Pauline Anderson

Dietary intake of polyunsaturated fatty acids (PUFA), particularly omega 6, is associated with improved cognitive function in older adults, new research suggests.

The study provides important “pieces of the puzzle” of the diet and cognition connection, but the results aren’t “ready for prime time,” study investigator Roger S. McIntyre, MD, professor of psychiatry and pharmacology, University of Toronto, said in an interview.

“I don’t think we’re there yet when it comes to recommending supplementation to the general public,” said Dr. McIntyre, adding a larger “more compelling study” is needed.

The study was published online Jan. 14 in The American Journal of Geriatric Psychiatry.
 

Clinically meaningful?

Research shows that 25%-50% of community-dwelling adults aged 65-85 years have some cognitive impairment. Other evidence indicates cognition is affected by dietary fat intake.

Many lines of research show that alterations in lipid homeostasis can cause brain dysfunction, said Dr. McIntyre. “This shouldn’t surprise us because our brain is made up of protein, water, and fat.”

This new analysis used combined data from the 2011-2012 and 2013-2014 cycles of the National Health and Nutrition Examination Survey (NHANES), a series of ongoing cross-sectional surveys conducted by the Centers for Disease Control and Prevention. The data are collected in two phases, an in-home face-to-face interview and a physical examination.

Researchers obtained dietary intake information through two 24-hour dietary recall interviews. Dietary information included total energy (kcal/d), intakes in grams per day (g/d) of total fat, saturated fatty acid (SFAT), monounsaturated fatty acid (MUFA), PUFA, total omega-3 and total omega-6 fatty acids, and milligrams per day (mg/d) of cholesterol.

For cognitive function, the researchers used total and delayed recall scores of the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD), the animal fluency test, and the digit symbol substitution test (DSST).

The study included 2,253 adults aged 60 years and older (mean age, 69.4 years) and 51% were non-Hispanic White individuals.

After adjustment for age, sex, race/ethnicity, educational attainment, smoking status, alcohol consumption, income, and total energy, dietary intake of PUFA and omega-6 fatty acid was positively associated with DSST.

The DSST score increased about 0.06 standard deviation (SD) (about 1 score) with each SD increase in these fatty acids (8.8 g/d for PUFA and 7.9 g/d for omega-6) (P values were .02 for PUFA and .01 for omega-6).

However, it’s unclear what an improvement of 1 DSST score means clinically, said Dr. McIntyre. “The P value is significant, but how does that translate? Does this mean a person can now think more clearly or function better?”
 

‘Million dollar question’ remains unanswered

The fact that omega-6, considered neuroinflammatory, was associated with improved DSST score illustrates the complexity of this field, said Dr. McIntyre.

“We’re learning that when it comes to inflammation, many of the molecules in our brain that are implicated as anti-inflammatory can also be pro-inflammatory, so bad guys can be good guys and good guys can be bad guys.”

It speaks to the notion of homeostasis, he added. “Just like a seesaw; when you push this part down, that part goes up.”

The analysis showed the animal fluency score increased about 0.05 SD (around 0.3 score) with each SD (1.1 g/d) increase in dietary intake of omega-3.

There were no significant associations between other dietary fat intake and cognitive performance.

The researchers investigated the role of oxidative stress and antioxidant biomarkers (gamma glutamyl transpeptidase [GGT], bilirubin, uric acid, and vitamin D).

Cells produce oxidative radicals that are normally “mopped up” by our “innate antioxidant capability,” said Dr. McIntyre. “But in states of cognitive impairment, these oxidative stress markers accumulate and they exceed what the normal innate response is able to manage.”

The study showed GGT levels decreased with increased PUFA and omega-6 fatty acid intakes; levels of bilirubin decreased with increase in most dietary fat intakes; uric acid levels decreased with MUFA intake and omega-6/omega-3 ratio; and vitamin D levels increased with omega-3 fatty acid intake but decreased with SFAT intake.

Causal mediation analysis showed the association between dietary intake of fatty acids and DSST performance was partially mediated by GGT levels. However, Dr. McIntyre emphasized that this does not prove causality.

“The million dollar question is, is this the sole explanation for the association? In other words, is it the oxidative stress that caused the cognitive impairment and therefore correcting it improved it, or is it the case that oxidative stress is a proxy of other activities that are also taking place?”
 

A ‘plausible’ link

In an editorial, Candida Rebello, PhD, of the department of integrated physiology and molecular medicine at Pennington Biomedical Research Center, Baton Rouge, La., said the finding that omega-3 and omega-6 fatty acids are positively associated with cognition in older adults makes some sense.

She noted that aging is associated with an overt inflammatory phenotype, and evidence shows these fatty acids are precursors for bioactive molecules that play a role in self-limiting the acute inflammatory response.

Dr. Rebello said the positive association of omega-6 fatty acid with cognition shown in this study contrasts with the “common belief” that increasing dietary intake of these fatty acids enhances inflammation, but agreed the association is “plausible.”

She said it’s “essential” to determine “the underlying mechanisms that regulate the diverse features of inflammation and sort out the processes that protect from neuronal damage and those that contribute towards it.”

She noted the ratio of omega-6 to omega-3 is about 15:1 in the present day Western diet, as opposed to a 1:1 ratio in diets of the past. Omega-3 fatty acids are found in fish oil supplements and fatty fish like mackerel and salmon, while cereal, grains, and vegetable oil are sources of omega-6.

Attaining a measure of balance of fatty acids in the diet may be a “prudent approach,” said Dr. Rebello. “Substituting some meat entrées with fatty fish and polyunsaturated vegetable oils with monounsaturated fats such as olive oil are small changes that are likely to garner adherence.”

Dr. Rebello noted that the study used NHANES food intake data, which rely on participant self-report and so may not be accurate.

The study received funding from the MOE (Ministry of Education in China) Project of Humanities and Social Sciences and the Research Startup Fund of Southwest University. Dr. McIntyre has received research grant support from CIHR/GACD/Chinese National Natural Research Foundation and speaker/consultation fees from Lundbeck, Janssen, Purdue, Pfizer, Otsuka, Takeda, Neurocrine, Sunovion, Bausch Health, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular, NewBridge Pharmaceuticals, and AbbVie. He is a CEO of Braxia Scientific Corp.

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

Dietary intake of polyunsaturated fatty acids (PUFA), particularly omega 6, is associated with improved cognitive function in older adults, new research suggests.

The study provides important “pieces of the puzzle” of the diet and cognition connection, but the results aren’t “ready for prime time,” study investigator Roger S. McIntyre, MD, professor of psychiatry and pharmacology, University of Toronto, said in an interview.

“I don’t think we’re there yet when it comes to recommending supplementation to the general public,” said Dr. McIntyre, adding a larger “more compelling study” is needed.

The study was published online Jan. 14 in The American Journal of Geriatric Psychiatry.
 

Clinically meaningful?

Research shows that 25%-50% of community-dwelling adults aged 65-85 years have some cognitive impairment. Other evidence indicates cognition is affected by dietary fat intake.

Many lines of research show that alterations in lipid homeostasis can cause brain dysfunction, said Dr. McIntyre. “This shouldn’t surprise us because our brain is made up of protein, water, and fat.”

This new analysis used combined data from the 2011-2012 and 2013-2014 cycles of the National Health and Nutrition Examination Survey (NHANES), a series of ongoing cross-sectional surveys conducted by the Centers for Disease Control and Prevention. The data are collected in two phases, an in-home face-to-face interview and a physical examination.

Researchers obtained dietary intake information through two 24-hour dietary recall interviews. Dietary information included total energy (kcal/d), intakes in grams per day (g/d) of total fat, saturated fatty acid (SFAT), monounsaturated fatty acid (MUFA), PUFA, total omega-3 and total omega-6 fatty acids, and milligrams per day (mg/d) of cholesterol.

For cognitive function, the researchers used total and delayed recall scores of the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD), the animal fluency test, and the digit symbol substitution test (DSST).

The study included 2,253 adults aged 60 years and older (mean age, 69.4 years) and 51% were non-Hispanic White individuals.

After adjustment for age, sex, race/ethnicity, educational attainment, smoking status, alcohol consumption, income, and total energy, dietary intake of PUFA and omega-6 fatty acid was positively associated with DSST.

The DSST score increased about 0.06 standard deviation (SD) (about 1 score) with each SD increase in these fatty acids (8.8 g/d for PUFA and 7.9 g/d for omega-6) (P values were .02 for PUFA and .01 for omega-6).

However, it’s unclear what an improvement of 1 DSST score means clinically, said Dr. McIntyre. “The P value is significant, but how does that translate? Does this mean a person can now think more clearly or function better?”
 

‘Million dollar question’ remains unanswered

The fact that omega-6, considered neuroinflammatory, was associated with improved DSST score illustrates the complexity of this field, said Dr. McIntyre.

“We’re learning that when it comes to inflammation, many of the molecules in our brain that are implicated as anti-inflammatory can also be pro-inflammatory, so bad guys can be good guys and good guys can be bad guys.”

It speaks to the notion of homeostasis, he added. “Just like a seesaw; when you push this part down, that part goes up.”

The analysis showed the animal fluency score increased about 0.05 SD (around 0.3 score) with each SD (1.1 g/d) increase in dietary intake of omega-3.

There were no significant associations between other dietary fat intake and cognitive performance.

The researchers investigated the role of oxidative stress and antioxidant biomarkers (gamma glutamyl transpeptidase [GGT], bilirubin, uric acid, and vitamin D).

Cells produce oxidative radicals that are normally “mopped up” by our “innate antioxidant capability,” said Dr. McIntyre. “But in states of cognitive impairment, these oxidative stress markers accumulate and they exceed what the normal innate response is able to manage.”

The study showed GGT levels decreased with increased PUFA and omega-6 fatty acid intakes; levels of bilirubin decreased with increase in most dietary fat intakes; uric acid levels decreased with MUFA intake and omega-6/omega-3 ratio; and vitamin D levels increased with omega-3 fatty acid intake but decreased with SFAT intake.

Causal mediation analysis showed the association between dietary intake of fatty acids and DSST performance was partially mediated by GGT levels. However, Dr. McIntyre emphasized that this does not prove causality.

“The million dollar question is, is this the sole explanation for the association? In other words, is it the oxidative stress that caused the cognitive impairment and therefore correcting it improved it, or is it the case that oxidative stress is a proxy of other activities that are also taking place?”
 

A ‘plausible’ link

In an editorial, Candida Rebello, PhD, of the department of integrated physiology and molecular medicine at Pennington Biomedical Research Center, Baton Rouge, La., said the finding that omega-3 and omega-6 fatty acids are positively associated with cognition in older adults makes some sense.

She noted that aging is associated with an overt inflammatory phenotype, and evidence shows these fatty acids are precursors for bioactive molecules that play a role in self-limiting the acute inflammatory response.

Dr. Rebello said the positive association of omega-6 fatty acid with cognition shown in this study contrasts with the “common belief” that increasing dietary intake of these fatty acids enhances inflammation, but agreed the association is “plausible.”

She said it’s “essential” to determine “the underlying mechanisms that regulate the diverse features of inflammation and sort out the processes that protect from neuronal damage and those that contribute towards it.”

She noted the ratio of omega-6 to omega-3 is about 15:1 in the present day Western diet, as opposed to a 1:1 ratio in diets of the past. Omega-3 fatty acids are found in fish oil supplements and fatty fish like mackerel and salmon, while cereal, grains, and vegetable oil are sources of omega-6.

Attaining a measure of balance of fatty acids in the diet may be a “prudent approach,” said Dr. Rebello. “Substituting some meat entrées with fatty fish and polyunsaturated vegetable oils with monounsaturated fats such as olive oil are small changes that are likely to garner adherence.”

Dr. Rebello noted that the study used NHANES food intake data, which rely on participant self-report and so may not be accurate.

The study received funding from the MOE (Ministry of Education in China) Project of Humanities and Social Sciences and the Research Startup Fund of Southwest University. Dr. McIntyre has received research grant support from CIHR/GACD/Chinese National Natural Research Foundation and speaker/consultation fees from Lundbeck, Janssen, Purdue, Pfizer, Otsuka, Takeda, Neurocrine, Sunovion, Bausch Health, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular, NewBridge Pharmaceuticals, and AbbVie. He is a CEO of Braxia Scientific Corp.

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

Dietary intake of polyunsaturated fatty acids (PUFA), particularly omega 6, is associated with improved cognitive function in older adults, new research suggests.

The study provides important “pieces of the puzzle” of the diet and cognition connection, but the results aren’t “ready for prime time,” study investigator Roger S. McIntyre, MD, professor of psychiatry and pharmacology, University of Toronto, said in an interview.

“I don’t think we’re there yet when it comes to recommending supplementation to the general public,” said Dr. McIntyre, adding a larger “more compelling study” is needed.

The study was published online Jan. 14 in The American Journal of Geriatric Psychiatry.
 

Clinically meaningful?

Research shows that 25%-50% of community-dwelling adults aged 65-85 years have some cognitive impairment. Other evidence indicates cognition is affected by dietary fat intake.

Many lines of research show that alterations in lipid homeostasis can cause brain dysfunction, said Dr. McIntyre. “This shouldn’t surprise us because our brain is made up of protein, water, and fat.”

This new analysis used combined data from the 2011-2012 and 2013-2014 cycles of the National Health and Nutrition Examination Survey (NHANES), a series of ongoing cross-sectional surveys conducted by the Centers for Disease Control and Prevention. The data are collected in two phases, an in-home face-to-face interview and a physical examination.

Researchers obtained dietary intake information through two 24-hour dietary recall interviews. Dietary information included total energy (kcal/d), intakes in grams per day (g/d) of total fat, saturated fatty acid (SFAT), monounsaturated fatty acid (MUFA), PUFA, total omega-3 and total omega-6 fatty acids, and milligrams per day (mg/d) of cholesterol.

For cognitive function, the researchers used total and delayed recall scores of the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD), the animal fluency test, and the digit symbol substitution test (DSST).

The study included 2,253 adults aged 60 years and older (mean age, 69.4 years) and 51% were non-Hispanic White individuals.

After adjustment for age, sex, race/ethnicity, educational attainment, smoking status, alcohol consumption, income, and total energy, dietary intake of PUFA and omega-6 fatty acid was positively associated with DSST.

The DSST score increased about 0.06 standard deviation (SD) (about 1 score) with each SD increase in these fatty acids (8.8 g/d for PUFA and 7.9 g/d for omega-6) (P values were .02 for PUFA and .01 for omega-6).

However, it’s unclear what an improvement of 1 DSST score means clinically, said Dr. McIntyre. “The P value is significant, but how does that translate? Does this mean a person can now think more clearly or function better?”
 

‘Million dollar question’ remains unanswered

The fact that omega-6, considered neuroinflammatory, was associated with improved DSST score illustrates the complexity of this field, said Dr. McIntyre.

“We’re learning that when it comes to inflammation, many of the molecules in our brain that are implicated as anti-inflammatory can also be pro-inflammatory, so bad guys can be good guys and good guys can be bad guys.”

It speaks to the notion of homeostasis, he added. “Just like a seesaw; when you push this part down, that part goes up.”

The analysis showed the animal fluency score increased about 0.05 SD (around 0.3 score) with each SD (1.1 g/d) increase in dietary intake of omega-3.

There were no significant associations between other dietary fat intake and cognitive performance.

The researchers investigated the role of oxidative stress and antioxidant biomarkers (gamma glutamyl transpeptidase [GGT], bilirubin, uric acid, and vitamin D).

Cells produce oxidative radicals that are normally “mopped up” by our “innate antioxidant capability,” said Dr. McIntyre. “But in states of cognitive impairment, these oxidative stress markers accumulate and they exceed what the normal innate response is able to manage.”

The study showed GGT levels decreased with increased PUFA and omega-6 fatty acid intakes; levels of bilirubin decreased with increase in most dietary fat intakes; uric acid levels decreased with MUFA intake and omega-6/omega-3 ratio; and vitamin D levels increased with omega-3 fatty acid intake but decreased with SFAT intake.

Causal mediation analysis showed the association between dietary intake of fatty acids and DSST performance was partially mediated by GGT levels. However, Dr. McIntyre emphasized that this does not prove causality.

“The million dollar question is, is this the sole explanation for the association? In other words, is it the oxidative stress that caused the cognitive impairment and therefore correcting it improved it, or is it the case that oxidative stress is a proxy of other activities that are also taking place?”
 

A ‘plausible’ link

In an editorial, Candida Rebello, PhD, of the department of integrated physiology and molecular medicine at Pennington Biomedical Research Center, Baton Rouge, La., said the finding that omega-3 and omega-6 fatty acids are positively associated with cognition in older adults makes some sense.

She noted that aging is associated with an overt inflammatory phenotype, and evidence shows these fatty acids are precursors for bioactive molecules that play a role in self-limiting the acute inflammatory response.

Dr. Rebello said the positive association of omega-6 fatty acid with cognition shown in this study contrasts with the “common belief” that increasing dietary intake of these fatty acids enhances inflammation, but agreed the association is “plausible.”

She said it’s “essential” to determine “the underlying mechanisms that regulate the diverse features of inflammation and sort out the processes that protect from neuronal damage and those that contribute towards it.”

She noted the ratio of omega-6 to omega-3 is about 15:1 in the present day Western diet, as opposed to a 1:1 ratio in diets of the past. Omega-3 fatty acids are found in fish oil supplements and fatty fish like mackerel and salmon, while cereal, grains, and vegetable oil are sources of omega-6.

Attaining a measure of balance of fatty acids in the diet may be a “prudent approach,” said Dr. Rebello. “Substituting some meat entrées with fatty fish and polyunsaturated vegetable oils with monounsaturated fats such as olive oil are small changes that are likely to garner adherence.”

Dr. Rebello noted that the study used NHANES food intake data, which rely on participant self-report and so may not be accurate.

The study received funding from the MOE (Ministry of Education in China) Project of Humanities and Social Sciences and the Research Startup Fund of Southwest University. Dr. McIntyre has received research grant support from CIHR/GACD/Chinese National Natural Research Foundation and speaker/consultation fees from Lundbeck, Janssen, Purdue, Pfizer, Otsuka, Takeda, Neurocrine, Sunovion, Bausch Health, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular, NewBridge Pharmaceuticals, and AbbVie. He is a CEO of Braxia Scientific Corp.

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

Berries, red wine, and other foods rich in flavonoids are associated with a lower risk for death in patients with Parkinson’s disease (PD), new research suggests.

In a prospective analysis of more than 1,200 participants with an eventual PD diagnosis, those who ate three or more servings of flavonoid-rich foods a week had a 70% lower mortality versus those consuming one or fewer servings of such foods per month.

“Adopting a healthy dietary pattern that is high in colorful fruits and veggies like berries, even after a Parkinson diagnosis, could slow disease progression and improve survival rate,” study investigator Xiang Gao, MD, PhD, professor and director, Nutritional Epidemiology Lab, department of nutritional sciences, Penn State University, University Park, said in an interview.

The findings were published online Jan. 26, 2022, in Neurology.

First evidence of survival advantage

Flavonoids are plant-derived polyphenolic molecules found in fruits such as berries, apples, and oranges; vegetables such as kale and broccoli; and beverages, including tea and red wine. They are the dietary components that give many foods their vibrant color.

Certain flavonoids have been shown previously to have antioxidant and anti-inflammatory properties.

A previous study by Dr. Gao and colleagues showed that flavonoids were associated with a lower future risk for developing PD. However, it did not provide evidence these nutrients improved survival rates among PD patients.

The new analysis included participants from the ongoing Nurses’ Health Study (NHS) of female registered nurses, which began in 1976, and male participants from the ongoing Health Professionals Follow-up Study (HPFS), which began in 1986.

All participants answered questionnaires at baseline and then biennially to update information on demographics, lifestyle, medical history, and occurrence of chronic disease.

Using validated food-frequency questionnaires completed every 4 years, researchers assessed dietary intakes of total flavonoid, six flavonoid subclasses, and flavonoid-rich foods such as tea, apples, berries, oranges and orange juice, and red wine.

They examined flavonoid intake both before and after a PD diagnosis to minimize the potential for reverse causality. The investigators noted that patients with PD have difficulty swallowing and handling food and cutlery, which could impact their consumption of flavonoid-rich foods.

Frequency of consumption of flavonoid-rich foods was categorized into four groups: one or less servings per month (the reference group), one to three servings per month, one to two servings per week, and three or more servings per week.

The analysis included 599 women and 652 men who were newly diagnosed with PD. The mean age at PD diagnosis was 72 years, and the mean time between the last prediagnosis dietary assessment and PD diagnosis was 32 months.

The primary outcome measure was all-cause mortality. There were 528 deaths in men and 416 deaths in women during an average of 33 years of follow-up.
 

Neuroprotective pathway?

After controlling for age, lifestyle behaviors, medical history, and total energy and caffeine intake, results showed that higher total flavonoid intake before PD diagnosis was associated with a lower risk for all-cause mortality after diagnosis in men, with a hazard ratio of 0.53 (95% confidence interval, 0.39-0.71) when comparing the highest and lowest quartiles (P for trend < .001).

However, this association was not found in women (HR, 0.93; 95% CI, 0.68-1.28; P for trend = .69).

The pooled HR was 0.70 (95% CI, 0.40-1.22; P for trend = .25) with significant heterogeneity (P = .01).

There were significant associations between a higher prediagnosis intake of certain flavonoids and lower mortality risk. The pooled HR comparing the highest versus lowest intake quartiles was 0.66 for anthocyanin, 0.78 for flavones, and 0.69 for flavan-3-ols (P < .05 for all).

Compared with participants who consumed less than one serving a month, those consuming more than three servings a week prediagnosis of berries or red wine had a lower mortality risk (pooled HR, 0.77; 95% CI, 0.58-1.02 for berries and HR, 0.68; 95% CI, 0.51-0.91 for red wine).

After PD diagnosis, higher flavonoid consumption was associated with better survival rates in both men and women.

It’s unclear why there was a gender difference in the association between prediagnosis flavonoid intake and mortality but not for postdiagnosis flavonoid intakes, Dr. Gao said.

A potential neuroprotective pathway by which flavonoids reduce mortality in PD involves direct radical scavenging, which lowers oxidative stress and chronic neuroinflammation levels, he noted.

“Certain flavonoids, for example, anthocyanins, have been shown to exert antiapoptosis effects and protect cognition and motor functions. They could also increase dopamine release,” Dr. Gao added.

Study limitations included not having detailed information on participants’ PD disease severity and that both the NHS and HPFS include predominantly White health care professionals, which limits the generalizability of the results, the investigators noted.
 

No direct link

Commenting on the findings, Michael S. Okun, MD, medical advisor at the Parkinson’s Foundation and director of the Norman Fixel Institute for Neurological Diseases, University of Florida Health, Gainesville, said the study adds to growing evidence suggesting “subsets of flavonoids and especially berries and wine will have benefits pre- and post–Parkinson’s disease diagnosis.”

However, he emphasized that patients should not take up drinking red wine just to improve survival.

“We don’t recommend that folks who are already diagnosed with Parkinson’s drink alcohol, especially without physician supervision,” said Dr. Okun, who was not involved with the research.

Also commenting for this article, Gunter Kuhnle, PhD, professor of nutrition and food science, University of Reading (England), said because the study doesn’t appear to adjust for socioeconomic status, the results may be driven by factors such as income and education and not food intake.

The study found a beneficial association with anthocyanins, which are mainly found in expensive berries, and with flavan-3-ols found mainly in tea, which in the United States is often a marker of higher income, said Dr. Kuhnle.

The advantage of assessing dietary intake of flavonoids using a food-frequency questionnaire, as was done in this study, is that it captures long-term patterns. However, the disadvantage is a loss in “resolution” by combining similar foods, Dr. Kuhnle noted.

Since flavonoids are found in most fruits and vegetables, high flavonoid intake “might simply be a marker of fruit and vegetable intake and therefore a ‘healthy’ dietary pattern,” he concluded.

The study received funding from the National Institute of Neurological Disorders and Stroke. Dr. Gao and Dr. Okun reported no relevant financial relationships. Dr. Kuhnle has conducted research into the associations between flavanol and health, some of which has been funded by Mars.

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

Berries, red wine, and other foods rich in flavonoids are associated with a lower risk for death in patients with Parkinson’s disease (PD), new research suggests.

In a prospective analysis of more than 1,200 participants with an eventual PD diagnosis, those who ate three or more servings of flavonoid-rich foods a week had a 70% lower mortality versus those consuming one or fewer servings of such foods per month.

“Adopting a healthy dietary pattern that is high in colorful fruits and veggies like berries, even after a Parkinson diagnosis, could slow disease progression and improve survival rate,” study investigator Xiang Gao, MD, PhD, professor and director, Nutritional Epidemiology Lab, department of nutritional sciences, Penn State University, University Park, said in an interview.

The findings were published online Jan. 26, 2022, in Neurology.

First evidence of survival advantage

Flavonoids are plant-derived polyphenolic molecules found in fruits such as berries, apples, and oranges; vegetables such as kale and broccoli; and beverages, including tea and red wine. They are the dietary components that give many foods their vibrant color.

Certain flavonoids have been shown previously to have antioxidant and anti-inflammatory properties.

A previous study by Dr. Gao and colleagues showed that flavonoids were associated with a lower future risk for developing PD. However, it did not provide evidence these nutrients improved survival rates among PD patients.

The new analysis included participants from the ongoing Nurses’ Health Study (NHS) of female registered nurses, which began in 1976, and male participants from the ongoing Health Professionals Follow-up Study (HPFS), which began in 1986.

All participants answered questionnaires at baseline and then biennially to update information on demographics, lifestyle, medical history, and occurrence of chronic disease.

Using validated food-frequency questionnaires completed every 4 years, researchers assessed dietary intakes of total flavonoid, six flavonoid subclasses, and flavonoid-rich foods such as tea, apples, berries, oranges and orange juice, and red wine.

They examined flavonoid intake both before and after a PD diagnosis to minimize the potential for reverse causality. The investigators noted that patients with PD have difficulty swallowing and handling food and cutlery, which could impact their consumption of flavonoid-rich foods.

Frequency of consumption of flavonoid-rich foods was categorized into four groups: one or less servings per month (the reference group), one to three servings per month, one to two servings per week, and three or more servings per week.

The analysis included 599 women and 652 men who were newly diagnosed with PD. The mean age at PD diagnosis was 72 years, and the mean time between the last prediagnosis dietary assessment and PD diagnosis was 32 months.

The primary outcome measure was all-cause mortality. There were 528 deaths in men and 416 deaths in women during an average of 33 years of follow-up.
 

Neuroprotective pathway?

After controlling for age, lifestyle behaviors, medical history, and total energy and caffeine intake, results showed that higher total flavonoid intake before PD diagnosis was associated with a lower risk for all-cause mortality after diagnosis in men, with a hazard ratio of 0.53 (95% confidence interval, 0.39-0.71) when comparing the highest and lowest quartiles (P for trend < .001).

However, this association was not found in women (HR, 0.93; 95% CI, 0.68-1.28; P for trend = .69).

The pooled HR was 0.70 (95% CI, 0.40-1.22; P for trend = .25) with significant heterogeneity (P = .01).

There were significant associations between a higher prediagnosis intake of certain flavonoids and lower mortality risk. The pooled HR comparing the highest versus lowest intake quartiles was 0.66 for anthocyanin, 0.78 for flavones, and 0.69 for flavan-3-ols (P < .05 for all).

Compared with participants who consumed less than one serving a month, those consuming more than three servings a week prediagnosis of berries or red wine had a lower mortality risk (pooled HR, 0.77; 95% CI, 0.58-1.02 for berries and HR, 0.68; 95% CI, 0.51-0.91 for red wine).

After PD diagnosis, higher flavonoid consumption was associated with better survival rates in both men and women.

It’s unclear why there was a gender difference in the association between prediagnosis flavonoid intake and mortality but not for postdiagnosis flavonoid intakes, Dr. Gao said.

A potential neuroprotective pathway by which flavonoids reduce mortality in PD involves direct radical scavenging, which lowers oxidative stress and chronic neuroinflammation levels, he noted.

“Certain flavonoids, for example, anthocyanins, have been shown to exert antiapoptosis effects and protect cognition and motor functions. They could also increase dopamine release,” Dr. Gao added.

Study limitations included not having detailed information on participants’ PD disease severity and that both the NHS and HPFS include predominantly White health care professionals, which limits the generalizability of the results, the investigators noted.
 

No direct link

Commenting on the findings, Michael S. Okun, MD, medical advisor at the Parkinson’s Foundation and director of the Norman Fixel Institute for Neurological Diseases, University of Florida Health, Gainesville, said the study adds to growing evidence suggesting “subsets of flavonoids and especially berries and wine will have benefits pre- and post–Parkinson’s disease diagnosis.”

However, he emphasized that patients should not take up drinking red wine just to improve survival.

“We don’t recommend that folks who are already diagnosed with Parkinson’s drink alcohol, especially without physician supervision,” said Dr. Okun, who was not involved with the research.

Also commenting for this article, Gunter Kuhnle, PhD, professor of nutrition and food science, University of Reading (England), said because the study doesn’t appear to adjust for socioeconomic status, the results may be driven by factors such as income and education and not food intake.

The study found a beneficial association with anthocyanins, which are mainly found in expensive berries, and with flavan-3-ols found mainly in tea, which in the United States is often a marker of higher income, said Dr. Kuhnle.

The advantage of assessing dietary intake of flavonoids using a food-frequency questionnaire, as was done in this study, is that it captures long-term patterns. However, the disadvantage is a loss in “resolution” by combining similar foods, Dr. Kuhnle noted.

Since flavonoids are found in most fruits and vegetables, high flavonoid intake “might simply be a marker of fruit and vegetable intake and therefore a ‘healthy’ dietary pattern,” he concluded.

The study received funding from the National Institute of Neurological Disorders and Stroke. Dr. Gao and Dr. Okun reported no relevant financial relationships. Dr. Kuhnle has conducted research into the associations between flavanol and health, some of which has been funded by Mars.

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

Berries, red wine, and other foods rich in flavonoids are associated with a lower risk for death in patients with Parkinson’s disease (PD), new research suggests.

In a prospective analysis of more than 1,200 participants with an eventual PD diagnosis, those who ate three or more servings of flavonoid-rich foods a week had a 70% lower mortality versus those consuming one or fewer servings of such foods per month.

“Adopting a healthy dietary pattern that is high in colorful fruits and veggies like berries, even after a Parkinson diagnosis, could slow disease progression and improve survival rate,” study investigator Xiang Gao, MD, PhD, professor and director, Nutritional Epidemiology Lab, department of nutritional sciences, Penn State University, University Park, said in an interview.

The findings were published online Jan. 26, 2022, in Neurology.

First evidence of survival advantage

Flavonoids are plant-derived polyphenolic molecules found in fruits such as berries, apples, and oranges; vegetables such as kale and broccoli; and beverages, including tea and red wine. They are the dietary components that give many foods their vibrant color.

Certain flavonoids have been shown previously to have antioxidant and anti-inflammatory properties.

A previous study by Dr. Gao and colleagues showed that flavonoids were associated with a lower future risk for developing PD. However, it did not provide evidence these nutrients improved survival rates among PD patients.

The new analysis included participants from the ongoing Nurses’ Health Study (NHS) of female registered nurses, which began in 1976, and male participants from the ongoing Health Professionals Follow-up Study (HPFS), which began in 1986.

All participants answered questionnaires at baseline and then biennially to update information on demographics, lifestyle, medical history, and occurrence of chronic disease.

Using validated food-frequency questionnaires completed every 4 years, researchers assessed dietary intakes of total flavonoid, six flavonoid subclasses, and flavonoid-rich foods such as tea, apples, berries, oranges and orange juice, and red wine.

They examined flavonoid intake both before and after a PD diagnosis to minimize the potential for reverse causality. The investigators noted that patients with PD have difficulty swallowing and handling food and cutlery, which could impact their consumption of flavonoid-rich foods.

Frequency of consumption of flavonoid-rich foods was categorized into four groups: one or less servings per month (the reference group), one to three servings per month, one to two servings per week, and three or more servings per week.

The analysis included 599 women and 652 men who were newly diagnosed with PD. The mean age at PD diagnosis was 72 years, and the mean time between the last prediagnosis dietary assessment and PD diagnosis was 32 months.

The primary outcome measure was all-cause mortality. There were 528 deaths in men and 416 deaths in women during an average of 33 years of follow-up.
 

Neuroprotective pathway?

After controlling for age, lifestyle behaviors, medical history, and total energy and caffeine intake, results showed that higher total flavonoid intake before PD diagnosis was associated with a lower risk for all-cause mortality after diagnosis in men, with a hazard ratio of 0.53 (95% confidence interval, 0.39-0.71) when comparing the highest and lowest quartiles (P for trend < .001).

However, this association was not found in women (HR, 0.93; 95% CI, 0.68-1.28; P for trend = .69).

The pooled HR was 0.70 (95% CI, 0.40-1.22; P for trend = .25) with significant heterogeneity (P = .01).

There were significant associations between a higher prediagnosis intake of certain flavonoids and lower mortality risk. The pooled HR comparing the highest versus lowest intake quartiles was 0.66 for anthocyanin, 0.78 for flavones, and 0.69 for flavan-3-ols (P < .05 for all).

Compared with participants who consumed less than one serving a month, those consuming more than three servings a week prediagnosis of berries or red wine had a lower mortality risk (pooled HR, 0.77; 95% CI, 0.58-1.02 for berries and HR, 0.68; 95% CI, 0.51-0.91 for red wine).

After PD diagnosis, higher flavonoid consumption was associated with better survival rates in both men and women.

It’s unclear why there was a gender difference in the association between prediagnosis flavonoid intake and mortality but not for postdiagnosis flavonoid intakes, Dr. Gao said.

A potential neuroprotective pathway by which flavonoids reduce mortality in PD involves direct radical scavenging, which lowers oxidative stress and chronic neuroinflammation levels, he noted.

“Certain flavonoids, for example, anthocyanins, have been shown to exert antiapoptosis effects and protect cognition and motor functions. They could also increase dopamine release,” Dr. Gao added.

Study limitations included not having detailed information on participants’ PD disease severity and that both the NHS and HPFS include predominantly White health care professionals, which limits the generalizability of the results, the investigators noted.
 

No direct link

Commenting on the findings, Michael S. Okun, MD, medical advisor at the Parkinson’s Foundation and director of the Norman Fixel Institute for Neurological Diseases, University of Florida Health, Gainesville, said the study adds to growing evidence suggesting “subsets of flavonoids and especially berries and wine will have benefits pre- and post–Parkinson’s disease diagnosis.”

However, he emphasized that patients should not take up drinking red wine just to improve survival.

“We don’t recommend that folks who are already diagnosed with Parkinson’s drink alcohol, especially without physician supervision,” said Dr. Okun, who was not involved with the research.

Also commenting for this article, Gunter Kuhnle, PhD, professor of nutrition and food science, University of Reading (England), said because the study doesn’t appear to adjust for socioeconomic status, the results may be driven by factors such as income and education and not food intake.

The study found a beneficial association with anthocyanins, which are mainly found in expensive berries, and with flavan-3-ols found mainly in tea, which in the United States is often a marker of higher income, said Dr. Kuhnle.

The advantage of assessing dietary intake of flavonoids using a food-frequency questionnaire, as was done in this study, is that it captures long-term patterns. However, the disadvantage is a loss in “resolution” by combining similar foods, Dr. Kuhnle noted.

Since flavonoids are found in most fruits and vegetables, high flavonoid intake “might simply be a marker of fruit and vegetable intake and therefore a ‘healthy’ dietary pattern,” he concluded.

The study received funding from the National Institute of Neurological Disorders and Stroke. Dr. Gao and Dr. Okun reported no relevant financial relationships. Dr. Kuhnle has conducted research into the associations between flavanol and health, some of which has been funded by Mars.

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

Impaired cognition associated with COVID-19 appears to have a biological versus psychological basis, early research suggests. Investigators found abnormalities in cerebrospinal fluid (CSF) and other risk factors, including diabetes and hypertension, present in individuals with mild COVID-19 experiencing persistent cognitive problems, often referred to as “brain fog.”

“We’re seeing changes to the [CSF] in the brain of most people who report cognitive changes,” said Joanna Hellmuth, MD, assistant professor of neurology, Memory and Aging Center, University of California, San Francisco. “We’re just in the beginning stages, but I hope this study will provide some legitimacy to this being a true neurologic condition.”

The study was published online Jan. 18, 2022, in Annals of Clinical and Translational Neurology.
 

No guidance

There is currently no guidance on how to identify patients with COVID-related cognitive changes, said Dr. Hellmuth. “The term ‘brain fog’ is not based in science or medicine, but that’s the most common term we use to describe this.”

The analysis included adults with confirmed SARS-CoV-2 infection not requiring hospitalization who were enrolled in the Long-term Impact of Infection with Novel Coronavirus study.

Participants underwent a structured interview that covered COVID-19 illness, past medical history, preexisting cognitive risk factors, medications, and cognitive symptoms following onset of COVID-19. They also completed an in-person battery of cognitive tests.

The analysis included 22 participants with at least one new cognitive symptom who had cognitive post-acute sequelae of SARS-CoV-2 infection (PASC). Ten cognitive controls reported no new cognitive symptoms after acute infection.

Participants were a median age of 41 years, had a median of 16 years of education, and were assessed a median of 10.1 months from their first COVID-19 symptom. There were no group differences in terms of age, gender, years of education, or distribution of race/ethnicity (all P > .05).

Among those with cognitive PASC, 43% reported cognitive symptoms starting 1 or more months after the first COVID symptom. About 29% reported cognitive changes started 2 or more months after their first COVID symptom.

“The immune system could be altered in some way after the infection, and perhaps that’s what’s contributing to these delayed onset cognitive changes,” said Dr. Hellmuth.

Compared with controls, participants with cognitive PASC had more preexisting cognitive risk factors (a median of 2.5 vs. 0; P = .03). These included hypertension and diabetes, which increase the risk of stroke, mild cognitive impairment, vascular dementia, traumatic brain injury, (TBI), learning disabilities, anxiety, depression, stimulant use, and ADHD, which may make the brain more vulnerable to executive functioning problems.

Dr. Hellmuth noted that the study wasn’t powered to determine whether any individual risk factor was associated with risk of cognitive changes.

As there are no published neuropsychological testing criteria for cognitive PASC, the researchers applied the equivalent criteria for HIV-associated neurocognitive disorder (HAND), a similar, virally associated cognitive disorder. Only 59% of those with cognitive PASC met equivalent HAND criteria for objective cognitive impairment versus 70% of cognitive controls. This, the investigators noted, highlights “the challenges and incongruities of using subjective, versus objective cognitive assessments for diagnosis.”
 

Is self-report enough?

While there is currently “nothing objective doctors can hang their hats on to say ‘you do’ or ‘you don’t’ have cognitive changes related to COVID,” using the HAND criteria is “not particularly helpful,” said Dr. Hellmuth. “Comparing an individual to a population-based norm in this case is really nuanced, and we shouldn’t rely on this solely to determine whether they do, or don’t, have cognitive changes.”

Perhaps self-reports in this case are “enough” said Dr. Hellmuth. “People know their brains better than anyone else, better than any doctor will.”

A total of 13 in the cognitive PASC group and 4 in the control group consented to a lumbar puncture. Cognitive PASC participants were older than controls (median of 47 vs. 28 years; P = .03) with no other between-group differences.

Overall, 77% of participants with cognitive PASC had a CSF abnormality, compared with 0% of cognitive controls (P = .01). CSF abnormalities included elevated protein levels with no other explainable cause in 2 of the 13 subjects with PASC, which Dr. Hellmuth said is typically a marker of inflammation.

Researchers also noted abnormal oligoclonal banding, a collection of antibodies, in the blood or brain fluid. These were identified in 69% of participants with cognitive PASC, compared with 0% of cognitive controls (P = .03).

“When we find this pattern in both blood and brain, it suggests a systemic inflammatory disorder,” although “we have no idea what these antibodies are targeting,” said Dr. Hellmuth.

The study represents “the very beginning stages” of PASC becoming a medical diagnosis “where doctors know what to call it, how to treat it, and how to do blood and cerebrospinal fluid tests to diagnose it,” said Dr. Hellmuth.

She hopes PASC will receive medical legitimacy just as TBI has. In years past, a player was hit on the head or had their “bell rung,” simply returned to the field. “Now that we understand the science, we call it a mild TBI or concussion, and we have a very different medical approach to it.”

A limitation of the study was the small sample size, which may hinder the results’ validity. In addition, the study demographics may not reflect the broader population of those impacted by PASC.
 

‘A first substantial step’

Commenting on the research, William Schaffner, MD, professor, division of infectious diseases, Vanderbilt University Medical Center, Nashville, Tenn., said the new results represent “a first substantial step on the road to trying to find out what’s going on” with COVID patients dealing with cognitive issues.

Dr. Schaffner noted that elevated protein levels, identified in some study subjects, “is usually a consequence of previous inflammation” and is “a very interesting” finding. “In people who are otherwise normal, if you do a lumbar puncture, you don’t find elevated proteins.”

However, he noted the “diversity of results” from CSF examinations. “A single pattern does not leap out.”

What the researchers are observing “is not just a phenomenon of the mind or just something psychological,” said Dr. Schaffner. “Something physical is going on here.”

The study was funded by grants from the National Institute of Mental Health and the National Institute of Neurological Disorders and Stroke. Dr. Hellmuth received grant support from the National Institutes of Health/NIMH supporting this work and personal fees for medical-legal consultation outside of the submitted work. Dr. Schaffner has disclosed not relevant financial relationships.

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

Impaired cognition associated with COVID-19 appears to have a biological versus psychological basis, early research suggests. Investigators found abnormalities in cerebrospinal fluid (CSF) and other risk factors, including diabetes and hypertension, present in individuals with mild COVID-19 experiencing persistent cognitive problems, often referred to as “brain fog.”

“We’re seeing changes to the [CSF] in the brain of most people who report cognitive changes,” said Joanna Hellmuth, MD, assistant professor of neurology, Memory and Aging Center, University of California, San Francisco. “We’re just in the beginning stages, but I hope this study will provide some legitimacy to this being a true neurologic condition.”

The study was published online Jan. 18, 2022, in Annals of Clinical and Translational Neurology.
 

No guidance

There is currently no guidance on how to identify patients with COVID-related cognitive changes, said Dr. Hellmuth. “The term ‘brain fog’ is not based in science or medicine, but that’s the most common term we use to describe this.”

The analysis included adults with confirmed SARS-CoV-2 infection not requiring hospitalization who were enrolled in the Long-term Impact of Infection with Novel Coronavirus study.

Participants underwent a structured interview that covered COVID-19 illness, past medical history, preexisting cognitive risk factors, medications, and cognitive symptoms following onset of COVID-19. They also completed an in-person battery of cognitive tests.

The analysis included 22 participants with at least one new cognitive symptom who had cognitive post-acute sequelae of SARS-CoV-2 infection (PASC). Ten cognitive controls reported no new cognitive symptoms after acute infection.

Participants were a median age of 41 years, had a median of 16 years of education, and were assessed a median of 10.1 months from their first COVID-19 symptom. There were no group differences in terms of age, gender, years of education, or distribution of race/ethnicity (all P > .05).

Among those with cognitive PASC, 43% reported cognitive symptoms starting 1 or more months after the first COVID symptom. About 29% reported cognitive changes started 2 or more months after their first COVID symptom.

“The immune system could be altered in some way after the infection, and perhaps that’s what’s contributing to these delayed onset cognitive changes,” said Dr. Hellmuth.

Compared with controls, participants with cognitive PASC had more preexisting cognitive risk factors (a median of 2.5 vs. 0; P = .03). These included hypertension and diabetes, which increase the risk of stroke, mild cognitive impairment, vascular dementia, traumatic brain injury, (TBI), learning disabilities, anxiety, depression, stimulant use, and ADHD, which may make the brain more vulnerable to executive functioning problems.

Dr. Hellmuth noted that the study wasn’t powered to determine whether any individual risk factor was associated with risk of cognitive changes.

As there are no published neuropsychological testing criteria for cognitive PASC, the researchers applied the equivalent criteria for HIV-associated neurocognitive disorder (HAND), a similar, virally associated cognitive disorder. Only 59% of those with cognitive PASC met equivalent HAND criteria for objective cognitive impairment versus 70% of cognitive controls. This, the investigators noted, highlights “the challenges and incongruities of using subjective, versus objective cognitive assessments for diagnosis.”
 

Is self-report enough?

While there is currently “nothing objective doctors can hang their hats on to say ‘you do’ or ‘you don’t’ have cognitive changes related to COVID,” using the HAND criteria is “not particularly helpful,” said Dr. Hellmuth. “Comparing an individual to a population-based norm in this case is really nuanced, and we shouldn’t rely on this solely to determine whether they do, or don’t, have cognitive changes.”

Perhaps self-reports in this case are “enough” said Dr. Hellmuth. “People know their brains better than anyone else, better than any doctor will.”

A total of 13 in the cognitive PASC group and 4 in the control group consented to a lumbar puncture. Cognitive PASC participants were older than controls (median of 47 vs. 28 years; P = .03) with no other between-group differences.

Overall, 77% of participants with cognitive PASC had a CSF abnormality, compared with 0% of cognitive controls (P = .01). CSF abnormalities included elevated protein levels with no other explainable cause in 2 of the 13 subjects with PASC, which Dr. Hellmuth said is typically a marker of inflammation.

Researchers also noted abnormal oligoclonal banding, a collection of antibodies, in the blood or brain fluid. These were identified in 69% of participants with cognitive PASC, compared with 0% of cognitive controls (P = .03).

“When we find this pattern in both blood and brain, it suggests a systemic inflammatory disorder,” although “we have no idea what these antibodies are targeting,” said Dr. Hellmuth.

The study represents “the very beginning stages” of PASC becoming a medical diagnosis “where doctors know what to call it, how to treat it, and how to do blood and cerebrospinal fluid tests to diagnose it,” said Dr. Hellmuth.

She hopes PASC will receive medical legitimacy just as TBI has. In years past, a player was hit on the head or had their “bell rung,” simply returned to the field. “Now that we understand the science, we call it a mild TBI or concussion, and we have a very different medical approach to it.”

A limitation of the study was the small sample size, which may hinder the results’ validity. In addition, the study demographics may not reflect the broader population of those impacted by PASC.
 

‘A first substantial step’

Commenting on the research, William Schaffner, MD, professor, division of infectious diseases, Vanderbilt University Medical Center, Nashville, Tenn., said the new results represent “a first substantial step on the road to trying to find out what’s going on” with COVID patients dealing with cognitive issues.

Dr. Schaffner noted that elevated protein levels, identified in some study subjects, “is usually a consequence of previous inflammation” and is “a very interesting” finding. “In people who are otherwise normal, if you do a lumbar puncture, you don’t find elevated proteins.”

However, he noted the “diversity of results” from CSF examinations. “A single pattern does not leap out.”

What the researchers are observing “is not just a phenomenon of the mind or just something psychological,” said Dr. Schaffner. “Something physical is going on here.”

The study was funded by grants from the National Institute of Mental Health and the National Institute of Neurological Disorders and Stroke. Dr. Hellmuth received grant support from the National Institutes of Health/NIMH supporting this work and personal fees for medical-legal consultation outside of the submitted work. Dr. Schaffner has disclosed not relevant financial relationships.

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

Impaired cognition associated with COVID-19 appears to have a biological versus psychological basis, early research suggests. Investigators found abnormalities in cerebrospinal fluid (CSF) and other risk factors, including diabetes and hypertension, present in individuals with mild COVID-19 experiencing persistent cognitive problems, often referred to as “brain fog.”

“We’re seeing changes to the [CSF] in the brain of most people who report cognitive changes,” said Joanna Hellmuth, MD, assistant professor of neurology, Memory and Aging Center, University of California, San Francisco. “We’re just in the beginning stages, but I hope this study will provide some legitimacy to this being a true neurologic condition.”

The study was published online Jan. 18, 2022, in Annals of Clinical and Translational Neurology.
 

No guidance

There is currently no guidance on how to identify patients with COVID-related cognitive changes, said Dr. Hellmuth. “The term ‘brain fog’ is not based in science or medicine, but that’s the most common term we use to describe this.”

The analysis included adults with confirmed SARS-CoV-2 infection not requiring hospitalization who were enrolled in the Long-term Impact of Infection with Novel Coronavirus study.

Participants underwent a structured interview that covered COVID-19 illness, past medical history, preexisting cognitive risk factors, medications, and cognitive symptoms following onset of COVID-19. They also completed an in-person battery of cognitive tests.

The analysis included 22 participants with at least one new cognitive symptom who had cognitive post-acute sequelae of SARS-CoV-2 infection (PASC). Ten cognitive controls reported no new cognitive symptoms after acute infection.

Participants were a median age of 41 years, had a median of 16 years of education, and were assessed a median of 10.1 months from their first COVID-19 symptom. There were no group differences in terms of age, gender, years of education, or distribution of race/ethnicity (all P > .05).

Among those with cognitive PASC, 43% reported cognitive symptoms starting 1 or more months after the first COVID symptom. About 29% reported cognitive changes started 2 or more months after their first COVID symptom.

“The immune system could be altered in some way after the infection, and perhaps that’s what’s contributing to these delayed onset cognitive changes,” said Dr. Hellmuth.

Compared with controls, participants with cognitive PASC had more preexisting cognitive risk factors (a median of 2.5 vs. 0; P = .03). These included hypertension and diabetes, which increase the risk of stroke, mild cognitive impairment, vascular dementia, traumatic brain injury, (TBI), learning disabilities, anxiety, depression, stimulant use, and ADHD, which may make the brain more vulnerable to executive functioning problems.

Dr. Hellmuth noted that the study wasn’t powered to determine whether any individual risk factor was associated with risk of cognitive changes.

As there are no published neuropsychological testing criteria for cognitive PASC, the researchers applied the equivalent criteria for HIV-associated neurocognitive disorder (HAND), a similar, virally associated cognitive disorder. Only 59% of those with cognitive PASC met equivalent HAND criteria for objective cognitive impairment versus 70% of cognitive controls. This, the investigators noted, highlights “the challenges and incongruities of using subjective, versus objective cognitive assessments for diagnosis.”
 

Is self-report enough?

While there is currently “nothing objective doctors can hang their hats on to say ‘you do’ or ‘you don’t’ have cognitive changes related to COVID,” using the HAND criteria is “not particularly helpful,” said Dr. Hellmuth. “Comparing an individual to a population-based norm in this case is really nuanced, and we shouldn’t rely on this solely to determine whether they do, or don’t, have cognitive changes.”

Perhaps self-reports in this case are “enough” said Dr. Hellmuth. “People know their brains better than anyone else, better than any doctor will.”

A total of 13 in the cognitive PASC group and 4 in the control group consented to a lumbar puncture. Cognitive PASC participants were older than controls (median of 47 vs. 28 years; P = .03) with no other between-group differences.

Overall, 77% of participants with cognitive PASC had a CSF abnormality, compared with 0% of cognitive controls (P = .01). CSF abnormalities included elevated protein levels with no other explainable cause in 2 of the 13 subjects with PASC, which Dr. Hellmuth said is typically a marker of inflammation.

Researchers also noted abnormal oligoclonal banding, a collection of antibodies, in the blood or brain fluid. These were identified in 69% of participants with cognitive PASC, compared with 0% of cognitive controls (P = .03).

“When we find this pattern in both blood and brain, it suggests a systemic inflammatory disorder,” although “we have no idea what these antibodies are targeting,” said Dr. Hellmuth.

The study represents “the very beginning stages” of PASC becoming a medical diagnosis “where doctors know what to call it, how to treat it, and how to do blood and cerebrospinal fluid tests to diagnose it,” said Dr. Hellmuth.

She hopes PASC will receive medical legitimacy just as TBI has. In years past, a player was hit on the head or had their “bell rung,” simply returned to the field. “Now that we understand the science, we call it a mild TBI or concussion, and we have a very different medical approach to it.”

A limitation of the study was the small sample size, which may hinder the results’ validity. In addition, the study demographics may not reflect the broader population of those impacted by PASC.
 

‘A first substantial step’

Commenting on the research, William Schaffner, MD, professor, division of infectious diseases, Vanderbilt University Medical Center, Nashville, Tenn., said the new results represent “a first substantial step on the road to trying to find out what’s going on” with COVID patients dealing with cognitive issues.

Dr. Schaffner noted that elevated protein levels, identified in some study subjects, “is usually a consequence of previous inflammation” and is “a very interesting” finding. “In people who are otherwise normal, if you do a lumbar puncture, you don’t find elevated proteins.”

However, he noted the “diversity of results” from CSF examinations. “A single pattern does not leap out.”

What the researchers are observing “is not just a phenomenon of the mind or just something psychological,” said Dr. Schaffner. “Something physical is going on here.”

The study was funded by grants from the National Institute of Mental Health and the National Institute of Neurological Disorders and Stroke. Dr. Hellmuth received grant support from the National Institutes of Health/NIMH supporting this work and personal fees for medical-legal consultation outside of the submitted work. Dr. Schaffner has disclosed not relevant financial relationships.

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

Social rhythm therapy (SRT), which uses behavioral strategies to support healthy sleep and other routines, is linked to improved mood and reduced suicide risk in young people with bipolar disorder (BD), early research suggests.

The small study also showed SRT is both feasible and acceptable in this patient population.

Tab1962/iStockphoto.com

Results showed SRT, which was primarily delivered via telehealth sessions, began to show efficacy approximately 6 weeks into the 12-week therapeutic program, the researchers noted.

“Improving the regularity of daily rhythms like sleep, physical activity, and social activities can be really robust in improving mental health and even reducing suicide risk,” study investigator Hilary P. Blumberg, MD, the John and Hope Furth Professor of Psychiatric Neuroscience and director of the mood disorders research program at Yale University, New Haven, Conn., said in an interview.

The findings are published in the American Journal of Psychotherapy.
 

Trigger for depression, mania

Previous research shows unstable circadian rhythms may trigger depressive and manic symptoms – and are risk factors for suicidal thoughts and behaviors. Although interpersonal and social rhythm therapy has shown promise in patients with mood disorders, there is little research focusing only on the social rhythm aspect of the therapy.

The researchers only examined SRT, modified to create a therapeutic program aimed at adolescents and young adults.

The study included 13 participants (mean age, 20.5 years) with BD and a score of 15 or more on the 29-item Hamilton Depression Rating Scale (HDRS-29) and/or a score of 12 or more on the Young Mania Rating Scale (YMRS).

Participants were enrolled in the National Institute of Mental Health Brain Emotion Circuitry Targeted Self-Monitoring and Regulation Therapy (BE-SMART) program, which requires MRI sessions at three in-person visits to assess brain changes with the therapy. All but one participant was taking mood-stabilizing medications.

“We didn’t ask them to come off medications because we didn’t want to exacerbate things,” said Dr. Blumberg. She added the therapeutic approach “could be adjunctive to further improve symptoms and reduce risk.”

SRT was delivered in 12 weekly sessions. The majority occurred on a secure video platform. Three were conducted in person.

Working with a therapist, participants were taught how to follow a daily routine. Dr. Blumberg noted this is not just a matter of going to sleep and getting up at the same time every day, but thoroughly reviewing details of all daily activities and routines, including who participants eat with and when, their exercise schedule, and social engagements.

Each week, participants completed the five-item version of the Social Rhythm Metric. At the end of the intervention, they also completed the Client Satisfaction Questionnaire (CSQ). Scores on the CSQ range from 8 to 32, with scores of 26-32 indicating “excellent” satisfaction.

In addition, participants and therapists completed the Working Alliance Inventory, which assesses the client-therapist relationship by asking about such things as degree of comfort and respect.

Before and after the intervention, participants reported the regularity of their social rhythms using the Brief Social Rhythm Scale (BSRS) and risk for suicidal behavior using a subscale of the Concise Health Risk Tracking (CHRT) scale.
 

High retention, ‘excellent satisfaction’

Results showed 10 of the 13 participants (9 females) completed all study procedures, for a retention rate of 77%. Treatment satisfaction was excellent (mean CSQ, 29.4).

Both therapists and participants had high scores on all aspects of the Working Alliance Inventory scale.

“High treatment retention, excellent client satisfaction, and strong working alliance scores support the feasibility and acceptability of this intervention for adolescents and young adults with bipolar disorder,” the investigators wrote.

Participants showed significant improvement in social rhythm regularity and reductions in depression and manic symptoms as well as suicide propensity (P = .016 for BSRS; .024 for HDRS-29; .028 for YMRS; and .028 for CHRT suicide propensity). Effect sizes were in the moderate to high range.

By the midpoint of the therapy, there were significant improvements in social rhythm regularity and suicide propensity and trend-level reductions in depression, suggesting the potential for early benefits.

Dr. Blumberg noted it is difficult to find a therapy that helps with both depressive and mania symptoms. “An antidepressant may reduce depression, but sometimes can worsen manic symptoms.”
 

Impact on emotional brain circuitry?

The association between improved regularity of social rhythms and reduced suicide propensity persisted even after controlling for mood symptom changes.

“Suicide risk was reduced not just because subjects were less depressed. There’s something about regularizing rhythms that can reduce suicide risk,” said Dr. Blumberg.

The reviewers noted that SRT administered remotely improves accessibility; and this intervention “is well suited to the future of psychotherapy delivery, which will undoubtedly include remote treatment delivery.”

The absence of a comparator condition was cited as a study limitation. The investigators noted the small sample size means the findings should be interpreted cautiously and verified in an adequately powered randomized controlled trial.

The researchers now have early results from the brain scanning component of the study. “Preliminary findings suggest the intervention seems to benefit emotional brain circuitry,” Dr. Blumberg said.

The researchers are about to embark on a new study funded by a grant from the American Foundation of Suicide Prevention. It will investigate SRT in preventing suicide in adolescents and adults to age 29 years with depression or BD.

In addition, the researchers have secured support from the Klingenstein Third Generation Foundation to research prevention in youth at risk for BD – and from Women’s Health Access Matters to examine the therapy in women 50 and older with depression, a population possibly at increased risk for dementia.
 

‘Promising’ results

Commenting on the findings, Michael Thase, MD, professor of psychiatry, University of Pennsylvania, and research psychiatrist at the Corporal Michael J. Crescenz Veterans Affairs Medical Center, both in Philadelphia, praised the study.

“It’s a very, very promising initial study because even though there’s no control group, it does show that participants liked the program, most finished it, and on average, people got quite a bit better,” said Dr. Thase, who was not involved with the research.

The treatment may be especially beneficial for young patients with bipolar disorder who, just by their very age, experience lifestyle disruptions, Dr. Thase noted. Results from a previous study of the therapeutic approach in adults showed “probably half of the adults didn’t take to it.”

However, not everyone in this new study benefited either, as some dropped out, which Dr. Thase noted is not atypical.

“No form of intervention is suitable for everyone,” he said.

The study was supported by grants from the National Institute of Mental Health, AIM Youth Mental Health Foundation, Klingenstein Third Generation Foundation, American Foundation for Suicide Prevention, International Bipolar Foundation, MQ Brighter Futures Program, For the Love of Travis Foundation, and the John and Hope Furth Endowment. Dr. Blumberg and Dr. Thase reported no relevant financial relationships.

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

Social rhythm therapy (SRT), which uses behavioral strategies to support healthy sleep and other routines, is linked to improved mood and reduced suicide risk in young people with bipolar disorder (BD), early research suggests.

The small study also showed SRT is both feasible and acceptable in this patient population.

Tab1962/iStockphoto.com

Results showed SRT, which was primarily delivered via telehealth sessions, began to show efficacy approximately 6 weeks into the 12-week therapeutic program, the researchers noted.

“Improving the regularity of daily rhythms like sleep, physical activity, and social activities can be really robust in improving mental health and even reducing suicide risk,” study investigator Hilary P. Blumberg, MD, the John and Hope Furth Professor of Psychiatric Neuroscience and director of the mood disorders research program at Yale University, New Haven, Conn., said in an interview.

The findings are published in the American Journal of Psychotherapy.
 

Trigger for depression, mania

Previous research shows unstable circadian rhythms may trigger depressive and manic symptoms – and are risk factors for suicidal thoughts and behaviors. Although interpersonal and social rhythm therapy has shown promise in patients with mood disorders, there is little research focusing only on the social rhythm aspect of the therapy.

The researchers only examined SRT, modified to create a therapeutic program aimed at adolescents and young adults.

The study included 13 participants (mean age, 20.5 years) with BD and a score of 15 or more on the 29-item Hamilton Depression Rating Scale (HDRS-29) and/or a score of 12 or more on the Young Mania Rating Scale (YMRS).

Participants were enrolled in the National Institute of Mental Health Brain Emotion Circuitry Targeted Self-Monitoring and Regulation Therapy (BE-SMART) program, which requires MRI sessions at three in-person visits to assess brain changes with the therapy. All but one participant was taking mood-stabilizing medications.

“We didn’t ask them to come off medications because we didn’t want to exacerbate things,” said Dr. Blumberg. She added the therapeutic approach “could be adjunctive to further improve symptoms and reduce risk.”

SRT was delivered in 12 weekly sessions. The majority occurred on a secure video platform. Three were conducted in person.

Working with a therapist, participants were taught how to follow a daily routine. Dr. Blumberg noted this is not just a matter of going to sleep and getting up at the same time every day, but thoroughly reviewing details of all daily activities and routines, including who participants eat with and when, their exercise schedule, and social engagements.

Each week, participants completed the five-item version of the Social Rhythm Metric. At the end of the intervention, they also completed the Client Satisfaction Questionnaire (CSQ). Scores on the CSQ range from 8 to 32, with scores of 26-32 indicating “excellent” satisfaction.

In addition, participants and therapists completed the Working Alliance Inventory, which assesses the client-therapist relationship by asking about such things as degree of comfort and respect.

Before and after the intervention, participants reported the regularity of their social rhythms using the Brief Social Rhythm Scale (BSRS) and risk for suicidal behavior using a subscale of the Concise Health Risk Tracking (CHRT) scale.
 

High retention, ‘excellent satisfaction’

Results showed 10 of the 13 participants (9 females) completed all study procedures, for a retention rate of 77%. Treatment satisfaction was excellent (mean CSQ, 29.4).

Both therapists and participants had high scores on all aspects of the Working Alliance Inventory scale.

“High treatment retention, excellent client satisfaction, and strong working alliance scores support the feasibility and acceptability of this intervention for adolescents and young adults with bipolar disorder,” the investigators wrote.

Participants showed significant improvement in social rhythm regularity and reductions in depression and manic symptoms as well as suicide propensity (P = .016 for BSRS; .024 for HDRS-29; .028 for YMRS; and .028 for CHRT suicide propensity). Effect sizes were in the moderate to high range.

By the midpoint of the therapy, there were significant improvements in social rhythm regularity and suicide propensity and trend-level reductions in depression, suggesting the potential for early benefits.

Dr. Blumberg noted it is difficult to find a therapy that helps with both depressive and mania symptoms. “An antidepressant may reduce depression, but sometimes can worsen manic symptoms.”
 

Impact on emotional brain circuitry?

The association between improved regularity of social rhythms and reduced suicide propensity persisted even after controlling for mood symptom changes.

“Suicide risk was reduced not just because subjects were less depressed. There’s something about regularizing rhythms that can reduce suicide risk,” said Dr. Blumberg.

The reviewers noted that SRT administered remotely improves accessibility; and this intervention “is well suited to the future of psychotherapy delivery, which will undoubtedly include remote treatment delivery.”

The absence of a comparator condition was cited as a study limitation. The investigators noted the small sample size means the findings should be interpreted cautiously and verified in an adequately powered randomized controlled trial.

The researchers now have early results from the brain scanning component of the study. “Preliminary findings suggest the intervention seems to benefit emotional brain circuitry,” Dr. Blumberg said.

The researchers are about to embark on a new study funded by a grant from the American Foundation of Suicide Prevention. It will investigate SRT in preventing suicide in adolescents and adults to age 29 years with depression or BD.

In addition, the researchers have secured support from the Klingenstein Third Generation Foundation to research prevention in youth at risk for BD – and from Women’s Health Access Matters to examine the therapy in women 50 and older with depression, a population possibly at increased risk for dementia.
 

‘Promising’ results

Commenting on the findings, Michael Thase, MD, professor of psychiatry, University of Pennsylvania, and research psychiatrist at the Corporal Michael J. Crescenz Veterans Affairs Medical Center, both in Philadelphia, praised the study.

“It’s a very, very promising initial study because even though there’s no control group, it does show that participants liked the program, most finished it, and on average, people got quite a bit better,” said Dr. Thase, who was not involved with the research.

The treatment may be especially beneficial for young patients with bipolar disorder who, just by their very age, experience lifestyle disruptions, Dr. Thase noted. Results from a previous study of the therapeutic approach in adults showed “probably half of the adults didn’t take to it.”

However, not everyone in this new study benefited either, as some dropped out, which Dr. Thase noted is not atypical.

“No form of intervention is suitable for everyone,” he said.

The study was supported by grants from the National Institute of Mental Health, AIM Youth Mental Health Foundation, Klingenstein Third Generation Foundation, American Foundation for Suicide Prevention, International Bipolar Foundation, MQ Brighter Futures Program, For the Love of Travis Foundation, and the John and Hope Furth Endowment. Dr. Blumberg and Dr. Thase reported no relevant financial relationships.

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

Social rhythm therapy (SRT), which uses behavioral strategies to support healthy sleep and other routines, is linked to improved mood and reduced suicide risk in young people with bipolar disorder (BD), early research suggests.

The small study also showed SRT is both feasible and acceptable in this patient population.

Tab1962/iStockphoto.com

Results showed SRT, which was primarily delivered via telehealth sessions, began to show efficacy approximately 6 weeks into the 12-week therapeutic program, the researchers noted.

“Improving the regularity of daily rhythms like sleep, physical activity, and social activities can be really robust in improving mental health and even reducing suicide risk,” study investigator Hilary P. Blumberg, MD, the John and Hope Furth Professor of Psychiatric Neuroscience and director of the mood disorders research program at Yale University, New Haven, Conn., said in an interview.

The findings are published in the American Journal of Psychotherapy.
 

Trigger for depression, mania

Previous research shows unstable circadian rhythms may trigger depressive and manic symptoms – and are risk factors for suicidal thoughts and behaviors. Although interpersonal and social rhythm therapy has shown promise in patients with mood disorders, there is little research focusing only on the social rhythm aspect of the therapy.

The researchers only examined SRT, modified to create a therapeutic program aimed at adolescents and young adults.

The study included 13 participants (mean age, 20.5 years) with BD and a score of 15 or more on the 29-item Hamilton Depression Rating Scale (HDRS-29) and/or a score of 12 or more on the Young Mania Rating Scale (YMRS).

Participants were enrolled in the National Institute of Mental Health Brain Emotion Circuitry Targeted Self-Monitoring and Regulation Therapy (BE-SMART) program, which requires MRI sessions at three in-person visits to assess brain changes with the therapy. All but one participant was taking mood-stabilizing medications.

“We didn’t ask them to come off medications because we didn’t want to exacerbate things,” said Dr. Blumberg. She added the therapeutic approach “could be adjunctive to further improve symptoms and reduce risk.”

SRT was delivered in 12 weekly sessions. The majority occurred on a secure video platform. Three were conducted in person.

Working with a therapist, participants were taught how to follow a daily routine. Dr. Blumberg noted this is not just a matter of going to sleep and getting up at the same time every day, but thoroughly reviewing details of all daily activities and routines, including who participants eat with and when, their exercise schedule, and social engagements.

Each week, participants completed the five-item version of the Social Rhythm Metric. At the end of the intervention, they also completed the Client Satisfaction Questionnaire (CSQ). Scores on the CSQ range from 8 to 32, with scores of 26-32 indicating “excellent” satisfaction.

In addition, participants and therapists completed the Working Alliance Inventory, which assesses the client-therapist relationship by asking about such things as degree of comfort and respect.

Before and after the intervention, participants reported the regularity of their social rhythms using the Brief Social Rhythm Scale (BSRS) and risk for suicidal behavior using a subscale of the Concise Health Risk Tracking (CHRT) scale.
 

High retention, ‘excellent satisfaction’

Results showed 10 of the 13 participants (9 females) completed all study procedures, for a retention rate of 77%. Treatment satisfaction was excellent (mean CSQ, 29.4).

Both therapists and participants had high scores on all aspects of the Working Alliance Inventory scale.

“High treatment retention, excellent client satisfaction, and strong working alliance scores support the feasibility and acceptability of this intervention for adolescents and young adults with bipolar disorder,” the investigators wrote.

Participants showed significant improvement in social rhythm regularity and reductions in depression and manic symptoms as well as suicide propensity (P = .016 for BSRS; .024 for HDRS-29; .028 for YMRS; and .028 for CHRT suicide propensity). Effect sizes were in the moderate to high range.

By the midpoint of the therapy, there were significant improvements in social rhythm regularity and suicide propensity and trend-level reductions in depression, suggesting the potential for early benefits.

Dr. Blumberg noted it is difficult to find a therapy that helps with both depressive and mania symptoms. “An antidepressant may reduce depression, but sometimes can worsen manic symptoms.”
 

Impact on emotional brain circuitry?

The association between improved regularity of social rhythms and reduced suicide propensity persisted even after controlling for mood symptom changes.

“Suicide risk was reduced not just because subjects were less depressed. There’s something about regularizing rhythms that can reduce suicide risk,” said Dr. Blumberg.

The reviewers noted that SRT administered remotely improves accessibility; and this intervention “is well suited to the future of psychotherapy delivery, which will undoubtedly include remote treatment delivery.”

The absence of a comparator condition was cited as a study limitation. The investigators noted the small sample size means the findings should be interpreted cautiously and verified in an adequately powered randomized controlled trial.

The researchers now have early results from the brain scanning component of the study. “Preliminary findings suggest the intervention seems to benefit emotional brain circuitry,” Dr. Blumberg said.

The researchers are about to embark on a new study funded by a grant from the American Foundation of Suicide Prevention. It will investigate SRT in preventing suicide in adolescents and adults to age 29 years with depression or BD.

In addition, the researchers have secured support from the Klingenstein Third Generation Foundation to research prevention in youth at risk for BD – and from Women’s Health Access Matters to examine the therapy in women 50 and older with depression, a population possibly at increased risk for dementia.
 

‘Promising’ results

Commenting on the findings, Michael Thase, MD, professor of psychiatry, University of Pennsylvania, and research psychiatrist at the Corporal Michael J. Crescenz Veterans Affairs Medical Center, both in Philadelphia, praised the study.

“It’s a very, very promising initial study because even though there’s no control group, it does show that participants liked the program, most finished it, and on average, people got quite a bit better,” said Dr. Thase, who was not involved with the research.

The treatment may be especially beneficial for young patients with bipolar disorder who, just by their very age, experience lifestyle disruptions, Dr. Thase noted. Results from a previous study of the therapeutic approach in adults showed “probably half of the adults didn’t take to it.”

However, not everyone in this new study benefited either, as some dropped out, which Dr. Thase noted is not atypical.

“No form of intervention is suitable for everyone,” he said.

The study was supported by grants from the National Institute of Mental Health, AIM Youth Mental Health Foundation, Klingenstein Third Generation Foundation, American Foundation for Suicide Prevention, International Bipolar Foundation, MQ Brighter Futures Program, For the Love of Travis Foundation, and the John and Hope Furth Endowment. Dr. Blumberg and Dr. Thase reported no relevant financial relationships.

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

Epstein-Barr virus (EBV) is the likely cause of multiple sclerosis (MS), new research confirms. Investigators found the risk of MS increased 32-fold following EBV infection.

This study is the first to provide compelling evidence of a causal link between EBV and MS, principal investigator Alberto Ascherio, MD, DrPH, professor of epidemiology, Harvard T. H. Chan School of Public Health, and professor of medicine, Harvard Medical School, Boston, told this news organization.

The “prevailing” view has been that MS is “an autoimmune disease of unknown etiology,” said Dr. Ascherio. “Now we know MS is a complication of a viral infection.” With this knowledge, he added, “we can redirect research” to find antiviral drugs to treat the disease.

The study was published online Jan. 13 in Science.
 

Unique dataset

A chronic disease of the central nervous system, MS involves an inflammatory attack on the myelin sheath and the axons it insulates. The disease affects 2.8 million people worldwide.

EBV is a human herpesvirus that can cause infectious mononucleosis. After infection, it persists in latent form in B-lymphocytes.

EBV is common and infects about 95% of adults. Most individuals are already infected with the virus by age 18 or 20 years, making it difficult to study uninfected populations, said Dr. Ascherio.

However, access to a “huge” database of more than 10 million active-duty U.S. service personnel made this possible, he said.

Service members are screened for HIV at the start of their service care and biennially thereafter. The investigators used stored blood samples to determine the relation between EBV infection and MS over a 20-year period from 1993 to 2013.

Researchers examined 801 MS case patients and 1,566 matched controls without MS. Most individuals were under 20 at the time of their first blood collection. Symptom onset for those who developed MS was a median of 10 years after the first sample was obtained.

Only one of the 801 MS case patients had no serologic evidence of EBV. This individual may have been infected with the virus after the last blood collection, failed to seroconvert in response to infection, or was misdiagnosed, the investigators note.

The hazard ratio for MS between EBV seroconversion versus persistent EBV seronegative was 32.4 (95% CI, 4.3-245.3; P < .001).
 

An MS vaccine?

MS risk was not increased after infection with cytomegalovirus, a herpesvirus that is transmitted through saliva, as is EBV.

Researchers measured serum concentrations of neurofilament light chain (sNflL), a biomarker of neuroaxonal degeneration, in samples from EBV-negative individuals at baseline. There were no signs of neuroaxonal degeneration before EBV seroconversion in subjects who later developed MS.

This indicates that “EBV infection preceded not only symptom onset but also the time of the first detectable pathological mechanisms underlying MS,” the investigators note.

The very magnitude of increased MS risk of MS observed EBV almost completely rules out confounding by known risk factors. Smoking and vitamin D deficiency double the risk, and genetic predisposition and childhood obesity also only raise the risks of MS to a “moderate” degree, said Dr. Ascherio.

It’s not clear why only some people infected with EBV go on to develop MS, he said.

The idea that reverse causation – that immune dysregulation during the preclinical phase of MS increases susceptibility to EBV infection – is unlikely, the investigators note. For instance, EBV seroconversion occurs before elevation of sNfL levels, an early marker of preclinical MS.

Since most MS cases appear to be caused by EBV, a suitable vaccine might thwart the disease. “A vaccine could, in theory, prevent infection and prevent MS,” said Dr. Ascherio, adding that there’s ongoing work to develop such a vaccine.

Another approach is to target the virus driving MS disease progression. Developing appropriate antivirals might treat and even cure MS, said Dr. Ascherio.
 

‘Compelling data’

In an accompanying commentary, William H. Robinson, MD, PhD, professor, Division of Immunology and Rheumatology, department of medicine, Stanford (Calif.) University, and a colleague said the study findings “provide compelling data that implicate EBV as the trigger for the development of MS.”

The mechanism or mechanisms by which EBV leads to MS “remain elusive,” the commentary authors write.

“Possibilities include molecular mimicry, through which EBV viral protein sequences mimic human myelin proteins and other CNS proteins and thereby induce autoimmunity against myelin and CNS antigens,” they note.

As other factors, including genetic susceptibility, are important to MS, EBV infection is likely necessary but not sufficient to trigger MS, said the commentary. “Infection with EBV is the initial pathogenic step in MS, but additional fuses must be ignited for the full pathophysiology.”

The commentary authors query whether there may be “new opportunities” for therapy with vaccines or antivirals. “Now that the initial trigger for MS has been identified, perhaps MS could be eradicated.”

In a statement from the Science Media Center, an independent venture promoting views from the scientific community, two other experts offered their take on the study.

Paul Farrell, PhD, professor of tumor virology, Imperial College London, said the paper “provides very clear confirmation of a causal role for EBV in most cases of MS.”

While there’s evidence that a vaccine can prevent the EBV disease infectious mononucleosis, no vaccine candidate has yet prevented the virus from infecting and establishing long-term persistence in people, noted Dr. Farrell.

“So, at this stage it is not clear whether a vaccine of the types currently being developed would be able to prevent the long-term effects of EBV in MS,” he said.

Daniel Davis, PhD, professor of immunology, University of Manchester, United Kingdom, commented that the value of this new discovery is not an immediate medical cure or treatment but is “a major step forward” in understanding MS.

The study “sets up new research working out the precise details of how this virus can sometimes lead to an autoimmune disease,” said Dr. Davis. “There is no shortage of ideas in how this might happen in principle and hopefully the correct details will emerge soon.”

The study received funding from the National Institute of Neurological Disorders and Stroke, National Institutes of Health, National Multiple Sclerosis Society, the German Research Foundation, the National Institutes of Health, and the Howard Hughes Medical Institute. Dr. Ascherio reports no relevant financial relaitonships. Dr. Robinson is a coinventor on a patent application filed by Stanford University that includes antibodies to EBV. Dr. Farrell reports serving on an ad hoc review panel for GSK on EBV vaccines in 2019 as a one off. He has a current grant from MRC on EBV biology, including some EBV sequence variation, but the grant is not about MS. Dr. Davis reports no relevant financial relationships.

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

Epstein-Barr virus (EBV) is the likely cause of multiple sclerosis (MS), new research confirms. Investigators found the risk of MS increased 32-fold following EBV infection.

This study is the first to provide compelling evidence of a causal link between EBV and MS, principal investigator Alberto Ascherio, MD, DrPH, professor of epidemiology, Harvard T. H. Chan School of Public Health, and professor of medicine, Harvard Medical School, Boston, told this news organization.

The “prevailing” view has been that MS is “an autoimmune disease of unknown etiology,” said Dr. Ascherio. “Now we know MS is a complication of a viral infection.” With this knowledge, he added, “we can redirect research” to find antiviral drugs to treat the disease.

The study was published online Jan. 13 in Science.
 

Unique dataset

A chronic disease of the central nervous system, MS involves an inflammatory attack on the myelin sheath and the axons it insulates. The disease affects 2.8 million people worldwide.

EBV is a human herpesvirus that can cause infectious mononucleosis. After infection, it persists in latent form in B-lymphocytes.

EBV is common and infects about 95% of adults. Most individuals are already infected with the virus by age 18 or 20 years, making it difficult to study uninfected populations, said Dr. Ascherio.

However, access to a “huge” database of more than 10 million active-duty U.S. service personnel made this possible, he said.

Service members are screened for HIV at the start of their service care and biennially thereafter. The investigators used stored blood samples to determine the relation between EBV infection and MS over a 20-year period from 1993 to 2013.

Researchers examined 801 MS case patients and 1,566 matched controls without MS. Most individuals were under 20 at the time of their first blood collection. Symptom onset for those who developed MS was a median of 10 years after the first sample was obtained.

Only one of the 801 MS case patients had no serologic evidence of EBV. This individual may have been infected with the virus after the last blood collection, failed to seroconvert in response to infection, or was misdiagnosed, the investigators note.

The hazard ratio for MS between EBV seroconversion versus persistent EBV seronegative was 32.4 (95% CI, 4.3-245.3; P < .001).
 

An MS vaccine?

MS risk was not increased after infection with cytomegalovirus, a herpesvirus that is transmitted through saliva, as is EBV.

Researchers measured serum concentrations of neurofilament light chain (sNflL), a biomarker of neuroaxonal degeneration, in samples from EBV-negative individuals at baseline. There were no signs of neuroaxonal degeneration before EBV seroconversion in subjects who later developed MS.

This indicates that “EBV infection preceded not only symptom onset but also the time of the first detectable pathological mechanisms underlying MS,” the investigators note.

The very magnitude of increased MS risk of MS observed EBV almost completely rules out confounding by known risk factors. Smoking and vitamin D deficiency double the risk, and genetic predisposition and childhood obesity also only raise the risks of MS to a “moderate” degree, said Dr. Ascherio.

It’s not clear why only some people infected with EBV go on to develop MS, he said.

The idea that reverse causation – that immune dysregulation during the preclinical phase of MS increases susceptibility to EBV infection – is unlikely, the investigators note. For instance, EBV seroconversion occurs before elevation of sNfL levels, an early marker of preclinical MS.

Since most MS cases appear to be caused by EBV, a suitable vaccine might thwart the disease. “A vaccine could, in theory, prevent infection and prevent MS,” said Dr. Ascherio, adding that there’s ongoing work to develop such a vaccine.

Another approach is to target the virus driving MS disease progression. Developing appropriate antivirals might treat and even cure MS, said Dr. Ascherio.
 

‘Compelling data’

In an accompanying commentary, William H. Robinson, MD, PhD, professor, Division of Immunology and Rheumatology, department of medicine, Stanford (Calif.) University, and a colleague said the study findings “provide compelling data that implicate EBV as the trigger for the development of MS.”

The mechanism or mechanisms by which EBV leads to MS “remain elusive,” the commentary authors write.

“Possibilities include molecular mimicry, through which EBV viral protein sequences mimic human myelin proteins and other CNS proteins and thereby induce autoimmunity against myelin and CNS antigens,” they note.

As other factors, including genetic susceptibility, are important to MS, EBV infection is likely necessary but not sufficient to trigger MS, said the commentary. “Infection with EBV is the initial pathogenic step in MS, but additional fuses must be ignited for the full pathophysiology.”

The commentary authors query whether there may be “new opportunities” for therapy with vaccines or antivirals. “Now that the initial trigger for MS has been identified, perhaps MS could be eradicated.”

In a statement from the Science Media Center, an independent venture promoting views from the scientific community, two other experts offered their take on the study.

Paul Farrell, PhD, professor of tumor virology, Imperial College London, said the paper “provides very clear confirmation of a causal role for EBV in most cases of MS.”

While there’s evidence that a vaccine can prevent the EBV disease infectious mononucleosis, no vaccine candidate has yet prevented the virus from infecting and establishing long-term persistence in people, noted Dr. Farrell.

“So, at this stage it is not clear whether a vaccine of the types currently being developed would be able to prevent the long-term effects of EBV in MS,” he said.

Daniel Davis, PhD, professor of immunology, University of Manchester, United Kingdom, commented that the value of this new discovery is not an immediate medical cure or treatment but is “a major step forward” in understanding MS.

The study “sets up new research working out the precise details of how this virus can sometimes lead to an autoimmune disease,” said Dr. Davis. “There is no shortage of ideas in how this might happen in principle and hopefully the correct details will emerge soon.”

The study received funding from the National Institute of Neurological Disorders and Stroke, National Institutes of Health, National Multiple Sclerosis Society, the German Research Foundation, the National Institutes of Health, and the Howard Hughes Medical Institute. Dr. Ascherio reports no relevant financial relaitonships. Dr. Robinson is a coinventor on a patent application filed by Stanford University that includes antibodies to EBV. Dr. Farrell reports serving on an ad hoc review panel for GSK on EBV vaccines in 2019 as a one off. He has a current grant from MRC on EBV biology, including some EBV sequence variation, but the grant is not about MS. Dr. Davis reports no relevant financial relationships.

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

Epstein-Barr virus (EBV) is the likely cause of multiple sclerosis (MS), new research confirms. Investigators found the risk of MS increased 32-fold following EBV infection.

This study is the first to provide compelling evidence of a causal link between EBV and MS, principal investigator Alberto Ascherio, MD, DrPH, professor of epidemiology, Harvard T. H. Chan School of Public Health, and professor of medicine, Harvard Medical School, Boston, told this news organization.

The “prevailing” view has been that MS is “an autoimmune disease of unknown etiology,” said Dr. Ascherio. “Now we know MS is a complication of a viral infection.” With this knowledge, he added, “we can redirect research” to find antiviral drugs to treat the disease.

The study was published online Jan. 13 in Science.
 

Unique dataset

A chronic disease of the central nervous system, MS involves an inflammatory attack on the myelin sheath and the axons it insulates. The disease affects 2.8 million people worldwide.

EBV is a human herpesvirus that can cause infectious mononucleosis. After infection, it persists in latent form in B-lymphocytes.

EBV is common and infects about 95% of adults. Most individuals are already infected with the virus by age 18 or 20 years, making it difficult to study uninfected populations, said Dr. Ascherio.

However, access to a “huge” database of more than 10 million active-duty U.S. service personnel made this possible, he said.

Service members are screened for HIV at the start of their service care and biennially thereafter. The investigators used stored blood samples to determine the relation between EBV infection and MS over a 20-year period from 1993 to 2013.

Researchers examined 801 MS case patients and 1,566 matched controls without MS. Most individuals were under 20 at the time of their first blood collection. Symptom onset for those who developed MS was a median of 10 years after the first sample was obtained.

Only one of the 801 MS case patients had no serologic evidence of EBV. This individual may have been infected with the virus after the last blood collection, failed to seroconvert in response to infection, or was misdiagnosed, the investigators note.

The hazard ratio for MS between EBV seroconversion versus persistent EBV seronegative was 32.4 (95% CI, 4.3-245.3; P < .001).
 

An MS vaccine?

MS risk was not increased after infection with cytomegalovirus, a herpesvirus that is transmitted through saliva, as is EBV.

Researchers measured serum concentrations of neurofilament light chain (sNflL), a biomarker of neuroaxonal degeneration, in samples from EBV-negative individuals at baseline. There were no signs of neuroaxonal degeneration before EBV seroconversion in subjects who later developed MS.

This indicates that “EBV infection preceded not only symptom onset but also the time of the first detectable pathological mechanisms underlying MS,” the investigators note.

The very magnitude of increased MS risk of MS observed EBV almost completely rules out confounding by known risk factors. Smoking and vitamin D deficiency double the risk, and genetic predisposition and childhood obesity also only raise the risks of MS to a “moderate” degree, said Dr. Ascherio.

It’s not clear why only some people infected with EBV go on to develop MS, he said.

The idea that reverse causation – that immune dysregulation during the preclinical phase of MS increases susceptibility to EBV infection – is unlikely, the investigators note. For instance, EBV seroconversion occurs before elevation of sNfL levels, an early marker of preclinical MS.

Since most MS cases appear to be caused by EBV, a suitable vaccine might thwart the disease. “A vaccine could, in theory, prevent infection and prevent MS,” said Dr. Ascherio, adding that there’s ongoing work to develop such a vaccine.

Another approach is to target the virus driving MS disease progression. Developing appropriate antivirals might treat and even cure MS, said Dr. Ascherio.
 

‘Compelling data’

In an accompanying commentary, William H. Robinson, MD, PhD, professor, Division of Immunology and Rheumatology, department of medicine, Stanford (Calif.) University, and a colleague said the study findings “provide compelling data that implicate EBV as the trigger for the development of MS.”

The mechanism or mechanisms by which EBV leads to MS “remain elusive,” the commentary authors write.

“Possibilities include molecular mimicry, through which EBV viral protein sequences mimic human myelin proteins and other CNS proteins and thereby induce autoimmunity against myelin and CNS antigens,” they note.

As other factors, including genetic susceptibility, are important to MS, EBV infection is likely necessary but not sufficient to trigger MS, said the commentary. “Infection with EBV is the initial pathogenic step in MS, but additional fuses must be ignited for the full pathophysiology.”

The commentary authors query whether there may be “new opportunities” for therapy with vaccines or antivirals. “Now that the initial trigger for MS has been identified, perhaps MS could be eradicated.”

In a statement from the Science Media Center, an independent venture promoting views from the scientific community, two other experts offered their take on the study.

Paul Farrell, PhD, professor of tumor virology, Imperial College London, said the paper “provides very clear confirmation of a causal role for EBV in most cases of MS.”

While there’s evidence that a vaccine can prevent the EBV disease infectious mononucleosis, no vaccine candidate has yet prevented the virus from infecting and establishing long-term persistence in people, noted Dr. Farrell.

“So, at this stage it is not clear whether a vaccine of the types currently being developed would be able to prevent the long-term effects of EBV in MS,” he said.

Daniel Davis, PhD, professor of immunology, University of Manchester, United Kingdom, commented that the value of this new discovery is not an immediate medical cure or treatment but is “a major step forward” in understanding MS.

The study “sets up new research working out the precise details of how this virus can sometimes lead to an autoimmune disease,” said Dr. Davis. “There is no shortage of ideas in how this might happen in principle and hopefully the correct details will emerge soon.”

The study received funding from the National Institute of Neurological Disorders and Stroke, National Institutes of Health, National Multiple Sclerosis Society, the German Research Foundation, the National Institutes of Health, and the Howard Hughes Medical Institute. Dr. Ascherio reports no relevant financial relaitonships. Dr. Robinson is a coinventor on a patent application filed by Stanford University that includes antibodies to EBV. Dr. Farrell reports serving on an ad hoc review panel for GSK on EBV vaccines in 2019 as a one off. He has a current grant from MRC on EBV biology, including some EBV sequence variation, but the grant is not about MS. Dr. Davis reports no relevant financial relationships.

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

Even though men in midlife have more cardiovascular (CV) conditions and risk factors than women of the same age, women are more affected by these conditions in terms of cognitive decline, new research suggests.

Analyses of almost 1,400 participants in the population-based Mayo Clinic Study of Aging showed that diabetes, dyslipidemia, and coronary heart disease (CHD) all had stronger associations with global cognitive decline in women than in men.

“All men and women should be treated for cardiovascular risk factors and conditions, but this study really highlights the importance of very early and perhaps more aggressive treatment in women with these conditions,” co-investigator Michelle M. Mielke, PhD, professor of epidemiology and neurology, Mayo Clinic, Rochester, Minn., told this news organization.

The findings were published online Jan. 5 in Neurology.
 

Assessing sex differences

Most previous studies in this area have focused on CV risk factors in midlife in relation to late-life dementia (after age 75) or on late-life vascular risk factors and late-life dementia, Dr. Mielke noted.

However, a few recent studies have suggested vascular risk factors can affect cognition even in midlife. The current investigators sought to determine whether there are sex differences in these associations.

They assessed 1,857 nondemented participants aged 50 to 69 years from the Mayo Clinic Study on Aging. The mean education level was 14.9 years, and the mean body mass index (BMI) was 29.7.

Among the participants, 78.9% had at least one CV condition or risk factor, and the proportion was higher in men than women (83.4% vs. 74.5%; P < .0001).

Frequency of each individual CV condition or risk factor was also higher in men than women, and they had more years of education and higher BMI but took fewer medications.

Every 15 months, participants had an in-person interview and physical examination that included a neurologic assessment and short test of memory.

The neuropsychological battery included nine tests across four domains: memory, language, executive function, and visuospatial skills. Researchers calculated z-scores for these domains and for global cognition.
 

Multiple cognitive domains

Whereas this study evaluated multiple cognitive domains, most previous research has focused on global cognitive decline and/or decline in only one or two cognitive domains, the investigators note.

They collected information from medical records on CV conditions such as CHD, arrhythmias, congestive heart failure, peripheral vascular disease (PVD), and stroke; and CV risk factors such as hypertension, diabetes, dyslipidemia, smoking status, and BMI.

Because of the small number of patients with stroke and PVD, these were classified as “other cardiovascular conditions” in the statistical analysis.

Researchers adjusted for sex, age, years of education, depressive symptoms, comorbidities, medications, and apolipoprotein E (APOE) genotyping. The mean follow-up was 3 years and did not differ by sex.

As some participants didn’t have a follow-up visit, the current analysis included 1,394 individuals. Those without follow-up visits were younger, had less education and more comorbidities, and took more medications compared with those with a follow-up.

Results showed most CV conditions were more strongly associated with cognitive function among women than men. For example, CHD was associated with global decline only in women (P < .05).

CHD, diabetes, and dyslipidemia were associated with language decline in women only (all, P < .05), but congestive heart failure was significantly associated with language decline in men only.

Dr. Mielke cautioned about reading too much into the language results for women.

“It’s an intriguing finding and definitely we need to follow up on it,” she said. However, “more studies are needed to examine sex differences before we start saying it only has an effect on language.”
 

‘Treat aggressively and right away’

The researchers were somewhat surprised by the study findings. Because there is a higher prevalence of CV conditions and risk factors in men, they presumed men would be more affected by these conditions, said Dr. Mielke.

“But that’s not what we saw; we saw the reverse. It was actually the women who were affected more by these cardiovascular risk factors and conditions,” she said.

As midlife is when women enter menopause, fluctuating estrogen levels may help explain the differential impact on cognition among women. But Dr. Mielke said she wants to “move beyond” just looking at hormones.

She pointed out there are a variety of psychosocial factors that may also contribute to an imbalance in the cognitive impact of CV conditions on women.

“Midlife is when many women are still taking care of their children at home, are also taking care of their adult parents, and may be undergoing more stress while continuing to do a job,” Dr. Miekle said.

Structural brain development and genetics may also contribute to the greater effect on cognition in women, the investigators note.

Dr. Mielke stressed that the current study only identifies associations. “The next steps are to understand what some of the underlying mechanisms for this are,” she said.

In the meantime, these new results suggest middle-aged women with high blood pressure, cholesterol, or glucose measures “should be treated aggressively and right away” said Dr. Mielke.

“For example, for women who are just starting to become hypertensive, clinicians should treat them right away and not watch and wait.”

Study limitations cited include that its sample was limited to Olmsted County, Minnesota – so results may not be generalized to other populations. Also, as researchers combined PVD and stroke into one group, larger sample sizes are needed, especially for stroke. Another limitation was the study did not have information on duration of all CV conditions or risk factors.
 

Helpful for tailoring interventions?

Commenting on the study, Glen R. Finney, MD, director, Memory and Cognition Program, Geisinger Health Clinic, Wilkes-Barre, Pennsylvania, said the results are important.

“The more we understand about risk factors for the development of Alzheimer’s disease and related dementias, the better we understand how we can reduce the risks,” said Dr. Finney, who was not involved with the research.

Awareness that CV conditions are major risk factors in midlife has been “definitely rising,” said Dr. Finney. “Many studies originally were looking at late life and are now looking more at earlier in the disease process, and I think that’s important.”

Understanding how sex, ethnicity, and other demographic variables affect risks can help to “tailor interventions” for individual patients, he said.

The study was supported by the National Institutes of Health, the GHR Foundation, and the Rochester Epidemiology Project. Dr. Mielke is a consultant for Biogen and Brain Protection Company and is on the editorial boards of Neurology and Alzheimer’s and Dementia. Dr. Finney has reported no relevant financial relationships.

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

Even though men in midlife have more cardiovascular (CV) conditions and risk factors than women of the same age, women are more affected by these conditions in terms of cognitive decline, new research suggests.

Analyses of almost 1,400 participants in the population-based Mayo Clinic Study of Aging showed that diabetes, dyslipidemia, and coronary heart disease (CHD) all had stronger associations with global cognitive decline in women than in men.

“All men and women should be treated for cardiovascular risk factors and conditions, but this study really highlights the importance of very early and perhaps more aggressive treatment in women with these conditions,” co-investigator Michelle M. Mielke, PhD, professor of epidemiology and neurology, Mayo Clinic, Rochester, Minn., told this news organization.

The findings were published online Jan. 5 in Neurology.
 

Assessing sex differences

Most previous studies in this area have focused on CV risk factors in midlife in relation to late-life dementia (after age 75) or on late-life vascular risk factors and late-life dementia, Dr. Mielke noted.

However, a few recent studies have suggested vascular risk factors can affect cognition even in midlife. The current investigators sought to determine whether there are sex differences in these associations.

They assessed 1,857 nondemented participants aged 50 to 69 years from the Mayo Clinic Study on Aging. The mean education level was 14.9 years, and the mean body mass index (BMI) was 29.7.

Among the participants, 78.9% had at least one CV condition or risk factor, and the proportion was higher in men than women (83.4% vs. 74.5%; P < .0001).

Frequency of each individual CV condition or risk factor was also higher in men than women, and they had more years of education and higher BMI but took fewer medications.

Every 15 months, participants had an in-person interview and physical examination that included a neurologic assessment and short test of memory.

The neuropsychological battery included nine tests across four domains: memory, language, executive function, and visuospatial skills. Researchers calculated z-scores for these domains and for global cognition.
 

Multiple cognitive domains

Whereas this study evaluated multiple cognitive domains, most previous research has focused on global cognitive decline and/or decline in only one or two cognitive domains, the investigators note.

They collected information from medical records on CV conditions such as CHD, arrhythmias, congestive heart failure, peripheral vascular disease (PVD), and stroke; and CV risk factors such as hypertension, diabetes, dyslipidemia, smoking status, and BMI.

Because of the small number of patients with stroke and PVD, these were classified as “other cardiovascular conditions” in the statistical analysis.

Researchers adjusted for sex, age, years of education, depressive symptoms, comorbidities, medications, and apolipoprotein E (APOE) genotyping. The mean follow-up was 3 years and did not differ by sex.

As some participants didn’t have a follow-up visit, the current analysis included 1,394 individuals. Those without follow-up visits were younger, had less education and more comorbidities, and took more medications compared with those with a follow-up.

Results showed most CV conditions were more strongly associated with cognitive function among women than men. For example, CHD was associated with global decline only in women (P < .05).

CHD, diabetes, and dyslipidemia were associated with language decline in women only (all, P < .05), but congestive heart failure was significantly associated with language decline in men only.

Dr. Mielke cautioned about reading too much into the language results for women.

“It’s an intriguing finding and definitely we need to follow up on it,” she said. However, “more studies are needed to examine sex differences before we start saying it only has an effect on language.”
 

‘Treat aggressively and right away’

The researchers were somewhat surprised by the study findings. Because there is a higher prevalence of CV conditions and risk factors in men, they presumed men would be more affected by these conditions, said Dr. Mielke.

“But that’s not what we saw; we saw the reverse. It was actually the women who were affected more by these cardiovascular risk factors and conditions,” she said.

As midlife is when women enter menopause, fluctuating estrogen levels may help explain the differential impact on cognition among women. But Dr. Mielke said she wants to “move beyond” just looking at hormones.

She pointed out there are a variety of psychosocial factors that may also contribute to an imbalance in the cognitive impact of CV conditions on women.

“Midlife is when many women are still taking care of their children at home, are also taking care of their adult parents, and may be undergoing more stress while continuing to do a job,” Dr. Miekle said.

Structural brain development and genetics may also contribute to the greater effect on cognition in women, the investigators note.

Dr. Mielke stressed that the current study only identifies associations. “The next steps are to understand what some of the underlying mechanisms for this are,” she said.

In the meantime, these new results suggest middle-aged women with high blood pressure, cholesterol, or glucose measures “should be treated aggressively and right away” said Dr. Mielke.

“For example, for women who are just starting to become hypertensive, clinicians should treat them right away and not watch and wait.”

Study limitations cited include that its sample was limited to Olmsted County, Minnesota – so results may not be generalized to other populations. Also, as researchers combined PVD and stroke into one group, larger sample sizes are needed, especially for stroke. Another limitation was the study did not have information on duration of all CV conditions or risk factors.
 

Helpful for tailoring interventions?

Commenting on the study, Glen R. Finney, MD, director, Memory and Cognition Program, Geisinger Health Clinic, Wilkes-Barre, Pennsylvania, said the results are important.

“The more we understand about risk factors for the development of Alzheimer’s disease and related dementias, the better we understand how we can reduce the risks,” said Dr. Finney, who was not involved with the research.

Awareness that CV conditions are major risk factors in midlife has been “definitely rising,” said Dr. Finney. “Many studies originally were looking at late life and are now looking more at earlier in the disease process, and I think that’s important.”

Understanding how sex, ethnicity, and other demographic variables affect risks can help to “tailor interventions” for individual patients, he said.

The study was supported by the National Institutes of Health, the GHR Foundation, and the Rochester Epidemiology Project. Dr. Mielke is a consultant for Biogen and Brain Protection Company and is on the editorial boards of Neurology and Alzheimer’s and Dementia. Dr. Finney has reported no relevant financial relationships.

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

Even though men in midlife have more cardiovascular (CV) conditions and risk factors than women of the same age, women are more affected by these conditions in terms of cognitive decline, new research suggests.

Analyses of almost 1,400 participants in the population-based Mayo Clinic Study of Aging showed that diabetes, dyslipidemia, and coronary heart disease (CHD) all had stronger associations with global cognitive decline in women than in men.

“All men and women should be treated for cardiovascular risk factors and conditions, but this study really highlights the importance of very early and perhaps more aggressive treatment in women with these conditions,” co-investigator Michelle M. Mielke, PhD, professor of epidemiology and neurology, Mayo Clinic, Rochester, Minn., told this news organization.

The findings were published online Jan. 5 in Neurology.
 

Assessing sex differences

Most previous studies in this area have focused on CV risk factors in midlife in relation to late-life dementia (after age 75) or on late-life vascular risk factors and late-life dementia, Dr. Mielke noted.

However, a few recent studies have suggested vascular risk factors can affect cognition even in midlife. The current investigators sought to determine whether there are sex differences in these associations.

They assessed 1,857 nondemented participants aged 50 to 69 years from the Mayo Clinic Study on Aging. The mean education level was 14.9 years, and the mean body mass index (BMI) was 29.7.

Among the participants, 78.9% had at least one CV condition or risk factor, and the proportion was higher in men than women (83.4% vs. 74.5%; P < .0001).

Frequency of each individual CV condition or risk factor was also higher in men than women, and they had more years of education and higher BMI but took fewer medications.

Every 15 months, participants had an in-person interview and physical examination that included a neurologic assessment and short test of memory.

The neuropsychological battery included nine tests across four domains: memory, language, executive function, and visuospatial skills. Researchers calculated z-scores for these domains and for global cognition.
 

Multiple cognitive domains

Whereas this study evaluated multiple cognitive domains, most previous research has focused on global cognitive decline and/or decline in only one or two cognitive domains, the investigators note.

They collected information from medical records on CV conditions such as CHD, arrhythmias, congestive heart failure, peripheral vascular disease (PVD), and stroke; and CV risk factors such as hypertension, diabetes, dyslipidemia, smoking status, and BMI.

Because of the small number of patients with stroke and PVD, these were classified as “other cardiovascular conditions” in the statistical analysis.

Researchers adjusted for sex, age, years of education, depressive symptoms, comorbidities, medications, and apolipoprotein E (APOE) genotyping. The mean follow-up was 3 years and did not differ by sex.

As some participants didn’t have a follow-up visit, the current analysis included 1,394 individuals. Those without follow-up visits were younger, had less education and more comorbidities, and took more medications compared with those with a follow-up.

Results showed most CV conditions were more strongly associated with cognitive function among women than men. For example, CHD was associated with global decline only in women (P < .05).

CHD, diabetes, and dyslipidemia were associated with language decline in women only (all, P < .05), but congestive heart failure was significantly associated with language decline in men only.

Dr. Mielke cautioned about reading too much into the language results for women.

“It’s an intriguing finding and definitely we need to follow up on it,” she said. However, “more studies are needed to examine sex differences before we start saying it only has an effect on language.”
 

‘Treat aggressively and right away’

The researchers were somewhat surprised by the study findings. Because there is a higher prevalence of CV conditions and risk factors in men, they presumed men would be more affected by these conditions, said Dr. Mielke.

“But that’s not what we saw; we saw the reverse. It was actually the women who were affected more by these cardiovascular risk factors and conditions,” she said.

As midlife is when women enter menopause, fluctuating estrogen levels may help explain the differential impact on cognition among women. But Dr. Mielke said she wants to “move beyond” just looking at hormones.

She pointed out there are a variety of psychosocial factors that may also contribute to an imbalance in the cognitive impact of CV conditions on women.

“Midlife is when many women are still taking care of their children at home, are also taking care of their adult parents, and may be undergoing more stress while continuing to do a job,” Dr. Miekle said.

Structural brain development and genetics may also contribute to the greater effect on cognition in women, the investigators note.

Dr. Mielke stressed that the current study only identifies associations. “The next steps are to understand what some of the underlying mechanisms for this are,” she said.

In the meantime, these new results suggest middle-aged women with high blood pressure, cholesterol, or glucose measures “should be treated aggressively and right away” said Dr. Mielke.

“For example, for women who are just starting to become hypertensive, clinicians should treat them right away and not watch and wait.”

Study limitations cited include that its sample was limited to Olmsted County, Minnesota – so results may not be generalized to other populations. Also, as researchers combined PVD and stroke into one group, larger sample sizes are needed, especially for stroke. Another limitation was the study did not have information on duration of all CV conditions or risk factors.
 

Helpful for tailoring interventions?

Commenting on the study, Glen R. Finney, MD, director, Memory and Cognition Program, Geisinger Health Clinic, Wilkes-Barre, Pennsylvania, said the results are important.

“The more we understand about risk factors for the development of Alzheimer’s disease and related dementias, the better we understand how we can reduce the risks,” said Dr. Finney, who was not involved with the research.

Awareness that CV conditions are major risk factors in midlife has been “definitely rising,” said Dr. Finney. “Many studies originally were looking at late life and are now looking more at earlier in the disease process, and I think that’s important.”

Understanding how sex, ethnicity, and other demographic variables affect risks can help to “tailor interventions” for individual patients, he said.

The study was supported by the National Institutes of Health, the GHR Foundation, and the Rochester Epidemiology Project. Dr. Mielke is a consultant for Biogen and Brain Protection Company and is on the editorial boards of Neurology and Alzheimer’s and Dementia. Dr. Finney has reported no relevant financial relationships.

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

Early interventions that focus on clinical case management and psychiatric care, and not necessarily on individual psychotherapy, are effective for young patients with borderline personality disorder (BPD), new research suggests.

Findings from the Monitoring Outcomes of Borderline Personality Disorder in Youth (MOBY) trial also showed improved psychosocial functioning and reduced suicide ideation with these therapies.

The results suggest that, contrary to common belief, psychotherapy is not the only effective approach for early BPD, lead author Andrew M. Chanen, PhD, director of clinical programs and services and head of personality disorder research at Orygen, Melbourne, told this news organization.

“We can say that early diagnosis and early treatment is effective, and the treatment doesn’t need to involve individual psychotherapy but does need to involve clinical case management and psychiatric care,” said Dr. Chanen, a professorial fellow at the Centre for Youth Mental Health, University of Melbourne.

The findings were published online in JAMA Psychiatry.
 

Extreme sensitivity

Patients with BPD have “extreme sensitivity to interpersonal slights” and often exhibit intense and volatile emotions and impulsive behavior, Dr. Chanen noted. Many will self-harm, abuse drugs, or attempt suicide; the suicide rate among patients with BPD is 8%-10%.

The condition is typically diagnosed in puberty or early adulthood, affecting about 3% of young people and a little more than 1% of adults.

Because of their aggression and interpersonal difficulties, patients with BPD are often discriminated against by health professionals and end up not getting treated, said Dr. Chanen.

Those who are treated often receive individual psychotherapy, such as dialectical behavior therapy (DBT). That type of therapy, which teaches healthy ways to cope with stress and regulate emotions, is very effective, Dr. Chanen said.

The MOBY trial examined three treatment approaches: the Helping Young People Early (HYPE) model, HYPE combined with weekly “befriending,” and a general youth mental health service (YMHS) model combined with befriending.

A key element of HYPE is cognitive analytic therapy, a psychotherapy program focused on understanding problematic self-management and interpersonal relationship patterns. The model includes clinical case management, such as attending to housing, vocational and educational issues, other mental health needs, and physical health needs.

In the second model, the psychotherapy of the HYPE program was replaced with befriending, which involves chatting with a patient about neutral topics such as sports and avoiding emotionally loaded topics such as interpersonal problems.

For YMHS plus befriending, experts trained in treating young people, but not specialized in treating BPD, were involved in managing patients.

‘High satisfaction’

Researchers randomly assigned 139 participants aged 15-25 years (80.6% women; mean age, 19.1 years) with BPD to one of the treatment arms. Of these, 128 (92.1%) were included in the intent-to-treat analysis.

The primary endpoint was psychosocial functioning, as measured by the Inventory of Interpersonal Problems Circumplex Version and the Social Adjustment Scale–Self-Report. Secondary endpoints included suicidal ideation, suicide attempts, nonsuicidal self-injury, depression, substance use, and treatment satisfaction.

The investigators reported group averages, but the study’s noninferiority design did not allow for determining if one treatment had superior efficacy.

All groups improved significantly on the primary endpoint. At 12 months, there was a mean 28.91-point (23.8%) drop in interpersonal problems and a mean 0.55-point (19.3%) drop in social adjustment scores.

For secondary outcomes, mean improvements at 12 months ranged from 40.7% (17.64 points) on the depression scale to 52.7% (6.22 points) for suicide ideation.

“The only area where the treatment didn’t really have an impact was substance use,” said Dr. Chanen. “Satisfaction was high for all three interventions throughout the study, and it’s hard to improve on high satisfaction.”

‘Turns things upside down’

That patients across all groups had marked and sustained improvements “in ways you wouldn’t expect for BPD” supports the conclusion that the interventions had a true effect, Dr. Chanen said.

The results suggest early diagnosis and “a not very complicated treatment [will] drastically improve the lives of these young people,” he added.

They also imply there are effective alternatives to psychotherapy, which many individuals in the field insist is the only way to treat BPD. “This study turns things upside down and says actually it’s not. It’s the basics of treatment that are important,” Dr. Chanen said.

When a patient presents at the emergency department following a severe overdose, “it’s a reflex” for clinicians to refer that person to a psychotherapy program. “The problem is, these programs are not plentiful enough to be able to service the needs of this group,” Dr. Chanen noted.

On the other hand, the skills for clinical case management and psychiatric care “are available throughout the mental health systems,” he added.

The researchers are planning another analysis to determine whether age and sex predict better outcomes in these patients with BPD.
 

Unique contribution

Commenting for this news organization, John M. Oldham, MD, distinguished emeritus professor, Baylor College of Medicine, Houston, said a “unique and important contribution” of the study is the focus on early intervention.

“The general standard approach in psychiatry and the diagnostic world has been to not even consider anything until after somebody is 18 years of age, which is a mistake because these kids can become quite impaired earlier than that,” he said.

Dr. Oldham, who was not involved with the research, chaired the American Psychiatric Association workgroup that developed the 2001 evidence-based practice guideline for treating BPD, which recommended psychotherapy as the primary treatment. The guideline was last updated in 2005 – and another update is currently being developed, he noted.

There is an emerging trend toward “good psychiatric management” that focuses on level of functioning rather than on a specific strategy requiring a certificate of training that “not many people out there have,” said Dr. Oldham.

“You’re not going to make much headway with these kids if you’re going to be searching around for a DBT-certified therapist. What you need is to bring them in, get them to trust you, and in a sense be a kind of overall behavioral medicine navigator for them,” he added.

Dr. Oldham noted that, although the primary study outcome improved between 19% and 24%, “that means three-quarters of the people didn’t improve.”

He also pointed out this was only a 1-year trial. “Sometimes treatment for people with a personality disorder such as borderline takes a lot longer than that,” Dr. Oldham concluded.

The trial was funded by the National Health and Medical Research Council. Dr. Chanen reports receiving grants from the Australian government’s National Health and Medical Research Council during the conduct of the study and other support from the Helping Young People Early (HYPE) translational program outside the submitted work. He and another investigator cofounded and lead the HYPE clinical program, a government-funded program with continuous support, and the HYPE translational program, a not-for-profit training program. Dr. Oldham reported no relevant financial relationships.

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

Early interventions that focus on clinical case management and psychiatric care, and not necessarily on individual psychotherapy, are effective for young patients with borderline personality disorder (BPD), new research suggests.

Findings from the Monitoring Outcomes of Borderline Personality Disorder in Youth (MOBY) trial also showed improved psychosocial functioning and reduced suicide ideation with these therapies.

The results suggest that, contrary to common belief, psychotherapy is not the only effective approach for early BPD, lead author Andrew M. Chanen, PhD, director of clinical programs and services and head of personality disorder research at Orygen, Melbourne, told this news organization.

“We can say that early diagnosis and early treatment is effective, and the treatment doesn’t need to involve individual psychotherapy but does need to involve clinical case management and psychiatric care,” said Dr. Chanen, a professorial fellow at the Centre for Youth Mental Health, University of Melbourne.

The findings were published online in JAMA Psychiatry.
 

Extreme sensitivity

Patients with BPD have “extreme sensitivity to interpersonal slights” and often exhibit intense and volatile emotions and impulsive behavior, Dr. Chanen noted. Many will self-harm, abuse drugs, or attempt suicide; the suicide rate among patients with BPD is 8%-10%.

The condition is typically diagnosed in puberty or early adulthood, affecting about 3% of young people and a little more than 1% of adults.

Because of their aggression and interpersonal difficulties, patients with BPD are often discriminated against by health professionals and end up not getting treated, said Dr. Chanen.

Those who are treated often receive individual psychotherapy, such as dialectical behavior therapy (DBT). That type of therapy, which teaches healthy ways to cope with stress and regulate emotions, is very effective, Dr. Chanen said.

The MOBY trial examined three treatment approaches: the Helping Young People Early (HYPE) model, HYPE combined with weekly “befriending,” and a general youth mental health service (YMHS) model combined with befriending.

A key element of HYPE is cognitive analytic therapy, a psychotherapy program focused on understanding problematic self-management and interpersonal relationship patterns. The model includes clinical case management, such as attending to housing, vocational and educational issues, other mental health needs, and physical health needs.

In the second model, the psychotherapy of the HYPE program was replaced with befriending, which involves chatting with a patient about neutral topics such as sports and avoiding emotionally loaded topics such as interpersonal problems.

For YMHS plus befriending, experts trained in treating young people, but not specialized in treating BPD, were involved in managing patients.

‘High satisfaction’

Researchers randomly assigned 139 participants aged 15-25 years (80.6% women; mean age, 19.1 years) with BPD to one of the treatment arms. Of these, 128 (92.1%) were included in the intent-to-treat analysis.

The primary endpoint was psychosocial functioning, as measured by the Inventory of Interpersonal Problems Circumplex Version and the Social Adjustment Scale–Self-Report. Secondary endpoints included suicidal ideation, suicide attempts, nonsuicidal self-injury, depression, substance use, and treatment satisfaction.

The investigators reported group averages, but the study’s noninferiority design did not allow for determining if one treatment had superior efficacy.

All groups improved significantly on the primary endpoint. At 12 months, there was a mean 28.91-point (23.8%) drop in interpersonal problems and a mean 0.55-point (19.3%) drop in social adjustment scores.

For secondary outcomes, mean improvements at 12 months ranged from 40.7% (17.64 points) on the depression scale to 52.7% (6.22 points) for suicide ideation.

“The only area where the treatment didn’t really have an impact was substance use,” said Dr. Chanen. “Satisfaction was high for all three interventions throughout the study, and it’s hard to improve on high satisfaction.”

‘Turns things upside down’

That patients across all groups had marked and sustained improvements “in ways you wouldn’t expect for BPD” supports the conclusion that the interventions had a true effect, Dr. Chanen said.

The results suggest early diagnosis and “a not very complicated treatment [will] drastically improve the lives of these young people,” he added.

They also imply there are effective alternatives to psychotherapy, which many individuals in the field insist is the only way to treat BPD. “This study turns things upside down and says actually it’s not. It’s the basics of treatment that are important,” Dr. Chanen said.

When a patient presents at the emergency department following a severe overdose, “it’s a reflex” for clinicians to refer that person to a psychotherapy program. “The problem is, these programs are not plentiful enough to be able to service the needs of this group,” Dr. Chanen noted.

On the other hand, the skills for clinical case management and psychiatric care “are available throughout the mental health systems,” he added.

The researchers are planning another analysis to determine whether age and sex predict better outcomes in these patients with BPD.
 

Unique contribution

Commenting for this news organization, John M. Oldham, MD, distinguished emeritus professor, Baylor College of Medicine, Houston, said a “unique and important contribution” of the study is the focus on early intervention.

“The general standard approach in psychiatry and the diagnostic world has been to not even consider anything until after somebody is 18 years of age, which is a mistake because these kids can become quite impaired earlier than that,” he said.

Dr. Oldham, who was not involved with the research, chaired the American Psychiatric Association workgroup that developed the 2001 evidence-based practice guideline for treating BPD, which recommended psychotherapy as the primary treatment. The guideline was last updated in 2005 – and another update is currently being developed, he noted.

There is an emerging trend toward “good psychiatric management” that focuses on level of functioning rather than on a specific strategy requiring a certificate of training that “not many people out there have,” said Dr. Oldham.

“You’re not going to make much headway with these kids if you’re going to be searching around for a DBT-certified therapist. What you need is to bring them in, get them to trust you, and in a sense be a kind of overall behavioral medicine navigator for them,” he added.

Dr. Oldham noted that, although the primary study outcome improved between 19% and 24%, “that means three-quarters of the people didn’t improve.”

He also pointed out this was only a 1-year trial. “Sometimes treatment for people with a personality disorder such as borderline takes a lot longer than that,” Dr. Oldham concluded.

The trial was funded by the National Health and Medical Research Council. Dr. Chanen reports receiving grants from the Australian government’s National Health and Medical Research Council during the conduct of the study and other support from the Helping Young People Early (HYPE) translational program outside the submitted work. He and another investigator cofounded and lead the HYPE clinical program, a government-funded program with continuous support, and the HYPE translational program, a not-for-profit training program. Dr. Oldham reported no relevant financial relationships.

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

Early interventions that focus on clinical case management and psychiatric care, and not necessarily on individual psychotherapy, are effective for young patients with borderline personality disorder (BPD), new research suggests.

Findings from the Monitoring Outcomes of Borderline Personality Disorder in Youth (MOBY) trial also showed improved psychosocial functioning and reduced suicide ideation with these therapies.

The results suggest that, contrary to common belief, psychotherapy is not the only effective approach for early BPD, lead author Andrew M. Chanen, PhD, director of clinical programs and services and head of personality disorder research at Orygen, Melbourne, told this news organization.

“We can say that early diagnosis and early treatment is effective, and the treatment doesn’t need to involve individual psychotherapy but does need to involve clinical case management and psychiatric care,” said Dr. Chanen, a professorial fellow at the Centre for Youth Mental Health, University of Melbourne.

The findings were published online in JAMA Psychiatry.
 

Extreme sensitivity

Patients with BPD have “extreme sensitivity to interpersonal slights” and often exhibit intense and volatile emotions and impulsive behavior, Dr. Chanen noted. Many will self-harm, abuse drugs, or attempt suicide; the suicide rate among patients with BPD is 8%-10%.

The condition is typically diagnosed in puberty or early adulthood, affecting about 3% of young people and a little more than 1% of adults.

Because of their aggression and interpersonal difficulties, patients with BPD are often discriminated against by health professionals and end up not getting treated, said Dr. Chanen.

Those who are treated often receive individual psychotherapy, such as dialectical behavior therapy (DBT). That type of therapy, which teaches healthy ways to cope with stress and regulate emotions, is very effective, Dr. Chanen said.

The MOBY trial examined three treatment approaches: the Helping Young People Early (HYPE) model, HYPE combined with weekly “befriending,” and a general youth mental health service (YMHS) model combined with befriending.

A key element of HYPE is cognitive analytic therapy, a psychotherapy program focused on understanding problematic self-management and interpersonal relationship patterns. The model includes clinical case management, such as attending to housing, vocational and educational issues, other mental health needs, and physical health needs.

In the second model, the psychotherapy of the HYPE program was replaced with befriending, which involves chatting with a patient about neutral topics such as sports and avoiding emotionally loaded topics such as interpersonal problems.

For YMHS plus befriending, experts trained in treating young people, but not specialized in treating BPD, were involved in managing patients.

‘High satisfaction’

Researchers randomly assigned 139 participants aged 15-25 years (80.6% women; mean age, 19.1 years) with BPD to one of the treatment arms. Of these, 128 (92.1%) were included in the intent-to-treat analysis.

The primary endpoint was psychosocial functioning, as measured by the Inventory of Interpersonal Problems Circumplex Version and the Social Adjustment Scale–Self-Report. Secondary endpoints included suicidal ideation, suicide attempts, nonsuicidal self-injury, depression, substance use, and treatment satisfaction.

The investigators reported group averages, but the study’s noninferiority design did not allow for determining if one treatment had superior efficacy.

All groups improved significantly on the primary endpoint. At 12 months, there was a mean 28.91-point (23.8%) drop in interpersonal problems and a mean 0.55-point (19.3%) drop in social adjustment scores.

For secondary outcomes, mean improvements at 12 months ranged from 40.7% (17.64 points) on the depression scale to 52.7% (6.22 points) for suicide ideation.

“The only area where the treatment didn’t really have an impact was substance use,” said Dr. Chanen. “Satisfaction was high for all three interventions throughout the study, and it’s hard to improve on high satisfaction.”

‘Turns things upside down’

That patients across all groups had marked and sustained improvements “in ways you wouldn’t expect for BPD” supports the conclusion that the interventions had a true effect, Dr. Chanen said.

The results suggest early diagnosis and “a not very complicated treatment [will] drastically improve the lives of these young people,” he added.

They also imply there are effective alternatives to psychotherapy, which many individuals in the field insist is the only way to treat BPD. “This study turns things upside down and says actually it’s not. It’s the basics of treatment that are important,” Dr. Chanen said.

When a patient presents at the emergency department following a severe overdose, “it’s a reflex” for clinicians to refer that person to a psychotherapy program. “The problem is, these programs are not plentiful enough to be able to service the needs of this group,” Dr. Chanen noted.

On the other hand, the skills for clinical case management and psychiatric care “are available throughout the mental health systems,” he added.

The researchers are planning another analysis to determine whether age and sex predict better outcomes in these patients with BPD.
 

Unique contribution

Commenting for this news organization, John M. Oldham, MD, distinguished emeritus professor, Baylor College of Medicine, Houston, said a “unique and important contribution” of the study is the focus on early intervention.

“The general standard approach in psychiatry and the diagnostic world has been to not even consider anything until after somebody is 18 years of age, which is a mistake because these kids can become quite impaired earlier than that,” he said.

Dr. Oldham, who was not involved with the research, chaired the American Psychiatric Association workgroup that developed the 2001 evidence-based practice guideline for treating BPD, which recommended psychotherapy as the primary treatment. The guideline was last updated in 2005 – and another update is currently being developed, he noted.

There is an emerging trend toward “good psychiatric management” that focuses on level of functioning rather than on a specific strategy requiring a certificate of training that “not many people out there have,” said Dr. Oldham.

“You’re not going to make much headway with these kids if you’re going to be searching around for a DBT-certified therapist. What you need is to bring them in, get them to trust you, and in a sense be a kind of overall behavioral medicine navigator for them,” he added.

Dr. Oldham noted that, although the primary study outcome improved between 19% and 24%, “that means three-quarters of the people didn’t improve.”

He also pointed out this was only a 1-year trial. “Sometimes treatment for people with a personality disorder such as borderline takes a lot longer than that,” Dr. Oldham concluded.

The trial was funded by the National Health and Medical Research Council. Dr. Chanen reports receiving grants from the Australian government’s National Health and Medical Research Council during the conduct of the study and other support from the Helping Young People Early (HYPE) translational program outside the submitted work. He and another investigator cofounded and lead the HYPE clinical program, a government-funded program with continuous support, and the HYPE translational program, a not-for-profit training program. Dr. Oldham reported no relevant financial relationships.

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

A distinct pattern of frontal-temporal atrophy discernible on magnetic resonance imaging (MRI) may flag chronic traumatic encephalopathy (CTE) in living patients, new research suggests.

“These new results offer some hope for clinicians who are really struggling to confidently diagnose or detect CTE during life,” said lead author Michael L. Alosco, PhD, associate professor of neurology, codirector of the Boston University Alzheimer’s Disease Research Center, and investigator at the Boston University CTE Center.

The findings were published online Dec. 7, 2021, in Alzheimer’s Research & Therapy.
 

A new way to diagnose?

CTE is a neurodegenerative disease associated with exposure to repetitive blows to the head, such as those sustained playing contact sports. Currently, the condition can only be reliably diagnosed at autopsy using neuropathological diagnostic criteria.

There are four pathological stages of CTE, ranging from mild to severe. Each progressive stage reflects mounting accumulation of hyperphosphorylated tau (p-tau).

The study included 55 male brain donors with confirmed CTE, all with a history of repetitive head injury. Most (n = 52) played football, but two played ice hockey and one had military and combat exposure. The analysis also included 31 men with normal cognition (NC). Of these, some were living and some were deceased.

The study sample was restricted to participants age 60 and older and to those who had an MRI obtained through a medical record request.

Most referrals for MRI in the CTE group were related to dementia or neurodegenerative disease (65%). In the NC group, MRI indications were mostly related to cerebrovascular causes (22.6%), memory complaints (16.1%), or vertigo (9.7%).

From MRIs, neuroradiologists visually rated patterns of shrinkage in the brain, microvascular disease, and presence of cavum septum pellucidum (CSP) – a large hole in the tissue separating ventricles of the brain.
 

More atrophy

Results showed that compared with the NC group, the CTE group had significantly greater atrophy in several brain regions, including the orbital-frontal cortex, dorsolateral frontal cortex, superior frontal cortex, anterior temporal lobes, and medial temporal lobe.

The dorsolateral frontal cortex showed the largest group difference (estimated marginal mean difference, 1.31; 95% confidence interval, .42-2.19; false discovery rate-adjusted P = .01).

Previous research has shown early p-tau involvement in this area among CTE patients. Although the hippocampus is also affected in CTE, this occurs later in the disease course, the investigators noted.

The unique pattern, type, and distribution of p-tau pathology in CTE is different from Alzheimer’s disease. CTE is also distinct from Alzheimer’s disease in that there is no accumulation of beta-amyloid plaque.

The new results add to “converging evidence” for frontotemporal and medial temporal lobe atrophy in CTE “that might be able to be visualized on MRI,” the investigators noted.

Almost two-thirds of the CTE group had an additional neurodegenerative disease. Furthermore, the effect sizes remained similar in analyses that excluded CTE donors with frontotemporal lobar degeneration or Alzheimer’s disease.

“This suggests to us that these other diseases were not accounting for the atrophy,” Dr. Alosco said.

Individuals with CTE were 6.7 times more likely to have a CSP versus those with NC (odds ratio, 6.7; 95% CI, 1.5-50.1; P = .049).

Although previous research suggested an association between CSP and repetitive concussion, CSP is also frequently found in the general adult population. However, when combined with data on frontal lobe shrinkage, it may be a supportive differential diagnostic feature for CTE, Dr. Alosco said.
 

An important first step

The investigators also examined ventricle size. The lateral ventricles in the CTE group were significantly larger (mean difference, 1.72; 95% CI, .62-2.82; P = .01), as was the third ventricle (mean difference, .80; 95% CI, .26-1.35; P = .01).

When neuropathologists rated tau severity and atrophy at autopsy, they found that more severe p-tau pathology was associated with greater atrophy among those with CTE (beta = .68; P < .01).

Dr. Alosco called the finding “exciting,” noting that it suggests “this tau is a precipitant for neurodegeneration.”

He noted that, although some researchers have used positron emission tomography (PET) tau tracers to uncover a CTE pattern, MRI is relatively inexpensive and routinely used as part of dementia assessment.

While the new study is “an important first step” in using MRI to diagnose CTE, larger sample sizes are needed, Dr. Alosco said. “We also need to look at other disease groups and really nail down the difference with CTE in terms of patterns” (vs. Alzheimer’s disease and vs. frontotemporal lobar degeneration), he added.

“Once those differences are cleared, we will be ready to be more confident when we interpret these images.”.
 

‘Not unexpected’

Commenting on the research, neurologist and concussion expert Francis X. Conidi, DO, director, Florida Center for Headache and Sports Neurology, Port St. Lucie, said that, although the study was “well thought out and interesting,” the results were “not completely unexpected.”

Frontal and anterior temporal lobe atrophy and prominent third ventricles are very common in patients with traumatic brain injury (TBI), which is “a prerequisite to develop CTE,” said Dr. Conidi, who was not involved with the research.

The current study’s findings mirror observations found in a National Football League cohort he and his colleagues are following – and in his patients with TBI in general.

Dr. Conidi noted that there is a “significant subjective component” to the study results because they relied on the opinion of neuroradiologists. He is not convinced MRI findings of frontotemporal and medial temporal lobe atrophy necessarily represent CTE and not TBI. In fact, he noted that patients with TBI have a significantly greater chance of not developing a neurodegenerative disorder.

Dr. Conidi added that he doesn’t think MRI will ever be the gold standard for diagnosing or even assessing risk of developing CTE. “That lies in tau PET imaging,” he said.
 

Overstated conclusion?

Also commenting on the research findings, Kristen Dams-O’Connor, PhD, professor, vice chair of research, and director, Brain Injury Research Center, Department of Rehabilitation Medicine, Icahn School of Medicine at Mount Sinai in New York, said the sensitivity analyses, particularly those designed to clarify contributions of Alzheimer’s disease and other neuropathological contributions to associations between p-tau and atrophy, “increase our confidence” in the findings.

“What’s exciting about this paper is that it provides very preliminary support for adding another tool to our arsenal as we try to establish a constellation of in vivo diagnostic markers that, together, will help us rule in a post-traumatic neurodegenerative process and rule out other brain diseases.”

A possible study limitation is that the MRI scans were from low-field strength magnets, although that makes the study more “ecologically valid”, said Dr. Dams-O’Connor. “Many clinical scanners are built around a 1.5T magnet, so what the researchers see in this study is what a radiologist may see in the clinic.”

The conclusion that frontal-temporal atrophy is an MRI marker of CTE is “an overstatement” as this pattern of atrophy is not specific to CTE, said Dr. Dams-O’Connor. “The association of p-tau with atrophy is unsurprising and doesn’t bring us much closer to understanding how, or whether, the patterns of p-tau accumulation observed in CTE contribute to the clinical expression of symptoms.”

Dr. Alosco and Dr. Conidi report no relevant financial relationships. Disclosures for the other study authors are listed in the original journal article. The study was funded by grants from the National Institute on Aging, the National Institute on Neurological Disorders and Stroke, National Institute of Aging Boston University AD Center, Department of Veterans Affairs Merit Award, the Nick and Lynn Buoniconti Foundation, and BU-CTSI.

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

A distinct pattern of frontal-temporal atrophy discernible on magnetic resonance imaging (MRI) may flag chronic traumatic encephalopathy (CTE) in living patients, new research suggests.

“These new results offer some hope for clinicians who are really struggling to confidently diagnose or detect CTE during life,” said lead author Michael L. Alosco, PhD, associate professor of neurology, codirector of the Boston University Alzheimer’s Disease Research Center, and investigator at the Boston University CTE Center.

The findings were published online Dec. 7, 2021, in Alzheimer’s Research & Therapy.
 

A new way to diagnose?

CTE is a neurodegenerative disease associated with exposure to repetitive blows to the head, such as those sustained playing contact sports. Currently, the condition can only be reliably diagnosed at autopsy using neuropathological diagnostic criteria.

There are four pathological stages of CTE, ranging from mild to severe. Each progressive stage reflects mounting accumulation of hyperphosphorylated tau (p-tau).

The study included 55 male brain donors with confirmed CTE, all with a history of repetitive head injury. Most (n = 52) played football, but two played ice hockey and one had military and combat exposure. The analysis also included 31 men with normal cognition (NC). Of these, some were living and some were deceased.

The study sample was restricted to participants age 60 and older and to those who had an MRI obtained through a medical record request.

Most referrals for MRI in the CTE group were related to dementia or neurodegenerative disease (65%). In the NC group, MRI indications were mostly related to cerebrovascular causes (22.6%), memory complaints (16.1%), or vertigo (9.7%).

From MRIs, neuroradiologists visually rated patterns of shrinkage in the brain, microvascular disease, and presence of cavum septum pellucidum (CSP) – a large hole in the tissue separating ventricles of the brain.
 

More atrophy

Results showed that compared with the NC group, the CTE group had significantly greater atrophy in several brain regions, including the orbital-frontal cortex, dorsolateral frontal cortex, superior frontal cortex, anterior temporal lobes, and medial temporal lobe.

The dorsolateral frontal cortex showed the largest group difference (estimated marginal mean difference, 1.31; 95% confidence interval, .42-2.19; false discovery rate-adjusted P = .01).

Previous research has shown early p-tau involvement in this area among CTE patients. Although the hippocampus is also affected in CTE, this occurs later in the disease course, the investigators noted.

The unique pattern, type, and distribution of p-tau pathology in CTE is different from Alzheimer’s disease. CTE is also distinct from Alzheimer’s disease in that there is no accumulation of beta-amyloid plaque.

The new results add to “converging evidence” for frontotemporal and medial temporal lobe atrophy in CTE “that might be able to be visualized on MRI,” the investigators noted.

Almost two-thirds of the CTE group had an additional neurodegenerative disease. Furthermore, the effect sizes remained similar in analyses that excluded CTE donors with frontotemporal lobar degeneration or Alzheimer’s disease.

“This suggests to us that these other diseases were not accounting for the atrophy,” Dr. Alosco said.

Individuals with CTE were 6.7 times more likely to have a CSP versus those with NC (odds ratio, 6.7; 95% CI, 1.5-50.1; P = .049).

Although previous research suggested an association between CSP and repetitive concussion, CSP is also frequently found in the general adult population. However, when combined with data on frontal lobe shrinkage, it may be a supportive differential diagnostic feature for CTE, Dr. Alosco said.
 

An important first step

The investigators also examined ventricle size. The lateral ventricles in the CTE group were significantly larger (mean difference, 1.72; 95% CI, .62-2.82; P = .01), as was the third ventricle (mean difference, .80; 95% CI, .26-1.35; P = .01).

When neuropathologists rated tau severity and atrophy at autopsy, they found that more severe p-tau pathology was associated with greater atrophy among those with CTE (beta = .68; P < .01).

Dr. Alosco called the finding “exciting,” noting that it suggests “this tau is a precipitant for neurodegeneration.”

He noted that, although some researchers have used positron emission tomography (PET) tau tracers to uncover a CTE pattern, MRI is relatively inexpensive and routinely used as part of dementia assessment.

While the new study is “an important first step” in using MRI to diagnose CTE, larger sample sizes are needed, Dr. Alosco said. “We also need to look at other disease groups and really nail down the difference with CTE in terms of patterns” (vs. Alzheimer’s disease and vs. frontotemporal lobar degeneration), he added.

“Once those differences are cleared, we will be ready to be more confident when we interpret these images.”.
 

‘Not unexpected’

Commenting on the research, neurologist and concussion expert Francis X. Conidi, DO, director, Florida Center for Headache and Sports Neurology, Port St. Lucie, said that, although the study was “well thought out and interesting,” the results were “not completely unexpected.”

Frontal and anterior temporal lobe atrophy and prominent third ventricles are very common in patients with traumatic brain injury (TBI), which is “a prerequisite to develop CTE,” said Dr. Conidi, who was not involved with the research.

The current study’s findings mirror observations found in a National Football League cohort he and his colleagues are following – and in his patients with TBI in general.

Dr. Conidi noted that there is a “significant subjective component” to the study results because they relied on the opinion of neuroradiologists. He is not convinced MRI findings of frontotemporal and medial temporal lobe atrophy necessarily represent CTE and not TBI. In fact, he noted that patients with TBI have a significantly greater chance of not developing a neurodegenerative disorder.

Dr. Conidi added that he doesn’t think MRI will ever be the gold standard for diagnosing or even assessing risk of developing CTE. “That lies in tau PET imaging,” he said.
 

Overstated conclusion?

Also commenting on the research findings, Kristen Dams-O’Connor, PhD, professor, vice chair of research, and director, Brain Injury Research Center, Department of Rehabilitation Medicine, Icahn School of Medicine at Mount Sinai in New York, said the sensitivity analyses, particularly those designed to clarify contributions of Alzheimer’s disease and other neuropathological contributions to associations between p-tau and atrophy, “increase our confidence” in the findings.

“What’s exciting about this paper is that it provides very preliminary support for adding another tool to our arsenal as we try to establish a constellation of in vivo diagnostic markers that, together, will help us rule in a post-traumatic neurodegenerative process and rule out other brain diseases.”

A possible study limitation is that the MRI scans were from low-field strength magnets, although that makes the study more “ecologically valid”, said Dr. Dams-O’Connor. “Many clinical scanners are built around a 1.5T magnet, so what the researchers see in this study is what a radiologist may see in the clinic.”

The conclusion that frontal-temporal atrophy is an MRI marker of CTE is “an overstatement” as this pattern of atrophy is not specific to CTE, said Dr. Dams-O’Connor. “The association of p-tau with atrophy is unsurprising and doesn’t bring us much closer to understanding how, or whether, the patterns of p-tau accumulation observed in CTE contribute to the clinical expression of symptoms.”

Dr. Alosco and Dr. Conidi report no relevant financial relationships. Disclosures for the other study authors are listed in the original journal article. The study was funded by grants from the National Institute on Aging, the National Institute on Neurological Disorders and Stroke, National Institute of Aging Boston University AD Center, Department of Veterans Affairs Merit Award, the Nick and Lynn Buoniconti Foundation, and BU-CTSI.

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

A distinct pattern of frontal-temporal atrophy discernible on magnetic resonance imaging (MRI) may flag chronic traumatic encephalopathy (CTE) in living patients, new research suggests.

“These new results offer some hope for clinicians who are really struggling to confidently diagnose or detect CTE during life,” said lead author Michael L. Alosco, PhD, associate professor of neurology, codirector of the Boston University Alzheimer’s Disease Research Center, and investigator at the Boston University CTE Center.

The findings were published online Dec. 7, 2021, in Alzheimer’s Research & Therapy.
 

A new way to diagnose?

CTE is a neurodegenerative disease associated with exposure to repetitive blows to the head, such as those sustained playing contact sports. Currently, the condition can only be reliably diagnosed at autopsy using neuropathological diagnostic criteria.

There are four pathological stages of CTE, ranging from mild to severe. Each progressive stage reflects mounting accumulation of hyperphosphorylated tau (p-tau).

The study included 55 male brain donors with confirmed CTE, all with a history of repetitive head injury. Most (n = 52) played football, but two played ice hockey and one had military and combat exposure. The analysis also included 31 men with normal cognition (NC). Of these, some were living and some were deceased.

The study sample was restricted to participants age 60 and older and to those who had an MRI obtained through a medical record request.

Most referrals for MRI in the CTE group were related to dementia or neurodegenerative disease (65%). In the NC group, MRI indications were mostly related to cerebrovascular causes (22.6%), memory complaints (16.1%), or vertigo (9.7%).

From MRIs, neuroradiologists visually rated patterns of shrinkage in the brain, microvascular disease, and presence of cavum septum pellucidum (CSP) – a large hole in the tissue separating ventricles of the brain.
 

More atrophy

Results showed that compared with the NC group, the CTE group had significantly greater atrophy in several brain regions, including the orbital-frontal cortex, dorsolateral frontal cortex, superior frontal cortex, anterior temporal lobes, and medial temporal lobe.

The dorsolateral frontal cortex showed the largest group difference (estimated marginal mean difference, 1.31; 95% confidence interval, .42-2.19; false discovery rate-adjusted P = .01).

Previous research has shown early p-tau involvement in this area among CTE patients. Although the hippocampus is also affected in CTE, this occurs later in the disease course, the investigators noted.

The unique pattern, type, and distribution of p-tau pathology in CTE is different from Alzheimer’s disease. CTE is also distinct from Alzheimer’s disease in that there is no accumulation of beta-amyloid plaque.

The new results add to “converging evidence” for frontotemporal and medial temporal lobe atrophy in CTE “that might be able to be visualized on MRI,” the investigators noted.

Almost two-thirds of the CTE group had an additional neurodegenerative disease. Furthermore, the effect sizes remained similar in analyses that excluded CTE donors with frontotemporal lobar degeneration or Alzheimer’s disease.

“This suggests to us that these other diseases were not accounting for the atrophy,” Dr. Alosco said.

Individuals with CTE were 6.7 times more likely to have a CSP versus those with NC (odds ratio, 6.7; 95% CI, 1.5-50.1; P = .049).

Although previous research suggested an association between CSP and repetitive concussion, CSP is also frequently found in the general adult population. However, when combined with data on frontal lobe shrinkage, it may be a supportive differential diagnostic feature for CTE, Dr. Alosco said.
 

An important first step

The investigators also examined ventricle size. The lateral ventricles in the CTE group were significantly larger (mean difference, 1.72; 95% CI, .62-2.82; P = .01), as was the third ventricle (mean difference, .80; 95% CI, .26-1.35; P = .01).

When neuropathologists rated tau severity and atrophy at autopsy, they found that more severe p-tau pathology was associated with greater atrophy among those with CTE (beta = .68; P < .01).

Dr. Alosco called the finding “exciting,” noting that it suggests “this tau is a precipitant for neurodegeneration.”

He noted that, although some researchers have used positron emission tomography (PET) tau tracers to uncover a CTE pattern, MRI is relatively inexpensive and routinely used as part of dementia assessment.

While the new study is “an important first step” in using MRI to diagnose CTE, larger sample sizes are needed, Dr. Alosco said. “We also need to look at other disease groups and really nail down the difference with CTE in terms of patterns” (vs. Alzheimer’s disease and vs. frontotemporal lobar degeneration), he added.

“Once those differences are cleared, we will be ready to be more confident when we interpret these images.”.
 

‘Not unexpected’

Commenting on the research, neurologist and concussion expert Francis X. Conidi, DO, director, Florida Center for Headache and Sports Neurology, Port St. Lucie, said that, although the study was “well thought out and interesting,” the results were “not completely unexpected.”

Frontal and anterior temporal lobe atrophy and prominent third ventricles are very common in patients with traumatic brain injury (TBI), which is “a prerequisite to develop CTE,” said Dr. Conidi, who was not involved with the research.

The current study’s findings mirror observations found in a National Football League cohort he and his colleagues are following – and in his patients with TBI in general.

Dr. Conidi noted that there is a “significant subjective component” to the study results because they relied on the opinion of neuroradiologists. He is not convinced MRI findings of frontotemporal and medial temporal lobe atrophy necessarily represent CTE and not TBI. In fact, he noted that patients with TBI have a significantly greater chance of not developing a neurodegenerative disorder.

Dr. Conidi added that he doesn’t think MRI will ever be the gold standard for diagnosing or even assessing risk of developing CTE. “That lies in tau PET imaging,” he said.
 

Overstated conclusion?

Also commenting on the research findings, Kristen Dams-O’Connor, PhD, professor, vice chair of research, and director, Brain Injury Research Center, Department of Rehabilitation Medicine, Icahn School of Medicine at Mount Sinai in New York, said the sensitivity analyses, particularly those designed to clarify contributions of Alzheimer’s disease and other neuropathological contributions to associations between p-tau and atrophy, “increase our confidence” in the findings.

“What’s exciting about this paper is that it provides very preliminary support for adding another tool to our arsenal as we try to establish a constellation of in vivo diagnostic markers that, together, will help us rule in a post-traumatic neurodegenerative process and rule out other brain diseases.”

A possible study limitation is that the MRI scans were from low-field strength magnets, although that makes the study more “ecologically valid”, said Dr. Dams-O’Connor. “Many clinical scanners are built around a 1.5T magnet, so what the researchers see in this study is what a radiologist may see in the clinic.”

The conclusion that frontal-temporal atrophy is an MRI marker of CTE is “an overstatement” as this pattern of atrophy is not specific to CTE, said Dr. Dams-O’Connor. “The association of p-tau with atrophy is unsurprising and doesn’t bring us much closer to understanding how, or whether, the patterns of p-tau accumulation observed in CTE contribute to the clinical expression of symptoms.”

Dr. Alosco and Dr. Conidi report no relevant financial relationships. Disclosures for the other study authors are listed in the original journal article. The study was funded by grants from the National Institute on Aging, the National Institute on Neurological Disorders and Stroke, National Institute of Aging Boston University AD Center, Department of Veterans Affairs Merit Award, the Nick and Lynn Buoniconti Foundation, and BU-CTSI.

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

A traumatic brain injury (TBI), even a mild type, can lead to posttraumatic epilepsy up to 1 year after the head injury occurs, new research suggests.

Results from a multicenter, prospective cohort study showed 2.7% of nearly 1,500 participants with TBI reported also having posttraumatic epilepsy, and these patients had significantly worse outcomes than those without posttraumatic epilepsy.

“Posttraumatic epilepsy is common even in so-called mild TBI, and we should be on the lookout for patients reporting these kinds of spells,” said coinvestigator Ramon Diaz-Arrastia, MD, PhD, professor of neurology and director of the TBI Clinical Research Center, University of Pennsylvania, Philadelphia.

Dr. Diaz-Arrastia said he dislikes the term “mild TBI” because many of these injuries have “pretty substantial consequences.”

The findings were published online Dec. 29 in JAMA Network Open.
 

Novel study

Seizures can occur after TBI, most commonly after a severe brain injury, such as those leading to coma or bleeding in the brain or requiring surgical intervention. However, there have been “hints” that some patients with milder brain injuries are also at increased risk for epilepsy, said Dr. Diaz-Arrastia.

To investigate, the researchers assessed data from the large, multicenter Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) database. Participants with TBI, defined as a Glasgow Coma Scale (GCS) score of 3-15, had presented to a level I trauma center within 24 hours of a head trauma needing evaluation with a CT scan.

The study included patients with relatively mild TBI (GCS score, 13-15), which is a “novel feature” of the study, the authors noted. Most prior studies of posttraumatic epilepsy focused on moderate to severe TBI.

The researchers included two sex- and age-matched control groups. The orthopedic trauma control (OTC) group consisted of patients with isolated trauma to the limbs, pelvis, and/or ribs. The “friend” or peer control group had backgrounds and lifestyles similar to those with TBI but had no history of TBI, concussion, or traumatic injury in the previous year.

The analysis included 1,885 participants (mean age, 41.3 years; 65.8% men). Of these, 1,493 had TBI, 182 were in the OTC group, and 210 were in the friends group. At 6- and 12-month follow-ups, investigators administered the Epilepsy Screening Questionnaire (ESQ), developed by the National Institute of Neurological Disorders and Stroke (NINDS).
 

Confirmatory data

Participants were asked about experiencing uncontrolled movements, unexplained changes in mental state, and repeated unusual attacks or convulsions, and whether they had been told they had epilepsy or seizures. If they answered yes to any of these questions, they received second-level screening, which asked about seizures.

Patients were deemed to have posttraumatic epilepsy if they answered affirmatively to any first-level screening item, experienced seizures 7 days after injury, and were diagnosed with epilepsy.

The primary outcome was rate of positive posttraumatic epilepsy diagnoses. At 12 months, 2.7% of those with TBI reported a posttraumatic epilepsy diagnosis compared with none of either of the control groups (P < .001).

This rate is consistent with prior literature and is “pretty close to what we expected,” said Dr. Diaz-Arrastia.

Among those with TBI and posttraumatic epilepsy, 12.2% had GCS scores of 3-8 (severe), 5.3% had scores of 9-12 (moderate), and 0.9% had scores of 13-15 (mild). That figure for mild TBI is not insignificant, said Dr. Diaz-Arrastia.

“Probably 90% of all those coming to the emergency room with a brain injury are diagnosed with mild TBI not requiring admission,” he noted.

The risk for posttraumatic epilepsy was higher the more severe the head injury, and among those with hemorrhage on head CT imaging. In patients with mild TBI, hemorrhage was associated with a two- to threefold risk of developing posttraumatic epilepsy.

“This prospective observational study confirms the epidemiologic data that even after mild brain injury, there is an increased risk for epilepsy,” said Dr. Diaz-Arrastia.
 

Universal screening?

The researchers also looked at whether seizures worsen other outcomes. Compared with those who had TBI but not posttraumatic epilepsy, those with posttraumatic epilepsy had significantly lower Glasgow Outcome Scale Extended (GOSE) scores (mean, 4.7 vs. 6.1; P < .001), higher Brief Symptom Inventory (BSI) scores (58.6 vs. 50.2; P = .02), and higher Rivermead Cognitive Metric (RCM) scores (5.3 vs. 3.1; P = .002) at 12 months after adjustment for age, initial GCS score, and imaging findings.

Higher GOSE and RCM scores reflect better outcomes, but a higher score on the BSI, which assesses overall mood, reflects a worse outcome, the investigators noted.

Previous evidence suggests prophylactic use of antiepileptic drugs in patients with TBI does not reduce risks. These drugs “are neither 100% safe nor 100% effective,” said Dr. Diaz-Arrastia. Some studies showed that certain agents actually worsen outcomes, he added.

What the field needs instead are antiepileptogenic drugs – those that interfere with the maladaptive synaptic plasticity that ends up in an epileptic circuit, he noted.

The new results suggest screening for posttraumatic epilepsy using the NINDS-ESQ “should be done pretty much routinely as a follow-up for all brain injuries,” Dr. Diaz-Arrastia said.

The investigators plan to have study participants assessed by an epileptologist later. A significant number of people with TBI, he noted, won’t develop posttraumatic epilepsy until 1-5 years after their injury – and even later in some cases.

A limitation of the study was that some patients reporting posttraumatic epilepsy may have had psychogenic nonepileptiform seizures, which are common in TBI patients, the investigators noted.

The study was supported by grants from One Mind, National Institutes of Health (NIH), National Institute of Neurological Disorders and Stroke (NINDS, and Department of Defence. Dr. Diaz-Arrastia reported receiving grants from the NIH, NINDS, and DOD during the conduct of the study.

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

A traumatic brain injury (TBI), even a mild type, can lead to posttraumatic epilepsy up to 1 year after the head injury occurs, new research suggests.

Results from a multicenter, prospective cohort study showed 2.7% of nearly 1,500 participants with TBI reported also having posttraumatic epilepsy, and these patients had significantly worse outcomes than those without posttraumatic epilepsy.

“Posttraumatic epilepsy is common even in so-called mild TBI, and we should be on the lookout for patients reporting these kinds of spells,” said coinvestigator Ramon Diaz-Arrastia, MD, PhD, professor of neurology and director of the TBI Clinical Research Center, University of Pennsylvania, Philadelphia.

Dr. Diaz-Arrastia said he dislikes the term “mild TBI” because many of these injuries have “pretty substantial consequences.”

The findings were published online Dec. 29 in JAMA Network Open.
 

Novel study

Seizures can occur after TBI, most commonly after a severe brain injury, such as those leading to coma or bleeding in the brain or requiring surgical intervention. However, there have been “hints” that some patients with milder brain injuries are also at increased risk for epilepsy, said Dr. Diaz-Arrastia.

To investigate, the researchers assessed data from the large, multicenter Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) database. Participants with TBI, defined as a Glasgow Coma Scale (GCS) score of 3-15, had presented to a level I trauma center within 24 hours of a head trauma needing evaluation with a CT scan.

The study included patients with relatively mild TBI (GCS score, 13-15), which is a “novel feature” of the study, the authors noted. Most prior studies of posttraumatic epilepsy focused on moderate to severe TBI.

The researchers included two sex- and age-matched control groups. The orthopedic trauma control (OTC) group consisted of patients with isolated trauma to the limbs, pelvis, and/or ribs. The “friend” or peer control group had backgrounds and lifestyles similar to those with TBI but had no history of TBI, concussion, or traumatic injury in the previous year.

The analysis included 1,885 participants (mean age, 41.3 years; 65.8% men). Of these, 1,493 had TBI, 182 were in the OTC group, and 210 were in the friends group. At 6- and 12-month follow-ups, investigators administered the Epilepsy Screening Questionnaire (ESQ), developed by the National Institute of Neurological Disorders and Stroke (NINDS).
 

Confirmatory data

Participants were asked about experiencing uncontrolled movements, unexplained changes in mental state, and repeated unusual attacks or convulsions, and whether they had been told they had epilepsy or seizures. If they answered yes to any of these questions, they received second-level screening, which asked about seizures.

Patients were deemed to have posttraumatic epilepsy if they answered affirmatively to any first-level screening item, experienced seizures 7 days after injury, and were diagnosed with epilepsy.

The primary outcome was rate of positive posttraumatic epilepsy diagnoses. At 12 months, 2.7% of those with TBI reported a posttraumatic epilepsy diagnosis compared with none of either of the control groups (P < .001).

This rate is consistent with prior literature and is “pretty close to what we expected,” said Dr. Diaz-Arrastia.

Among those with TBI and posttraumatic epilepsy, 12.2% had GCS scores of 3-8 (severe), 5.3% had scores of 9-12 (moderate), and 0.9% had scores of 13-15 (mild). That figure for mild TBI is not insignificant, said Dr. Diaz-Arrastia.

“Probably 90% of all those coming to the emergency room with a brain injury are diagnosed with mild TBI not requiring admission,” he noted.

The risk for posttraumatic epilepsy was higher the more severe the head injury, and among those with hemorrhage on head CT imaging. In patients with mild TBI, hemorrhage was associated with a two- to threefold risk of developing posttraumatic epilepsy.

“This prospective observational study confirms the epidemiologic data that even after mild brain injury, there is an increased risk for epilepsy,” said Dr. Diaz-Arrastia.
 

Universal screening?

The researchers also looked at whether seizures worsen other outcomes. Compared with those who had TBI but not posttraumatic epilepsy, those with posttraumatic epilepsy had significantly lower Glasgow Outcome Scale Extended (GOSE) scores (mean, 4.7 vs. 6.1; P < .001), higher Brief Symptom Inventory (BSI) scores (58.6 vs. 50.2; P = .02), and higher Rivermead Cognitive Metric (RCM) scores (5.3 vs. 3.1; P = .002) at 12 months after adjustment for age, initial GCS score, and imaging findings.

Higher GOSE and RCM scores reflect better outcomes, but a higher score on the BSI, which assesses overall mood, reflects a worse outcome, the investigators noted.

Previous evidence suggests prophylactic use of antiepileptic drugs in patients with TBI does not reduce risks. These drugs “are neither 100% safe nor 100% effective,” said Dr. Diaz-Arrastia. Some studies showed that certain agents actually worsen outcomes, he added.

What the field needs instead are antiepileptogenic drugs – those that interfere with the maladaptive synaptic plasticity that ends up in an epileptic circuit, he noted.

The new results suggest screening for posttraumatic epilepsy using the NINDS-ESQ “should be done pretty much routinely as a follow-up for all brain injuries,” Dr. Diaz-Arrastia said.

The investigators plan to have study participants assessed by an epileptologist later. A significant number of people with TBI, he noted, won’t develop posttraumatic epilepsy until 1-5 years after their injury – and even later in some cases.

A limitation of the study was that some patients reporting posttraumatic epilepsy may have had psychogenic nonepileptiform seizures, which are common in TBI patients, the investigators noted.

The study was supported by grants from One Mind, National Institutes of Health (NIH), National Institute of Neurological Disorders and Stroke (NINDS, and Department of Defence. Dr. Diaz-Arrastia reported receiving grants from the NIH, NINDS, and DOD during the conduct of the study.

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

A traumatic brain injury (TBI), even a mild type, can lead to posttraumatic epilepsy up to 1 year after the head injury occurs, new research suggests.

Results from a multicenter, prospective cohort study showed 2.7% of nearly 1,500 participants with TBI reported also having posttraumatic epilepsy, and these patients had significantly worse outcomes than those without posttraumatic epilepsy.

“Posttraumatic epilepsy is common even in so-called mild TBI, and we should be on the lookout for patients reporting these kinds of spells,” said coinvestigator Ramon Diaz-Arrastia, MD, PhD, professor of neurology and director of the TBI Clinical Research Center, University of Pennsylvania, Philadelphia.

Dr. Diaz-Arrastia said he dislikes the term “mild TBI” because many of these injuries have “pretty substantial consequences.”

The findings were published online Dec. 29 in JAMA Network Open.
 

Novel study

Seizures can occur after TBI, most commonly after a severe brain injury, such as those leading to coma or bleeding in the brain or requiring surgical intervention. However, there have been “hints” that some patients with milder brain injuries are also at increased risk for epilepsy, said Dr. Diaz-Arrastia.

To investigate, the researchers assessed data from the large, multicenter Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) database. Participants with TBI, defined as a Glasgow Coma Scale (GCS) score of 3-15, had presented to a level I trauma center within 24 hours of a head trauma needing evaluation with a CT scan.

The study included patients with relatively mild TBI (GCS score, 13-15), which is a “novel feature” of the study, the authors noted. Most prior studies of posttraumatic epilepsy focused on moderate to severe TBI.

The researchers included two sex- and age-matched control groups. The orthopedic trauma control (OTC) group consisted of patients with isolated trauma to the limbs, pelvis, and/or ribs. The “friend” or peer control group had backgrounds and lifestyles similar to those with TBI but had no history of TBI, concussion, or traumatic injury in the previous year.

The analysis included 1,885 participants (mean age, 41.3 years; 65.8% men). Of these, 1,493 had TBI, 182 were in the OTC group, and 210 were in the friends group. At 6- and 12-month follow-ups, investigators administered the Epilepsy Screening Questionnaire (ESQ), developed by the National Institute of Neurological Disorders and Stroke (NINDS).
 

Confirmatory data

Participants were asked about experiencing uncontrolled movements, unexplained changes in mental state, and repeated unusual attacks or convulsions, and whether they had been told they had epilepsy or seizures. If they answered yes to any of these questions, they received second-level screening, which asked about seizures.

Patients were deemed to have posttraumatic epilepsy if they answered affirmatively to any first-level screening item, experienced seizures 7 days after injury, and were diagnosed with epilepsy.

The primary outcome was rate of positive posttraumatic epilepsy diagnoses. At 12 months, 2.7% of those with TBI reported a posttraumatic epilepsy diagnosis compared with none of either of the control groups (P < .001).

This rate is consistent with prior literature and is “pretty close to what we expected,” said Dr. Diaz-Arrastia.

Among those with TBI and posttraumatic epilepsy, 12.2% had GCS scores of 3-8 (severe), 5.3% had scores of 9-12 (moderate), and 0.9% had scores of 13-15 (mild). That figure for mild TBI is not insignificant, said Dr. Diaz-Arrastia.

“Probably 90% of all those coming to the emergency room with a brain injury are diagnosed with mild TBI not requiring admission,” he noted.

The risk for posttraumatic epilepsy was higher the more severe the head injury, and among those with hemorrhage on head CT imaging. In patients with mild TBI, hemorrhage was associated with a two- to threefold risk of developing posttraumatic epilepsy.

“This prospective observational study confirms the epidemiologic data that even after mild brain injury, there is an increased risk for epilepsy,” said Dr. Diaz-Arrastia.
 

Universal screening?

The researchers also looked at whether seizures worsen other outcomes. Compared with those who had TBI but not posttraumatic epilepsy, those with posttraumatic epilepsy had significantly lower Glasgow Outcome Scale Extended (GOSE) scores (mean, 4.7 vs. 6.1; P < .001), higher Brief Symptom Inventory (BSI) scores (58.6 vs. 50.2; P = .02), and higher Rivermead Cognitive Metric (RCM) scores (5.3 vs. 3.1; P = .002) at 12 months after adjustment for age, initial GCS score, and imaging findings.

Higher GOSE and RCM scores reflect better outcomes, but a higher score on the BSI, which assesses overall mood, reflects a worse outcome, the investigators noted.

Previous evidence suggests prophylactic use of antiepileptic drugs in patients with TBI does not reduce risks. These drugs “are neither 100% safe nor 100% effective,” said Dr. Diaz-Arrastia. Some studies showed that certain agents actually worsen outcomes, he added.

What the field needs instead are antiepileptogenic drugs – those that interfere with the maladaptive synaptic plasticity that ends up in an epileptic circuit, he noted.

The new results suggest screening for posttraumatic epilepsy using the NINDS-ESQ “should be done pretty much routinely as a follow-up for all brain injuries,” Dr. Diaz-Arrastia said.

The investigators plan to have study participants assessed by an epileptologist later. A significant number of people with TBI, he noted, won’t develop posttraumatic epilepsy until 1-5 years after their injury – and even later in some cases.

A limitation of the study was that some patients reporting posttraumatic epilepsy may have had psychogenic nonepileptiform seizures, which are common in TBI patients, the investigators noted.

The study was supported by grants from One Mind, National Institutes of Health (NIH), National Institute of Neurological Disorders and Stroke (NINDS, and Department of Defence. Dr. Diaz-Arrastia reported receiving grants from the NIH, NINDS, and DOD during the conduct of the study.

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

Researchers have known for some time that depression is associated with Alzheimer’s disease (AD), but a causal link has been elusive. Now, using newly available data, they have uncovered genetic evidence of a causal role for depression in AD.

As depression typically affects those in early or midlife and dementia often occurs in later life, “it’s fascinating to see a connection between the two brain illnesses that manifest in different time windows,” coinvestigator Aliza P. Wingo, MD, associate professor of psychiatry and behavioral science, Emory University, Atlanta, said in an interview.

“If we can treat the depression early on, we may help reduce risk for dementia for our patients later in life,” Dr. Wingo said.

The findings were published online Dec. 16, 2021, in Biological Psychiatry.

Postmortem data

The investigators, who are all from the Emory University Center for Neurodegenerative Disease, wanted to clarify the genetic basis underlying the association between the established link between depression and dementia risk.

They used data from the largest and most recent genomewide association studies (GWAS). These included a 2019 analysis of depression among 807,553 individuals and a 2019 study of AD among 455,258 individuals, all of European ancestry. For sensitivity analyses, they used results from two additional AD GWAS.

The researchers also accessed postmortem brain samples from participants in the Religious Orders Study (ROS) and the Rush Memory and Aging Project (MAP). These participants were cognitively normal at enrollment, underwent annual clinical evaluations, and agreed to donate their brains.

They also assessed brain samples donated by participants in the Banner Sun Health Research Institute longitudinal study of healthy aging, Alzheimer’s, and Parkinson’s disease.

The brain samples allowed researchers to use deep brain proteomic data to help determine molecular links between depression and AD.

After quality control, the analysis included 8,356 proteins in 391 ROS/MAP participants and 7,854 proteins in 196 Banner participants.

Results showed a small but significant positive genetic correlation between depression and AD, suggesting the two conditions have a shared genetic basis.

The investigators also applied a framework called “Mendelian randomization” to determine causality between depression and AD.

After assessing the effect of 115 independent single-nucleotide polymorphisms (SNPs) from the GWAS of depression, they uncovered significant evidence “that the SNPs cause depression, which in turn cause AD,” said Dr. Wingo.
 

One-way relationship

The researchers conducted the same analysis on 61 significant SNPs from the GWAS of AD but did not find evidence to conclude AD causes depression.

“We found genetic evidence supporting a causal role of depression in AD but not vice versa,” Dr. Wingo said.

In addition, the investigators identified 75 brain transcripts (messenger RNA) and 28 brain proteins regulated by the depression-predisposing genetic variants. Of these, 46 brain transcripts and seven proteins were significantly associated with at least one AD feature – for example, beta-amyloid, tau tangles, and cognitive trajectory.

“These findings support the notion that the depression risk variants contribute to AD via regulating expression of their corresponding transcripts in the brain,” the investigators wrote.

It is only recently that large enough studies have allowed researchers sufficient power to reach these conclusions, coinvestigator Thomas Wingo, MD, said in an interview.

These additional “insights” into the relationship between depression and AD might “motivate” clinicians more to screen for and treat depressive symptoms, Dr. Aliza Wingo noted.

The new results also have implications for developing therapeutics to treat depression, she said. “If we target the genes, the brain proteins, that are shared risk between depression and AD, the medications that target that gene might mitigate risk for AD later on.”

However, the investigators advised caution. “A lot of this is still unknown,” said Dr. Thomas Wingo.

For example, it is not clear whether successfully treating depression mitigates the eventual risk of dementia, which is “a very important topic of inquiry and one we continue to work on,” he said, adding that a significant number of patients do not respond well to existing antidepressants such as SSRIs.
 

Need for further research

Commenting on the findings, Claire Sexton, DPhil, director of scientific programs and outreach, Alzheimer’s Association, said the study contributes to the debate about whether depression increases risk for AD, whether AD increases risk for depression, or both.

“These newly published findings strengthen our understanding of the role of depression as a risk factor for Alzheimer’s dementia,” said Dr. Sexton, who was not involved with the research.

While experts do not yet fully understand the impact of treating depression on dementia risk, “the findings emphasize the importance of assessing mental health status, particularly depression, and getting it properly diagnosed and treated in a timely manner,” she said.

However, she agreed more research in this area is needed. “Importantly, these findings need replication in broader, more diverse study populations,” Dr. Sexton said.

A study funded by the Alzheimer’s Association may provide more information on the link between depression and AD. It will investigate whether machine learning, an advanced computer science technique, can better predict cognitive decline, compared with traditional methods.

Over a period of 6 months, researchers will collect smartphone conversations from 225 older adults with dementia, mild cognitive impairment, or no cognitive impairment. They will also have data from cognitive tests, brain scans, and biomarkers such as cerebrospinal fluid samples to study brain changes associated with AD.

The novel method of analysis should be able to identify subtle differences in speech quality to indicate which depressive symptoms an individual might be experiencing.

“The study could help us further understand the potential impact of depression in the risk of developing dementia,” said Dr. Sexton.

Dr. Aliza Wingo and Dr. Thomas Wingo reported no relevant financial relationships.

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

Researchers have known for some time that depression is associated with Alzheimer’s disease (AD), but a causal link has been elusive. Now, using newly available data, they have uncovered genetic evidence of a causal role for depression in AD.

As depression typically affects those in early or midlife and dementia often occurs in later life, “it’s fascinating to see a connection between the two brain illnesses that manifest in different time windows,” coinvestigator Aliza P. Wingo, MD, associate professor of psychiatry and behavioral science, Emory University, Atlanta, said in an interview.

“If we can treat the depression early on, we may help reduce risk for dementia for our patients later in life,” Dr. Wingo said.

The findings were published online Dec. 16, 2021, in Biological Psychiatry.

Postmortem data

The investigators, who are all from the Emory University Center for Neurodegenerative Disease, wanted to clarify the genetic basis underlying the association between the established link between depression and dementia risk.

They used data from the largest and most recent genomewide association studies (GWAS). These included a 2019 analysis of depression among 807,553 individuals and a 2019 study of AD among 455,258 individuals, all of European ancestry. For sensitivity analyses, they used results from two additional AD GWAS.

The researchers also accessed postmortem brain samples from participants in the Religious Orders Study (ROS) and the Rush Memory and Aging Project (MAP). These participants were cognitively normal at enrollment, underwent annual clinical evaluations, and agreed to donate their brains.

They also assessed brain samples donated by participants in the Banner Sun Health Research Institute longitudinal study of healthy aging, Alzheimer’s, and Parkinson’s disease.

The brain samples allowed researchers to use deep brain proteomic data to help determine molecular links between depression and AD.

After quality control, the analysis included 8,356 proteins in 391 ROS/MAP participants and 7,854 proteins in 196 Banner participants.

Results showed a small but significant positive genetic correlation between depression and AD, suggesting the two conditions have a shared genetic basis.

The investigators also applied a framework called “Mendelian randomization” to determine causality between depression and AD.

After assessing the effect of 115 independent single-nucleotide polymorphisms (SNPs) from the GWAS of depression, they uncovered significant evidence “that the SNPs cause depression, which in turn cause AD,” said Dr. Wingo.
 

One-way relationship

The researchers conducted the same analysis on 61 significant SNPs from the GWAS of AD but did not find evidence to conclude AD causes depression.

“We found genetic evidence supporting a causal role of depression in AD but not vice versa,” Dr. Wingo said.

In addition, the investigators identified 75 brain transcripts (messenger RNA) and 28 brain proteins regulated by the depression-predisposing genetic variants. Of these, 46 brain transcripts and seven proteins were significantly associated with at least one AD feature – for example, beta-amyloid, tau tangles, and cognitive trajectory.

“These findings support the notion that the depression risk variants contribute to AD via regulating expression of their corresponding transcripts in the brain,” the investigators wrote.

It is only recently that large enough studies have allowed researchers sufficient power to reach these conclusions, coinvestigator Thomas Wingo, MD, said in an interview.

These additional “insights” into the relationship between depression and AD might “motivate” clinicians more to screen for and treat depressive symptoms, Dr. Aliza Wingo noted.

The new results also have implications for developing therapeutics to treat depression, she said. “If we target the genes, the brain proteins, that are shared risk between depression and AD, the medications that target that gene might mitigate risk for AD later on.”

However, the investigators advised caution. “A lot of this is still unknown,” said Dr. Thomas Wingo.

For example, it is not clear whether successfully treating depression mitigates the eventual risk of dementia, which is “a very important topic of inquiry and one we continue to work on,” he said, adding that a significant number of patients do not respond well to existing antidepressants such as SSRIs.
 

Need for further research

Commenting on the findings, Claire Sexton, DPhil, director of scientific programs and outreach, Alzheimer’s Association, said the study contributes to the debate about whether depression increases risk for AD, whether AD increases risk for depression, or both.

“These newly published findings strengthen our understanding of the role of depression as a risk factor for Alzheimer’s dementia,” said Dr. Sexton, who was not involved with the research.

While experts do not yet fully understand the impact of treating depression on dementia risk, “the findings emphasize the importance of assessing mental health status, particularly depression, and getting it properly diagnosed and treated in a timely manner,” she said.

However, she agreed more research in this area is needed. “Importantly, these findings need replication in broader, more diverse study populations,” Dr. Sexton said.

A study funded by the Alzheimer’s Association may provide more information on the link between depression and AD. It will investigate whether machine learning, an advanced computer science technique, can better predict cognitive decline, compared with traditional methods.

Over a period of 6 months, researchers will collect smartphone conversations from 225 older adults with dementia, mild cognitive impairment, or no cognitive impairment. They will also have data from cognitive tests, brain scans, and biomarkers such as cerebrospinal fluid samples to study brain changes associated with AD.

The novel method of analysis should be able to identify subtle differences in speech quality to indicate which depressive symptoms an individual might be experiencing.

“The study could help us further understand the potential impact of depression in the risk of developing dementia,” said Dr. Sexton.

Dr. Aliza Wingo and Dr. Thomas Wingo reported no relevant financial relationships.

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

Researchers have known for some time that depression is associated with Alzheimer’s disease (AD), but a causal link has been elusive. Now, using newly available data, they have uncovered genetic evidence of a causal role for depression in AD.

As depression typically affects those in early or midlife and dementia often occurs in later life, “it’s fascinating to see a connection between the two brain illnesses that manifest in different time windows,” coinvestigator Aliza P. Wingo, MD, associate professor of psychiatry and behavioral science, Emory University, Atlanta, said in an interview.

“If we can treat the depression early on, we may help reduce risk for dementia for our patients later in life,” Dr. Wingo said.

The findings were published online Dec. 16, 2021, in Biological Psychiatry.

Postmortem data

The investigators, who are all from the Emory University Center for Neurodegenerative Disease, wanted to clarify the genetic basis underlying the association between the established link between depression and dementia risk.

They used data from the largest and most recent genomewide association studies (GWAS). These included a 2019 analysis of depression among 807,553 individuals and a 2019 study of AD among 455,258 individuals, all of European ancestry. For sensitivity analyses, they used results from two additional AD GWAS.

The researchers also accessed postmortem brain samples from participants in the Religious Orders Study (ROS) and the Rush Memory and Aging Project (MAP). These participants were cognitively normal at enrollment, underwent annual clinical evaluations, and agreed to donate their brains.

They also assessed brain samples donated by participants in the Banner Sun Health Research Institute longitudinal study of healthy aging, Alzheimer’s, and Parkinson’s disease.

The brain samples allowed researchers to use deep brain proteomic data to help determine molecular links between depression and AD.

After quality control, the analysis included 8,356 proteins in 391 ROS/MAP participants and 7,854 proteins in 196 Banner participants.

Results showed a small but significant positive genetic correlation between depression and AD, suggesting the two conditions have a shared genetic basis.

The investigators also applied a framework called “Mendelian randomization” to determine causality between depression and AD.

After assessing the effect of 115 independent single-nucleotide polymorphisms (SNPs) from the GWAS of depression, they uncovered significant evidence “that the SNPs cause depression, which in turn cause AD,” said Dr. Wingo.
 

One-way relationship

The researchers conducted the same analysis on 61 significant SNPs from the GWAS of AD but did not find evidence to conclude AD causes depression.

“We found genetic evidence supporting a causal role of depression in AD but not vice versa,” Dr. Wingo said.

In addition, the investigators identified 75 brain transcripts (messenger RNA) and 28 brain proteins regulated by the depression-predisposing genetic variants. Of these, 46 brain transcripts and seven proteins were significantly associated with at least one AD feature – for example, beta-amyloid, tau tangles, and cognitive trajectory.

“These findings support the notion that the depression risk variants contribute to AD via regulating expression of their corresponding transcripts in the brain,” the investigators wrote.

It is only recently that large enough studies have allowed researchers sufficient power to reach these conclusions, coinvestigator Thomas Wingo, MD, said in an interview.

These additional “insights” into the relationship between depression and AD might “motivate” clinicians more to screen for and treat depressive symptoms, Dr. Aliza Wingo noted.

The new results also have implications for developing therapeutics to treat depression, she said. “If we target the genes, the brain proteins, that are shared risk between depression and AD, the medications that target that gene might mitigate risk for AD later on.”

However, the investigators advised caution. “A lot of this is still unknown,” said Dr. Thomas Wingo.

For example, it is not clear whether successfully treating depression mitigates the eventual risk of dementia, which is “a very important topic of inquiry and one we continue to work on,” he said, adding that a significant number of patients do not respond well to existing antidepressants such as SSRIs.
 

Need for further research

Commenting on the findings, Claire Sexton, DPhil, director of scientific programs and outreach, Alzheimer’s Association, said the study contributes to the debate about whether depression increases risk for AD, whether AD increases risk for depression, or both.

“These newly published findings strengthen our understanding of the role of depression as a risk factor for Alzheimer’s dementia,” said Dr. Sexton, who was not involved with the research.

While experts do not yet fully understand the impact of treating depression on dementia risk, “the findings emphasize the importance of assessing mental health status, particularly depression, and getting it properly diagnosed and treated in a timely manner,” she said.

However, she agreed more research in this area is needed. “Importantly, these findings need replication in broader, more diverse study populations,” Dr. Sexton said.

A study funded by the Alzheimer’s Association may provide more information on the link between depression and AD. It will investigate whether machine learning, an advanced computer science technique, can better predict cognitive decline, compared with traditional methods.

Over a period of 6 months, researchers will collect smartphone conversations from 225 older adults with dementia, mild cognitive impairment, or no cognitive impairment. They will also have data from cognitive tests, brain scans, and biomarkers such as cerebrospinal fluid samples to study brain changes associated with AD.

The novel method of analysis should be able to identify subtle differences in speech quality to indicate which depressive symptoms an individual might be experiencing.

“The study could help us further understand the potential impact of depression in the risk of developing dementia,” said Dr. Sexton.

Dr. Aliza Wingo and Dr. Thomas Wingo reported no relevant financial relationships.

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