Literature Review

The first official U.S. case of Guillain-Barré syndrome (GBS) associated with COVID-19 has been reported by neurologists from Allegheny General Hospital in Pittsburgh, further supporting a link between the virus and neurologic complications, including GBS.

Physicians in China reported the first case of COVID-19 that initially presented as acute GBS. The patient was a 61-year-old woman returning home from Wuhan during the pandemic.

Subsequently, physicians in Italy reported five cases of GBS in association with COVID-19.

The first U.S. case is described in the June issue of the Journal of Clinical Neuromuscular Disease.

Like cases from China and Italy, the U.S. patient’s symptoms of GBS reportedly occurred within days of being infected with SARS-CoV-2. “This onset is similar to a case report of acute Zika virus infection with concurrent GBS suggesting a parainfectious complication,” first author Sandeep Rana, MD, and colleagues noted.

The 54-year-old man was transferred to Allegheny General Hospital after developing ascending limb weakness and numbness that followed symptoms of a respiratory infection. Two weeks earlier, he initially developed rhinorrhea, odynophagia, fevers, chills, and night sweats. The man reported that his wife had tested positive for COVID-19 and that his symptoms started soon after her illness. The man also tested positive for COVID-19.

His deficits were characterized by quadriparesis and areflexia, burning dysesthesias, mild ophthalmoparesis, and dysautonomia. He did not have the loss of smell and taste documented in other COVID-19 patients. He briefly required mechanical ventilation and was successfully weaned after receiving a course of intravenous immunoglobulin.

Compared with other cases reported in the literature, the unique clinical features in the U.S. case are urinary retention secondary to dysautonomia and ocular symptoms of diplopia. These highlight the variability in the clinical presentation of GBS associated with COVID-19, the researchers noted.

They added that, with the Pittsburgh patient, electrophysiological findings were typical of demyelinating polyneuropathy seen in patients with GBS. The case series from Italy suggests that axonal variants could be as common in COVID-19–associated GBS.

“Although the number of documented cases internationally is notably small to date, it’s not completely surprising that a COVID-19 diagnosis may lead to a patient developing GBS. The increase of inflammation and inflammatory cells caused by the infection may trigger an irregular immune response that leads to the hallmark symptoms of this neurological disorder,” Dr. Rana said in a news release.

“Since GBS can significantly affect the respiratory system and other vital organs being pushed into overdrive during a COVID-19 immune response, it will be critically important to further investigate and understand this potential connection,” he added.

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

The first official U.S. case of Guillain-Barré syndrome (GBS) associated with COVID-19 has been reported by neurologists from Allegheny General Hospital in Pittsburgh, further supporting a link between the virus and neurologic complications, including GBS.

Physicians in China reported the first case of COVID-19 that initially presented as acute GBS. The patient was a 61-year-old woman returning home from Wuhan during the pandemic.

Subsequently, physicians in Italy reported five cases of GBS in association with COVID-19.

The first U.S. case is described in the June issue of the Journal of Clinical Neuromuscular Disease.

Like cases from China and Italy, the U.S. patient’s symptoms of GBS reportedly occurred within days of being infected with SARS-CoV-2. “This onset is similar to a case report of acute Zika virus infection with concurrent GBS suggesting a parainfectious complication,” first author Sandeep Rana, MD, and colleagues noted.

The 54-year-old man was transferred to Allegheny General Hospital after developing ascending limb weakness and numbness that followed symptoms of a respiratory infection. Two weeks earlier, he initially developed rhinorrhea, odynophagia, fevers, chills, and night sweats. The man reported that his wife had tested positive for COVID-19 and that his symptoms started soon after her illness. The man also tested positive for COVID-19.

His deficits were characterized by quadriparesis and areflexia, burning dysesthesias, mild ophthalmoparesis, and dysautonomia. He did not have the loss of smell and taste documented in other COVID-19 patients. He briefly required mechanical ventilation and was successfully weaned after receiving a course of intravenous immunoglobulin.

Compared with other cases reported in the literature, the unique clinical features in the U.S. case are urinary retention secondary to dysautonomia and ocular symptoms of diplopia. These highlight the variability in the clinical presentation of GBS associated with COVID-19, the researchers noted.

They added that, with the Pittsburgh patient, electrophysiological findings were typical of demyelinating polyneuropathy seen in patients with GBS. The case series from Italy suggests that axonal variants could be as common in COVID-19–associated GBS.

“Although the number of documented cases internationally is notably small to date, it’s not completely surprising that a COVID-19 diagnosis may lead to a patient developing GBS. The increase of inflammation and inflammatory cells caused by the infection may trigger an irregular immune response that leads to the hallmark symptoms of this neurological disorder,” Dr. Rana said in a news release.

“Since GBS can significantly affect the respiratory system and other vital organs being pushed into overdrive during a COVID-19 immune response, it will be critically important to further investigate and understand this potential connection,” he added.

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

The first official U.S. case of Guillain-Barré syndrome (GBS) associated with COVID-19 has been reported by neurologists from Allegheny General Hospital in Pittsburgh, further supporting a link between the virus and neurologic complications, including GBS.

Physicians in China reported the first case of COVID-19 that initially presented as acute GBS. The patient was a 61-year-old woman returning home from Wuhan during the pandemic.

Subsequently, physicians in Italy reported five cases of GBS in association with COVID-19.

The first U.S. case is described in the June issue of the Journal of Clinical Neuromuscular Disease.

Like cases from China and Italy, the U.S. patient’s symptoms of GBS reportedly occurred within days of being infected with SARS-CoV-2. “This onset is similar to a case report of acute Zika virus infection with concurrent GBS suggesting a parainfectious complication,” first author Sandeep Rana, MD, and colleagues noted.

The 54-year-old man was transferred to Allegheny General Hospital after developing ascending limb weakness and numbness that followed symptoms of a respiratory infection. Two weeks earlier, he initially developed rhinorrhea, odynophagia, fevers, chills, and night sweats. The man reported that his wife had tested positive for COVID-19 and that his symptoms started soon after her illness. The man also tested positive for COVID-19.

His deficits were characterized by quadriparesis and areflexia, burning dysesthesias, mild ophthalmoparesis, and dysautonomia. He did not have the loss of smell and taste documented in other COVID-19 patients. He briefly required mechanical ventilation and was successfully weaned after receiving a course of intravenous immunoglobulin.

Compared with other cases reported in the literature, the unique clinical features in the U.S. case are urinary retention secondary to dysautonomia and ocular symptoms of diplopia. These highlight the variability in the clinical presentation of GBS associated with COVID-19, the researchers noted.

They added that, with the Pittsburgh patient, electrophysiological findings were typical of demyelinating polyneuropathy seen in patients with GBS. The case series from Italy suggests that axonal variants could be as common in COVID-19–associated GBS.

“Although the number of documented cases internationally is notably small to date, it’s not completely surprising that a COVID-19 diagnosis may lead to a patient developing GBS. The increase of inflammation and inflammatory cells caused by the infection may trigger an irregular immune response that leads to the hallmark symptoms of this neurological disorder,” Dr. Rana said in a news release.

“Since GBS can significantly affect the respiratory system and other vital organs being pushed into overdrive during a COVID-19 immune response, it will be critically important to further investigate and understand this potential connection,” he added.

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

Combining four of five healthy lifestyle choices has been linked to up to a 60% reduced risk for Alzheimer’s dementia in new research that strengthens ties between healthy behaviors and lower dementia risk. “I hope this study will motivate people to engage in a healthy lifestyle by not smoking, being physically and cognitively active, and having a high-quality diet,” lead investigator Klodian Dhana, MD, PhD, department of internal medicine, Rush University Medical Center, Chicago, said in an interview.

The study was published online June 17 in Neurology.
 

Risk-modifying behaviors

To help quantify the impact of a healthy life on risk for Alzheimer’s dementia, Dr. Dhana and colleagues reviewed data from two longitudinal study populations: the Chicago Health and Aging Project (CHAP), with 1,845 participants, and the Memory and Aging Project (MAP), with 920 participants.

They defined a healthy lifestyle score on the basis of the following factors: not smoking; engaging in 150 min/wk or more of physical exercise of moderate to vigorous intensity; light to moderate alcohol consumption (between 1 and less than 15 g/day for women and between 1 and less than 30 g/day for men); consuming a high-quality Mediterranean-DASH Diet Intervention for Neurodegenerative Delay diet (upper 40%); and engaging in late-life cognitive activities (upper 40%). The overall score ranged from 0 to 5.

At baseline, the mean age of participants was 73.2 years in the CHAP study and 81.1 years in the MAP study; 62.4% of the CHAP participants and 75.2% of the MAP participants were women.

During a median follow-up of 5.8 years in CHAP and 6.0 years in MAP, a total of 379 and 229 participants, respectively, developed Alzheimer’s dementia. Rates of dementia decreased with an increasing number of healthy lifestyle behaviors.

In multivariable-adjusted models across the two cohorts, the risk for Alzheimer’s dementia was 27% lower with each additional healthy lifestyle factor (pooled hazard ratio, 0.73; 95% confidence interval, 0.66-0.80).

Compared with individuals with a healthy lifestyle score of 0-1, the risk was 37% lower (pooled HR, 0.63; 95% CI, 0.47-0.84) for those with two or three healthy lifestyle factors and 60% lower (pooled HR, 0.40; 95% CI, 0.28-0.56) for those with four or five healthy lifestyle factors.

“From these findings and the fact that the lifestyle factors we studied are modifiable and in direct control of the individual, it is imperative to promote them concurrently among older adults as a strategy to delay or prevent Alzheimer’s dementia,” Dr. Dhana and colleagues concluded.

In a statement, Dallas Anderson, PhD, program director, division of neuroscience, National Institute on Aging, said the findings help “paint the picture of how multiple factors are likely playing parts in Alzheimer’s disease risk.”

“It’s not a clear cause-and-effect result, but a strong finding because of the dual data sets and combination of modifiable lifestyle factors that appear to lead to risk reduction,” Dr. Anderson added.

Essential questions remain

Commenting on the new study, Luca Giliberto, MD, PhD, neurologist with the Litwin-Zucker Research Center for Alzheimer’s Disease and Memory Disorders at the Feinstein Institutes for Medical Research in Manhasset, N.Y., said this analysis is “further demonstration that a healthy lifestyle is essential to overcome or curb” the risk for Alzheimer’s disease.

“What needs to be determined is how early should we start ‘behaving.’ We should all aim to score four to five factors across our entire lifespan, but this is not always feasible. So, when is the time to behave? Also, what is the relative weight of each of these factors?” said Dr. Giliberto.

Of note, he added, although addressing vascular risk factors such as hypertension, hyperlipidemia, and diabetes “may require an extensive mindful and logistic effort, a healthy diet is effortlessly achieved in some countries, where both the DASH and MIND diets do not need to be ‘prescribed’ but are rather culturally engraved in the population.

“This is, in part, related to the wide availability of high-quality food in these countries, which is not the same in the U.S. This work is one more demonstration of the need to revisit our take on quality of food in the U.S.,” said Dr. Giliberto.

Numerous clinical trials testing lifestyle interventions for dementia prevention are currently underway. The MIND Diet Intervention to Prevent Alzheimer’s Disease, for example, is an interventional clinical trial comparing parallel groups with two different diets. MIND has enrolled more than 600 participants and is ongoing. The anticipated completion date is 2021. Another is the U.S. Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk (U.S. POINTER), a multisite randomized clinical trial evaluating whether lifestyle interventions – including exercise, cognitively stimulating activities, and the MIND diet – may protect cognitive function in older adults who are at increased risk for cognitive decline.

Funding for the current study was provided by the National Institutes of Health and the National Institute on Aging. Dr. Dhana and Dr. Giliberto have disclosed no relevant financial relationships.

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

Combining four of five healthy lifestyle choices has been linked to up to a 60% reduced risk for Alzheimer’s dementia in new research that strengthens ties between healthy behaviors and lower dementia risk. “I hope this study will motivate people to engage in a healthy lifestyle by not smoking, being physically and cognitively active, and having a high-quality diet,” lead investigator Klodian Dhana, MD, PhD, department of internal medicine, Rush University Medical Center, Chicago, said in an interview.

The study was published online June 17 in Neurology.
 

Risk-modifying behaviors

To help quantify the impact of a healthy life on risk for Alzheimer’s dementia, Dr. Dhana and colleagues reviewed data from two longitudinal study populations: the Chicago Health and Aging Project (CHAP), with 1,845 participants, and the Memory and Aging Project (MAP), with 920 participants.

They defined a healthy lifestyle score on the basis of the following factors: not smoking; engaging in 150 min/wk or more of physical exercise of moderate to vigorous intensity; light to moderate alcohol consumption (between 1 and less than 15 g/day for women and between 1 and less than 30 g/day for men); consuming a high-quality Mediterranean-DASH Diet Intervention for Neurodegenerative Delay diet (upper 40%); and engaging in late-life cognitive activities (upper 40%). The overall score ranged from 0 to 5.

At baseline, the mean age of participants was 73.2 years in the CHAP study and 81.1 years in the MAP study; 62.4% of the CHAP participants and 75.2% of the MAP participants were women.

During a median follow-up of 5.8 years in CHAP and 6.0 years in MAP, a total of 379 and 229 participants, respectively, developed Alzheimer’s dementia. Rates of dementia decreased with an increasing number of healthy lifestyle behaviors.

In multivariable-adjusted models across the two cohorts, the risk for Alzheimer’s dementia was 27% lower with each additional healthy lifestyle factor (pooled hazard ratio, 0.73; 95% confidence interval, 0.66-0.80).

Compared with individuals with a healthy lifestyle score of 0-1, the risk was 37% lower (pooled HR, 0.63; 95% CI, 0.47-0.84) for those with two or three healthy lifestyle factors and 60% lower (pooled HR, 0.40; 95% CI, 0.28-0.56) for those with four or five healthy lifestyle factors.

“From these findings and the fact that the lifestyle factors we studied are modifiable and in direct control of the individual, it is imperative to promote them concurrently among older adults as a strategy to delay or prevent Alzheimer’s dementia,” Dr. Dhana and colleagues concluded.

In a statement, Dallas Anderson, PhD, program director, division of neuroscience, National Institute on Aging, said the findings help “paint the picture of how multiple factors are likely playing parts in Alzheimer’s disease risk.”

“It’s not a clear cause-and-effect result, but a strong finding because of the dual data sets and combination of modifiable lifestyle factors that appear to lead to risk reduction,” Dr. Anderson added.

Essential questions remain

Commenting on the new study, Luca Giliberto, MD, PhD, neurologist with the Litwin-Zucker Research Center for Alzheimer’s Disease and Memory Disorders at the Feinstein Institutes for Medical Research in Manhasset, N.Y., said this analysis is “further demonstration that a healthy lifestyle is essential to overcome or curb” the risk for Alzheimer’s disease.

“What needs to be determined is how early should we start ‘behaving.’ We should all aim to score four to five factors across our entire lifespan, but this is not always feasible. So, when is the time to behave? Also, what is the relative weight of each of these factors?” said Dr. Giliberto.

Of note, he added, although addressing vascular risk factors such as hypertension, hyperlipidemia, and diabetes “may require an extensive mindful and logistic effort, a healthy diet is effortlessly achieved in some countries, where both the DASH and MIND diets do not need to be ‘prescribed’ but are rather culturally engraved in the population.

“This is, in part, related to the wide availability of high-quality food in these countries, which is not the same in the U.S. This work is one more demonstration of the need to revisit our take on quality of food in the U.S.,” said Dr. Giliberto.

Numerous clinical trials testing lifestyle interventions for dementia prevention are currently underway. The MIND Diet Intervention to Prevent Alzheimer’s Disease, for example, is an interventional clinical trial comparing parallel groups with two different diets. MIND has enrolled more than 600 participants and is ongoing. The anticipated completion date is 2021. Another is the U.S. Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk (U.S. POINTER), a multisite randomized clinical trial evaluating whether lifestyle interventions – including exercise, cognitively stimulating activities, and the MIND diet – may protect cognitive function in older adults who are at increased risk for cognitive decline.

Funding for the current study was provided by the National Institutes of Health and the National Institute on Aging. Dr. Dhana and Dr. Giliberto have disclosed no relevant financial relationships.

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

Combining four of five healthy lifestyle choices has been linked to up to a 60% reduced risk for Alzheimer’s dementia in new research that strengthens ties between healthy behaviors and lower dementia risk. “I hope this study will motivate people to engage in a healthy lifestyle by not smoking, being physically and cognitively active, and having a high-quality diet,” lead investigator Klodian Dhana, MD, PhD, department of internal medicine, Rush University Medical Center, Chicago, said in an interview.

The study was published online June 17 in Neurology.
 

Risk-modifying behaviors

To help quantify the impact of a healthy life on risk for Alzheimer’s dementia, Dr. Dhana and colleagues reviewed data from two longitudinal study populations: the Chicago Health and Aging Project (CHAP), with 1,845 participants, and the Memory and Aging Project (MAP), with 920 participants.

They defined a healthy lifestyle score on the basis of the following factors: not smoking; engaging in 150 min/wk or more of physical exercise of moderate to vigorous intensity; light to moderate alcohol consumption (between 1 and less than 15 g/day for women and between 1 and less than 30 g/day for men); consuming a high-quality Mediterranean-DASH Diet Intervention for Neurodegenerative Delay diet (upper 40%); and engaging in late-life cognitive activities (upper 40%). The overall score ranged from 0 to 5.

At baseline, the mean age of participants was 73.2 years in the CHAP study and 81.1 years in the MAP study; 62.4% of the CHAP participants and 75.2% of the MAP participants were women.

During a median follow-up of 5.8 years in CHAP and 6.0 years in MAP, a total of 379 and 229 participants, respectively, developed Alzheimer’s dementia. Rates of dementia decreased with an increasing number of healthy lifestyle behaviors.

In multivariable-adjusted models across the two cohorts, the risk for Alzheimer’s dementia was 27% lower with each additional healthy lifestyle factor (pooled hazard ratio, 0.73; 95% confidence interval, 0.66-0.80).

Compared with individuals with a healthy lifestyle score of 0-1, the risk was 37% lower (pooled HR, 0.63; 95% CI, 0.47-0.84) for those with two or three healthy lifestyle factors and 60% lower (pooled HR, 0.40; 95% CI, 0.28-0.56) for those with four or five healthy lifestyle factors.

“From these findings and the fact that the lifestyle factors we studied are modifiable and in direct control of the individual, it is imperative to promote them concurrently among older adults as a strategy to delay or prevent Alzheimer’s dementia,” Dr. Dhana and colleagues concluded.

In a statement, Dallas Anderson, PhD, program director, division of neuroscience, National Institute on Aging, said the findings help “paint the picture of how multiple factors are likely playing parts in Alzheimer’s disease risk.”

“It’s not a clear cause-and-effect result, but a strong finding because of the dual data sets and combination of modifiable lifestyle factors that appear to lead to risk reduction,” Dr. Anderson added.

Essential questions remain

Commenting on the new study, Luca Giliberto, MD, PhD, neurologist with the Litwin-Zucker Research Center for Alzheimer’s Disease and Memory Disorders at the Feinstein Institutes for Medical Research in Manhasset, N.Y., said this analysis is “further demonstration that a healthy lifestyle is essential to overcome or curb” the risk for Alzheimer’s disease.

“What needs to be determined is how early should we start ‘behaving.’ We should all aim to score four to five factors across our entire lifespan, but this is not always feasible. So, when is the time to behave? Also, what is the relative weight of each of these factors?” said Dr. Giliberto.

Of note, he added, although addressing vascular risk factors such as hypertension, hyperlipidemia, and diabetes “may require an extensive mindful and logistic effort, a healthy diet is effortlessly achieved in some countries, where both the DASH and MIND diets do not need to be ‘prescribed’ but are rather culturally engraved in the population.

“This is, in part, related to the wide availability of high-quality food in these countries, which is not the same in the U.S. This work is one more demonstration of the need to revisit our take on quality of food in the U.S.,” said Dr. Giliberto.

Numerous clinical trials testing lifestyle interventions for dementia prevention are currently underway. The MIND Diet Intervention to Prevent Alzheimer’s Disease, for example, is an interventional clinical trial comparing parallel groups with two different diets. MIND has enrolled more than 600 participants and is ongoing. The anticipated completion date is 2021. Another is the U.S. Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk (U.S. POINTER), a multisite randomized clinical trial evaluating whether lifestyle interventions – including exercise, cognitively stimulating activities, and the MIND diet – may protect cognitive function in older adults who are at increased risk for cognitive decline.

Funding for the current study was provided by the National Institutes of Health and the National Institute on Aging. Dr. Dhana and Dr. Giliberto have disclosed no relevant financial relationships.

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

Abnormalities in circadian rhythm may represent an important feature in the very early stages of Parkinson’s disease before symptoms develop, a new study suggests. “We found that men with abnormal circadian rhythms had three times the risk of developing Parkinson’s disease over an 11-year follow-up period,” lead author, Yue Leng, MD, University of California, San Francisco, said in an interview.

“If confirmed to be a risk factor for Parkinson’s disease, then circadian rhythmicity could be a promising intervention target and will open new opportunities for the prevention and management of Parkinson’s disease,” the researchers concluded.

The study was published online in JAMA Neurology on June 15.

Circadian disruption is very common in neurodegenerative diseases such as Parkinson’s disease, but there isn’t much information on how it may predict the disease, Dr. Leng explained. “We wanted to see whether circadian abnormalities may predict Parkinson’s disease,” she said. “Parkinson’s disease has a long prodromal phase where brain changes have started to occur but no clinical symptoms have become evident. It would be useful to be able to identify these patients, and maybe changes in circadian rhythms may help us to do that,” she added.

For the study, the researchers analyzed data from 2,930 community-dwelling men aged 65 years or older (mean age, 76 years) who participated in the Osteoporotic Fractures in Men Study, in which they underwent comprehensive sleep and rest-activity rhythms assessment. “Patterns of rest and activity were measured with an actigraph device, which is worn on the wrist like a watch and captures movements which are translated into a rest-activity rhythm model – one of the most commonly used and evidence-based measures of circadian rhythm,” Dr. Leng said. Men were asked to wear the actigraphs continuously for a minimum of three 24-hour periods.

Results showed that 78 men (2.7%) developed Parkinson’s disease during the 11-year follow-up. After accounting for all covariates, the risk of Parkinson’s disease increased with decreasing circadian amplitude (strength of the rhythm) with an odds ratio of 1.77 per each decrease by one standard deviation; mesor (mean level of activity) with an odds ratio of 1.64; or robustness (how closely activity follows a 24-hour pattern) with an odds ratio of 1.54.

Those in the lowest quartile of amplitude, mesor, or robustness had approximately three times the risk of developing Parkinson’s disease compared with those in the highest quartile of amplitude. The association remained after further adjustment for nighttime sleep disturbances.

“It has previously been shown that daytime napping has been linked to risk of developing Parkinson’s disease. Now we have shown that abnormalities in the overall 24-hour circadian rest activity rhythm are also present in the prodromal phase of Parkinson’s disease, and this association was independent of several confounders, including nighttime sleep disturbances,” Dr. Leng said.

“This raises awareness of the importance of circadian rhythm in older individuals and changes in their 24-hour pattern of behavior could be an early signal of Parkinson’s disease,” she said.

“This study does not tell us whether these circadian changes are causal for Parkinson’s or not,” Dr. Leng noted.

Future studies are needed to explore underlying mechanisms and to determine whether circadian disruption itself might contribute to the development of Parkinson’s disease, the researchers said.

“If there is a causal link, then using techniques to improve circadian rhythm could help to prevent or slow the onset of Parkinson’s disease,” Dr. Leng suggested. There are many established therapies that act on circadian rhythm including bright light therapy, melatonin, and chronotherapy, she added.

Support for this study was provided by the National Institute on Aging (NIA); the National Institute of Arthritis and Musculoskeletal and Skin Diseases; the National Center for Advancing Translational Sciences; the National Heart, Lung, and Blood Institute; and the Weill Pilot Award. Dr. Leng reported grants from the NIA and the University of California, San Francisco, Weill Institute for Neurosciences during the conduct of the study; and grants from Global Brain Health Institute, the Alzheimer’s Association, and the Alzheimer’s Society outside the submitted work.

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

Abnormalities in circadian rhythm may represent an important feature in the very early stages of Parkinson’s disease before symptoms develop, a new study suggests. “We found that men with abnormal circadian rhythms had three times the risk of developing Parkinson’s disease over an 11-year follow-up period,” lead author, Yue Leng, MD, University of California, San Francisco, said in an interview.

“If confirmed to be a risk factor for Parkinson’s disease, then circadian rhythmicity could be a promising intervention target and will open new opportunities for the prevention and management of Parkinson’s disease,” the researchers concluded.

The study was published online in JAMA Neurology on June 15.

Circadian disruption is very common in neurodegenerative diseases such as Parkinson’s disease, but there isn’t much information on how it may predict the disease, Dr. Leng explained. “We wanted to see whether circadian abnormalities may predict Parkinson’s disease,” she said. “Parkinson’s disease has a long prodromal phase where brain changes have started to occur but no clinical symptoms have become evident. It would be useful to be able to identify these patients, and maybe changes in circadian rhythms may help us to do that,” she added.

For the study, the researchers analyzed data from 2,930 community-dwelling men aged 65 years or older (mean age, 76 years) who participated in the Osteoporotic Fractures in Men Study, in which they underwent comprehensive sleep and rest-activity rhythms assessment. “Patterns of rest and activity were measured with an actigraph device, which is worn on the wrist like a watch and captures movements which are translated into a rest-activity rhythm model – one of the most commonly used and evidence-based measures of circadian rhythm,” Dr. Leng said. Men were asked to wear the actigraphs continuously for a minimum of three 24-hour periods.

Results showed that 78 men (2.7%) developed Parkinson’s disease during the 11-year follow-up. After accounting for all covariates, the risk of Parkinson’s disease increased with decreasing circadian amplitude (strength of the rhythm) with an odds ratio of 1.77 per each decrease by one standard deviation; mesor (mean level of activity) with an odds ratio of 1.64; or robustness (how closely activity follows a 24-hour pattern) with an odds ratio of 1.54.

Those in the lowest quartile of amplitude, mesor, or robustness had approximately three times the risk of developing Parkinson’s disease compared with those in the highest quartile of amplitude. The association remained after further adjustment for nighttime sleep disturbances.

“It has previously been shown that daytime napping has been linked to risk of developing Parkinson’s disease. Now we have shown that abnormalities in the overall 24-hour circadian rest activity rhythm are also present in the prodromal phase of Parkinson’s disease, and this association was independent of several confounders, including nighttime sleep disturbances,” Dr. Leng said.

“This raises awareness of the importance of circadian rhythm in older individuals and changes in their 24-hour pattern of behavior could be an early signal of Parkinson’s disease,” she said.

“This study does not tell us whether these circadian changes are causal for Parkinson’s or not,” Dr. Leng noted.

Future studies are needed to explore underlying mechanisms and to determine whether circadian disruption itself might contribute to the development of Parkinson’s disease, the researchers said.

“If there is a causal link, then using techniques to improve circadian rhythm could help to prevent or slow the onset of Parkinson’s disease,” Dr. Leng suggested. There are many established therapies that act on circadian rhythm including bright light therapy, melatonin, and chronotherapy, she added.

Support for this study was provided by the National Institute on Aging (NIA); the National Institute of Arthritis and Musculoskeletal and Skin Diseases; the National Center for Advancing Translational Sciences; the National Heart, Lung, and Blood Institute; and the Weill Pilot Award. Dr. Leng reported grants from the NIA and the University of California, San Francisco, Weill Institute for Neurosciences during the conduct of the study; and grants from Global Brain Health Institute, the Alzheimer’s Association, and the Alzheimer’s Society outside the submitted work.

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

Abnormalities in circadian rhythm may represent an important feature in the very early stages of Parkinson’s disease before symptoms develop, a new study suggests. “We found that men with abnormal circadian rhythms had three times the risk of developing Parkinson’s disease over an 11-year follow-up period,” lead author, Yue Leng, MD, University of California, San Francisco, said in an interview.

“If confirmed to be a risk factor for Parkinson’s disease, then circadian rhythmicity could be a promising intervention target and will open new opportunities for the prevention and management of Parkinson’s disease,” the researchers concluded.

The study was published online in JAMA Neurology on June 15.

Circadian disruption is very common in neurodegenerative diseases such as Parkinson’s disease, but there isn’t much information on how it may predict the disease, Dr. Leng explained. “We wanted to see whether circadian abnormalities may predict Parkinson’s disease,” she said. “Parkinson’s disease has a long prodromal phase where brain changes have started to occur but no clinical symptoms have become evident. It would be useful to be able to identify these patients, and maybe changes in circadian rhythms may help us to do that,” she added.

For the study, the researchers analyzed data from 2,930 community-dwelling men aged 65 years or older (mean age, 76 years) who participated in the Osteoporotic Fractures in Men Study, in which they underwent comprehensive sleep and rest-activity rhythms assessment. “Patterns of rest and activity were measured with an actigraph device, which is worn on the wrist like a watch and captures movements which are translated into a rest-activity rhythm model – one of the most commonly used and evidence-based measures of circadian rhythm,” Dr. Leng said. Men were asked to wear the actigraphs continuously for a minimum of three 24-hour periods.

Results showed that 78 men (2.7%) developed Parkinson’s disease during the 11-year follow-up. After accounting for all covariates, the risk of Parkinson’s disease increased with decreasing circadian amplitude (strength of the rhythm) with an odds ratio of 1.77 per each decrease by one standard deviation; mesor (mean level of activity) with an odds ratio of 1.64; or robustness (how closely activity follows a 24-hour pattern) with an odds ratio of 1.54.

Those in the lowest quartile of amplitude, mesor, or robustness had approximately three times the risk of developing Parkinson’s disease compared with those in the highest quartile of amplitude. The association remained after further adjustment for nighttime sleep disturbances.

“It has previously been shown that daytime napping has been linked to risk of developing Parkinson’s disease. Now we have shown that abnormalities in the overall 24-hour circadian rest activity rhythm are also present in the prodromal phase of Parkinson’s disease, and this association was independent of several confounders, including nighttime sleep disturbances,” Dr. Leng said.

“This raises awareness of the importance of circadian rhythm in older individuals and changes in their 24-hour pattern of behavior could be an early signal of Parkinson’s disease,” she said.

“This study does not tell us whether these circadian changes are causal for Parkinson’s or not,” Dr. Leng noted.

Future studies are needed to explore underlying mechanisms and to determine whether circadian disruption itself might contribute to the development of Parkinson’s disease, the researchers said.

“If there is a causal link, then using techniques to improve circadian rhythm could help to prevent or slow the onset of Parkinson’s disease,” Dr. Leng suggested. There are many established therapies that act on circadian rhythm including bright light therapy, melatonin, and chronotherapy, she added.

Support for this study was provided by the National Institute on Aging (NIA); the National Institute of Arthritis and Musculoskeletal and Skin Diseases; the National Center for Advancing Translational Sciences; the National Heart, Lung, and Blood Institute; and the Weill Pilot Award. Dr. Leng reported grants from the NIA and the University of California, San Francisco, Weill Institute for Neurosciences during the conduct of the study; and grants from Global Brain Health Institute, the Alzheimer’s Association, and the Alzheimer’s Society outside the submitted work.

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

Most disability accumulation in relapsing multiple sclerosis (MS) is not associated with overt relapses, challenging the current clinical distinction of relapsing and progressive forms of the disease, a new analysis shows. “We have to abandon the distinction between relapsing and progressive MS being different populations,” said lead author Ludwig Kappos, MD, University of Basel (Switzerland). “The disease appears to be more of a continuum of disability progression, which is sometimes also accompanied by relapses.”

The analysis was published online June 8 in JAMA Neurology.
 

Assessing disability progression

Noting that there are mounting data to suggest patients with relapsing MS frequently experience worsening disability over time – even when relapse activity appears well controlled – the researchers aimed to investigate the relative contributions of progression independent of relapse activity and relapse-associated worsening to overall accumulating disability in patients with relapsing multiple sclerosis. To do this, they analyzed data from two identical randomized clinical trials (OPERA I and OPERA II) conducted between 2011 and 2015, which compared treatment with the new B-cell–depleting therapy ocrelizumab with interferon beta-1a in 1,656 patients with relapsing MS.

Confirmed disability accumulation was defined by an increase in 1 or more of 3 measures (Expanded Disability Status Scale, timed 25-ft walk, or 9-hole peg test), confirmed after 3 or 6 months, and was classified as being related to a clinical relapse or occurring in the absence of a relapse.

Results showed that after 96 weeks (1.8 years) of treatment, 12-week composite confirmed disability accumulation had occurred in 29.6% of patients receiving interferon beta-1a and 21.1% of those given ocrelizumab; 24-week composite confirmed disability accumulation occurred in 22.7% of interferon beta-1a patients and 16.2% of the ocrelizumab group.

In both treatment groups, the vast majority of events contributing to disability accumulation occurred independently of relapse activity. In the interferon group, 78% of events contributing to 12-week confirmed disability accumulation and 80.6% of events contributing to 24-week confirmed disability accumulation occurred in the absence of clinical relapses, with the corresponding figures in the ocrelizumab group being 88.0% (12 weeks) and 89.1% (24 weeks).

Only a minority of patients (about 17% in both groups) had confirmed disability accumulation accompanied by clinical relapses. Very few patients with confirmed disability accumulation (4% to 5%) experienced disability worsening both associated and independent of relapses. Ocrelizumab was associated with a reduced risk of both relapse-associated and relapse-independent confirmed disability accumulation, compared with interferon beta-1a.

“We found that there was progression of disability in both groups, and the really astonishing finding was that although all patients were classified as having relapsing remitting MS, actually most of the disability progression occurred without preceding relapses,” Dr. Kappos commented. He noted that there have been two previous observational studies that have shown a high rate of disability progressions without temporal association to relapses in relapsing remitting patients, but this is the first time that this progression of disability independent of relapses has been shown in the controlled setting of two prospective, randomized clinical trials over a 2-year period.

“While we expected to see some disability progression independent of relapses, we were surprised to see that the disability progression occurring in both studies was almost exclusively happening without temporal relation to relapses. That was certainly an unexpected finding,” Dr. Kappos said. “These observations make it difficult to keep the current definitions of ‘relapsing remitting’ and ‘secondary progressive’ MS, [ones] that suggest a clear-cut distinction marked by the presence or absence of relapses. This can no longer be justified,” he stressed.

“We are not saying that relapses do not contribute to disability progression. There are a lot of data to support the fact that they do. But I think what we might be seeing is that the drug therapy is quite effective in reducing disability due to relapses but only partially effective in reducing progression independent of relapses,” Dr. Kappos explained.

Although there have been many advances in reducing relapses with drug therapy, focus now needs to shift to the other more continuous process of disability progression independent of relapses, Dr. Kappos said. “There is still a lot of room for improvement here.”

“If continuous progression independent of relapses is already present in the early phases of MS, it is reasonable to study the effects of intervention on steady progression already in this early phase,” he noted. “This might help to capture patients at earlier stages who better respond to treatment aimed at halting progression.”

Dr. Kappos also called for more subtle measurements of disability than the EDSS alone, including measures such as the 9-hole peg test and the 25-ft walk as they did in this analysis. But other measures could also be added that would characterize continuous disease activity and progression, such as laboratory values (e.g., neurofilament light chain) and advanced, more tissue-specific quantitative MRI techniques and digital biomarkers to detect subtle changes in neurologic function.
 

An artificial distinction?

Commenting on the study, Jeffrey Cohen, MD, director of the experimental therapeutics program at the Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic, said he too sees very little distinction between relapsing remitting and progressive forms of the disease.

“This study confirms what has been suspected for quite a few years –that if one looks sufficiently and carefully, there is gradual worsening of some aspects of the disease in many patients from the earliest stages,” Dr. Cohen said. “Conversely, some patients with progressive MS have superimposed relapses or MRI lesion activity.

“Thus, the distinction between relapsing-remitting and progressive MS subtypes appears artificial,” he concluded.

This study was sponsored by F. Hoffmann–La Roche. Dr. Kappos has received research support from the company.

This article first appeared on Medscape.com.

Most disability accumulation in relapsing multiple sclerosis (MS) is not associated with overt relapses, challenging the current clinical distinction of relapsing and progressive forms of the disease, a new analysis shows. “We have to abandon the distinction between relapsing and progressive MS being different populations,” said lead author Ludwig Kappos, MD, University of Basel (Switzerland). “The disease appears to be more of a continuum of disability progression, which is sometimes also accompanied by relapses.”

The analysis was published online June 8 in JAMA Neurology.
 

Assessing disability progression

Noting that there are mounting data to suggest patients with relapsing MS frequently experience worsening disability over time – even when relapse activity appears well controlled – the researchers aimed to investigate the relative contributions of progression independent of relapse activity and relapse-associated worsening to overall accumulating disability in patients with relapsing multiple sclerosis. To do this, they analyzed data from two identical randomized clinical trials (OPERA I and OPERA II) conducted between 2011 and 2015, which compared treatment with the new B-cell–depleting therapy ocrelizumab with interferon beta-1a in 1,656 patients with relapsing MS.

Confirmed disability accumulation was defined by an increase in 1 or more of 3 measures (Expanded Disability Status Scale, timed 25-ft walk, or 9-hole peg test), confirmed after 3 or 6 months, and was classified as being related to a clinical relapse or occurring in the absence of a relapse.

Results showed that after 96 weeks (1.8 years) of treatment, 12-week composite confirmed disability accumulation had occurred in 29.6% of patients receiving interferon beta-1a and 21.1% of those given ocrelizumab; 24-week composite confirmed disability accumulation occurred in 22.7% of interferon beta-1a patients and 16.2% of the ocrelizumab group.

In both treatment groups, the vast majority of events contributing to disability accumulation occurred independently of relapse activity. In the interferon group, 78% of events contributing to 12-week confirmed disability accumulation and 80.6% of events contributing to 24-week confirmed disability accumulation occurred in the absence of clinical relapses, with the corresponding figures in the ocrelizumab group being 88.0% (12 weeks) and 89.1% (24 weeks).

Only a minority of patients (about 17% in both groups) had confirmed disability accumulation accompanied by clinical relapses. Very few patients with confirmed disability accumulation (4% to 5%) experienced disability worsening both associated and independent of relapses. Ocrelizumab was associated with a reduced risk of both relapse-associated and relapse-independent confirmed disability accumulation, compared with interferon beta-1a.

“We found that there was progression of disability in both groups, and the really astonishing finding was that although all patients were classified as having relapsing remitting MS, actually most of the disability progression occurred without preceding relapses,” Dr. Kappos commented. He noted that there have been two previous observational studies that have shown a high rate of disability progressions without temporal association to relapses in relapsing remitting patients, but this is the first time that this progression of disability independent of relapses has been shown in the controlled setting of two prospective, randomized clinical trials over a 2-year period.

“While we expected to see some disability progression independent of relapses, we were surprised to see that the disability progression occurring in both studies was almost exclusively happening without temporal relation to relapses. That was certainly an unexpected finding,” Dr. Kappos said. “These observations make it difficult to keep the current definitions of ‘relapsing remitting’ and ‘secondary progressive’ MS, [ones] that suggest a clear-cut distinction marked by the presence or absence of relapses. This can no longer be justified,” he stressed.

“We are not saying that relapses do not contribute to disability progression. There are a lot of data to support the fact that they do. But I think what we might be seeing is that the drug therapy is quite effective in reducing disability due to relapses but only partially effective in reducing progression independent of relapses,” Dr. Kappos explained.

Although there have been many advances in reducing relapses with drug therapy, focus now needs to shift to the other more continuous process of disability progression independent of relapses, Dr. Kappos said. “There is still a lot of room for improvement here.”

“If continuous progression independent of relapses is already present in the early phases of MS, it is reasonable to study the effects of intervention on steady progression already in this early phase,” he noted. “This might help to capture patients at earlier stages who better respond to treatment aimed at halting progression.”

Dr. Kappos also called for more subtle measurements of disability than the EDSS alone, including measures such as the 9-hole peg test and the 25-ft walk as they did in this analysis. But other measures could also be added that would characterize continuous disease activity and progression, such as laboratory values (e.g., neurofilament light chain) and advanced, more tissue-specific quantitative MRI techniques and digital biomarkers to detect subtle changes in neurologic function.
 

An artificial distinction?

Commenting on the study, Jeffrey Cohen, MD, director of the experimental therapeutics program at the Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic, said he too sees very little distinction between relapsing remitting and progressive forms of the disease.

“This study confirms what has been suspected for quite a few years –that if one looks sufficiently and carefully, there is gradual worsening of some aspects of the disease in many patients from the earliest stages,” Dr. Cohen said. “Conversely, some patients with progressive MS have superimposed relapses or MRI lesion activity.

“Thus, the distinction between relapsing-remitting and progressive MS subtypes appears artificial,” he concluded.

This study was sponsored by F. Hoffmann–La Roche. Dr. Kappos has received research support from the company.

This article first appeared on Medscape.com.

Most disability accumulation in relapsing multiple sclerosis (MS) is not associated with overt relapses, challenging the current clinical distinction of relapsing and progressive forms of the disease, a new analysis shows. “We have to abandon the distinction between relapsing and progressive MS being different populations,” said lead author Ludwig Kappos, MD, University of Basel (Switzerland). “The disease appears to be more of a continuum of disability progression, which is sometimes also accompanied by relapses.”

The analysis was published online June 8 in JAMA Neurology.
 

Assessing disability progression

Noting that there are mounting data to suggest patients with relapsing MS frequently experience worsening disability over time – even when relapse activity appears well controlled – the researchers aimed to investigate the relative contributions of progression independent of relapse activity and relapse-associated worsening to overall accumulating disability in patients with relapsing multiple sclerosis. To do this, they analyzed data from two identical randomized clinical trials (OPERA I and OPERA II) conducted between 2011 and 2015, which compared treatment with the new B-cell–depleting therapy ocrelizumab with interferon beta-1a in 1,656 patients with relapsing MS.

Confirmed disability accumulation was defined by an increase in 1 or more of 3 measures (Expanded Disability Status Scale, timed 25-ft walk, or 9-hole peg test), confirmed after 3 or 6 months, and was classified as being related to a clinical relapse or occurring in the absence of a relapse.

Results showed that after 96 weeks (1.8 years) of treatment, 12-week composite confirmed disability accumulation had occurred in 29.6% of patients receiving interferon beta-1a and 21.1% of those given ocrelizumab; 24-week composite confirmed disability accumulation occurred in 22.7% of interferon beta-1a patients and 16.2% of the ocrelizumab group.

In both treatment groups, the vast majority of events contributing to disability accumulation occurred independently of relapse activity. In the interferon group, 78% of events contributing to 12-week confirmed disability accumulation and 80.6% of events contributing to 24-week confirmed disability accumulation occurred in the absence of clinical relapses, with the corresponding figures in the ocrelizumab group being 88.0% (12 weeks) and 89.1% (24 weeks).

Only a minority of patients (about 17% in both groups) had confirmed disability accumulation accompanied by clinical relapses. Very few patients with confirmed disability accumulation (4% to 5%) experienced disability worsening both associated and independent of relapses. Ocrelizumab was associated with a reduced risk of both relapse-associated and relapse-independent confirmed disability accumulation, compared with interferon beta-1a.

“We found that there was progression of disability in both groups, and the really astonishing finding was that although all patients were classified as having relapsing remitting MS, actually most of the disability progression occurred without preceding relapses,” Dr. Kappos commented. He noted that there have been two previous observational studies that have shown a high rate of disability progressions without temporal association to relapses in relapsing remitting patients, but this is the first time that this progression of disability independent of relapses has been shown in the controlled setting of two prospective, randomized clinical trials over a 2-year period.

“While we expected to see some disability progression independent of relapses, we were surprised to see that the disability progression occurring in both studies was almost exclusively happening without temporal relation to relapses. That was certainly an unexpected finding,” Dr. Kappos said. “These observations make it difficult to keep the current definitions of ‘relapsing remitting’ and ‘secondary progressive’ MS, [ones] that suggest a clear-cut distinction marked by the presence or absence of relapses. This can no longer be justified,” he stressed.

“We are not saying that relapses do not contribute to disability progression. There are a lot of data to support the fact that they do. But I think what we might be seeing is that the drug therapy is quite effective in reducing disability due to relapses but only partially effective in reducing progression independent of relapses,” Dr. Kappos explained.

Although there have been many advances in reducing relapses with drug therapy, focus now needs to shift to the other more continuous process of disability progression independent of relapses, Dr. Kappos said. “There is still a lot of room for improvement here.”

“If continuous progression independent of relapses is already present in the early phases of MS, it is reasonable to study the effects of intervention on steady progression already in this early phase,” he noted. “This might help to capture patients at earlier stages who better respond to treatment aimed at halting progression.”

Dr. Kappos also called for more subtle measurements of disability than the EDSS alone, including measures such as the 9-hole peg test and the 25-ft walk as they did in this analysis. But other measures could also be added that would characterize continuous disease activity and progression, such as laboratory values (e.g., neurofilament light chain) and advanced, more tissue-specific quantitative MRI techniques and digital biomarkers to detect subtle changes in neurologic function.
 

An artificial distinction?

Commenting on the study, Jeffrey Cohen, MD, director of the experimental therapeutics program at the Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic, said he too sees very little distinction between relapsing remitting and progressive forms of the disease.

“This study confirms what has been suspected for quite a few years –that if one looks sufficiently and carefully, there is gradual worsening of some aspects of the disease in many patients from the earliest stages,” Dr. Cohen said. “Conversely, some patients with progressive MS have superimposed relapses or MRI lesion activity.

“Thus, the distinction between relapsing-remitting and progressive MS subtypes appears artificial,” he concluded.

This study was sponsored by F. Hoffmann–La Roche. Dr. Kappos has received research support from the company.

This article first appeared on Medscape.com.

Early signs of neurodegeneration appeared in young adult carriers of the Huntington’s disease gene mutation approximately 24 years before the clinical onset of symptoms, according to a study published in the June Lancet Neurology. The data come from the Huntington’s disease Young Adult Study (HD-YAS) conducted in the United Kingdom.

The genetic cause of Huntington’s disease provides a potential target for biomarker treatment, wrote joint first authors Rachael I. Scahill, PhD, and Paul Zeun, BMBS, of University College London and colleagues.

“A detailed characterization of the premanifest period in Huntington’s disease is crucial for disease staging, informing the optimum time to initiate treatments, and identifying biomarkers for future trials in people with premanifest Huntington’s disease (preHD),” they said.

Identifying biomarkers of pre-Huntington’s disease

For their study, the researchers recruited 64 young adults with presymptomatic Huntington’s disease (preHD) and 67 controls, with an average age of 29 years. Brain imaging was conducted between Aug. 2, 2017, and April 25, 2019. Individuals with preexisting measurable cognitive and psychiatric disorders were excluded.

The researchers found no significant evidence of cognitive or psychiatric impairment in the preHD group at 23.6 years from the predicted onset of symptoms. The preHD group showed smaller putamen volumes, compared with controls, but this difference had no apparent relation to the timing of symptom onset, the researchers said.

Brain imaging revealed elevations in the CSF mutant huntingtin, neurofilament light protein (NfL), YKL-40, and plasma NfL among individuals with preHD, compared with controls. Of these, CSF NfL showed the highest effect size of measures in the study and showed a significant increasing association with estimated years to the onset of clinical symptoms of HD carriers. Overall, 53% of individuals with preHD had CSF NfL values in the normal range, and 47% had elevated values, compared with controls.

“NfL is therefore a potential candidate to provide a measure of disease progression in early preHD and might eventually be used as a marker of response to treatment in future preventive trials,” the researchers said.

The study findings were limited by several factors including potential underpowering to detect associations with age and CAG gene segment repeats, the researchers noted.

However, “By identifying a cohort of individuals with preHD and no detectable functional impairment but who begin to exhibit subtle elevations in select biological measures of neurodegeneration, we have highlighted a crucial point early in the disease process,” they concluded.

“Intervening at this stage might offer the prospect of delaying or preventing further neurodegeneration while function is intact, giving gene carriers many more years of life without impairment,” they added.

What is the best window for treatment?

The study is “particularly important since the absence of any subclinical symptoms in preHD individuals far from onset shows that the abnormal developmental aspect of Huntington’s disease has no substantial effect on adults’ clinical pattern,” wrote Anne-Catherine Bachoud-Lévi, MD, of Université Paris Est, Créteil, France, in an accompanying comment.

“The most robust findings of [the study] are the sensitiveness of NfL, compared with mutant huntingtin in CSF of individuals with preHD, and that degenerative rather than developmental disorders are clinically relevant,” she said. However, potential limitations to the study include the exclusion absence of language and calculation as part of the cognitive assessments, she noted. “Ideally, more sensitive cognitive tasks including these domains should be designed for preHD participants.”

In addition, the risks versus benefits of any long-term treatment must be considered, Dr. Bachoud-Lévi noted.

“The best window for treatment should instead target the time when a detectable subclinical slope of cognitive performance allows for predicting disease onset within a few years,” she said. “Turning to machine learning methodology, such as that in oncology, might also permit combining the best window and the best disease-modifying therapy for individuals with preHD,” she added.

The study was supported by the Wellcome Trust, CHDI Foundation. The researchers had no financial conflicts to disclose. Dr. Bachoud-Lévi disclosed grants and personal fees from Roche, and grants from the French Ministry of Health and Direction de la Recherche Clinique.

SOURCES: Scahill RI et al. Lancet Neurol. 2020 June;19:502-12; Bachoud-Lévi A-C. Lancet Neurol. 2020 June;19:473-5.

Early signs of neurodegeneration appeared in young adult carriers of the Huntington’s disease gene mutation approximately 24 years before the clinical onset of symptoms, according to a study published in the June Lancet Neurology. The data come from the Huntington’s disease Young Adult Study (HD-YAS) conducted in the United Kingdom.

The genetic cause of Huntington’s disease provides a potential target for biomarker treatment, wrote joint first authors Rachael I. Scahill, PhD, and Paul Zeun, BMBS, of University College London and colleagues.

“A detailed characterization of the premanifest period in Huntington’s disease is crucial for disease staging, informing the optimum time to initiate treatments, and identifying biomarkers for future trials in people with premanifest Huntington’s disease (preHD),” they said.

Identifying biomarkers of pre-Huntington’s disease

For their study, the researchers recruited 64 young adults with presymptomatic Huntington’s disease (preHD) and 67 controls, with an average age of 29 years. Brain imaging was conducted between Aug. 2, 2017, and April 25, 2019. Individuals with preexisting measurable cognitive and psychiatric disorders were excluded.

The researchers found no significant evidence of cognitive or psychiatric impairment in the preHD group at 23.6 years from the predicted onset of symptoms. The preHD group showed smaller putamen volumes, compared with controls, but this difference had no apparent relation to the timing of symptom onset, the researchers said.

Brain imaging revealed elevations in the CSF mutant huntingtin, neurofilament light protein (NfL), YKL-40, and plasma NfL among individuals with preHD, compared with controls. Of these, CSF NfL showed the highest effect size of measures in the study and showed a significant increasing association with estimated years to the onset of clinical symptoms of HD carriers. Overall, 53% of individuals with preHD had CSF NfL values in the normal range, and 47% had elevated values, compared with controls.

“NfL is therefore a potential candidate to provide a measure of disease progression in early preHD and might eventually be used as a marker of response to treatment in future preventive trials,” the researchers said.

The study findings were limited by several factors including potential underpowering to detect associations with age and CAG gene segment repeats, the researchers noted.

However, “By identifying a cohort of individuals with preHD and no detectable functional impairment but who begin to exhibit subtle elevations in select biological measures of neurodegeneration, we have highlighted a crucial point early in the disease process,” they concluded.

“Intervening at this stage might offer the prospect of delaying or preventing further neurodegeneration while function is intact, giving gene carriers many more years of life without impairment,” they added.

What is the best window for treatment?

The study is “particularly important since the absence of any subclinical symptoms in preHD individuals far from onset shows that the abnormal developmental aspect of Huntington’s disease has no substantial effect on adults’ clinical pattern,” wrote Anne-Catherine Bachoud-Lévi, MD, of Université Paris Est, Créteil, France, in an accompanying comment.

“The most robust findings of [the study] are the sensitiveness of NfL, compared with mutant huntingtin in CSF of individuals with preHD, and that degenerative rather than developmental disorders are clinically relevant,” she said. However, potential limitations to the study include the exclusion absence of language and calculation as part of the cognitive assessments, she noted. “Ideally, more sensitive cognitive tasks including these domains should be designed for preHD participants.”

In addition, the risks versus benefits of any long-term treatment must be considered, Dr. Bachoud-Lévi noted.

“The best window for treatment should instead target the time when a detectable subclinical slope of cognitive performance allows for predicting disease onset within a few years,” she said. “Turning to machine learning methodology, such as that in oncology, might also permit combining the best window and the best disease-modifying therapy for individuals with preHD,” she added.

The study was supported by the Wellcome Trust, CHDI Foundation. The researchers had no financial conflicts to disclose. Dr. Bachoud-Lévi disclosed grants and personal fees from Roche, and grants from the French Ministry of Health and Direction de la Recherche Clinique.

SOURCES: Scahill RI et al. Lancet Neurol. 2020 June;19:502-12; Bachoud-Lévi A-C. Lancet Neurol. 2020 June;19:473-5.

Early signs of neurodegeneration appeared in young adult carriers of the Huntington’s disease gene mutation approximately 24 years before the clinical onset of symptoms, according to a study published in the June Lancet Neurology. The data come from the Huntington’s disease Young Adult Study (HD-YAS) conducted in the United Kingdom.

The genetic cause of Huntington’s disease provides a potential target for biomarker treatment, wrote joint first authors Rachael I. Scahill, PhD, and Paul Zeun, BMBS, of University College London and colleagues.

“A detailed characterization of the premanifest period in Huntington’s disease is crucial for disease staging, informing the optimum time to initiate treatments, and identifying biomarkers for future trials in people with premanifest Huntington’s disease (preHD),” they said.

Identifying biomarkers of pre-Huntington’s disease

For their study, the researchers recruited 64 young adults with presymptomatic Huntington’s disease (preHD) and 67 controls, with an average age of 29 years. Brain imaging was conducted between Aug. 2, 2017, and April 25, 2019. Individuals with preexisting measurable cognitive and psychiatric disorders were excluded.

The researchers found no significant evidence of cognitive or psychiatric impairment in the preHD group at 23.6 years from the predicted onset of symptoms. The preHD group showed smaller putamen volumes, compared with controls, but this difference had no apparent relation to the timing of symptom onset, the researchers said.

Brain imaging revealed elevations in the CSF mutant huntingtin, neurofilament light protein (NfL), YKL-40, and plasma NfL among individuals with preHD, compared with controls. Of these, CSF NfL showed the highest effect size of measures in the study and showed a significant increasing association with estimated years to the onset of clinical symptoms of HD carriers. Overall, 53% of individuals with preHD had CSF NfL values in the normal range, and 47% had elevated values, compared with controls.

“NfL is therefore a potential candidate to provide a measure of disease progression in early preHD and might eventually be used as a marker of response to treatment in future preventive trials,” the researchers said.

The study findings were limited by several factors including potential underpowering to detect associations with age and CAG gene segment repeats, the researchers noted.

However, “By identifying a cohort of individuals with preHD and no detectable functional impairment but who begin to exhibit subtle elevations in select biological measures of neurodegeneration, we have highlighted a crucial point early in the disease process,” they concluded.

“Intervening at this stage might offer the prospect of delaying or preventing further neurodegeneration while function is intact, giving gene carriers many more years of life without impairment,” they added.

What is the best window for treatment?

The study is “particularly important since the absence of any subclinical symptoms in preHD individuals far from onset shows that the abnormal developmental aspect of Huntington’s disease has no substantial effect on adults’ clinical pattern,” wrote Anne-Catherine Bachoud-Lévi, MD, of Université Paris Est, Créteil, France, in an accompanying comment.

“The most robust findings of [the study] are the sensitiveness of NfL, compared with mutant huntingtin in CSF of individuals with preHD, and that degenerative rather than developmental disorders are clinically relevant,” she said. However, potential limitations to the study include the exclusion absence of language and calculation as part of the cognitive assessments, she noted. “Ideally, more sensitive cognitive tasks including these domains should be designed for preHD participants.”

In addition, the risks versus benefits of any long-term treatment must be considered, Dr. Bachoud-Lévi noted.

“The best window for treatment should instead target the time when a detectable subclinical slope of cognitive performance allows for predicting disease onset within a few years,” she said. “Turning to machine learning methodology, such as that in oncology, might also permit combining the best window and the best disease-modifying therapy for individuals with preHD,” she added.

The study was supported by the Wellcome Trust, CHDI Foundation. The researchers had no financial conflicts to disclose. Dr. Bachoud-Lévi disclosed grants and personal fees from Roche, and grants from the French Ministry of Health and Direction de la Recherche Clinique.

SOURCES: Scahill RI et al. Lancet Neurol. 2020 June;19:502-12; Bachoud-Lévi A-C. Lancet Neurol. 2020 June;19:473-5.

Neurologic effects can be a significant part of COVID-19, but does the SARS-CoV-2 virus directly damage the central nervous system or are the neurologic symptoms attributable to secondary mechanisms? A new review article summarizes what is known so far, and what clinicians need to look out for.

“We frequently see neurological conditions in people with COVID-19, but we understand very little about these effects. Is it the virus entering the brain/nerves or are they a result of a general inflammation or immune response – a bystander effect of people being severely ill. It is probably a combination of both,” said senior author Serena Spudich, MD, Gilbert H. Glaser Professor of Neurology; division chief of neurological infections & global neurology; and codirector of the Center for Neuroepidemiology and Clinical Neurological Research at Yale University, New Haven, Conn.

“Our message is that there are fairly frequent neurological sequelae of COVID-19 and we need to be alert to these, and to try to understand the potential long-term consequences,” she said.

The review was published online May 29 in JAMA Neurology.
 

Brain changes linked to loss of smell

In a separate article also published online in JAMA Neurology the same day, an Italian group describes a COVID-19 patient with anosmia (loss of sense of smell) who showed brain abnormalities on MRI in the areas associated with smell – the right gyrus rectus and the olfactory bulbs. These changes were resolved on later scan and the patient recovered her sense of smell.

“Based on the MRI findings, we can speculate that SARS-CoV-2 might invade the brain through the olfactory pathway,” conclude the researchers, led by first author Letterio S. Politi, MD, of the department of neuroradiology at IRCCS Istituto Clinico Humanitas and Humanitas University, Milan, Italy.
 

Can coronaviruses enter the CNS?

Dr. Spudich described this case report as “compelling evidence suggesting that loss of smell is a neurologic effect.”

“Loss of smell and/or taste is a common symptom in COVID-19, so this may suggest that an awful lot of people have some neurological involvement,” Dr. Spudich commented. “While a transient loss of smell or taste is not serious, if the virus has infected brain tissue the question is could this then spread to other parts of the brain and cause other more serious neurological effects,” she added.

In their review article, Dr. Spudich and colleagues present evidence showing that coronaviruses can enter the CNS.

“We know that SARS-1 and MERS have been shown to enter the nervous system and several coronaviruses have been shown to cause direct brain effects,” she said. “There is also some evidence that SARS-CoV-2 can do this too. As well as these latest MRI findings linked to loss of smell, there is a report of the virus being found in endothelial cells in the brain and a French autopsy study has also detected virus in the brain.”
 

Complications of other systemic effects?

Dr. Spudich is a neurologist specializing in neurologic consequences of infectious disease. “We don’t normally have such vast numbers of patients but in the last 3 months there has been an avalanche,” she says. From her personal experience, she believes the majority of neurologic symptoms in COVID-19 patients are most probably complications of other systemic effects, such as kidney, heart, or liver problems. But there is likely also a direct viral effect on the CNS in some patients.

“Reports from China suggested that serious neurologic effects were present in about one-third of hospitalized COVID-19 patients. I would say in our experience the figure would be less than that – maybe around 10%,” she noted.

Some COVID-19 patients are presenting with primary neurologic symptoms. For example, an elderly person may first develop confusion rather than a cough or shortness of breath; others have had severe headache as an initial COVID-19 symptom, Dr. Spudich reported. “Medical staff need to be aware of this – a severe headache in a patient who doesn’t normally get headaches could be a sign of the virus.”

Some of the neurologic symptoms could be caused by autoimmunity. Dr. Spudich explained that, in acute HIV infection a small proportion of patients can first present with autoimmune neurologic effects such as Guillain-Barré syndrome, an autoimmune condition of the nerves which causes a tingling sensation in the hands and feet. “This is well described in HIV, but we are also now seeing this in COVID-19 patients too,” she said. “A panoply of conditions can be caused by autoimmunity.”

On the increase in strokes that has been reported in COVID-19 patients, Dr. Spudich said, “this could be due to direct effects of the virus (e.g., causing an increase in coagulation or infecting the endothelial cells in the brain) or it could just be the final trigger for patients who were at risk of stroke anyway.”

There have been some very high-profile reports of younger patients with major strokes, she said, “but we haven’t seen that in our hospital. For the most part in my experience, strokes are happening in older COVID-19 patients with stroke risk factors such as AF [atrial fibrillation], hypertension, and diabetes. We haven’t seen a preponderance of strokes in young, otherwise healthy people.”

Even in patients who have neurologic effects as the first sign of COVID-19 infection, it is not known whether these symptoms are caused directly by the virus.

“We know that flu can cause people to have headaches, but that is because of an increase in inflammatory cytokines. On the other hand, patients with acute HIV infection often have headaches as a result of the virus getting into the brain. We don’t know where in this [cluster] COVID-19 virus falls,” Dr. Spudich said.
 

Much is still unknown

“The information we have is very sparse at this point. We need far more systematic information on this from CSF samples and imaging.” Dr. Spudich urged clinicians to try to collect such information in patients with neurologic symptoms.

Acknowledging that fewer such tests are being done at present because of concerns over infection risk, Dr. Spudich suggested that some changes in procedure may help. “In our hospital we have a portable MRI scanner which can be brought to the patient. This means the patient does not have to move across the hospital for a scan. This helps us to decide whether the patient has had a stroke, which can be missed when patients are on a ventilator.”

It is also unclear whether the neurologic effects seen during COVID-19 infection will last long term.

Dr. Spudich noted that there have been reports of COVID-19 patients discharged from intensive care having difficulty with higher cognitive function for some time thereafter. “This can happen after being in ICU but is it more pronounced in COVID-19 patients? An ongoing study is underway to look at this,” she said.

This article first appeared on Medscape.com.

Neurologic effects can be a significant part of COVID-19, but does the SARS-CoV-2 virus directly damage the central nervous system or are the neurologic symptoms attributable to secondary mechanisms? A new review article summarizes what is known so far, and what clinicians need to look out for.

“We frequently see neurological conditions in people with COVID-19, but we understand very little about these effects. Is it the virus entering the brain/nerves or are they a result of a general inflammation or immune response – a bystander effect of people being severely ill. It is probably a combination of both,” said senior author Serena Spudich, MD, Gilbert H. Glaser Professor of Neurology; division chief of neurological infections & global neurology; and codirector of the Center for Neuroepidemiology and Clinical Neurological Research at Yale University, New Haven, Conn.

“Our message is that there are fairly frequent neurological sequelae of COVID-19 and we need to be alert to these, and to try to understand the potential long-term consequences,” she said.

The review was published online May 29 in JAMA Neurology.
 

Brain changes linked to loss of smell

In a separate article also published online in JAMA Neurology the same day, an Italian group describes a COVID-19 patient with anosmia (loss of sense of smell) who showed brain abnormalities on MRI in the areas associated with smell – the right gyrus rectus and the olfactory bulbs. These changes were resolved on later scan and the patient recovered her sense of smell.

“Based on the MRI findings, we can speculate that SARS-CoV-2 might invade the brain through the olfactory pathway,” conclude the researchers, led by first author Letterio S. Politi, MD, of the department of neuroradiology at IRCCS Istituto Clinico Humanitas and Humanitas University, Milan, Italy.
 

Can coronaviruses enter the CNS?

Dr. Spudich described this case report as “compelling evidence suggesting that loss of smell is a neurologic effect.”

“Loss of smell and/or taste is a common symptom in COVID-19, so this may suggest that an awful lot of people have some neurological involvement,” Dr. Spudich commented. “While a transient loss of smell or taste is not serious, if the virus has infected brain tissue the question is could this then spread to other parts of the brain and cause other more serious neurological effects,” she added.

In their review article, Dr. Spudich and colleagues present evidence showing that coronaviruses can enter the CNS.

“We know that SARS-1 and MERS have been shown to enter the nervous system and several coronaviruses have been shown to cause direct brain effects,” she said. “There is also some evidence that SARS-CoV-2 can do this too. As well as these latest MRI findings linked to loss of smell, there is a report of the virus being found in endothelial cells in the brain and a French autopsy study has also detected virus in the brain.”
 

Complications of other systemic effects?

Dr. Spudich is a neurologist specializing in neurologic consequences of infectious disease. “We don’t normally have such vast numbers of patients but in the last 3 months there has been an avalanche,” she says. From her personal experience, she believes the majority of neurologic symptoms in COVID-19 patients are most probably complications of other systemic effects, such as kidney, heart, or liver problems. But there is likely also a direct viral effect on the CNS in some patients.

“Reports from China suggested that serious neurologic effects were present in about one-third of hospitalized COVID-19 patients. I would say in our experience the figure would be less than that – maybe around 10%,” she noted.

Some COVID-19 patients are presenting with primary neurologic symptoms. For example, an elderly person may first develop confusion rather than a cough or shortness of breath; others have had severe headache as an initial COVID-19 symptom, Dr. Spudich reported. “Medical staff need to be aware of this – a severe headache in a patient who doesn’t normally get headaches could be a sign of the virus.”

Some of the neurologic symptoms could be caused by autoimmunity. Dr. Spudich explained that, in acute HIV infection a small proportion of patients can first present with autoimmune neurologic effects such as Guillain-Barré syndrome, an autoimmune condition of the nerves which causes a tingling sensation in the hands and feet. “This is well described in HIV, but we are also now seeing this in COVID-19 patients too,” she said. “A panoply of conditions can be caused by autoimmunity.”

On the increase in strokes that has been reported in COVID-19 patients, Dr. Spudich said, “this could be due to direct effects of the virus (e.g., causing an increase in coagulation or infecting the endothelial cells in the brain) or it could just be the final trigger for patients who were at risk of stroke anyway.”

There have been some very high-profile reports of younger patients with major strokes, she said, “but we haven’t seen that in our hospital. For the most part in my experience, strokes are happening in older COVID-19 patients with stroke risk factors such as AF [atrial fibrillation], hypertension, and diabetes. We haven’t seen a preponderance of strokes in young, otherwise healthy people.”

Even in patients who have neurologic effects as the first sign of COVID-19 infection, it is not known whether these symptoms are caused directly by the virus.

“We know that flu can cause people to have headaches, but that is because of an increase in inflammatory cytokines. On the other hand, patients with acute HIV infection often have headaches as a result of the virus getting into the brain. We don’t know where in this [cluster] COVID-19 virus falls,” Dr. Spudich said.
 

Much is still unknown

“The information we have is very sparse at this point. We need far more systematic information on this from CSF samples and imaging.” Dr. Spudich urged clinicians to try to collect such information in patients with neurologic symptoms.

Acknowledging that fewer such tests are being done at present because of concerns over infection risk, Dr. Spudich suggested that some changes in procedure may help. “In our hospital we have a portable MRI scanner which can be brought to the patient. This means the patient does not have to move across the hospital for a scan. This helps us to decide whether the patient has had a stroke, which can be missed when patients are on a ventilator.”

It is also unclear whether the neurologic effects seen during COVID-19 infection will last long term.

Dr. Spudich noted that there have been reports of COVID-19 patients discharged from intensive care having difficulty with higher cognitive function for some time thereafter. “This can happen after being in ICU but is it more pronounced in COVID-19 patients? An ongoing study is underway to look at this,” she said.

This article first appeared on Medscape.com.

Neurologic effects can be a significant part of COVID-19, but does the SARS-CoV-2 virus directly damage the central nervous system or are the neurologic symptoms attributable to secondary mechanisms? A new review article summarizes what is known so far, and what clinicians need to look out for.

“We frequently see neurological conditions in people with COVID-19, but we understand very little about these effects. Is it the virus entering the brain/nerves or are they a result of a general inflammation or immune response – a bystander effect of people being severely ill. It is probably a combination of both,” said senior author Serena Spudich, MD, Gilbert H. Glaser Professor of Neurology; division chief of neurological infections & global neurology; and codirector of the Center for Neuroepidemiology and Clinical Neurological Research at Yale University, New Haven, Conn.

“Our message is that there are fairly frequent neurological sequelae of COVID-19 and we need to be alert to these, and to try to understand the potential long-term consequences,” she said.

The review was published online May 29 in JAMA Neurology.
 

Brain changes linked to loss of smell

In a separate article also published online in JAMA Neurology the same day, an Italian group describes a COVID-19 patient with anosmia (loss of sense of smell) who showed brain abnormalities on MRI in the areas associated with smell – the right gyrus rectus and the olfactory bulbs. These changes were resolved on later scan and the patient recovered her sense of smell.

“Based on the MRI findings, we can speculate that SARS-CoV-2 might invade the brain through the olfactory pathway,” conclude the researchers, led by first author Letterio S. Politi, MD, of the department of neuroradiology at IRCCS Istituto Clinico Humanitas and Humanitas University, Milan, Italy.
 

Can coronaviruses enter the CNS?

Dr. Spudich described this case report as “compelling evidence suggesting that loss of smell is a neurologic effect.”

“Loss of smell and/or taste is a common symptom in COVID-19, so this may suggest that an awful lot of people have some neurological involvement,” Dr. Spudich commented. “While a transient loss of smell or taste is not serious, if the virus has infected brain tissue the question is could this then spread to other parts of the brain and cause other more serious neurological effects,” she added.

In their review article, Dr. Spudich and colleagues present evidence showing that coronaviruses can enter the CNS.

“We know that SARS-1 and MERS have been shown to enter the nervous system and several coronaviruses have been shown to cause direct brain effects,” she said. “There is also some evidence that SARS-CoV-2 can do this too. As well as these latest MRI findings linked to loss of smell, there is a report of the virus being found in endothelial cells in the brain and a French autopsy study has also detected virus in the brain.”
 

Complications of other systemic effects?

Dr. Spudich is a neurologist specializing in neurologic consequences of infectious disease. “We don’t normally have such vast numbers of patients but in the last 3 months there has been an avalanche,” she says. From her personal experience, she believes the majority of neurologic symptoms in COVID-19 patients are most probably complications of other systemic effects, such as kidney, heart, or liver problems. But there is likely also a direct viral effect on the CNS in some patients.

“Reports from China suggested that serious neurologic effects were present in about one-third of hospitalized COVID-19 patients. I would say in our experience the figure would be less than that – maybe around 10%,” she noted.

Some COVID-19 patients are presenting with primary neurologic symptoms. For example, an elderly person may first develop confusion rather than a cough or shortness of breath; others have had severe headache as an initial COVID-19 symptom, Dr. Spudich reported. “Medical staff need to be aware of this – a severe headache in a patient who doesn’t normally get headaches could be a sign of the virus.”

Some of the neurologic symptoms could be caused by autoimmunity. Dr. Spudich explained that, in acute HIV infection a small proportion of patients can first present with autoimmune neurologic effects such as Guillain-Barré syndrome, an autoimmune condition of the nerves which causes a tingling sensation in the hands and feet. “This is well described in HIV, but we are also now seeing this in COVID-19 patients too,” she said. “A panoply of conditions can be caused by autoimmunity.”

On the increase in strokes that has been reported in COVID-19 patients, Dr. Spudich said, “this could be due to direct effects of the virus (e.g., causing an increase in coagulation or infecting the endothelial cells in the brain) or it could just be the final trigger for patients who were at risk of stroke anyway.”

There have been some very high-profile reports of younger patients with major strokes, she said, “but we haven’t seen that in our hospital. For the most part in my experience, strokes are happening in older COVID-19 patients with stroke risk factors such as AF [atrial fibrillation], hypertension, and diabetes. We haven’t seen a preponderance of strokes in young, otherwise healthy people.”

Even in patients who have neurologic effects as the first sign of COVID-19 infection, it is not known whether these symptoms are caused directly by the virus.

“We know that flu can cause people to have headaches, but that is because of an increase in inflammatory cytokines. On the other hand, patients with acute HIV infection often have headaches as a result of the virus getting into the brain. We don’t know where in this [cluster] COVID-19 virus falls,” Dr. Spudich said.
 

Much is still unknown

“The information we have is very sparse at this point. We need far more systematic information on this from CSF samples and imaging.” Dr. Spudich urged clinicians to try to collect such information in patients with neurologic symptoms.

Acknowledging that fewer such tests are being done at present because of concerns over infection risk, Dr. Spudich suggested that some changes in procedure may help. “In our hospital we have a portable MRI scanner which can be brought to the patient. This means the patient does not have to move across the hospital for a scan. This helps us to decide whether the patient has had a stroke, which can be missed when patients are on a ventilator.”

It is also unclear whether the neurologic effects seen during COVID-19 infection will last long term.

Dr. Spudich noted that there have been reports of COVID-19 patients discharged from intensive care having difficulty with higher cognitive function for some time thereafter. “This can happen after being in ICU but is it more pronounced in COVID-19 patients? An ongoing study is underway to look at this,” she said.

This article first appeared on Medscape.com.

According to study of a cluster of patients in France and Switzerland, children may experience an acute cardiac decompensation from the severe inflammatory state following SARS-CoV-2 infection, termed multisystem inflammatory syndrome in children (MIS-C). Treatment with immunoglobulin appears to be associated with recovery of left ventricular systolic function.

“The pediatric and cardiology communities should be acutely aware of this new disease probably related to SARS-CoV-2 infection (MIS-C), that shares similarities with Kawasaki disease but has specificities in its presentation,” researchers led by Zahra Belhadjer, MD, of Necker-Enfants Malades Hospital in Paris, wrote in a cases series report published online in Circulation “Early diagnosis and management appear to lead to favorable outcome using classical therapies. Elucidating the immune mechanisms of this disease will afford further insights for treatment and potential global prevention of severe forms.”

Over a 2-month period that coincided with the SARS-CoV-2 pandemic in France and Switzerland, the researchers retrospectively collected clinical, biological, therapeutic, and early-outcomes data in 35 children who were admitted to pediatric ICUs in 14 centers for cardiogenic shock, left ventricular dysfunction, and severe inflammatory state. Their median age was 10 years, all presented with a fever, 80% had gastrointestinal symptoms of abdominal pain, vomiting, or diarrhea, and 28% had comorbidities that included body mass index of greater than 25 kg/m² (17%), asthma (9%), and lupus (3%), and overweight. Only 17% presented with chest pain. The researchers observed that left ventricular ejection fraction was less than 30% in 28% of patients, and 80% required inotropic support with 28% treated with extracorporeal membrane oxygenation (ECMO). All patients presented with a severe inflammatory state evidenced by elevated C-reactive protein and d-dimer. Interleukin 6 was elevated to a median of 135 pg/mL in 13 of the patients. Elevation of troponin I was constant but mild to moderate, and NT-proBNP or BNP elevation was present in all children.

Nearly all patients 35 (88%) patients tested positive for SARS-CoV-2 infection by polymerase chain reaction of nasopharyngeal swab or serology. Most patients (80%) received IV inotropic support, 71% received first-line IV immunoglobulin, 65% received anticoagulation with heparin, 34% received IV steroids having been considered high-risk patients with symptoms similar to an incomplete form of Kawasaki disease, and 8% received treatment with an interleukin-1 receptor antagonist because of a persistent severe inflammatory state. Left ventricular function was restored in 71% of those discharged from the intensive care unit. No patient died, and all patients treated with ECMO were successfully weaned after a median of 4.5 days.

“Some aspects of this emerging pediatric disease (MIS-C) are similar to those of Kawasaki disease: prolonged fever, multisystem inflammation with skin rash, lymphadenopathy, diarrhea, meningism, and high levels of inflammatory biomarkers,” the researchers wrote. “But differences are important and raise the question as to whether this syndrome is Kawasaki disease with SARS-CoV-2 as the triggering agent, or represents a different syndrome (MIS-C). Kawasaki disease predominantly affects young children younger than 5 years, whereas the median age in our series is 10 years. Incomplete forms of Kawasaki disease occur in infants who may have fever as the sole clinical finding, whereas older patients are more prone to exhibit the complete form.”

They went on to note that the overlapping features between MIS-C and Kawasaki disease “may be due to similar pathophysiology. The etiologic agent of Kawasaki disease is unknown but likely to be ubiquitous, causing asymptomatic childhood infection but triggering the immunologic cascade of Kawasaki disease in genetically susceptible individuals. Please note that infection with a novel RNA virus that enters through the upper respiratory tract has been proposed to be the cause of the disease (see PLoS One. 2008 Feb 13;3:e1582 and J Infect Dis. 2011 Apr 1;203:1021-30).”

Based on the work of authors, it appears that a high index of suspicion for MIS-C is important for children who develop Kawasaki-like symptoms, David J. Goldberg, MD, said in an interview. “Although children have largely been spared from the acute respiratory presentation of the SARS-CoV-2 pandemic, the recognition and understanding of what appears to be a postviral inflammatory response is a critical first step in developing treatment algorithms for this disease process,” said Dr. Goldberg, a board-certified attending cardiologist in the cardiac center and fetal heart program at Children’s Hospital of Philadelphia. “If inflammatory markers are elevated, particularly if there are accompanying gastrointestinal symptoms, the possibility of cardiac involvement suggests the utility of screening echocardiography. Given the potential need for inotropic or mechanical circulatory support, the presence of myocardial dysfunction dictates care in an intensive care unit capable of providing advanced therapies. While the evidence from Dr. Belhadjer’s cohort suggests that full recovery is probable, there is still much to be learned about this unique inflammatory syndrome and the alarm has rightly been sounded.”

The researchers and Dr. Goldberg reported having no disclosures.

[email protected]

SOURCE: Belhadjer Z et al. Circulation 2020 May 17; doi: 10.1161/circulationaha.120.048360.

According to study of a cluster of patients in France and Switzerland, children may experience an acute cardiac decompensation from the severe inflammatory state following SARS-CoV-2 infection, termed multisystem inflammatory syndrome in children (MIS-C). Treatment with immunoglobulin appears to be associated with recovery of left ventricular systolic function.

“The pediatric and cardiology communities should be acutely aware of this new disease probably related to SARS-CoV-2 infection (MIS-C), that shares similarities with Kawasaki disease but has specificities in its presentation,” researchers led by Zahra Belhadjer, MD, of Necker-Enfants Malades Hospital in Paris, wrote in a cases series report published online in Circulation “Early diagnosis and management appear to lead to favorable outcome using classical therapies. Elucidating the immune mechanisms of this disease will afford further insights for treatment and potential global prevention of severe forms.”

Over a 2-month period that coincided with the SARS-CoV-2 pandemic in France and Switzerland, the researchers retrospectively collected clinical, biological, therapeutic, and early-outcomes data in 35 children who were admitted to pediatric ICUs in 14 centers for cardiogenic shock, left ventricular dysfunction, and severe inflammatory state. Their median age was 10 years, all presented with a fever, 80% had gastrointestinal symptoms of abdominal pain, vomiting, or diarrhea, and 28% had comorbidities that included body mass index of greater than 25 kg/m² (17%), asthma (9%), and lupus (3%), and overweight. Only 17% presented with chest pain. The researchers observed that left ventricular ejection fraction was less than 30% in 28% of patients, and 80% required inotropic support with 28% treated with extracorporeal membrane oxygenation (ECMO). All patients presented with a severe inflammatory state evidenced by elevated C-reactive protein and d-dimer. Interleukin 6 was elevated to a median of 135 pg/mL in 13 of the patients. Elevation of troponin I was constant but mild to moderate, and NT-proBNP or BNP elevation was present in all children.

Nearly all patients 35 (88%) patients tested positive for SARS-CoV-2 infection by polymerase chain reaction of nasopharyngeal swab or serology. Most patients (80%) received IV inotropic support, 71% received first-line IV immunoglobulin, 65% received anticoagulation with heparin, 34% received IV steroids having been considered high-risk patients with symptoms similar to an incomplete form of Kawasaki disease, and 8% received treatment with an interleukin-1 receptor antagonist because of a persistent severe inflammatory state. Left ventricular function was restored in 71% of those discharged from the intensive care unit. No patient died, and all patients treated with ECMO were successfully weaned after a median of 4.5 days.

“Some aspects of this emerging pediatric disease (MIS-C) are similar to those of Kawasaki disease: prolonged fever, multisystem inflammation with skin rash, lymphadenopathy, diarrhea, meningism, and high levels of inflammatory biomarkers,” the researchers wrote. “But differences are important and raise the question as to whether this syndrome is Kawasaki disease with SARS-CoV-2 as the triggering agent, or represents a different syndrome (MIS-C). Kawasaki disease predominantly affects young children younger than 5 years, whereas the median age in our series is 10 years. Incomplete forms of Kawasaki disease occur in infants who may have fever as the sole clinical finding, whereas older patients are more prone to exhibit the complete form.”

They went on to note that the overlapping features between MIS-C and Kawasaki disease “may be due to similar pathophysiology. The etiologic agent of Kawasaki disease is unknown but likely to be ubiquitous, causing asymptomatic childhood infection but triggering the immunologic cascade of Kawasaki disease in genetically susceptible individuals. Please note that infection with a novel RNA virus that enters through the upper respiratory tract has been proposed to be the cause of the disease (see PLoS One. 2008 Feb 13;3:e1582 and J Infect Dis. 2011 Apr 1;203:1021-30).”

Based on the work of authors, it appears that a high index of suspicion for MIS-C is important for children who develop Kawasaki-like symptoms, David J. Goldberg, MD, said in an interview. “Although children have largely been spared from the acute respiratory presentation of the SARS-CoV-2 pandemic, the recognition and understanding of what appears to be a postviral inflammatory response is a critical first step in developing treatment algorithms for this disease process,” said Dr. Goldberg, a board-certified attending cardiologist in the cardiac center and fetal heart program at Children’s Hospital of Philadelphia. “If inflammatory markers are elevated, particularly if there are accompanying gastrointestinal symptoms, the possibility of cardiac involvement suggests the utility of screening echocardiography. Given the potential need for inotropic or mechanical circulatory support, the presence of myocardial dysfunction dictates care in an intensive care unit capable of providing advanced therapies. While the evidence from Dr. Belhadjer’s cohort suggests that full recovery is probable, there is still much to be learned about this unique inflammatory syndrome and the alarm has rightly been sounded.”

The researchers and Dr. Goldberg reported having no disclosures.

[email protected]

SOURCE: Belhadjer Z et al. Circulation 2020 May 17; doi: 10.1161/circulationaha.120.048360.

According to study of a cluster of patients in France and Switzerland, children may experience an acute cardiac decompensation from the severe inflammatory state following SARS-CoV-2 infection, termed multisystem inflammatory syndrome in children (MIS-C). Treatment with immunoglobulin appears to be associated with recovery of left ventricular systolic function.

“The pediatric and cardiology communities should be acutely aware of this new disease probably related to SARS-CoV-2 infection (MIS-C), that shares similarities with Kawasaki disease but has specificities in its presentation,” researchers led by Zahra Belhadjer, MD, of Necker-Enfants Malades Hospital in Paris, wrote in a cases series report published online in Circulation “Early diagnosis and management appear to lead to favorable outcome using classical therapies. Elucidating the immune mechanisms of this disease will afford further insights for treatment and potential global prevention of severe forms.”

Over a 2-month period that coincided with the SARS-CoV-2 pandemic in France and Switzerland, the researchers retrospectively collected clinical, biological, therapeutic, and early-outcomes data in 35 children who were admitted to pediatric ICUs in 14 centers for cardiogenic shock, left ventricular dysfunction, and severe inflammatory state. Their median age was 10 years, all presented with a fever, 80% had gastrointestinal symptoms of abdominal pain, vomiting, or diarrhea, and 28% had comorbidities that included body mass index of greater than 25 kg/m² (17%), asthma (9%), and lupus (3%), and overweight. Only 17% presented with chest pain. The researchers observed that left ventricular ejection fraction was less than 30% in 28% of patients, and 80% required inotropic support with 28% treated with extracorporeal membrane oxygenation (ECMO). All patients presented with a severe inflammatory state evidenced by elevated C-reactive protein and d-dimer. Interleukin 6 was elevated to a median of 135 pg/mL in 13 of the patients. Elevation of troponin I was constant but mild to moderate, and NT-proBNP or BNP elevation was present in all children.

Nearly all patients 35 (88%) patients tested positive for SARS-CoV-2 infection by polymerase chain reaction of nasopharyngeal swab or serology. Most patients (80%) received IV inotropic support, 71% received first-line IV immunoglobulin, 65% received anticoagulation with heparin, 34% received IV steroids having been considered high-risk patients with symptoms similar to an incomplete form of Kawasaki disease, and 8% received treatment with an interleukin-1 receptor antagonist because of a persistent severe inflammatory state. Left ventricular function was restored in 71% of those discharged from the intensive care unit. No patient died, and all patients treated with ECMO were successfully weaned after a median of 4.5 days.

“Some aspects of this emerging pediatric disease (MIS-C) are similar to those of Kawasaki disease: prolonged fever, multisystem inflammation with skin rash, lymphadenopathy, diarrhea, meningism, and high levels of inflammatory biomarkers,” the researchers wrote. “But differences are important and raise the question as to whether this syndrome is Kawasaki disease with SARS-CoV-2 as the triggering agent, or represents a different syndrome (MIS-C). Kawasaki disease predominantly affects young children younger than 5 years, whereas the median age in our series is 10 years. Incomplete forms of Kawasaki disease occur in infants who may have fever as the sole clinical finding, whereas older patients are more prone to exhibit the complete form.”

They went on to note that the overlapping features between MIS-C and Kawasaki disease “may be due to similar pathophysiology. The etiologic agent of Kawasaki disease is unknown but likely to be ubiquitous, causing asymptomatic childhood infection but triggering the immunologic cascade of Kawasaki disease in genetically susceptible individuals. Please note that infection with a novel RNA virus that enters through the upper respiratory tract has been proposed to be the cause of the disease (see PLoS One. 2008 Feb 13;3:e1582 and J Infect Dis. 2011 Apr 1;203:1021-30).”

Based on the work of authors, it appears that a high index of suspicion for MIS-C is important for children who develop Kawasaki-like symptoms, David J. Goldberg, MD, said in an interview. “Although children have largely been spared from the acute respiratory presentation of the SARS-CoV-2 pandemic, the recognition and understanding of what appears to be a postviral inflammatory response is a critical first step in developing treatment algorithms for this disease process,” said Dr. Goldberg, a board-certified attending cardiologist in the cardiac center and fetal heart program at Children’s Hospital of Philadelphia. “If inflammatory markers are elevated, particularly if there are accompanying gastrointestinal symptoms, the possibility of cardiac involvement suggests the utility of screening echocardiography. Given the potential need for inotropic or mechanical circulatory support, the presence of myocardial dysfunction dictates care in an intensive care unit capable of providing advanced therapies. While the evidence from Dr. Belhadjer’s cohort suggests that full recovery is probable, there is still much to be learned about this unique inflammatory syndrome and the alarm has rightly been sounded.”

The researchers and Dr. Goldberg reported having no disclosures.

[email protected]

SOURCE: Belhadjer Z et al. Circulation 2020 May 17; doi: 10.1161/circulationaha.120.048360.

Higher cardiovascular risk burden, as measured by the Framingham General Cardiovascular Risk Score (FGCRS), is associated with neurodegenerative signs in the brain and may predict cognitive decline over time.

“In the absence of effective treatments for dementia, we need to monitor and control cardiovascular risk burden as a way to maintain patient’s cognitive health as they age,” said Weili Xu, PhD, Department of Epidemiology and Biostatistics, School of Public Health, Tianjin Medical University, Tianjin, China, in a press release.

“Given the progressive increase in the number of dementia cases worldwide, our findings have both clinical and public health relevance.”

Dr. Xu and first author Ruixue Song, MSc, also from Tianjin Medical University, published their findings online ahead of print May 18 in the Journal of the American College of Cardiology.

The World Health Organization projects that up to 82 million people will have dementia by 2050. Given the lack of effective treatments for dementia, identifying modifiable risk factors for cognitive decline and aggressively managing them is an increasingly appealing strategy.
 

Assessing cardiovascular risk and cognition

The researchers followed 1,588 dementia-free participants from the Rush Memory and Aging Project for 21 years (median, 5.8 years). FGCRS was assessed at baseline and categorized into tertiles (lowest, middle, and highest). Mean age of the studied population was 79.5 years, 75.8% of participants were female, and mean Framingham score was 15.6 (range, 4 to 28).

Annual evaluations included assessment of episodic memory (memory of everyday events), semantic memory (long-term memory), working memory (short-term memory), visuospatial ability (capacity to identify visual and spatial relationships among objects), and perceptual speed (ability to accurately and completely compare letters, numbers, objects, pictures, or patterns) using 19 tests to derive a composite score.

A subsample (n = 378) of participants underwent MRI, and structural total and regional brain volumes were estimated.

Linear regression was used to estimate beta-coefficients for the relationship between cardiovascular risk burden at baseline and longitudinally. If the beta-coefficient is negative, the interpretation is that for every 1-unit increase in the predictor variable (FGCRS), the outcome variable (cognitive function) will decrease by the beta-coefficient value.

At baseline, higher FGCRS was related to small but consistent (although not usually statistically significant) decreases in hippocampal volume, gray matter, and total brain volume.

Considered longitudinally, participants in the highest-risk tertile of FGCRS experienced faster decline in global cognition (beta = −0.019), episodic memory (beta = −0.023), working memory (beta = −0.021), and perceptual speed (beta = −0.027) during follow-up (P < .05 for all) than those in the lowest-risk tertile.

The declines in semantic memory (beta = –0.012) and visuospatial ability (beta = –0.010) did not reach statistical significance.

Bringing dementia prevention into the exam room early

Commenting on the research, Costantino Iadecola, MD, director of the Feil Family Brain and Mind Research Institute at Weill Cornell Medicine in New York City, said the study has immediate clinical usefulness.

“The link between the cardiovascular risk factors and dementia is well known, but in your doctor’s office, that link is not seen. If your GP or cardiologist sees you with high blood pressure, he’s not immediately going to think about the risk of dementia 20 years later,” said Dr. Iadecola.

“What this study does is it directly links a simple score that’s commonly used to assess cardiovascular risk to dementia risk, which can be used to counsel patients and, hopefully, reduce the risk of both cardiovascular disease and cognitive disorders.”

Dr. Iadecola wrote an editorial together with Neal S. Parikh, MD, MS, also from Weill Cornell Medicine, that accompanied the findings of the trial.

Even neurologists sometimes fail to make the connection between vascular risk and dementia, he said. “They think that by making a stroke patient move their hand better, they’re treating them, but 30% of stroke patients get dementia 6 or 8 months later and they’re missing this link between cerebrovascular pathology and dementia.

Dr. Iadecola is one of 26 experts who authored the recent Berlin Manifesto, an effort led by Vladimir Hachinski, MD, professor of neurology and epidemiology at Western University in Ontario, Canada, to raise awareness of the link between cardiovascular and brain health.

Dr. Hachinski coined the term “brain attack” and devised the Hachinski Ischemic Score that remains the standard for identifying a vascular component of cognitive impairment.

The current study has some strengths and limitations, noted Dr. Iadecola. The average age of participants was 80 years, which is appropriate given the high risk for cognitive decline at this age, but the generalizability of the study may be limited given that most participants were white women.

Going forward, he said, rigorous studies are needed to confirm these findings and to determine how to best prevent dementia through treatment of individual cardiovascular risk factors.

Dr. Xu has received grants from nonindustry entities, including the Swedish Research Council and the National Natural Science Foundation of China. The study was funded by the European Union’s Horizon 320230 research and innovation program. Dr. Iadecola is a member of the scientific advisory board for Broadview Ventures.

This article appeared on Medscape.com.

Higher cardiovascular risk burden, as measured by the Framingham General Cardiovascular Risk Score (FGCRS), is associated with neurodegenerative signs in the brain and may predict cognitive decline over time.

“In the absence of effective treatments for dementia, we need to monitor and control cardiovascular risk burden as a way to maintain patient’s cognitive health as they age,” said Weili Xu, PhD, Department of Epidemiology and Biostatistics, School of Public Health, Tianjin Medical University, Tianjin, China, in a press release.

“Given the progressive increase in the number of dementia cases worldwide, our findings have both clinical and public health relevance.”

Dr. Xu and first author Ruixue Song, MSc, also from Tianjin Medical University, published their findings online ahead of print May 18 in the Journal of the American College of Cardiology.

The World Health Organization projects that up to 82 million people will have dementia by 2050. Given the lack of effective treatments for dementia, identifying modifiable risk factors for cognitive decline and aggressively managing them is an increasingly appealing strategy.
 

Assessing cardiovascular risk and cognition

The researchers followed 1,588 dementia-free participants from the Rush Memory and Aging Project for 21 years (median, 5.8 years). FGCRS was assessed at baseline and categorized into tertiles (lowest, middle, and highest). Mean age of the studied population was 79.5 years, 75.8% of participants were female, and mean Framingham score was 15.6 (range, 4 to 28).

Annual evaluations included assessment of episodic memory (memory of everyday events), semantic memory (long-term memory), working memory (short-term memory), visuospatial ability (capacity to identify visual and spatial relationships among objects), and perceptual speed (ability to accurately and completely compare letters, numbers, objects, pictures, or patterns) using 19 tests to derive a composite score.

A subsample (n = 378) of participants underwent MRI, and structural total and regional brain volumes were estimated.

Linear regression was used to estimate beta-coefficients for the relationship between cardiovascular risk burden at baseline and longitudinally. If the beta-coefficient is negative, the interpretation is that for every 1-unit increase in the predictor variable (FGCRS), the outcome variable (cognitive function) will decrease by the beta-coefficient value.

At baseline, higher FGCRS was related to small but consistent (although not usually statistically significant) decreases in hippocampal volume, gray matter, and total brain volume.

Considered longitudinally, participants in the highest-risk tertile of FGCRS experienced faster decline in global cognition (beta = −0.019), episodic memory (beta = −0.023), working memory (beta = −0.021), and perceptual speed (beta = −0.027) during follow-up (P < .05 for all) than those in the lowest-risk tertile.

The declines in semantic memory (beta = –0.012) and visuospatial ability (beta = –0.010) did not reach statistical significance.

Bringing dementia prevention into the exam room early

Commenting on the research, Costantino Iadecola, MD, director of the Feil Family Brain and Mind Research Institute at Weill Cornell Medicine in New York City, said the study has immediate clinical usefulness.

“The link between the cardiovascular risk factors and dementia is well known, but in your doctor’s office, that link is not seen. If your GP or cardiologist sees you with high blood pressure, he’s not immediately going to think about the risk of dementia 20 years later,” said Dr. Iadecola.

“What this study does is it directly links a simple score that’s commonly used to assess cardiovascular risk to dementia risk, which can be used to counsel patients and, hopefully, reduce the risk of both cardiovascular disease and cognitive disorders.”

Dr. Iadecola wrote an editorial together with Neal S. Parikh, MD, MS, also from Weill Cornell Medicine, that accompanied the findings of the trial.

Even neurologists sometimes fail to make the connection between vascular risk and dementia, he said. “They think that by making a stroke patient move their hand better, they’re treating them, but 30% of stroke patients get dementia 6 or 8 months later and they’re missing this link between cerebrovascular pathology and dementia.

Dr. Iadecola is one of 26 experts who authored the recent Berlin Manifesto, an effort led by Vladimir Hachinski, MD, professor of neurology and epidemiology at Western University in Ontario, Canada, to raise awareness of the link between cardiovascular and brain health.

Dr. Hachinski coined the term “brain attack” and devised the Hachinski Ischemic Score that remains the standard for identifying a vascular component of cognitive impairment.

The current study has some strengths and limitations, noted Dr. Iadecola. The average age of participants was 80 years, which is appropriate given the high risk for cognitive decline at this age, but the generalizability of the study may be limited given that most participants were white women.

Going forward, he said, rigorous studies are needed to confirm these findings and to determine how to best prevent dementia through treatment of individual cardiovascular risk factors.

Dr. Xu has received grants from nonindustry entities, including the Swedish Research Council and the National Natural Science Foundation of China. The study was funded by the European Union’s Horizon 320230 research and innovation program. Dr. Iadecola is a member of the scientific advisory board for Broadview Ventures.

This article appeared on Medscape.com.

Higher cardiovascular risk burden, as measured by the Framingham General Cardiovascular Risk Score (FGCRS), is associated with neurodegenerative signs in the brain and may predict cognitive decline over time.

“In the absence of effective treatments for dementia, we need to monitor and control cardiovascular risk burden as a way to maintain patient’s cognitive health as they age,” said Weili Xu, PhD, Department of Epidemiology and Biostatistics, School of Public Health, Tianjin Medical University, Tianjin, China, in a press release.

“Given the progressive increase in the number of dementia cases worldwide, our findings have both clinical and public health relevance.”

Dr. Xu and first author Ruixue Song, MSc, also from Tianjin Medical University, published their findings online ahead of print May 18 in the Journal of the American College of Cardiology.

The World Health Organization projects that up to 82 million people will have dementia by 2050. Given the lack of effective treatments for dementia, identifying modifiable risk factors for cognitive decline and aggressively managing them is an increasingly appealing strategy.
 

Assessing cardiovascular risk and cognition

The researchers followed 1,588 dementia-free participants from the Rush Memory and Aging Project for 21 years (median, 5.8 years). FGCRS was assessed at baseline and categorized into tertiles (lowest, middle, and highest). Mean age of the studied population was 79.5 years, 75.8% of participants were female, and mean Framingham score was 15.6 (range, 4 to 28).

Annual evaluations included assessment of episodic memory (memory of everyday events), semantic memory (long-term memory), working memory (short-term memory), visuospatial ability (capacity to identify visual and spatial relationships among objects), and perceptual speed (ability to accurately and completely compare letters, numbers, objects, pictures, or patterns) using 19 tests to derive a composite score.

A subsample (n = 378) of participants underwent MRI, and structural total and regional brain volumes were estimated.

Linear regression was used to estimate beta-coefficients for the relationship between cardiovascular risk burden at baseline and longitudinally. If the beta-coefficient is negative, the interpretation is that for every 1-unit increase in the predictor variable (FGCRS), the outcome variable (cognitive function) will decrease by the beta-coefficient value.

At baseline, higher FGCRS was related to small but consistent (although not usually statistically significant) decreases in hippocampal volume, gray matter, and total brain volume.

Considered longitudinally, participants in the highest-risk tertile of FGCRS experienced faster decline in global cognition (beta = −0.019), episodic memory (beta = −0.023), working memory (beta = −0.021), and perceptual speed (beta = −0.027) during follow-up (P < .05 for all) than those in the lowest-risk tertile.

The declines in semantic memory (beta = –0.012) and visuospatial ability (beta = –0.010) did not reach statistical significance.

Bringing dementia prevention into the exam room early

Commenting on the research, Costantino Iadecola, MD, director of the Feil Family Brain and Mind Research Institute at Weill Cornell Medicine in New York City, said the study has immediate clinical usefulness.

“The link between the cardiovascular risk factors and dementia is well known, but in your doctor’s office, that link is not seen. If your GP or cardiologist sees you with high blood pressure, he’s not immediately going to think about the risk of dementia 20 years later,” said Dr. Iadecola.

“What this study does is it directly links a simple score that’s commonly used to assess cardiovascular risk to dementia risk, which can be used to counsel patients and, hopefully, reduce the risk of both cardiovascular disease and cognitive disorders.”

Dr. Iadecola wrote an editorial together with Neal S. Parikh, MD, MS, also from Weill Cornell Medicine, that accompanied the findings of the trial.

Even neurologists sometimes fail to make the connection between vascular risk and dementia, he said. “They think that by making a stroke patient move their hand better, they’re treating them, but 30% of stroke patients get dementia 6 or 8 months later and they’re missing this link between cerebrovascular pathology and dementia.

Dr. Iadecola is one of 26 experts who authored the recent Berlin Manifesto, an effort led by Vladimir Hachinski, MD, professor of neurology and epidemiology at Western University in Ontario, Canada, to raise awareness of the link between cardiovascular and brain health.

Dr. Hachinski coined the term “brain attack” and devised the Hachinski Ischemic Score that remains the standard for identifying a vascular component of cognitive impairment.

The current study has some strengths and limitations, noted Dr. Iadecola. The average age of participants was 80 years, which is appropriate given the high risk for cognitive decline at this age, but the generalizability of the study may be limited given that most participants were white women.

Going forward, he said, rigorous studies are needed to confirm these findings and to determine how to best prevent dementia through treatment of individual cardiovascular risk factors.

Dr. Xu has received grants from nonindustry entities, including the Swedish Research Council and the National Natural Science Foundation of China. The study was funded by the European Union’s Horizon 320230 research and innovation program. Dr. Iadecola is a member of the scientific advisory board for Broadview Ventures.

This article appeared on Medscape.com.

The American Academy of Neurology has published a position statement providing ethical guidance for neurologists caring for patients with neurologic disorders during the COVID-19 pandemic. The document, which was published online May 15 in Neurology, reviews adaptations to the inpatient and outpatient settings and addresses the need to develop protocols for the allocation of scarce medical resources. The guidance is the product of a joint committee of the AAN, the American Neurological Association, the Child Neurology Society, and the Neurocritical Care Society Ethics Committee.

“Now is one of the most challenging times of our careers as neurologists,” said James C. Stevens, MD, president of the AAN, in a press release. “Clinics and hospitals are adapting to caring for the most ill, managing scarce resources, and trying to protect people without the disease. As neurologists, we must continue to adapt our daily practice, continue to care for our most ill neurology patients, and help contribute to the care of those afflicted with COVID-19.”
 

The role of telehealth

The authors recommended that ordinary appointments be held using telehealth, which, they say, already has become part of patient care. Telehealth enables neurologists to continue providing care while reducing the risk of exposure to and spread of SARS-CoV-2. The disadvantages of telehealth are that it limits physical examinations and behavioral health examinations, the authors acknowledged. “Each clinician should decide, in concert with his or her patient, if an in-person evaluation warrants the risk of an encounter,” according to the guidance.

Neurologists also should advise their patients that their neurologic condition could affect their relative risk of hospitalization and death resulting from COVID-19. Patients with multiple sclerosis or myasthenia gravis, for example, may be receiving corticosteroids or immunomodulatory therapies that make them more vulnerable to COVID-19 infection. “Even if desired services are available, neurologists and their patients ought to consider whether their care plans can safely be delayed in order to mitigate risk,” wrote the authors. Neurologists must try to maintain the customary standard of care, however, for patients with neurologic disease severe enough to warrant hospitalization, such as stroke or epilepsy.
 

The potential need for triage

Resources such as ventilators and ICU beds are limited, and health care facilities have had to triage them during the pandemic. Patients with a neurologic disease that decreases their likelihood of survival from a respiratory illness may not be offered these resources. Neurologists should discuss with patients and decision makers the ways in which reduced resources might affect patient care. Neurologists must “be aware of the burden of disease in their local community and how healthcare leaders plan on coping with a surge,” according to the guidance.

Advance directives, which should be a standard part of clinical care, take on increased importance during the pandemic. Patients who have not completed advance care planning documents should be encouraged to do so, according to the authors. These documents include patients’ preferences for “do not attempt resuscitation” status. Nevertheless, “we must assure patients with chronic illness that diminished resources in this healthcare crisis will not restrict their access to comfort and palliative care,” the document states.
 

Scarce resource allocation protocols

In the event that a surge in patients overwhelms a hospital’s contingencies and forces it to operate in crisis mode, it should have a scarce resource allocation protocol in place.

“This will surely be the most challenging aspect of patient care during this pandemic public health emergency,” wrote the authors. To ensure transparency and to mitigate the emotional effect of these decisions on patients and clinicians, scarce resource allocation protocols should be developed by teams that include intensivists, clinical ethicists, and nursing representatives who are not directly involved in the care of the critically ill patients. The goal of these protocols is to maximize the number of lives saved. They generally include an initial patient assessment followed by regular reevaluations to determine whether patients using scarce resources are benefiting less than other patients who need the same resources. The protocols should consider not only patients with COVID-19 infection, but also patients with stroke, traumatic injury, influenza, and heart failure who may need the same resources. Race, gender, ethnicity, socioeconomics, and perceived social worth should not influence care decisions, according to the guidance. Validated mortality prediction scales, such as the Glasgow Outcome Scale, can contribute to care decisions. Obtaining community input into these protocols will ensure trust in the health care system.

“If the situation necessitates hard decisions, we need to be fair, objective, transparent, and adamantly preserve our professional integrity,” wrote the authors. “Through it all, we owe it to our patients and families, as well as ourselves, to maintain our own health and wellness.”

The guidance was developed without funding, and the authors reported no relevant disclosures.

[email protected]

SOURCE: Rubin MA et al. Neurology. 2020 May 15. doi: 10.1212/WNL.0000000000009744.

The American Academy of Neurology has published a position statement providing ethical guidance for neurologists caring for patients with neurologic disorders during the COVID-19 pandemic. The document, which was published online May 15 in Neurology, reviews adaptations to the inpatient and outpatient settings and addresses the need to develop protocols for the allocation of scarce medical resources. The guidance is the product of a joint committee of the AAN, the American Neurological Association, the Child Neurology Society, and the Neurocritical Care Society Ethics Committee.

“Now is one of the most challenging times of our careers as neurologists,” said James C. Stevens, MD, president of the AAN, in a press release. “Clinics and hospitals are adapting to caring for the most ill, managing scarce resources, and trying to protect people without the disease. As neurologists, we must continue to adapt our daily practice, continue to care for our most ill neurology patients, and help contribute to the care of those afflicted with COVID-19.”
 

The role of telehealth

The authors recommended that ordinary appointments be held using telehealth, which, they say, already has become part of patient care. Telehealth enables neurologists to continue providing care while reducing the risk of exposure to and spread of SARS-CoV-2. The disadvantages of telehealth are that it limits physical examinations and behavioral health examinations, the authors acknowledged. “Each clinician should decide, in concert with his or her patient, if an in-person evaluation warrants the risk of an encounter,” according to the guidance.

Neurologists also should advise their patients that their neurologic condition could affect their relative risk of hospitalization and death resulting from COVID-19. Patients with multiple sclerosis or myasthenia gravis, for example, may be receiving corticosteroids or immunomodulatory therapies that make them more vulnerable to COVID-19 infection. “Even if desired services are available, neurologists and their patients ought to consider whether their care plans can safely be delayed in order to mitigate risk,” wrote the authors. Neurologists must try to maintain the customary standard of care, however, for patients with neurologic disease severe enough to warrant hospitalization, such as stroke or epilepsy.
 

The potential need for triage

Resources such as ventilators and ICU beds are limited, and health care facilities have had to triage them during the pandemic. Patients with a neurologic disease that decreases their likelihood of survival from a respiratory illness may not be offered these resources. Neurologists should discuss with patients and decision makers the ways in which reduced resources might affect patient care. Neurologists must “be aware of the burden of disease in their local community and how healthcare leaders plan on coping with a surge,” according to the guidance.

Advance directives, which should be a standard part of clinical care, take on increased importance during the pandemic. Patients who have not completed advance care planning documents should be encouraged to do so, according to the authors. These documents include patients’ preferences for “do not attempt resuscitation” status. Nevertheless, “we must assure patients with chronic illness that diminished resources in this healthcare crisis will not restrict their access to comfort and palliative care,” the document states.
 

Scarce resource allocation protocols

In the event that a surge in patients overwhelms a hospital’s contingencies and forces it to operate in crisis mode, it should have a scarce resource allocation protocol in place.

“This will surely be the most challenging aspect of patient care during this pandemic public health emergency,” wrote the authors. To ensure transparency and to mitigate the emotional effect of these decisions on patients and clinicians, scarce resource allocation protocols should be developed by teams that include intensivists, clinical ethicists, and nursing representatives who are not directly involved in the care of the critically ill patients. The goal of these protocols is to maximize the number of lives saved. They generally include an initial patient assessment followed by regular reevaluations to determine whether patients using scarce resources are benefiting less than other patients who need the same resources. The protocols should consider not only patients with COVID-19 infection, but also patients with stroke, traumatic injury, influenza, and heart failure who may need the same resources. Race, gender, ethnicity, socioeconomics, and perceived social worth should not influence care decisions, according to the guidance. Validated mortality prediction scales, such as the Glasgow Outcome Scale, can contribute to care decisions. Obtaining community input into these protocols will ensure trust in the health care system.

“If the situation necessitates hard decisions, we need to be fair, objective, transparent, and adamantly preserve our professional integrity,” wrote the authors. “Through it all, we owe it to our patients and families, as well as ourselves, to maintain our own health and wellness.”

The guidance was developed without funding, and the authors reported no relevant disclosures.

[email protected]

SOURCE: Rubin MA et al. Neurology. 2020 May 15. doi: 10.1212/WNL.0000000000009744.

The American Academy of Neurology has published a position statement providing ethical guidance for neurologists caring for patients with neurologic disorders during the COVID-19 pandemic. The document, which was published online May 15 in Neurology, reviews adaptations to the inpatient and outpatient settings and addresses the need to develop protocols for the allocation of scarce medical resources. The guidance is the product of a joint committee of the AAN, the American Neurological Association, the Child Neurology Society, and the Neurocritical Care Society Ethics Committee.

“Now is one of the most challenging times of our careers as neurologists,” said James C. Stevens, MD, president of the AAN, in a press release. “Clinics and hospitals are adapting to caring for the most ill, managing scarce resources, and trying to protect people without the disease. As neurologists, we must continue to adapt our daily practice, continue to care for our most ill neurology patients, and help contribute to the care of those afflicted with COVID-19.”
 

The role of telehealth

The authors recommended that ordinary appointments be held using telehealth, which, they say, already has become part of patient care. Telehealth enables neurologists to continue providing care while reducing the risk of exposure to and spread of SARS-CoV-2. The disadvantages of telehealth are that it limits physical examinations and behavioral health examinations, the authors acknowledged. “Each clinician should decide, in concert with his or her patient, if an in-person evaluation warrants the risk of an encounter,” according to the guidance.

Neurologists also should advise their patients that their neurologic condition could affect their relative risk of hospitalization and death resulting from COVID-19. Patients with multiple sclerosis or myasthenia gravis, for example, may be receiving corticosteroids or immunomodulatory therapies that make them more vulnerable to COVID-19 infection. “Even if desired services are available, neurologists and their patients ought to consider whether their care plans can safely be delayed in order to mitigate risk,” wrote the authors. Neurologists must try to maintain the customary standard of care, however, for patients with neurologic disease severe enough to warrant hospitalization, such as stroke or epilepsy.
 

The potential need for triage

Resources such as ventilators and ICU beds are limited, and health care facilities have had to triage them during the pandemic. Patients with a neurologic disease that decreases their likelihood of survival from a respiratory illness may not be offered these resources. Neurologists should discuss with patients and decision makers the ways in which reduced resources might affect patient care. Neurologists must “be aware of the burden of disease in their local community and how healthcare leaders plan on coping with a surge,” according to the guidance.

Advance directives, which should be a standard part of clinical care, take on increased importance during the pandemic. Patients who have not completed advance care planning documents should be encouraged to do so, according to the authors. These documents include patients’ preferences for “do not attempt resuscitation” status. Nevertheless, “we must assure patients with chronic illness that diminished resources in this healthcare crisis will not restrict their access to comfort and palliative care,” the document states.
 

Scarce resource allocation protocols

In the event that a surge in patients overwhelms a hospital’s contingencies and forces it to operate in crisis mode, it should have a scarce resource allocation protocol in place.

“This will surely be the most challenging aspect of patient care during this pandemic public health emergency,” wrote the authors. To ensure transparency and to mitigate the emotional effect of these decisions on patients and clinicians, scarce resource allocation protocols should be developed by teams that include intensivists, clinical ethicists, and nursing representatives who are not directly involved in the care of the critically ill patients. The goal of these protocols is to maximize the number of lives saved. They generally include an initial patient assessment followed by regular reevaluations to determine whether patients using scarce resources are benefiting less than other patients who need the same resources. The protocols should consider not only patients with COVID-19 infection, but also patients with stroke, traumatic injury, influenza, and heart failure who may need the same resources. Race, gender, ethnicity, socioeconomics, and perceived social worth should not influence care decisions, according to the guidance. Validated mortality prediction scales, such as the Glasgow Outcome Scale, can contribute to care decisions. Obtaining community input into these protocols will ensure trust in the health care system.

“If the situation necessitates hard decisions, we need to be fair, objective, transparent, and adamantly preserve our professional integrity,” wrote the authors. “Through it all, we owe it to our patients and families, as well as ourselves, to maintain our own health and wellness.”

The guidance was developed without funding, and the authors reported no relevant disclosures.

[email protected]

SOURCE: Rubin MA et al. Neurology. 2020 May 15. doi: 10.1212/WNL.0000000000009744.

A meta-analysis of relevant clinical trials has found that lowering blood pressure with antihypertensive agents was statistically significantly associated with reducing the risk of dementia or cognitive impairment, though the risk reduction was modest.

“Although observational studies report hypertension to be an important risk factor for dementia, the benefit of blood pressure lowering on dementia or cognitive impairment in clinical trials is modest and lower than the risk reduction for stroke,” wrote Diarmaid Hughes, MB, of the NUI Galway and Saolta University Hospital Group in Galway, Ireland, and coauthors. They added, however, that “these findings have the potential to inform public health strategies to reduce the burden of dementia globally.” The study was published online ahead of print May 19 in JAMA.
 

A rich data set

To assess the relationship between lowering blood pressure and cognitive issues, the researchers performed a systemic search of randomized, clinical trials that compared blood pressure lowering via antihypertensive agents with a control, had at least 1 year of follow-up, included more than 1,000 participants, and reported on either dementia, cognitive impairment, cognitive decline, or a change in cognitive test scores as outcomes. Of the 14 studies deemed eligible, 12 reported either the incidence of dementia (n = 9) or a composite of dementia or cognitive impairment (n = 3) at follow-up and thus were included in the primary meta-analysis. The other two studies were used for secondary outcomes only.

The studies included 96,158 participants in total – 42.2% were women – and their mean age was 69 years. At baseline, participants’ mean systolic blood pressure was 154 mm Hg and their mean diastolic blood pressure was 83.3 mm Hg. The mean duration of follow-up was 49.24 months.

In the 12 trials that reported dementia or cognitive impairment, blood pressure lowering via antihypertensive agents, compared with control, was significantly associated with a reduction in those two outcomes (7.0% vs. 7.5% over a mean trial follow-up of 4.1 years; odds ratio, 0.93; 95% confidence interval, 0.88-0.98; absolute risk reduction, 0.39%; 95% CI, 0.09%-0.68%). Blood pressure lowering, compared with control, was also significantly associated with a reduction in cognitive decline (20.2% vs. 21.1% over a mean trial follow-up of 4.1 years; OR, 0.93; 95% CI, 0.88-0.99; ARR, 0.71%; 95% CI, 0.19%-1.2%) in the eight trials that reported it as an outcome. An analysis of the eight trials that reported a change in cognitive scores did not find a significant association between that outcome and blood pressure lowering.
 

Subpopulations should be examined

“This is a very broad brush stroke study, albeit a definitive one,” Richard J. Caselli, MD, of the Mayo Clinic in Phoenix said in an interview. “With all the thousands of people in this meta-analysis, there are going to be subpopulations of patients with certain characteristics or common conditions in which blood pressure lowering might have a bigger or a lesser impact on their risk factor. Is there a difference between certain racial groups? Does it matter what antihypertensive strategies are used? You can look at the interactions between blood pressure lowering and other conditions: diabetes, head injuries, air pollution, certain genetic risk factors. There are a number of additional findings that could come from a very rich data set like this.”

The authors acknowledged their study’s limitations, including the challenges of performing a meta-analysis of studies that drew from different populations and had potentially different definitions of dementia, cognitive impairment, and cognitive decline outcomes. In addition, the low incidence of dementia across clinical trials limited the researchers, and its underdetection in trials and the potential of survivor bias for healthier participants with blood pressure reductions were noted as “unmeasured sources of potential error.”

Three authors reported receiving grants or personal fees from the Wellcome Trust and the Health Research Board, the Chief Scientist Office, and Bayer AG, respectively.

SOURCE: Hughes D et al. JAMA. 2020 May 19. doi: 10.1001/jama.2020.4249.

A meta-analysis of relevant clinical trials has found that lowering blood pressure with antihypertensive agents was statistically significantly associated with reducing the risk of dementia or cognitive impairment, though the risk reduction was modest.

“Although observational studies report hypertension to be an important risk factor for dementia, the benefit of blood pressure lowering on dementia or cognitive impairment in clinical trials is modest and lower than the risk reduction for stroke,” wrote Diarmaid Hughes, MB, of the NUI Galway and Saolta University Hospital Group in Galway, Ireland, and coauthors. They added, however, that “these findings have the potential to inform public health strategies to reduce the burden of dementia globally.” The study was published online ahead of print May 19 in JAMA.
 

A rich data set

To assess the relationship between lowering blood pressure and cognitive issues, the researchers performed a systemic search of randomized, clinical trials that compared blood pressure lowering via antihypertensive agents with a control, had at least 1 year of follow-up, included more than 1,000 participants, and reported on either dementia, cognitive impairment, cognitive decline, or a change in cognitive test scores as outcomes. Of the 14 studies deemed eligible, 12 reported either the incidence of dementia (n = 9) or a composite of dementia or cognitive impairment (n = 3) at follow-up and thus were included in the primary meta-analysis. The other two studies were used for secondary outcomes only.

The studies included 96,158 participants in total – 42.2% were women – and their mean age was 69 years. At baseline, participants’ mean systolic blood pressure was 154 mm Hg and their mean diastolic blood pressure was 83.3 mm Hg. The mean duration of follow-up was 49.24 months.

In the 12 trials that reported dementia or cognitive impairment, blood pressure lowering via antihypertensive agents, compared with control, was significantly associated with a reduction in those two outcomes (7.0% vs. 7.5% over a mean trial follow-up of 4.1 years; odds ratio, 0.93; 95% confidence interval, 0.88-0.98; absolute risk reduction, 0.39%; 95% CI, 0.09%-0.68%). Blood pressure lowering, compared with control, was also significantly associated with a reduction in cognitive decline (20.2% vs. 21.1% over a mean trial follow-up of 4.1 years; OR, 0.93; 95% CI, 0.88-0.99; ARR, 0.71%; 95% CI, 0.19%-1.2%) in the eight trials that reported it as an outcome. An analysis of the eight trials that reported a change in cognitive scores did not find a significant association between that outcome and blood pressure lowering.
 

Subpopulations should be examined

“This is a very broad brush stroke study, albeit a definitive one,” Richard J. Caselli, MD, of the Mayo Clinic in Phoenix said in an interview. “With all the thousands of people in this meta-analysis, there are going to be subpopulations of patients with certain characteristics or common conditions in which blood pressure lowering might have a bigger or a lesser impact on their risk factor. Is there a difference between certain racial groups? Does it matter what antihypertensive strategies are used? You can look at the interactions between blood pressure lowering and other conditions: diabetes, head injuries, air pollution, certain genetic risk factors. There are a number of additional findings that could come from a very rich data set like this.”

The authors acknowledged their study’s limitations, including the challenges of performing a meta-analysis of studies that drew from different populations and had potentially different definitions of dementia, cognitive impairment, and cognitive decline outcomes. In addition, the low incidence of dementia across clinical trials limited the researchers, and its underdetection in trials and the potential of survivor bias for healthier participants with blood pressure reductions were noted as “unmeasured sources of potential error.”

Three authors reported receiving grants or personal fees from the Wellcome Trust and the Health Research Board, the Chief Scientist Office, and Bayer AG, respectively.

SOURCE: Hughes D et al. JAMA. 2020 May 19. doi: 10.1001/jama.2020.4249.

A meta-analysis of relevant clinical trials has found that lowering blood pressure with antihypertensive agents was statistically significantly associated with reducing the risk of dementia or cognitive impairment, though the risk reduction was modest.

“Although observational studies report hypertension to be an important risk factor for dementia, the benefit of blood pressure lowering on dementia or cognitive impairment in clinical trials is modest and lower than the risk reduction for stroke,” wrote Diarmaid Hughes, MB, of the NUI Galway and Saolta University Hospital Group in Galway, Ireland, and coauthors. They added, however, that “these findings have the potential to inform public health strategies to reduce the burden of dementia globally.” The study was published online ahead of print May 19 in JAMA.
 

A rich data set

To assess the relationship between lowering blood pressure and cognitive issues, the researchers performed a systemic search of randomized, clinical trials that compared blood pressure lowering via antihypertensive agents with a control, had at least 1 year of follow-up, included more than 1,000 participants, and reported on either dementia, cognitive impairment, cognitive decline, or a change in cognitive test scores as outcomes. Of the 14 studies deemed eligible, 12 reported either the incidence of dementia (n = 9) or a composite of dementia or cognitive impairment (n = 3) at follow-up and thus were included in the primary meta-analysis. The other two studies were used for secondary outcomes only.

The studies included 96,158 participants in total – 42.2% were women – and their mean age was 69 years. At baseline, participants’ mean systolic blood pressure was 154 mm Hg and their mean diastolic blood pressure was 83.3 mm Hg. The mean duration of follow-up was 49.24 months.

In the 12 trials that reported dementia or cognitive impairment, blood pressure lowering via antihypertensive agents, compared with control, was significantly associated with a reduction in those two outcomes (7.0% vs. 7.5% over a mean trial follow-up of 4.1 years; odds ratio, 0.93; 95% confidence interval, 0.88-0.98; absolute risk reduction, 0.39%; 95% CI, 0.09%-0.68%). Blood pressure lowering, compared with control, was also significantly associated with a reduction in cognitive decline (20.2% vs. 21.1% over a mean trial follow-up of 4.1 years; OR, 0.93; 95% CI, 0.88-0.99; ARR, 0.71%; 95% CI, 0.19%-1.2%) in the eight trials that reported it as an outcome. An analysis of the eight trials that reported a change in cognitive scores did not find a significant association between that outcome and blood pressure lowering.
 

Subpopulations should be examined

“This is a very broad brush stroke study, albeit a definitive one,” Richard J. Caselli, MD, of the Mayo Clinic in Phoenix said in an interview. “With all the thousands of people in this meta-analysis, there are going to be subpopulations of patients with certain characteristics or common conditions in which blood pressure lowering might have a bigger or a lesser impact on their risk factor. Is there a difference between certain racial groups? Does it matter what antihypertensive strategies are used? You can look at the interactions between blood pressure lowering and other conditions: diabetes, head injuries, air pollution, certain genetic risk factors. There are a number of additional findings that could come from a very rich data set like this.”

The authors acknowledged their study’s limitations, including the challenges of performing a meta-analysis of studies that drew from different populations and had potentially different definitions of dementia, cognitive impairment, and cognitive decline outcomes. In addition, the low incidence of dementia across clinical trials limited the researchers, and its underdetection in trials and the potential of survivor bias for healthier participants with blood pressure reductions were noted as “unmeasured sources of potential error.”

Three authors reported receiving grants or personal fees from the Wellcome Trust and the Health Research Board, the Chief Scientist Office, and Bayer AG, respectively.

SOURCE: Hughes D et al. JAMA. 2020 May 19. doi: 10.1001/jama.2020.4249.