudinal study, known as the China Cognition and Aging Study, that considered genetic risk as well as lifestyle factors.
The study began in 2009 and concluded in 2019. Participants were evaluated and underwent neuropsychological testing in 2012, 2014, 2016, and at the study’s conclusion.
Participants (n = 29,072; mean [SD] age, 72.23 [6.61] years; 48.54% women; 20.43% APOE4 carriers) were required to have normal cognitive function at baseline. Data on those whose condition progressed to mild cognitive impairment (MCI) or dementia during the follow-up period were excluded after their diagnosis.
The Mini–Mental State Examination was used to assess global cognitive function. Memory function was assessed using the World Health Organization/University of California, Los Angeles Auditory Verbal Learning Test.
“Lifestyle” consisted of six modifiable factors: physical exercise (weekly frequency and total time), smoking (current, former, or never-smokers), alcohol consumption (never drank, drank occasionally, low to excess drinking, and heavy drinking), diet (daily intake of 12 food items: fruits, vegetables, fish, meat, dairy products, salt, oil, eggs, cereals, legumes, nuts, tea), cognitive activity (writing, reading, playing cards, mahjong, other games), and social contact (participating in meetings, attending parties, visiting friends/relatives, traveling, chatting online).
Participants’ lifestyles were scored on the basis of the number of healthy factors they engaged in.
Participants were also stratified by APOE genotype into APOE4 carriers and noncarriers.
Demographic and other items of health information, including the presence of medical illness, were used as covariates. The researchers also included the “learning effect of each participant as a covariate, due to repeated cognitive assessments.”
Important for public health
During the 10-year period, 7,164 participants died, and 3,567 stopped participating.
Participants in the favorable and average groups showed slower memory decline per increased year of age (0.007 [0.005-0.009], P < .001; and 0.002 [0 .000-0.003], P = .033 points higher, respectively), compared with those in the unfavorable group.
Healthy diet had the strongest protective effect on memory.
Memory decline occurred faster in APOE4 vesus non-APOE4 carriers (0.002 points/year [95% confidence interval, 0.001-0.003]; P = .007).
But APOE4 carriers with favorable and average lifestyles showed slower memory decline (0.027 [0.023-0.031] and 0.014 [0.010-0.019], respectively), compared with those with unfavorable lifestyles. Similar findings were obtained in non-APOE4 carriers.
Those with favorable or average lifestyle were respectively almost 90% and 30% less likely to develop dementia or MCI, compared with those with an unfavorable lifestyle.
The authors acknowledge the study’s limitations, including its observational design and the potential for measurement errors, owing to self-reporting of lifestyle factors. Additionally, some participants did not return for follow-up evaluations, leading to potential selection bias.
Nevertheless, the findings “might offer important information for public health to protect older [people] against memory decline,” they note – especially since the study “provides evidence that these effects also include individuals with the APOE4 allele.”
‘Important, encouraging’ research
In a comment, Severine Sabia, PhD, a senior researcher at the Université Paris Cité, INSERM Institut National de la Santé et de la Recherche Medicalé, France, called the findings “important and encouraging.”
However, said Dr. Sabia, who was not involved with the study, “there remain important research questions that need to be investigated in order to identify key behaviors: which combination, the cutoff of risk, and when to intervene.”
Future research on prevention “should examine a wider range of possible risk factors” and should also “identify specific exposures associated with the greatest risk, while also considering the risk threshold and age at exposure for each one.”
In an accompanying editorial, Dr. Sabia and co-author Archana Singh-Manoux, PhD, note that the risk of cognitive decline and dementia are probably determined by multiple factors.
They liken it to the “multifactorial risk paradigm introduced by the Framingham study,” which has “led to a substantial reduction in cardiovascular disease.” A similar approach could be used with dementia prevention, they suggest.
The authors received support from the Xuanwu Hospital of Capital Medical University for the submitted work. One of the authors received a grant from the French National Research Agency. The other authors have disclosed no relevant financial relationships. Dr. Sabia received grant funding from the French National Research Agency. Dr. Singh-Manoux received grants from the National Institute on Aging of the National Institutes of Health.
A version of this article first appeared on Medscape.com.
FROM THE BMJ
Nine more minutes a day of vigorous exercise tied to better cognition
such as running and cycling, plays in brain health.
“Even minor differences in daily behavior appeared meaningful for cognition in this study,” researcher John J. Mitchell, MSci and PhD candidate, Medical Research Council, London, told this news organization.
The findings were published online in the Journal of Epidemiology and Community Health.
Research gap
Previous research has linked physical activity (PA) with increased cognitive reserve, which delays the onset of cognitive decline in later life. But disentangling the most important components of PA for cognition – such as intensity and volume – has not been well researched.
Previous studies didn’t capture sleep time, which typically takes up the largest component of the day. Sleep is “acutely relevant” when examining cognition, the investigators noted.
In addition, studies in this area often focus on just one or two activity components of the day, which “neglects the growing awareness” that movements “are all tightly interlinked,” said Mr. Mitchell.
The new study included 4,481 participants in the British Cohort Study who were born in 1970 across England, Scotland, and Wales. The participants were followed throughout childhood and adulthood.
The median age of the participants was 47 years, and they were predominantly White, female (52%), married (66%), and well educated. Most were occasional or nonrisky alcohol consumers, and half had never smoked.
The researchers collected biometric measurements and health, demographic, and lifestyle information. Participants wore a thigh-mounted accelerometer at least 7 consecutive hours a day for up to 7 days to track PA, sedentary behavior (SB), and sleep time.
The device used in the study could detect subtle movements as well as speed of accelerations, said Mr. Mitchell. “From this, we can distinguish MVPA from slow walking, standing, and sitting. It’s the current best practice for detecting the more subtle movements we make, such as brisk walking and stair climbing, beyond just ‘exercise,’ “ he added.
Light intensity PA (LIPA) describes movement such as walking and moving around the house or office, while MVPA includes activities such as brisk walking and running that accelerate the heart rate. SB, defined as time spent sitting or lying, is distinguished from standing by the thigh inclination.
On an average day, the cohort spent 51 minutes in MVPA; 5 hours, 42 minutes in LIPA; 9 hours, 16 minutes in SB; and 8 hours, 11 minutes sleeping.
Researchers calculated an overall global score for verbal memory and executive function.
The study used “compositional data analysis,” a statistical method that can examine the associations of cognition and PA in the context of all components of daily movement.
The analysis revealed a positive association between MVPA and cognition relative to all other behaviors, after adjustment for sociodemographic factors that included sex, age, education, and marital status. But the relationship lessened after further adjustment for health status – for example, cardiovascular disease or disability – and lifestyle factors, such as alcohol consumption and smoking status.
SB relative to all other movements remained positively associated with cognition after full adjustment. This, the authors speculated, may reflect engagement in cognitively stimulating activities such as reading.
To better understand the associations, the researchers used a statistical method to reallocate time in the cohort’s average day from one activity component to another.
“We held two of the components static but moved time between the other two and monitored the theoretical ramifications of that change for cognition,” said Mr. Mitchell.
Real cognitive change
There was a 1.31% improvement in cognition ranking compared to the sample average after replacing 9 minutes of sedentary activity with MVPA (1.31; 95% confidence interval [CI], 0.09-2.50). There was a 1.27% improvement after replacing 7 minutes of LIPA with MVPA, and a 1.2% improvement after replacing 7 minutes of sleep with MVPA.
Individuals might move up from about the 50th percentile to the 51st or 52nd percentile after just 9 minutes of more moderate to vigorous movement in place of sitting, said Mr. Mitchell. “This highlights how even very modest differences in people’s daily movement – less than 10 minutes – is linked to quite real changes in our cognitive health.”
The impact of physical activity appeared greatest on working memory and mental processes, such as planning and organization.
On the other hand, cognition declined by 1%-2% after replacing MVPA with 8 minutes of SB, 6 minutes of LIPA, or 7 minutes of sleep.
The activity tracking device couldn’t determine how well participants slept, which is “a clear limitation” of the study, said Mr. Mitchell. “We have to be cautious when trying to interpret our findings surrounding sleep.”
Another limitation is that despite a large sample size, people of color were underrepresented, limiting the generalizability of the findings. As well, other healthy pursuits – for example, reading – might have contributed to improved cognition.
Important findings
In a comment, Jennifer J. Heisz, PhD, associate professor and Canada research chair in brain health and aging, department of kinesiology, McMaster University, Hamilton, Ont., said the findings from the study are important.
“Through the statistical modelling, the authors demonstrate that swapping just 9 minutes of sedentary behavior with moderate to vigorous physical activity, such as a brisk walk or bike ride, was associated with an increase in cognition.”
She added that this seemed to be especially true for people who sit while at work.
The findings “confer with the growing consensus” that some exercise is better than none when it comes to brain health, said Dr. Heisz.
“Clinicians should encourage their patients to add a brisk, 10-minute walk to their daily routine and break up prolonged sitting with short movement breaks.”
She noted the study was cross-sectional, “so it is not possible to infer causation.”
The study received funding from the Medical Research Council and the British Heart Foundation. Mr. Mitchell and Dr. Heisz have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
such as running and cycling, plays in brain health.
“Even minor differences in daily behavior appeared meaningful for cognition in this study,” researcher John J. Mitchell, MSci and PhD candidate, Medical Research Council, London, told this news organization.
The findings were published online in the Journal of Epidemiology and Community Health.
Research gap
Previous research has linked physical activity (PA) with increased cognitive reserve, which delays the onset of cognitive decline in later life. But disentangling the most important components of PA for cognition – such as intensity and volume – has not been well researched.
Previous studies didn’t capture sleep time, which typically takes up the largest component of the day. Sleep is “acutely relevant” when examining cognition, the investigators noted.
In addition, studies in this area often focus on just one or two activity components of the day, which “neglects the growing awareness” that movements “are all tightly interlinked,” said Mr. Mitchell.
The new study included 4,481 participants in the British Cohort Study who were born in 1970 across England, Scotland, and Wales. The participants were followed throughout childhood and adulthood.
The median age of the participants was 47 years, and they were predominantly White, female (52%), married (66%), and well educated. Most were occasional or nonrisky alcohol consumers, and half had never smoked.
The researchers collected biometric measurements and health, demographic, and lifestyle information. Participants wore a thigh-mounted accelerometer at least 7 consecutive hours a day for up to 7 days to track PA, sedentary behavior (SB), and sleep time.
The device used in the study could detect subtle movements as well as speed of accelerations, said Mr. Mitchell. “From this, we can distinguish MVPA from slow walking, standing, and sitting. It’s the current best practice for detecting the more subtle movements we make, such as brisk walking and stair climbing, beyond just ‘exercise,’ “ he added.
Light intensity PA (LIPA) describes movement such as walking and moving around the house or office, while MVPA includes activities such as brisk walking and running that accelerate the heart rate. SB, defined as time spent sitting or lying, is distinguished from standing by the thigh inclination.
On an average day, the cohort spent 51 minutes in MVPA; 5 hours, 42 minutes in LIPA; 9 hours, 16 minutes in SB; and 8 hours, 11 minutes sleeping.
Researchers calculated an overall global score for verbal memory and executive function.
The study used “compositional data analysis,” a statistical method that can examine the associations of cognition and PA in the context of all components of daily movement.
The analysis revealed a positive association between MVPA and cognition relative to all other behaviors, after adjustment for sociodemographic factors that included sex, age, education, and marital status. But the relationship lessened after further adjustment for health status – for example, cardiovascular disease or disability – and lifestyle factors, such as alcohol consumption and smoking status.
SB relative to all other movements remained positively associated with cognition after full adjustment. This, the authors speculated, may reflect engagement in cognitively stimulating activities such as reading.
To better understand the associations, the researchers used a statistical method to reallocate time in the cohort’s average day from one activity component to another.
“We held two of the components static but moved time between the other two and monitored the theoretical ramifications of that change for cognition,” said Mr. Mitchell.
Real cognitive change
There was a 1.31% improvement in cognition ranking compared to the sample average after replacing 9 minutes of sedentary activity with MVPA (1.31; 95% confidence interval [CI], 0.09-2.50). There was a 1.27% improvement after replacing 7 minutes of LIPA with MVPA, and a 1.2% improvement after replacing 7 minutes of sleep with MVPA.
Individuals might move up from about the 50th percentile to the 51st or 52nd percentile after just 9 minutes of more moderate to vigorous movement in place of sitting, said Mr. Mitchell. “This highlights how even very modest differences in people’s daily movement – less than 10 minutes – is linked to quite real changes in our cognitive health.”
The impact of physical activity appeared greatest on working memory and mental processes, such as planning and organization.
On the other hand, cognition declined by 1%-2% after replacing MVPA with 8 minutes of SB, 6 minutes of LIPA, or 7 minutes of sleep.
The activity tracking device couldn’t determine how well participants slept, which is “a clear limitation” of the study, said Mr. Mitchell. “We have to be cautious when trying to interpret our findings surrounding sleep.”
Another limitation is that despite a large sample size, people of color were underrepresented, limiting the generalizability of the findings. As well, other healthy pursuits – for example, reading – might have contributed to improved cognition.
Important findings
In a comment, Jennifer J. Heisz, PhD, associate professor and Canada research chair in brain health and aging, department of kinesiology, McMaster University, Hamilton, Ont., said the findings from the study are important.
“Through the statistical modelling, the authors demonstrate that swapping just 9 minutes of sedentary behavior with moderate to vigorous physical activity, such as a brisk walk or bike ride, was associated with an increase in cognition.”
She added that this seemed to be especially true for people who sit while at work.
The findings “confer with the growing consensus” that some exercise is better than none when it comes to brain health, said Dr. Heisz.
“Clinicians should encourage their patients to add a brisk, 10-minute walk to their daily routine and break up prolonged sitting with short movement breaks.”
She noted the study was cross-sectional, “so it is not possible to infer causation.”
The study received funding from the Medical Research Council and the British Heart Foundation. Mr. Mitchell and Dr. Heisz have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
such as running and cycling, plays in brain health.
“Even minor differences in daily behavior appeared meaningful for cognition in this study,” researcher John J. Mitchell, MSci and PhD candidate, Medical Research Council, London, told this news organization.
The findings were published online in the Journal of Epidemiology and Community Health.
Research gap
Previous research has linked physical activity (PA) with increased cognitive reserve, which delays the onset of cognitive decline in later life. But disentangling the most important components of PA for cognition – such as intensity and volume – has not been well researched.
Previous studies didn’t capture sleep time, which typically takes up the largest component of the day. Sleep is “acutely relevant” when examining cognition, the investigators noted.
In addition, studies in this area often focus on just one or two activity components of the day, which “neglects the growing awareness” that movements “are all tightly interlinked,” said Mr. Mitchell.
The new study included 4,481 participants in the British Cohort Study who were born in 1970 across England, Scotland, and Wales. The participants were followed throughout childhood and adulthood.
The median age of the participants was 47 years, and they were predominantly White, female (52%), married (66%), and well educated. Most were occasional or nonrisky alcohol consumers, and half had never smoked.
The researchers collected biometric measurements and health, demographic, and lifestyle information. Participants wore a thigh-mounted accelerometer at least 7 consecutive hours a day for up to 7 days to track PA, sedentary behavior (SB), and sleep time.
The device used in the study could detect subtle movements as well as speed of accelerations, said Mr. Mitchell. “From this, we can distinguish MVPA from slow walking, standing, and sitting. It’s the current best practice for detecting the more subtle movements we make, such as brisk walking and stair climbing, beyond just ‘exercise,’ “ he added.
Light intensity PA (LIPA) describes movement such as walking and moving around the house or office, while MVPA includes activities such as brisk walking and running that accelerate the heart rate. SB, defined as time spent sitting or lying, is distinguished from standing by the thigh inclination.
On an average day, the cohort spent 51 minutes in MVPA; 5 hours, 42 minutes in LIPA; 9 hours, 16 minutes in SB; and 8 hours, 11 minutes sleeping.
Researchers calculated an overall global score for verbal memory and executive function.
The study used “compositional data analysis,” a statistical method that can examine the associations of cognition and PA in the context of all components of daily movement.
The analysis revealed a positive association between MVPA and cognition relative to all other behaviors, after adjustment for sociodemographic factors that included sex, age, education, and marital status. But the relationship lessened after further adjustment for health status – for example, cardiovascular disease or disability – and lifestyle factors, such as alcohol consumption and smoking status.
SB relative to all other movements remained positively associated with cognition after full adjustment. This, the authors speculated, may reflect engagement in cognitively stimulating activities such as reading.
To better understand the associations, the researchers used a statistical method to reallocate time in the cohort’s average day from one activity component to another.
“We held two of the components static but moved time between the other two and monitored the theoretical ramifications of that change for cognition,” said Mr. Mitchell.
Real cognitive change
There was a 1.31% improvement in cognition ranking compared to the sample average after replacing 9 minutes of sedentary activity with MVPA (1.31; 95% confidence interval [CI], 0.09-2.50). There was a 1.27% improvement after replacing 7 minutes of LIPA with MVPA, and a 1.2% improvement after replacing 7 minutes of sleep with MVPA.
Individuals might move up from about the 50th percentile to the 51st or 52nd percentile after just 9 minutes of more moderate to vigorous movement in place of sitting, said Mr. Mitchell. “This highlights how even very modest differences in people’s daily movement – less than 10 minutes – is linked to quite real changes in our cognitive health.”
The impact of physical activity appeared greatest on working memory and mental processes, such as planning and organization.
On the other hand, cognition declined by 1%-2% after replacing MVPA with 8 minutes of SB, 6 minutes of LIPA, or 7 minutes of sleep.
The activity tracking device couldn’t determine how well participants slept, which is “a clear limitation” of the study, said Mr. Mitchell. “We have to be cautious when trying to interpret our findings surrounding sleep.”
Another limitation is that despite a large sample size, people of color were underrepresented, limiting the generalizability of the findings. As well, other healthy pursuits – for example, reading – might have contributed to improved cognition.
Important findings
In a comment, Jennifer J. Heisz, PhD, associate professor and Canada research chair in brain health and aging, department of kinesiology, McMaster University, Hamilton, Ont., said the findings from the study are important.
“Through the statistical modelling, the authors demonstrate that swapping just 9 minutes of sedentary behavior with moderate to vigorous physical activity, such as a brisk walk or bike ride, was associated with an increase in cognition.”
She added that this seemed to be especially true for people who sit while at work.
The findings “confer with the growing consensus” that some exercise is better than none when it comes to brain health, said Dr. Heisz.
“Clinicians should encourage their patients to add a brisk, 10-minute walk to their daily routine and break up prolonged sitting with short movement breaks.”
She noted the study was cross-sectional, “so it is not possible to infer causation.”
The study received funding from the Medical Research Council and the British Heart Foundation. Mr. Mitchell and Dr. Heisz have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM THE JOURNAL OF EPIDEMIOLOGY AND COMMUNITY HEALTH
Geriatrician advises on use of vitamin D supplementation, lecanemab, and texting for her patients
Vitamin D supplementation and incident fractures
Vitamin D supplementation is a commonly recommended intervention for bone health, but data to support its impact on reducing fracture risk has been variable.
A study in the New England Journal of Medicine by LeBoff and colleagues has garnered much attention since its publication in July 2022.1 In the ancillary study of the Vitamin D and Omega-3-Trial (VITAL), the authors examined the impact of vitamin D supplementation versus placebo on incident fractures. The study found that vitamin D supplementation, as compared with placebo, led to no significant difference in the incidence of total, nonvertebral, and hip fractures in midlife and older adults over the 5-year period of follow-up.
The generalizability of these findings has been raised as a concern as the study does not describe adults at higher risk for fracture. The authors of the study specified in their conclusion that vitamin D supplementation does not reduce fracture risk in “generally healthy midlife and older adults who were not selected for vitamin D deficiency, low bone mass or osteoporosis.”
With a mean participant age of 67 and exclusion of participants with a history of cardiovascular disease, stroke, cirrhosis and other serious illnesses, the study does not reflect the multimorbid older adult population that geriatricians typically care for. Furthermore, efficacy of vitamin D supplementation on fracture risk may be the most impactful in those with osteoporosis and with severe vitamin D deficiency (defined by vitamin D 25[OH]D level less than 12 ng/mL).
In post hoc analyses, there was no significant difference in fracture risk in these subgroups, however the authors acknowledged that the findings may be limited by the small percentage of participants with severe vitamin D deficiency (2.4%) and osteoporosis included in the study (5%).
Lecanemab for mild cognitive impairment and early Alzheimer’s dementia
On Jan. 6, 2023, the Food and Drug Administration approved lecanemab, the second-ever disease-modifying treatment for Alzheimer’s dementia following the approval of aducanumab in 2021. Lecanemab is a monoclonal antibody targeting larger amyloid-beta oligomers, which has been shown in vitro to have higher affinity for amyloid-beta, compared with aducanumab. FDA approval followed shortly after the publication of the CLARITY-AD trial, which investigated the effect of lecanemab versus placebo on cognitive decline and burden of amyloid in adults with mild cognitive impairment and mild Alzheimer’s dementia. Over an 18-month period, the study found that participants who received lecanemab, compared with placebo, had a significantly smaller decline in cognition and function, and reduction in amyloid burden on PET CT.2
The clinical significance of these findings, however, is unclear. As noted by an editorial published in the Lancet in 2022, the difference in Clinical Dementia Rating-Sum of Boxes (CDR-SB) scale between the treatment and placebo groups was 0.45. On an 18-point scale, prior research has noted that a minimal clinically significance difference of 0.98 is necessary in those with mild cognitive impairment and 1.63 in mild Alzheimer dementia.3
Additionally, the CLARITY-AD trial reported that lecanemab resulted in infusion reactions in 26.4% of participants and brain edema (an amyloid-related imaging abnormality referred to as ARIA-E) in 12.6% of participants. This finding highlights concerns for safety and the need for close monitoring, as well as ongoing implications of economic feasibility and equitable access for all those who qualify for treatment.2
Social isolation and dementia risk
There is growing awareness of the impact of social isolation on health outcomes, particularly among older adults. Prior research has reported that one in four older adults are considered socially isolated and that social isolation increases risk of premature death, dementia, depression, and cardiovascular disease.4
A study by Huang and colleagues is the first nationally representative cohort study examining the association between social isolation and incident dementia for older adults in community dwelling settings. A cohort of 5,022 older adults participating in the National Health and Aging Trends Study was followed from 2011 to 2020. When adjusting for demographic and health factors, including race, level of education, and number of chronic health conditions, socially isolated adults had a greater risk of developing dementia, compared with adults who were not socially isolated (hazard ratio, 1.27; 95% confidence interval, 1.08-1.49). Potential mechanisms to explain this association include the increased risk of cardiovascular disease and depression in older adults who are socially isolated, thereby increasing dementia risk.
Decreased cognitive activity/engagement and access to resources such as caregiving and health care may also be linked to the increased risk of dementia in socially isolated older adults.5
Another observational cohort study from the National Health and Aging Trends Study investigated whether access and use of technology can lower the risk of social isolation. The study found that older adults who used email or text messaging had a lower risk of social isolation than older adults who did not use technology (incidence rate ratio, 0.64; 95% CI, 0.51-0.80).6 These findings highlight the importance of addressing social isolation as an important modifiable health risk factor, and the need for providing equitable access to technology in vulnerable populations as health intervention.
Dr. Mengru “Ruru” Wang is a geriatrician and internist at the University of Washington, Seattle. She practices full-spectrum medicine, seeing patients in primary care, nursing homes, and acute care. Dr. Wang has no disclosures related to this piece.
References
1. LeBoff MS et al. Supplemental vitamin D and incident fractures in midlife and older adults. N Engl J Med. 2022;387(4):299-30.
2. van Dyck CH et al. Lecanemab in early Alzheimer’s disease. N Engl J Med. 2023;388(1):9-21.
3. The Lancet. Lecanemab for Alzheimer’s disease: tempering hype and hope. Lancet. 2022; 400:1899.
4. National Academies of Sciences, Engineering, and Medicine. Social Isolation and Loneliness in Older Adults: Opportunities for the Health Care System. Washington, DC: 2020, The National Academies Press.
5. Huang, AR et al. Social isolation and 9-year dementia risk in community dwelling Medicare beneficiaries in the United States. J Am Geriatr Soc. 2023 Jan 11. doi: 10.1111/jgs18140.
6. Umoh ME etal. Impact of technology on social isolation: Longitudinal analysis from the National Health Aging Trends Study. J Am Geriatr Soc. 2022 Dec 15. doi 10.1111/jgs.18179.
Vitamin D supplementation and incident fractures
Vitamin D supplementation is a commonly recommended intervention for bone health, but data to support its impact on reducing fracture risk has been variable.
A study in the New England Journal of Medicine by LeBoff and colleagues has garnered much attention since its publication in July 2022.1 In the ancillary study of the Vitamin D and Omega-3-Trial (VITAL), the authors examined the impact of vitamin D supplementation versus placebo on incident fractures. The study found that vitamin D supplementation, as compared with placebo, led to no significant difference in the incidence of total, nonvertebral, and hip fractures in midlife and older adults over the 5-year period of follow-up.
The generalizability of these findings has been raised as a concern as the study does not describe adults at higher risk for fracture. The authors of the study specified in their conclusion that vitamin D supplementation does not reduce fracture risk in “generally healthy midlife and older adults who were not selected for vitamin D deficiency, low bone mass or osteoporosis.”
With a mean participant age of 67 and exclusion of participants with a history of cardiovascular disease, stroke, cirrhosis and other serious illnesses, the study does not reflect the multimorbid older adult population that geriatricians typically care for. Furthermore, efficacy of vitamin D supplementation on fracture risk may be the most impactful in those with osteoporosis and with severe vitamin D deficiency (defined by vitamin D 25[OH]D level less than 12 ng/mL).
In post hoc analyses, there was no significant difference in fracture risk in these subgroups, however the authors acknowledged that the findings may be limited by the small percentage of participants with severe vitamin D deficiency (2.4%) and osteoporosis included in the study (5%).
Lecanemab for mild cognitive impairment and early Alzheimer’s dementia
On Jan. 6, 2023, the Food and Drug Administration approved lecanemab, the second-ever disease-modifying treatment for Alzheimer’s dementia following the approval of aducanumab in 2021. Lecanemab is a monoclonal antibody targeting larger amyloid-beta oligomers, which has been shown in vitro to have higher affinity for amyloid-beta, compared with aducanumab. FDA approval followed shortly after the publication of the CLARITY-AD trial, which investigated the effect of lecanemab versus placebo on cognitive decline and burden of amyloid in adults with mild cognitive impairment and mild Alzheimer’s dementia. Over an 18-month period, the study found that participants who received lecanemab, compared with placebo, had a significantly smaller decline in cognition and function, and reduction in amyloid burden on PET CT.2
The clinical significance of these findings, however, is unclear. As noted by an editorial published in the Lancet in 2022, the difference in Clinical Dementia Rating-Sum of Boxes (CDR-SB) scale between the treatment and placebo groups was 0.45. On an 18-point scale, prior research has noted that a minimal clinically significance difference of 0.98 is necessary in those with mild cognitive impairment and 1.63 in mild Alzheimer dementia.3
Additionally, the CLARITY-AD trial reported that lecanemab resulted in infusion reactions in 26.4% of participants and brain edema (an amyloid-related imaging abnormality referred to as ARIA-E) in 12.6% of participants. This finding highlights concerns for safety and the need for close monitoring, as well as ongoing implications of economic feasibility and equitable access for all those who qualify for treatment.2
Social isolation and dementia risk
There is growing awareness of the impact of social isolation on health outcomes, particularly among older adults. Prior research has reported that one in four older adults are considered socially isolated and that social isolation increases risk of premature death, dementia, depression, and cardiovascular disease.4
A study by Huang and colleagues is the first nationally representative cohort study examining the association between social isolation and incident dementia for older adults in community dwelling settings. A cohort of 5,022 older adults participating in the National Health and Aging Trends Study was followed from 2011 to 2020. When adjusting for demographic and health factors, including race, level of education, and number of chronic health conditions, socially isolated adults had a greater risk of developing dementia, compared with adults who were not socially isolated (hazard ratio, 1.27; 95% confidence interval, 1.08-1.49). Potential mechanisms to explain this association include the increased risk of cardiovascular disease and depression in older adults who are socially isolated, thereby increasing dementia risk.
Decreased cognitive activity/engagement and access to resources such as caregiving and health care may also be linked to the increased risk of dementia in socially isolated older adults.5
Another observational cohort study from the National Health and Aging Trends Study investigated whether access and use of technology can lower the risk of social isolation. The study found that older adults who used email or text messaging had a lower risk of social isolation than older adults who did not use technology (incidence rate ratio, 0.64; 95% CI, 0.51-0.80).6 These findings highlight the importance of addressing social isolation as an important modifiable health risk factor, and the need for providing equitable access to technology in vulnerable populations as health intervention.
Dr. Mengru “Ruru” Wang is a geriatrician and internist at the University of Washington, Seattle. She practices full-spectrum medicine, seeing patients in primary care, nursing homes, and acute care. Dr. Wang has no disclosures related to this piece.
References
1. LeBoff MS et al. Supplemental vitamin D and incident fractures in midlife and older adults. N Engl J Med. 2022;387(4):299-30.
2. van Dyck CH et al. Lecanemab in early Alzheimer’s disease. N Engl J Med. 2023;388(1):9-21.
3. The Lancet. Lecanemab for Alzheimer’s disease: tempering hype and hope. Lancet. 2022; 400:1899.
4. National Academies of Sciences, Engineering, and Medicine. Social Isolation and Loneliness in Older Adults: Opportunities for the Health Care System. Washington, DC: 2020, The National Academies Press.
5. Huang, AR et al. Social isolation and 9-year dementia risk in community dwelling Medicare beneficiaries in the United States. J Am Geriatr Soc. 2023 Jan 11. doi: 10.1111/jgs18140.
6. Umoh ME etal. Impact of technology on social isolation: Longitudinal analysis from the National Health Aging Trends Study. J Am Geriatr Soc. 2022 Dec 15. doi 10.1111/jgs.18179.
Vitamin D supplementation and incident fractures
Vitamin D supplementation is a commonly recommended intervention for bone health, but data to support its impact on reducing fracture risk has been variable.
A study in the New England Journal of Medicine by LeBoff and colleagues has garnered much attention since its publication in July 2022.1 In the ancillary study of the Vitamin D and Omega-3-Trial (VITAL), the authors examined the impact of vitamin D supplementation versus placebo on incident fractures. The study found that vitamin D supplementation, as compared with placebo, led to no significant difference in the incidence of total, nonvertebral, and hip fractures in midlife and older adults over the 5-year period of follow-up.
The generalizability of these findings has been raised as a concern as the study does not describe adults at higher risk for fracture. The authors of the study specified in their conclusion that vitamin D supplementation does not reduce fracture risk in “generally healthy midlife and older adults who were not selected for vitamin D deficiency, low bone mass or osteoporosis.”
With a mean participant age of 67 and exclusion of participants with a history of cardiovascular disease, stroke, cirrhosis and other serious illnesses, the study does not reflect the multimorbid older adult population that geriatricians typically care for. Furthermore, efficacy of vitamin D supplementation on fracture risk may be the most impactful in those with osteoporosis and with severe vitamin D deficiency (defined by vitamin D 25[OH]D level less than 12 ng/mL).
In post hoc analyses, there was no significant difference in fracture risk in these subgroups, however the authors acknowledged that the findings may be limited by the small percentage of participants with severe vitamin D deficiency (2.4%) and osteoporosis included in the study (5%).
Lecanemab for mild cognitive impairment and early Alzheimer’s dementia
On Jan. 6, 2023, the Food and Drug Administration approved lecanemab, the second-ever disease-modifying treatment for Alzheimer’s dementia following the approval of aducanumab in 2021. Lecanemab is a monoclonal antibody targeting larger amyloid-beta oligomers, which has been shown in vitro to have higher affinity for amyloid-beta, compared with aducanumab. FDA approval followed shortly after the publication of the CLARITY-AD trial, which investigated the effect of lecanemab versus placebo on cognitive decline and burden of amyloid in adults with mild cognitive impairment and mild Alzheimer’s dementia. Over an 18-month period, the study found that participants who received lecanemab, compared with placebo, had a significantly smaller decline in cognition and function, and reduction in amyloid burden on PET CT.2
The clinical significance of these findings, however, is unclear. As noted by an editorial published in the Lancet in 2022, the difference in Clinical Dementia Rating-Sum of Boxes (CDR-SB) scale between the treatment and placebo groups was 0.45. On an 18-point scale, prior research has noted that a minimal clinically significance difference of 0.98 is necessary in those with mild cognitive impairment and 1.63 in mild Alzheimer dementia.3
Additionally, the CLARITY-AD trial reported that lecanemab resulted in infusion reactions in 26.4% of participants and brain edema (an amyloid-related imaging abnormality referred to as ARIA-E) in 12.6% of participants. This finding highlights concerns for safety and the need for close monitoring, as well as ongoing implications of economic feasibility and equitable access for all those who qualify for treatment.2
Social isolation and dementia risk
There is growing awareness of the impact of social isolation on health outcomes, particularly among older adults. Prior research has reported that one in four older adults are considered socially isolated and that social isolation increases risk of premature death, dementia, depression, and cardiovascular disease.4
A study by Huang and colleagues is the first nationally representative cohort study examining the association between social isolation and incident dementia for older adults in community dwelling settings. A cohort of 5,022 older adults participating in the National Health and Aging Trends Study was followed from 2011 to 2020. When adjusting for demographic and health factors, including race, level of education, and number of chronic health conditions, socially isolated adults had a greater risk of developing dementia, compared with adults who were not socially isolated (hazard ratio, 1.27; 95% confidence interval, 1.08-1.49). Potential mechanisms to explain this association include the increased risk of cardiovascular disease and depression in older adults who are socially isolated, thereby increasing dementia risk.
Decreased cognitive activity/engagement and access to resources such as caregiving and health care may also be linked to the increased risk of dementia in socially isolated older adults.5
Another observational cohort study from the National Health and Aging Trends Study investigated whether access and use of technology can lower the risk of social isolation. The study found that older adults who used email or text messaging had a lower risk of social isolation than older adults who did not use technology (incidence rate ratio, 0.64; 95% CI, 0.51-0.80).6 These findings highlight the importance of addressing social isolation as an important modifiable health risk factor, and the need for providing equitable access to technology in vulnerable populations as health intervention.
Dr. Mengru “Ruru” Wang is a geriatrician and internist at the University of Washington, Seattle. She practices full-spectrum medicine, seeing patients in primary care, nursing homes, and acute care. Dr. Wang has no disclosures related to this piece.
References
1. LeBoff MS et al. Supplemental vitamin D and incident fractures in midlife and older adults. N Engl J Med. 2022;387(4):299-30.
2. van Dyck CH et al. Lecanemab in early Alzheimer’s disease. N Engl J Med. 2023;388(1):9-21.
3. The Lancet. Lecanemab for Alzheimer’s disease: tempering hype and hope. Lancet. 2022; 400:1899.
4. National Academies of Sciences, Engineering, and Medicine. Social Isolation and Loneliness in Older Adults: Opportunities for the Health Care System. Washington, DC: 2020, The National Academies Press.
5. Huang, AR et al. Social isolation and 9-year dementia risk in community dwelling Medicare beneficiaries in the United States. J Am Geriatr Soc. 2023 Jan 11. doi: 10.1111/jgs18140.
6. Umoh ME etal. Impact of technology on social isolation: Longitudinal analysis from the National Health Aging Trends Study. J Am Geriatr Soc. 2022 Dec 15. doi 10.1111/jgs.18179.
Kids with concussions may benefit from early return to school
The timing for return to school after a concussion has been the subject of guidelines, but data on how the timing of school returns affects later symptom burdens are limited, Christopher G. Vaughan, PhD, of Children’s National Hospital, Rockville, Md., and colleagues wrote.
Examining how the timing of return to school (RTS) affects later symptoms is needed to inform early postinjury management, they said.
In the new study published in JAMA Network Open, the researchers identified 1,630 children and teens aged 5-18 years who were treated for concussions at nine Canadian pediatric EDs. The primary outcome was symptom burden at 14 days post concussion, based on the Post-Concussion Symptom Inventory (PCSI). Early RTS was defined as missing fewer than 3 days of school post concussion.
Overall, the mean number of missed school days was 3.74 (excluding weekends). When divided by age, the mean number of missed days was 2.61 for children aged 5-7 years, 3.26 for those aged 8-12 years, and 4.71 for those aged 13-18 years.
Slightly more than half (53.7%) of the participants had an early RTS of 2 missed days or fewer. Later RTS was most common in the oldest age group, followed by the middle and younger age groups.
The researchers used a propensity score–matched analysis to determine associations. At 14 days, an early RTS was associated with reduced symptoms among 8- to 12-year-olds and 13- to 18-year-olds, though not in the youngest patients aged 5-7 years. In addition, the researchers created quantiles based on initial symptom ratings.
For the youngest age group, the association between early RTS and reduced symptoms at day 14 was higher among those with lower initial symptoms.
For the two older groups, the association was higher for those with higher initial symptoms (based on the PCSI).
The findings that earlier RTS was associated with a lower symptom burden at day 14 for those with higher levels of symptoms at baseline was surprising, but the mechanisms of the timing and effect of RTS requires more study, the researchers wrote in their discussion.
The effect of early RTS on symptoms may be in part related to factors such as “the benefits of socialization, reduced stress from not missing too much school, maintaining or returning to a normal sleep-wake schedule, and returning to light to moderate physical activity (gym class and recreational activities),” the researchers noted.
Another study related to recovery and concussion recently appeared in Neurology. In that study, the authors found that those athletes who took a longer time to recover from a sports-related concussion could still return to play with additional time off, but the methods and populations differed from the current study, which focused on RTS rather than returning to play.
The current study findings were limited by several factors including the lack of randomization for RTS timing and a lack of data on the variety of potential supports and accommodations students received, the researchers noted.
However, the results were strengthened by the large size and diverse nature of the concussions, and the roughly equal representation of boys and girls, they said.
Although randomized trials are needed to determine the best timing for RTS, the current study suggests that RTS within 2 days of a concussion is associated with improved symptoms, “and may directly or indirectly promote faster recovery,” they concluded.
Early return remains feasible for most children and teens
“Return to school can be a complicated issue for children and teens with concussions,” said Caitlyn Mooney, MD, a pediatrician and specialist in sports medicine at the University of Texas Health Science Center, San Antonio, said in an interview. Although much research has focused on diagnosis and return to sport after a concussion, there has been less focus on returning to school and learning. Various issues post concussion can make schooling difficult, and students may experience trouble with vision, concentration, sleep, headaches, and more.
Despite this knowledge, studies that specifically address recommended school protocols are limited, Dr. Mooney said. “Additionally, all concussions are different; while some students will need minimal help to return and succeed in school, others may need individualized learning plans and accommodations for school.” A return to school ideally would be a team-based approach with input from the parent, patient, physician, and educators.
“The theory of cognitive rest stems from the idea that a concussion causes metabolic dysfunction in the brain, and that increasing the metabolic demands of the brain can result in symptoms and a delayed return to school,” said Dr. Mooney.
Evidence suggests that those who start resting early after a concussion improve more quickly, “but there has been ongoing discussion over the years of what is the correct balance of cognitive rest to returning to modified activity,” she said. “This has led to the current general recommendation of rest for 24-48 hours followed by a gradual return to school as tolerated.”
Although the current study is large, it is limited by the lack of randomization, Dr. Mooney noted, therefore conclusions cannot be made that the cause of the improved symptoms is a quicker return to school.
However, the results support data from previous studies, in that both of the older age groups showed less disease burden at 14 days after an earlier return to school, she said.
“With prolonged absences, adolescents get isolated at home away from friends, and they may have increased mood symptoms. Additionally, I have found a high number of my patients who do not go to school as quickly have more sleep disturbance, which seems to increase symptoms such as difficulty concentrating or headaches,” she said. “It seems like the students do benefit from a routine schedule even if they have to have some accommodations at school, especially older students who may have more stress about missing school and falling behind on schoolwork.”
The message for pediatricians is that return to school should be individualized, Dr. Mooney said.
Although the current study does not dictate the optimal return to school, the results support those of previous studies in showing that, after 1-2 days of rest, an early return does not harm children and teens and may improve symptoms in many cases, she said. “In my experience, sometimes schools find it easier to keep the student at home rather than manage rest or special accommodations,” but the current study suggests that delaying return to school may not be the right choice for many patients.
“I hope this study empowers clinicians to advocate for these students, that the right place for them is in the classroom even with rest, extra time, or other accommodations,” said Dr. Mooney.
“Each concussion should be evaluated and treated individually; there will likely be a few who may need to stay home for a longer period of time, but this study suggests that the majority of students will suffer no ill effects from returning to the normal routine after a 2-day rest,” she noted.
The study was supported by the Canadian Institutes for Health Research. Dr. Vaughan and several coauthors disclosed being authors of the Postconcussion Symptom Inventory outside of the current study. Dr. Mooney had no financial conflicts to disclose.
The timing for return to school after a concussion has been the subject of guidelines, but data on how the timing of school returns affects later symptom burdens are limited, Christopher G. Vaughan, PhD, of Children’s National Hospital, Rockville, Md., and colleagues wrote.
Examining how the timing of return to school (RTS) affects later symptoms is needed to inform early postinjury management, they said.
In the new study published in JAMA Network Open, the researchers identified 1,630 children and teens aged 5-18 years who were treated for concussions at nine Canadian pediatric EDs. The primary outcome was symptom burden at 14 days post concussion, based on the Post-Concussion Symptom Inventory (PCSI). Early RTS was defined as missing fewer than 3 days of school post concussion.
Overall, the mean number of missed school days was 3.74 (excluding weekends). When divided by age, the mean number of missed days was 2.61 for children aged 5-7 years, 3.26 for those aged 8-12 years, and 4.71 for those aged 13-18 years.
Slightly more than half (53.7%) of the participants had an early RTS of 2 missed days or fewer. Later RTS was most common in the oldest age group, followed by the middle and younger age groups.
The researchers used a propensity score–matched analysis to determine associations. At 14 days, an early RTS was associated with reduced symptoms among 8- to 12-year-olds and 13- to 18-year-olds, though not in the youngest patients aged 5-7 years. In addition, the researchers created quantiles based on initial symptom ratings.
For the youngest age group, the association between early RTS and reduced symptoms at day 14 was higher among those with lower initial symptoms.
For the two older groups, the association was higher for those with higher initial symptoms (based on the PCSI).
The findings that earlier RTS was associated with a lower symptom burden at day 14 for those with higher levels of symptoms at baseline was surprising, but the mechanisms of the timing and effect of RTS requires more study, the researchers wrote in their discussion.
The effect of early RTS on symptoms may be in part related to factors such as “the benefits of socialization, reduced stress from not missing too much school, maintaining or returning to a normal sleep-wake schedule, and returning to light to moderate physical activity (gym class and recreational activities),” the researchers noted.
Another study related to recovery and concussion recently appeared in Neurology. In that study, the authors found that those athletes who took a longer time to recover from a sports-related concussion could still return to play with additional time off, but the methods and populations differed from the current study, which focused on RTS rather than returning to play.
The current study findings were limited by several factors including the lack of randomization for RTS timing and a lack of data on the variety of potential supports and accommodations students received, the researchers noted.
However, the results were strengthened by the large size and diverse nature of the concussions, and the roughly equal representation of boys and girls, they said.
Although randomized trials are needed to determine the best timing for RTS, the current study suggests that RTS within 2 days of a concussion is associated with improved symptoms, “and may directly or indirectly promote faster recovery,” they concluded.
Early return remains feasible for most children and teens
“Return to school can be a complicated issue for children and teens with concussions,” said Caitlyn Mooney, MD, a pediatrician and specialist in sports medicine at the University of Texas Health Science Center, San Antonio, said in an interview. Although much research has focused on diagnosis and return to sport after a concussion, there has been less focus on returning to school and learning. Various issues post concussion can make schooling difficult, and students may experience trouble with vision, concentration, sleep, headaches, and more.
Despite this knowledge, studies that specifically address recommended school protocols are limited, Dr. Mooney said. “Additionally, all concussions are different; while some students will need minimal help to return and succeed in school, others may need individualized learning plans and accommodations for school.” A return to school ideally would be a team-based approach with input from the parent, patient, physician, and educators.
“The theory of cognitive rest stems from the idea that a concussion causes metabolic dysfunction in the brain, and that increasing the metabolic demands of the brain can result in symptoms and a delayed return to school,” said Dr. Mooney.
Evidence suggests that those who start resting early after a concussion improve more quickly, “but there has been ongoing discussion over the years of what is the correct balance of cognitive rest to returning to modified activity,” she said. “This has led to the current general recommendation of rest for 24-48 hours followed by a gradual return to school as tolerated.”
Although the current study is large, it is limited by the lack of randomization, Dr. Mooney noted, therefore conclusions cannot be made that the cause of the improved symptoms is a quicker return to school.
However, the results support data from previous studies, in that both of the older age groups showed less disease burden at 14 days after an earlier return to school, she said.
“With prolonged absences, adolescents get isolated at home away from friends, and they may have increased mood symptoms. Additionally, I have found a high number of my patients who do not go to school as quickly have more sleep disturbance, which seems to increase symptoms such as difficulty concentrating or headaches,” she said. “It seems like the students do benefit from a routine schedule even if they have to have some accommodations at school, especially older students who may have more stress about missing school and falling behind on schoolwork.”
The message for pediatricians is that return to school should be individualized, Dr. Mooney said.
Although the current study does not dictate the optimal return to school, the results support those of previous studies in showing that, after 1-2 days of rest, an early return does not harm children and teens and may improve symptoms in many cases, she said. “In my experience, sometimes schools find it easier to keep the student at home rather than manage rest or special accommodations,” but the current study suggests that delaying return to school may not be the right choice for many patients.
“I hope this study empowers clinicians to advocate for these students, that the right place for them is in the classroom even with rest, extra time, or other accommodations,” said Dr. Mooney.
“Each concussion should be evaluated and treated individually; there will likely be a few who may need to stay home for a longer period of time, but this study suggests that the majority of students will suffer no ill effects from returning to the normal routine after a 2-day rest,” she noted.
The study was supported by the Canadian Institutes for Health Research. Dr. Vaughan and several coauthors disclosed being authors of the Postconcussion Symptom Inventory outside of the current study. Dr. Mooney had no financial conflicts to disclose.
The timing for return to school after a concussion has been the subject of guidelines, but data on how the timing of school returns affects later symptom burdens are limited, Christopher G. Vaughan, PhD, of Children’s National Hospital, Rockville, Md., and colleagues wrote.
Examining how the timing of return to school (RTS) affects later symptoms is needed to inform early postinjury management, they said.
In the new study published in JAMA Network Open, the researchers identified 1,630 children and teens aged 5-18 years who were treated for concussions at nine Canadian pediatric EDs. The primary outcome was symptom burden at 14 days post concussion, based on the Post-Concussion Symptom Inventory (PCSI). Early RTS was defined as missing fewer than 3 days of school post concussion.
Overall, the mean number of missed school days was 3.74 (excluding weekends). When divided by age, the mean number of missed days was 2.61 for children aged 5-7 years, 3.26 for those aged 8-12 years, and 4.71 for those aged 13-18 years.
Slightly more than half (53.7%) of the participants had an early RTS of 2 missed days or fewer. Later RTS was most common in the oldest age group, followed by the middle and younger age groups.
The researchers used a propensity score–matched analysis to determine associations. At 14 days, an early RTS was associated with reduced symptoms among 8- to 12-year-olds and 13- to 18-year-olds, though not in the youngest patients aged 5-7 years. In addition, the researchers created quantiles based on initial symptom ratings.
For the youngest age group, the association between early RTS and reduced symptoms at day 14 was higher among those with lower initial symptoms.
For the two older groups, the association was higher for those with higher initial symptoms (based on the PCSI).
The findings that earlier RTS was associated with a lower symptom burden at day 14 for those with higher levels of symptoms at baseline was surprising, but the mechanisms of the timing and effect of RTS requires more study, the researchers wrote in their discussion.
The effect of early RTS on symptoms may be in part related to factors such as “the benefits of socialization, reduced stress from not missing too much school, maintaining or returning to a normal sleep-wake schedule, and returning to light to moderate physical activity (gym class and recreational activities),” the researchers noted.
Another study related to recovery and concussion recently appeared in Neurology. In that study, the authors found that those athletes who took a longer time to recover from a sports-related concussion could still return to play with additional time off, but the methods and populations differed from the current study, which focused on RTS rather than returning to play.
The current study findings were limited by several factors including the lack of randomization for RTS timing and a lack of data on the variety of potential supports and accommodations students received, the researchers noted.
However, the results were strengthened by the large size and diverse nature of the concussions, and the roughly equal representation of boys and girls, they said.
Although randomized trials are needed to determine the best timing for RTS, the current study suggests that RTS within 2 days of a concussion is associated with improved symptoms, “and may directly or indirectly promote faster recovery,” they concluded.
Early return remains feasible for most children and teens
“Return to school can be a complicated issue for children and teens with concussions,” said Caitlyn Mooney, MD, a pediatrician and specialist in sports medicine at the University of Texas Health Science Center, San Antonio, said in an interview. Although much research has focused on diagnosis and return to sport after a concussion, there has been less focus on returning to school and learning. Various issues post concussion can make schooling difficult, and students may experience trouble with vision, concentration, sleep, headaches, and more.
Despite this knowledge, studies that specifically address recommended school protocols are limited, Dr. Mooney said. “Additionally, all concussions are different; while some students will need minimal help to return and succeed in school, others may need individualized learning plans and accommodations for school.” A return to school ideally would be a team-based approach with input from the parent, patient, physician, and educators.
“The theory of cognitive rest stems from the idea that a concussion causes metabolic dysfunction in the brain, and that increasing the metabolic demands of the brain can result in symptoms and a delayed return to school,” said Dr. Mooney.
Evidence suggests that those who start resting early after a concussion improve more quickly, “but there has been ongoing discussion over the years of what is the correct balance of cognitive rest to returning to modified activity,” she said. “This has led to the current general recommendation of rest for 24-48 hours followed by a gradual return to school as tolerated.”
Although the current study is large, it is limited by the lack of randomization, Dr. Mooney noted, therefore conclusions cannot be made that the cause of the improved symptoms is a quicker return to school.
However, the results support data from previous studies, in that both of the older age groups showed less disease burden at 14 days after an earlier return to school, she said.
“With prolonged absences, adolescents get isolated at home away from friends, and they may have increased mood symptoms. Additionally, I have found a high number of my patients who do not go to school as quickly have more sleep disturbance, which seems to increase symptoms such as difficulty concentrating or headaches,” she said. “It seems like the students do benefit from a routine schedule even if they have to have some accommodations at school, especially older students who may have more stress about missing school and falling behind on schoolwork.”
The message for pediatricians is that return to school should be individualized, Dr. Mooney said.
Although the current study does not dictate the optimal return to school, the results support those of previous studies in showing that, after 1-2 days of rest, an early return does not harm children and teens and may improve symptoms in many cases, she said. “In my experience, sometimes schools find it easier to keep the student at home rather than manage rest or special accommodations,” but the current study suggests that delaying return to school may not be the right choice for many patients.
“I hope this study empowers clinicians to advocate for these students, that the right place for them is in the classroom even with rest, extra time, or other accommodations,” said Dr. Mooney.
“Each concussion should be evaluated and treated individually; there will likely be a few who may need to stay home for a longer period of time, but this study suggests that the majority of students will suffer no ill effects from returning to the normal routine after a 2-day rest,” she noted.
The study was supported by the Canadian Institutes for Health Research. Dr. Vaughan and several coauthors disclosed being authors of the Postconcussion Symptom Inventory outside of the current study. Dr. Mooney had no financial conflicts to disclose.
FROM JAMA NETWORK OPEN