Neurology

Electrical brain stimulation may have the potential to improve verbal memory, results of a small study of patients with epilepsy suggest.

Investigators observed improvements in patients implanted with a responsive neurostimulation system (RNS) to control seizures, in that the patients had improved word recall when the system was activated.

Beyond epilepsy, “we suspect that our results would be broadly applicable regardless of the underlying condition, for example, memory loss with Alzheimer’s disease or traumatic brain injury,” Zulfi Haneef, MBBS, MD, associate professor of neurology, Baylor College of Medicine, Houston, said in an interview.

“Mental health conditions such as depression or psychosis could also benefit from targeted electrical stimulation. While we focused on enhancing a preferred brain function [such as memory], parallel areas of research may target enhancing function [such as weakness following stroke] or suppressing function [to manage conditions such as chronic pain,]” Dr. Haneef added.

The study was published online Jan. 17, 2022, in Neurosurgery.

As reported by this news organization, the RNS system (NeuroPace) is approved by the Food and Drug Administration to treat medically refractory focal seizures in adults. Following implantation of the system, patients attend the clinic for adjustments about every 8-12 weeks.

The investigators studied 17 patients with epilepsy and RNS implants who attended the clinic for routine appointments. A clinical neuropsychologist administered the Hopkins Verbal Learning Test–Revised (HVLT-R), a well-validated list-learning measure of memory and verbal learning.

Patients were read a list of 12 semantically related words and asked to recall the list after three different learning trials. Active or sham stimulation was performed for every third word presented for immediate recall. 

The investigators found that the HVLT-R delayed recall raw score was higher for the stimulation condition, compared with the nonstimulation condition (paired t-test, P = .04; effect size, d = 0.627).

“The patients were not aware of when the RNS system was being activated. We alternated when patients were undergoing stimulation versus no stimulation, and still found that when patients’ RNS systems were activated, their memory recall score was greater than when there was no stimulation,” Dr. Haneef said in a release.

This suggests the “human memory can be potentially improved by direct electrical brain stimulation at extremely low currents,” Dr. Haneef said in an interview.

Most patients in the study had stimulation of the hippocampus, the brain’s memory center.

“Moving forward we would want to look at how different patterns or standardized stimulation patterns affect memory. Ultimately, the underlying brain rhythms responsible for these changes in brain function need to be understood so that a more targeted and precise application of electrical stimulation can be achieved,” Dr. Haneef said.

The researchers also caution that, for this preliminary study, no follow-up testing was conducted to determine whether the memory improvement was transient and settled back to baseline after a specified period.

However, they note, this study lays the groundwork for larger-scale and extensive studies examining the nuanced effects of brain stimulation on human cognition and memory.

The study was funded by the Mike Hogg Foundation. Dr. Haneef and two coauthors received coverage for travel expenses but no honorarium for a NeuroPace advisory meeting.

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

Electrical brain stimulation may have the potential to improve verbal memory, results of a small study of patients with epilepsy suggest.

Investigators observed improvements in patients implanted with a responsive neurostimulation system (RNS) to control seizures, in that the patients had improved word recall when the system was activated.

Beyond epilepsy, “we suspect that our results would be broadly applicable regardless of the underlying condition, for example, memory loss with Alzheimer’s disease or traumatic brain injury,” Zulfi Haneef, MBBS, MD, associate professor of neurology, Baylor College of Medicine, Houston, said in an interview.

“Mental health conditions such as depression or psychosis could also benefit from targeted electrical stimulation. While we focused on enhancing a preferred brain function [such as memory], parallel areas of research may target enhancing function [such as weakness following stroke] or suppressing function [to manage conditions such as chronic pain,]” Dr. Haneef added.

The study was published online Jan. 17, 2022, in Neurosurgery.

As reported by this news organization, the RNS system (NeuroPace) is approved by the Food and Drug Administration to treat medically refractory focal seizures in adults. Following implantation of the system, patients attend the clinic for adjustments about every 8-12 weeks.

The investigators studied 17 patients with epilepsy and RNS implants who attended the clinic for routine appointments. A clinical neuropsychologist administered the Hopkins Verbal Learning Test–Revised (HVLT-R), a well-validated list-learning measure of memory and verbal learning.

Patients were read a list of 12 semantically related words and asked to recall the list after three different learning trials. Active or sham stimulation was performed for every third word presented for immediate recall. 

The investigators found that the HVLT-R delayed recall raw score was higher for the stimulation condition, compared with the nonstimulation condition (paired t-test, P = .04; effect size, d = 0.627).

“The patients were not aware of when the RNS system was being activated. We alternated when patients were undergoing stimulation versus no stimulation, and still found that when patients’ RNS systems were activated, their memory recall score was greater than when there was no stimulation,” Dr. Haneef said in a release.

This suggests the “human memory can be potentially improved by direct electrical brain stimulation at extremely low currents,” Dr. Haneef said in an interview.

Most patients in the study had stimulation of the hippocampus, the brain’s memory center.

“Moving forward we would want to look at how different patterns or standardized stimulation patterns affect memory. Ultimately, the underlying brain rhythms responsible for these changes in brain function need to be understood so that a more targeted and precise application of electrical stimulation can be achieved,” Dr. Haneef said.

The researchers also caution that, for this preliminary study, no follow-up testing was conducted to determine whether the memory improvement was transient and settled back to baseline after a specified period.

However, they note, this study lays the groundwork for larger-scale and extensive studies examining the nuanced effects of brain stimulation on human cognition and memory.

The study was funded by the Mike Hogg Foundation. Dr. Haneef and two coauthors received coverage for travel expenses but no honorarium for a NeuroPace advisory meeting.

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

Electrical brain stimulation may have the potential to improve verbal memory, results of a small study of patients with epilepsy suggest.

Investigators observed improvements in patients implanted with a responsive neurostimulation system (RNS) to control seizures, in that the patients had improved word recall when the system was activated.

Beyond epilepsy, “we suspect that our results would be broadly applicable regardless of the underlying condition, for example, memory loss with Alzheimer’s disease or traumatic brain injury,” Zulfi Haneef, MBBS, MD, associate professor of neurology, Baylor College of Medicine, Houston, said in an interview.

“Mental health conditions such as depression or psychosis could also benefit from targeted electrical stimulation. While we focused on enhancing a preferred brain function [such as memory], parallel areas of research may target enhancing function [such as weakness following stroke] or suppressing function [to manage conditions such as chronic pain,]” Dr. Haneef added.

The study was published online Jan. 17, 2022, in Neurosurgery.

As reported by this news organization, the RNS system (NeuroPace) is approved by the Food and Drug Administration to treat medically refractory focal seizures in adults. Following implantation of the system, patients attend the clinic for adjustments about every 8-12 weeks.

The investigators studied 17 patients with epilepsy and RNS implants who attended the clinic for routine appointments. A clinical neuropsychologist administered the Hopkins Verbal Learning Test–Revised (HVLT-R), a well-validated list-learning measure of memory and verbal learning.

Patients were read a list of 12 semantically related words and asked to recall the list after three different learning trials. Active or sham stimulation was performed for every third word presented for immediate recall. 

The investigators found that the HVLT-R delayed recall raw score was higher for the stimulation condition, compared with the nonstimulation condition (paired t-test, P = .04; effect size, d = 0.627).

“The patients were not aware of when the RNS system was being activated. We alternated when patients were undergoing stimulation versus no stimulation, and still found that when patients’ RNS systems were activated, their memory recall score was greater than when there was no stimulation,” Dr. Haneef said in a release.

This suggests the “human memory can be potentially improved by direct electrical brain stimulation at extremely low currents,” Dr. Haneef said in an interview.

Most patients in the study had stimulation of the hippocampus, the brain’s memory center.

“Moving forward we would want to look at how different patterns or standardized stimulation patterns affect memory. Ultimately, the underlying brain rhythms responsible for these changes in brain function need to be understood so that a more targeted and precise application of electrical stimulation can be achieved,” Dr. Haneef said.

The researchers also caution that, for this preliminary study, no follow-up testing was conducted to determine whether the memory improvement was transient and settled back to baseline after a specified period.

However, they note, this study lays the groundwork for larger-scale and extensive studies examining the nuanced effects of brain stimulation on human cognition and memory.

The study was funded by the Mike Hogg Foundation. Dr. Haneef and two coauthors received coverage for travel expenses but no honorarium for a NeuroPace advisory meeting.

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

Subclinical changes in cardiac structure and diastolic function in early adulthood may serve as risk markers for cognitive decline in midlife, new research suggests.

Cardiovascular disease risk factors such as high blood pressure, high cholesterol, and diabetes have been associated with an increased risk for cognitive impairment, but much less is known about heart structure and function and the risks for cognition.

“We showed for the first time that, even before the occurrence of cardiovascular disease, people with abnormalities in cardiac structure and function as early as in young adulthood have lower midlife cognition,” investigators Laure Rouch, PharmD, PhD, and Kristine Yaffe, MD, both with the department of psychiatry, University of California, San Francisco, said in a joint email.

“This study reminds us that heart health is key to brain health and that the overlap and interplay between the two is not limited to patients with end-stage heart disease,” Dr. Rouch and Dr. Yaffe said.

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

Heart/brain connection

The analysis included 2,653 participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study.

Echocardiograms were obtained at year 5, 25, and 30 study visits – at mean ages of 30, 50, and 55 years, respectively. At year 30, participants underwent a standard battery of tests measuring global cognition, processing speed, executive function, delayed verbal memory, and verbal fluency.

Over 25 years, there was an average increase in left ventricular mass of 0.27 g/m2 per year – from a mean of 80.5 g/m² in year 5 to 86.0 g/m² in year 30.

Left atrial volume increased by an average of 0.42 mL/m2 per year, from 16 mL/m² in year 5 to 26 mL/m² in year 30.

Left ventricular ejection fraction (LVEF) decreased by 0.11% per year, from 63.3% in year 5 to 59.7% in year 30.

After adjustment for demographics and education, an increase in left ventricular mass of at least 1 standard deviation over 25 years was associated with lower cognition on most tests (P ≤ .02).

An increase in left atrial volume over the study period was associated with lower global cognition (P = .04), whereas a decrease in LVEF was not associated with cognition. Further adjustment for cardiovascular risk factors yielded similar results.

“A more effective collaboration is needed between cardiologists and neurologists to promote healthy brain aging,” Dr. Rouch and Dr. Yaffe said.

“Echocardiography is a widely available, relatively inexpensive, and noninvasive imaging method that could be integrated into a risk assessment for cognitive impairment,” they added.

Looking ahead, the investigators noted there is a need for further research to determine whether interventions to improve cardiac structure and diastolic function could also benefit brain health.

They should also investigate the role of arterial stiffness and cerebral small vessel disease in the relationship between cardiac structure, function, and cognition, the researchers added.
 

First structural biomarker

Commenting on the study, Shaheen E. Lakhan, MD, PhD, a neurologist in Newton, Mass., said the study is important because, “thus far, the connections have really been physiological parameters,” such as blood pressure and cognitive health.

“This is really strong evidence of a structural cardiac biomarker that can be measured before and independent of changes in physiology or diseased state,” said Dr. Lakhan, who was not involved with the research.

As more and more interventions are being introduced for addressing disorders of cognition, “this potential structural finding may serve as a solid biomarker to determine” what lifestyle or drug therapy should be taken, he added.

Also weighing in on the findings, Pierre Fayad, MD, professor in the department of neurological sciences and director of the Nebraska Stroke Center, University of Nebraska Medical Center, Omaha, said CARDIA is “an important study” providing “precious data.”

The reported changes in cardiac structure and function “precede the clinical symptomatology, as the follow-up stops before they enter into later adulthood, where the risk of clinical events dramatically rises. Meaning these patients still have not had stroke, congestive heart failure, heart attack or dementia, but some of them could be on that trajectory later in their life,” Dr. Fayad told this news organization.

Documenting such changes over time is “valuable to give an insight into what leads us to such progression,” he noted.

How reliably predictive the findings are for eventual clinical cognitive impairment “will need to be confirmed and verified” in future studies, he added.

“If verified, it could be helpful to provide interventions to those with the left atrial volume enlargement marker and see their effectiveness at preventing eventual clinical cognitive impairment,” said Dr. Fayad.

The CARDIA study is supported by the National Heart, Lung, and Blood Institute in collaboration with the University of Alabama at Birmingham, Northwestern University, the University of Minnesota, and the Kaiser Foundation Research Institute. Rouch, Lakhan, and Dr. Fayad have disclosed no relevant financial relationships.

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

Subclinical changes in cardiac structure and diastolic function in early adulthood may serve as risk markers for cognitive decline in midlife, new research suggests.

Cardiovascular disease risk factors such as high blood pressure, high cholesterol, and diabetes have been associated with an increased risk for cognitive impairment, but much less is known about heart structure and function and the risks for cognition.

“We showed for the first time that, even before the occurrence of cardiovascular disease, people with abnormalities in cardiac structure and function as early as in young adulthood have lower midlife cognition,” investigators Laure Rouch, PharmD, PhD, and Kristine Yaffe, MD, both with the department of psychiatry, University of California, San Francisco, said in a joint email.

“This study reminds us that heart health is key to brain health and that the overlap and interplay between the two is not limited to patients with end-stage heart disease,” Dr. Rouch and Dr. Yaffe said.

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

Heart/brain connection

The analysis included 2,653 participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study.

Echocardiograms were obtained at year 5, 25, and 30 study visits – at mean ages of 30, 50, and 55 years, respectively. At year 30, participants underwent a standard battery of tests measuring global cognition, processing speed, executive function, delayed verbal memory, and verbal fluency.

Over 25 years, there was an average increase in left ventricular mass of 0.27 g/m2 per year – from a mean of 80.5 g/m² in year 5 to 86.0 g/m² in year 30.

Left atrial volume increased by an average of 0.42 mL/m2 per year, from 16 mL/m² in year 5 to 26 mL/m² in year 30.

Left ventricular ejection fraction (LVEF) decreased by 0.11% per year, from 63.3% in year 5 to 59.7% in year 30.

After adjustment for demographics and education, an increase in left ventricular mass of at least 1 standard deviation over 25 years was associated with lower cognition on most tests (P ≤ .02).

An increase in left atrial volume over the study period was associated with lower global cognition (P = .04), whereas a decrease in LVEF was not associated with cognition. Further adjustment for cardiovascular risk factors yielded similar results.

“A more effective collaboration is needed between cardiologists and neurologists to promote healthy brain aging,” Dr. Rouch and Dr. Yaffe said.

“Echocardiography is a widely available, relatively inexpensive, and noninvasive imaging method that could be integrated into a risk assessment for cognitive impairment,” they added.

Looking ahead, the investigators noted there is a need for further research to determine whether interventions to improve cardiac structure and diastolic function could also benefit brain health.

They should also investigate the role of arterial stiffness and cerebral small vessel disease in the relationship between cardiac structure, function, and cognition, the researchers added.
 

First structural biomarker

Commenting on the study, Shaheen E. Lakhan, MD, PhD, a neurologist in Newton, Mass., said the study is important because, “thus far, the connections have really been physiological parameters,” such as blood pressure and cognitive health.

“This is really strong evidence of a structural cardiac biomarker that can be measured before and independent of changes in physiology or diseased state,” said Dr. Lakhan, who was not involved with the research.

As more and more interventions are being introduced for addressing disorders of cognition, “this potential structural finding may serve as a solid biomarker to determine” what lifestyle or drug therapy should be taken, he added.

Also weighing in on the findings, Pierre Fayad, MD, professor in the department of neurological sciences and director of the Nebraska Stroke Center, University of Nebraska Medical Center, Omaha, said CARDIA is “an important study” providing “precious data.”

The reported changes in cardiac structure and function “precede the clinical symptomatology, as the follow-up stops before they enter into later adulthood, where the risk of clinical events dramatically rises. Meaning these patients still have not had stroke, congestive heart failure, heart attack or dementia, but some of them could be on that trajectory later in their life,” Dr. Fayad told this news organization.

Documenting such changes over time is “valuable to give an insight into what leads us to such progression,” he noted.

How reliably predictive the findings are for eventual clinical cognitive impairment “will need to be confirmed and verified” in future studies, he added.

“If verified, it could be helpful to provide interventions to those with the left atrial volume enlargement marker and see their effectiveness at preventing eventual clinical cognitive impairment,” said Dr. Fayad.

The CARDIA study is supported by the National Heart, Lung, and Blood Institute in collaboration with the University of Alabama at Birmingham, Northwestern University, the University of Minnesota, and the Kaiser Foundation Research Institute. Rouch, Lakhan, and Dr. Fayad have disclosed no relevant financial relationships.

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

Subclinical changes in cardiac structure and diastolic function in early adulthood may serve as risk markers for cognitive decline in midlife, new research suggests.

Cardiovascular disease risk factors such as high blood pressure, high cholesterol, and diabetes have been associated with an increased risk for cognitive impairment, but much less is known about heart structure and function and the risks for cognition.

“We showed for the first time that, even before the occurrence of cardiovascular disease, people with abnormalities in cardiac structure and function as early as in young adulthood have lower midlife cognition,” investigators Laure Rouch, PharmD, PhD, and Kristine Yaffe, MD, both with the department of psychiatry, University of California, San Francisco, said in a joint email.

“This study reminds us that heart health is key to brain health and that the overlap and interplay between the two is not limited to patients with end-stage heart disease,” Dr. Rouch and Dr. Yaffe said.

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

Heart/brain connection

The analysis included 2,653 participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study.

Echocardiograms were obtained at year 5, 25, and 30 study visits – at mean ages of 30, 50, and 55 years, respectively. At year 30, participants underwent a standard battery of tests measuring global cognition, processing speed, executive function, delayed verbal memory, and verbal fluency.

Over 25 years, there was an average increase in left ventricular mass of 0.27 g/m2 per year – from a mean of 80.5 g/m² in year 5 to 86.0 g/m² in year 30.

Left atrial volume increased by an average of 0.42 mL/m2 per year, from 16 mL/m² in year 5 to 26 mL/m² in year 30.

Left ventricular ejection fraction (LVEF) decreased by 0.11% per year, from 63.3% in year 5 to 59.7% in year 30.

After adjustment for demographics and education, an increase in left ventricular mass of at least 1 standard deviation over 25 years was associated with lower cognition on most tests (P ≤ .02).

An increase in left atrial volume over the study period was associated with lower global cognition (P = .04), whereas a decrease in LVEF was not associated with cognition. Further adjustment for cardiovascular risk factors yielded similar results.

“A more effective collaboration is needed between cardiologists and neurologists to promote healthy brain aging,” Dr. Rouch and Dr. Yaffe said.

“Echocardiography is a widely available, relatively inexpensive, and noninvasive imaging method that could be integrated into a risk assessment for cognitive impairment,” they added.

Looking ahead, the investigators noted there is a need for further research to determine whether interventions to improve cardiac structure and diastolic function could also benefit brain health.

They should also investigate the role of arterial stiffness and cerebral small vessel disease in the relationship between cardiac structure, function, and cognition, the researchers added.
 

First structural biomarker

Commenting on the study, Shaheen E. Lakhan, MD, PhD, a neurologist in Newton, Mass., said the study is important because, “thus far, the connections have really been physiological parameters,” such as blood pressure and cognitive health.

“This is really strong evidence of a structural cardiac biomarker that can be measured before and independent of changes in physiology or diseased state,” said Dr. Lakhan, who was not involved with the research.

As more and more interventions are being introduced for addressing disorders of cognition, “this potential structural finding may serve as a solid biomarker to determine” what lifestyle or drug therapy should be taken, he added.

Also weighing in on the findings, Pierre Fayad, MD, professor in the department of neurological sciences and director of the Nebraska Stroke Center, University of Nebraska Medical Center, Omaha, said CARDIA is “an important study” providing “precious data.”

The reported changes in cardiac structure and function “precede the clinical symptomatology, as the follow-up stops before they enter into later adulthood, where the risk of clinical events dramatically rises. Meaning these patients still have not had stroke, congestive heart failure, heart attack or dementia, but some of them could be on that trajectory later in their life,” Dr. Fayad told this news organization.

Documenting such changes over time is “valuable to give an insight into what leads us to such progression,” he noted.

How reliably predictive the findings are for eventual clinical cognitive impairment “will need to be confirmed and verified” in future studies, he added.

“If verified, it could be helpful to provide interventions to those with the left atrial volume enlargement marker and see their effectiveness at preventing eventual clinical cognitive impairment,” said Dr. Fayad.

The CARDIA study is supported by the National Heart, Lung, and Blood Institute in collaboration with the University of Alabama at Birmingham, Northwestern University, the University of Minnesota, and the Kaiser Foundation Research Institute. Rouch, Lakhan, and Dr. Fayad have disclosed no relevant financial relationships.

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

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

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

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

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

First evidence of survival advantage

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

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

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

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

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

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

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

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

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

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

Neuroprotective pathway?

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

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

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

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

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

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

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

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

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

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

No direct link

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

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

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

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

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

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

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

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

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

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

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

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

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

First evidence of survival advantage

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

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

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

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

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

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

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

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

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

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

Neuroprotective pathway?

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

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

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

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

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

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

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

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

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

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

No direct link

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

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

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

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

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

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

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

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

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

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

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

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

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

First evidence of survival advantage

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

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

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

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

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

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

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

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

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

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

Neuroprotective pathway?

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

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

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

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

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

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

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

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

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

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

No direct link

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

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

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

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

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

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

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

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

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

The study covered in this summary was published in medRxiv.org as a preprint and has not yet been peer reviewed.

Key takeaways

• Measurement of the rate of cellular amyloid uptake and metabolic production of toxic amyloid species could be used as novel biomarkers for early and/or differential diagnosis of Alzheimer’s disease (AD).
• Estimated beta-amyloid (Aβ42) cellular uptake can be more than two times greater in AD patients compared to cognitively normal subjects. A less pronounced yet increased uptake rate was also observed in patients with late-onset mild cognitive impairment (MCI). This increased uptake may prove to be a key mechanism defining age-related AD progression.
• The increased cellular amyloid uptake in AD and LMCI may lead to quicker disease progression, but early-onset MCI may result from increased production of toxic amyloid metabolites.

Why this matters

• Additional biomarkers for AD could greatly aid diagnosis and course prediction, as they are currently limited to PET scan analysis of amyloid plaque deposits and concentration of Aβ42 in cerebrospinal fluid (CSF).
• Amyloid deposits found by PET have a positive correlation with AD diagnosis. In contrast, CSF-Aβ42 and AD diagnosis or cognitive decline are negatively correlated. Normal cognition (NC) is associated with higher CSF beta-amyloid levels, but previous research has not explained why CSF-Aβ42 levels can be equivalent in patients with NC but high amyloid load and patients with AD and low amyloid load.

Study design

• The authors of this retrospective study used anonymized data obtained from the Alzheimer’s’s Disease Neuroimaging Initiative (ADNI). ADNI’s goal has been to test whether serial MRI scans, PET scans, biomarkers, and clinical/neuropsychological assessment can be combined to measure the progression of MCI and AD.
• Study subjects had either an AD diagnosis or NC and were divided into two groups: low amyloid load and high amyloid load. The fraction of patients with an AD diagnosis was calculated as a function of CSF-Aβ42.
• Calculations and statistical comparisons were performed using Microsoft Excel and custom-written C++ programs.

Key results

• The lowest levels of CSF-Aβ42 correlated with the highest percentage of AD-diagnosed patients, estimated to be 27% in subjects with low amyloid deposit density and 65% in those with high deposit density.
• The relationship between CSF-Aβ42 levels and amyloid load can be described using a simple mathematical model: Amyloid concentration in the interstitial cells is equal to the synthesis rate divided by the density of amyloid deposits plus the sum of the rate of amyloid removal through the CSF and the cellular amyloid uptake rate.
• AD and late-onset MCI patients had a significantly higher amyloid removal rate compared to NC subjects.
• Early-onset MCI patients had Aβ42 turnover similar to that of NC subjects, pointing to a different underlying mechanism such as enzymatic disbalance.

Limitations

• The model used to explain amyloid exchange between the interstitial space and the CSF is oversimplified; the actual process is more complex.
• Synthesis and uptake rates of Aβ42 vary throughout areas of the brain. The model assumes a homogeneous distribution within the interstitial compartment.

Study disclosures

• Research reported in this publication was not supported by any external funding. Data collection and sharing for this project were funded by ADNI.

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

The study covered in this summary was published in medRxiv.org as a preprint and has not yet been peer reviewed.

Key takeaways

• Measurement of the rate of cellular amyloid uptake and metabolic production of toxic amyloid species could be used as novel biomarkers for early and/or differential diagnosis of Alzheimer’s disease (AD).
• Estimated beta-amyloid (Aβ42) cellular uptake can be more than two times greater in AD patients compared to cognitively normal subjects. A less pronounced yet increased uptake rate was also observed in patients with late-onset mild cognitive impairment (MCI). This increased uptake may prove to be a key mechanism defining age-related AD progression.
• The increased cellular amyloid uptake in AD and LMCI may lead to quicker disease progression, but early-onset MCI may result from increased production of toxic amyloid metabolites.

Why this matters

• Additional biomarkers for AD could greatly aid diagnosis and course prediction, as they are currently limited to PET scan analysis of amyloid plaque deposits and concentration of Aβ42 in cerebrospinal fluid (CSF).
• Amyloid deposits found by PET have a positive correlation with AD diagnosis. In contrast, CSF-Aβ42 and AD diagnosis or cognitive decline are negatively correlated. Normal cognition (NC) is associated with higher CSF beta-amyloid levels, but previous research has not explained why CSF-Aβ42 levels can be equivalent in patients with NC but high amyloid load and patients with AD and low amyloid load.

Study design

• The authors of this retrospective study used anonymized data obtained from the Alzheimer’s’s Disease Neuroimaging Initiative (ADNI). ADNI’s goal has been to test whether serial MRI scans, PET scans, biomarkers, and clinical/neuropsychological assessment can be combined to measure the progression of MCI and AD.
• Study subjects had either an AD diagnosis or NC and were divided into two groups: low amyloid load and high amyloid load. The fraction of patients with an AD diagnosis was calculated as a function of CSF-Aβ42.
• Calculations and statistical comparisons were performed using Microsoft Excel and custom-written C++ programs.

Key results

• The lowest levels of CSF-Aβ42 correlated with the highest percentage of AD-diagnosed patients, estimated to be 27% in subjects with low amyloid deposit density and 65% in those with high deposit density.
• The relationship between CSF-Aβ42 levels and amyloid load can be described using a simple mathematical model: Amyloid concentration in the interstitial cells is equal to the synthesis rate divided by the density of amyloid deposits plus the sum of the rate of amyloid removal through the CSF and the cellular amyloid uptake rate.
• AD and late-onset MCI patients had a significantly higher amyloid removal rate compared to NC subjects.
• Early-onset MCI patients had Aβ42 turnover similar to that of NC subjects, pointing to a different underlying mechanism such as enzymatic disbalance.

Limitations

• The model used to explain amyloid exchange between the interstitial space and the CSF is oversimplified; the actual process is more complex.
• Synthesis and uptake rates of Aβ42 vary throughout areas of the brain. The model assumes a homogeneous distribution within the interstitial compartment.

Study disclosures

• Research reported in this publication was not supported by any external funding. Data collection and sharing for this project were funded by ADNI.

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

The study covered in this summary was published in medRxiv.org as a preprint and has not yet been peer reviewed.

Key takeaways

• Measurement of the rate of cellular amyloid uptake and metabolic production of toxic amyloid species could be used as novel biomarkers for early and/or differential diagnosis of Alzheimer’s disease (AD).
• Estimated beta-amyloid (Aβ42) cellular uptake can be more than two times greater in AD patients compared to cognitively normal subjects. A less pronounced yet increased uptake rate was also observed in patients with late-onset mild cognitive impairment (MCI). This increased uptake may prove to be a key mechanism defining age-related AD progression.
• The increased cellular amyloid uptake in AD and LMCI may lead to quicker disease progression, but early-onset MCI may result from increased production of toxic amyloid metabolites.

Why this matters

• Additional biomarkers for AD could greatly aid diagnosis and course prediction, as they are currently limited to PET scan analysis of amyloid plaque deposits and concentration of Aβ42 in cerebrospinal fluid (CSF).
• Amyloid deposits found by PET have a positive correlation with AD diagnosis. In contrast, CSF-Aβ42 and AD diagnosis or cognitive decline are negatively correlated. Normal cognition (NC) is associated with higher CSF beta-amyloid levels, but previous research has not explained why CSF-Aβ42 levels can be equivalent in patients with NC but high amyloid load and patients with AD and low amyloid load.

Study design

• The authors of this retrospective study used anonymized data obtained from the Alzheimer’s’s Disease Neuroimaging Initiative (ADNI). ADNI’s goal has been to test whether serial MRI scans, PET scans, biomarkers, and clinical/neuropsychological assessment can be combined to measure the progression of MCI and AD.
• Study subjects had either an AD diagnosis or NC and were divided into two groups: low amyloid load and high amyloid load. The fraction of patients with an AD diagnosis was calculated as a function of CSF-Aβ42.
• Calculations and statistical comparisons were performed using Microsoft Excel and custom-written C++ programs.

Key results

• The lowest levels of CSF-Aβ42 correlated with the highest percentage of AD-diagnosed patients, estimated to be 27% in subjects with low amyloid deposit density and 65% in those with high deposit density.
• The relationship between CSF-Aβ42 levels and amyloid load can be described using a simple mathematical model: Amyloid concentration in the interstitial cells is equal to the synthesis rate divided by the density of amyloid deposits plus the sum of the rate of amyloid removal through the CSF and the cellular amyloid uptake rate.
• AD and late-onset MCI patients had a significantly higher amyloid removal rate compared to NC subjects.
• Early-onset MCI patients had Aβ42 turnover similar to that of NC subjects, pointing to a different underlying mechanism such as enzymatic disbalance.

Limitations

• The model used to explain amyloid exchange between the interstitial space and the CSF is oversimplified; the actual process is more complex.
• Synthesis and uptake rates of Aβ42 vary throughout areas of the brain. The model assumes a homogeneous distribution within the interstitial compartment.

Study disclosures

• Research reported in this publication was not supported by any external funding. Data collection and sharing for this project were funded by ADNI.

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

An adult brain contains about 86 billion neurons and even more supercomputing power to closely monitor the entire human brain.

All those neurons have trillions of synapses – or connection points – that make up the circuitry the brain uses to control everything we do from reasoning to breathing to walking. And scientists with the Human Brain Project are trying to build new computing tools that can zoom in on every one of these synapses, peer inside cells, and zoom out to focus on entire regions of the brain at once.

Imaging the human brain at the cellular level would require several petabytes of data, researchers from the Human Brain Project report in Science. If you have an old smartphone or tablet with 32GB of storage, you’d need more than 31,000 of them to get a single petabyte of storage.

Using an electron microscope to image the entire brain would require more than one exabyte of data, the scientists point out. That’s more than a million petabytes.

Giacomo Indiveri, PhD, professor of neuroinformatics at the University of Zurich, Switzerland, says we need to fundamentally change the way we build computers. Delivering the keynote address at the Human Brain Project Summit in October, he warned we will use 20% of all the world’s electricity on computing by the year 2025.

To meet the computing challenges posed by the quest to map every bit of the human brain, researchers are working to produce the first two exascale supercomputers within the next 5 years. When they’re done, these machines will provide brain scientists with supercomputers powerful enough to explore the human brain in all its complexities.

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

An adult brain contains about 86 billion neurons and even more supercomputing power to closely monitor the entire human brain.

All those neurons have trillions of synapses – or connection points – that make up the circuitry the brain uses to control everything we do from reasoning to breathing to walking. And scientists with the Human Brain Project are trying to build new computing tools that can zoom in on every one of these synapses, peer inside cells, and zoom out to focus on entire regions of the brain at once.

Imaging the human brain at the cellular level would require several petabytes of data, researchers from the Human Brain Project report in Science. If you have an old smartphone or tablet with 32GB of storage, you’d need more than 31,000 of them to get a single petabyte of storage.

Using an electron microscope to image the entire brain would require more than one exabyte of data, the scientists point out. That’s more than a million petabytes.

Giacomo Indiveri, PhD, professor of neuroinformatics at the University of Zurich, Switzerland, says we need to fundamentally change the way we build computers. Delivering the keynote address at the Human Brain Project Summit in October, he warned we will use 20% of all the world’s electricity on computing by the year 2025.

To meet the computing challenges posed by the quest to map every bit of the human brain, researchers are working to produce the first two exascale supercomputers within the next 5 years. When they’re done, these machines will provide brain scientists with supercomputers powerful enough to explore the human brain in all its complexities.

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

An adult brain contains about 86 billion neurons and even more supercomputing power to closely monitor the entire human brain.

All those neurons have trillions of synapses – or connection points – that make up the circuitry the brain uses to control everything we do from reasoning to breathing to walking. And scientists with the Human Brain Project are trying to build new computing tools that can zoom in on every one of these synapses, peer inside cells, and zoom out to focus on entire regions of the brain at once.

Imaging the human brain at the cellular level would require several petabytes of data, researchers from the Human Brain Project report in Science. If you have an old smartphone or tablet with 32GB of storage, you’d need more than 31,000 of them to get a single petabyte of storage.

Using an electron microscope to image the entire brain would require more than one exabyte of data, the scientists point out. That’s more than a million petabytes.

Giacomo Indiveri, PhD, professor of neuroinformatics at the University of Zurich, Switzerland, says we need to fundamentally change the way we build computers. Delivering the keynote address at the Human Brain Project Summit in October, he warned we will use 20% of all the world’s electricity on computing by the year 2025.

To meet the computing challenges posed by the quest to map every bit of the human brain, researchers are working to produce the first two exascale supercomputers within the next 5 years. When they’re done, these machines will provide brain scientists with supercomputers powerful enough to explore the human brain in all its complexities.

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

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

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

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

The study was published online Jan. 13 in Science.
 

Unique dataset

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

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

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

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

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

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

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

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

An MS vaccine?

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

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

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

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

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

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

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

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

‘Compelling data’

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

The study was published online Jan. 13 in Science.
 

Unique dataset

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

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

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

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

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

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

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

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

An MS vaccine?

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

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

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

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

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

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

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

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

‘Compelling data’

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

The study was published online Jan. 13 in Science.
 

Unique dataset

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

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

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

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

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

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

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

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

An MS vaccine?

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

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

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

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

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

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

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

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

‘Compelling data’

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

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

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

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

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

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

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

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

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

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

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

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

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

Medicare intends to limit coverage of the controversial Alzheimer’s drug aducanumab (Aduhelm, Biogen) via a special program intended to help assess how well this exorbitantly expensive medication works, federal officials announced Jan. 11.

On Dec. 20, 2021, Biogen announced a plan to reduce the annual U.S. cost of the drug by 50% – from $56,000 to $28,200 – as Centers for Medicare & Medicaid Services officials were deciding on Medicare’s coverage policy for the medication.

In making its proposed coverage decision, the CMS announced it will pay for aducanumab, a monoclonal antibody, under its coverage-with-evidence-development (CED) mechanism. In making its decision, the CMS approached aducanumab as the first of a potential new class of monoclonal antibodies for the treatment of Alzheimer’s disease. Food and Drug Administration–approved drugs in this class would be covered for those with Medicare only if they are enrolled in qualifying clinical trials, the CMS said. The agency will accept public comments on this decision for 30 days.  

In a statement, CMS Administrator Chiquita Brooks-LaSure said the agency is “committed to providing the American public with a clear, trusted, evidence-based decision that is made only after a thorough analysis of public feedback on the benefits and risks of coverage for Medicare patients.”

As previously reported, the FDA approved aducanumab on June 7, 2021, via an accelerated approval process. The approval, which set off a firestorm of controversy that included resignations of three FDA Peripheral and Central Nervous System Drugs Advisory Committee panel members, was granted based on the medication’s ability to reduce beta-amyloid plaque.

Under the accelerated approval mechanism, Biogen still must deliver solid scientific proof that aducanumab has clinically significant disease-modifying effects. However, the final evidence won’t be in any time soon. In its approval letter, the FDA set a 2030 deadline for a final report on this research.

 

‘Unusual but appropriate’ step

The Medicare decision marks something of a shift in the agency’s approach to paying for medications. On a call with reporters, Tamara Syrek Jensen, JD, director of CMS’ Coverage and Analysis Group, admitted that the agency had taken an “unusual but appropriate” step in trying to set a national policy regarding payment for a drug.

On the same call, Lee Fleisher, MD, CMS’ chief medical officer, addressed the challenges presented by aducanumab, given the serious need for treatments for Alzheimer’s disease. “As a practicing physician, I cannot overemphasize the need to understand the risks and benefits of a given treatment in order to better inform patients and their families,” Dr. Fleisher said. “We do know based on some of the evidence that there may be potential promise with this treatment. That’s why it is critical for us to pursue additional scientific evidence.”

The coverage-with-evidence program will allow Medicare to aid in gathering data, while protecting patients, Dr. Fleisher noted.

“CMS is using its authority provided by Congress to determine if the drug is considered reasonable and necessary, meaning that the benefits of improvement of cognition outweigh the harms in the Medicare population,” Dr. Fleisher said.
 

Biogen disappointed

Cambridge, Mass.–based Biogen urged the CMS to reconsider its approach to payment for aducanumab. In a statement, the company said Medicare should cover “the class of amyloid-directed therapies with the populations studied in the respective clinical trials and guided by expert recommendations for appropriate use.

“We believe Alzheimer’s patients should have access consistent with other therapies with FDA accelerated approval,” Biogen said in the release.

In the company’s view, the CED approach will “significantly limit patient access to an FDA-approved treatment, especially for underserved patients as evidenced in other CED determinations.

“CEDs can take months to years to initiate, and hundreds of Alzheimer’s patients – the majority of whom are Medicare beneficiaries – are progressing each day from mild to moderate disease stages, where treatment may no longer be an option,” Biogen said.

Drug makers had been worried about CMS opting for CED even before the draft decision was unveiled.
 

Others weigh in

BIO, the trade group for biotechnology companies, urged the CMS to provide access to aducanumab without excess restrictions.

There already are concerns among drug makers about CMS efforts “to impose new coverage barriers – and, in particular, coverage with evidence development,” Crystal Kuntz, vice president of policy and research at BIO, and Andy Cosgrove, the organization’s senior director for policy and research, noted in a July 2021 comment about the aducanumab review.

Medicare should instead continue to provide access to medicines for indications that the FDA has approved, with additional flexibility for off-label indications of cancer drugs, they noted. “We believe this should continue to be the case, to ensure that vulnerable Medicare beneficiaries have necessary access to life-altering and lifesaving medications,” the BIO officials wrote.

However, the CMS also received many pleas from physicians asking the agency to limit use of aducanumab at least until there is evidence that it produces a significant clinical benefit.

In a press release, Howard Fillit, MD, cofounder and chief science officer of the Alzheimer’s Drug Discovery Foundation, applauded the decision, describing it as “the right call.

“This decision supports conducting additional clinical trials, which are needed to obtain further insights into the clinical efficacy and safety profile of this drug in real-world populations. This decision has implications for other drugs in this class in late-stage development. If these trials show more clear and robust clinical efficacy, then it is possible the FDA will give these amyloid monoclonal antibodies full approval, and Medicare would be likely to provide full payment,” he added.

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

Medicare intends to limit coverage of the controversial Alzheimer’s drug aducanumab (Aduhelm, Biogen) via a special program intended to help assess how well this exorbitantly expensive medication works, federal officials announced Jan. 11.

On Dec. 20, 2021, Biogen announced a plan to reduce the annual U.S. cost of the drug by 50% – from $56,000 to $28,200 – as Centers for Medicare & Medicaid Services officials were deciding on Medicare’s coverage policy for the medication.

In making its proposed coverage decision, the CMS announced it will pay for aducanumab, a monoclonal antibody, under its coverage-with-evidence-development (CED) mechanism. In making its decision, the CMS approached aducanumab as the first of a potential new class of monoclonal antibodies for the treatment of Alzheimer’s disease. Food and Drug Administration–approved drugs in this class would be covered for those with Medicare only if they are enrolled in qualifying clinical trials, the CMS said. The agency will accept public comments on this decision for 30 days.  

In a statement, CMS Administrator Chiquita Brooks-LaSure said the agency is “committed to providing the American public with a clear, trusted, evidence-based decision that is made only after a thorough analysis of public feedback on the benefits and risks of coverage for Medicare patients.”

As previously reported, the FDA approved aducanumab on June 7, 2021, via an accelerated approval process. The approval, which set off a firestorm of controversy that included resignations of three FDA Peripheral and Central Nervous System Drugs Advisory Committee panel members, was granted based on the medication’s ability to reduce beta-amyloid plaque.

Under the accelerated approval mechanism, Biogen still must deliver solid scientific proof that aducanumab has clinically significant disease-modifying effects. However, the final evidence won’t be in any time soon. In its approval letter, the FDA set a 2030 deadline for a final report on this research.

 

‘Unusual but appropriate’ step

The Medicare decision marks something of a shift in the agency’s approach to paying for medications. On a call with reporters, Tamara Syrek Jensen, JD, director of CMS’ Coverage and Analysis Group, admitted that the agency had taken an “unusual but appropriate” step in trying to set a national policy regarding payment for a drug.

On the same call, Lee Fleisher, MD, CMS’ chief medical officer, addressed the challenges presented by aducanumab, given the serious need for treatments for Alzheimer’s disease. “As a practicing physician, I cannot overemphasize the need to understand the risks and benefits of a given treatment in order to better inform patients and their families,” Dr. Fleisher said. “We do know based on some of the evidence that there may be potential promise with this treatment. That’s why it is critical for us to pursue additional scientific evidence.”

The coverage-with-evidence program will allow Medicare to aid in gathering data, while protecting patients, Dr. Fleisher noted.

“CMS is using its authority provided by Congress to determine if the drug is considered reasonable and necessary, meaning that the benefits of improvement of cognition outweigh the harms in the Medicare population,” Dr. Fleisher said.
 

Biogen disappointed

Cambridge, Mass.–based Biogen urged the CMS to reconsider its approach to payment for aducanumab. In a statement, the company said Medicare should cover “the class of amyloid-directed therapies with the populations studied in the respective clinical trials and guided by expert recommendations for appropriate use.

“We believe Alzheimer’s patients should have access consistent with other therapies with FDA accelerated approval,” Biogen said in the release.

In the company’s view, the CED approach will “significantly limit patient access to an FDA-approved treatment, especially for underserved patients as evidenced in other CED determinations.

“CEDs can take months to years to initiate, and hundreds of Alzheimer’s patients – the majority of whom are Medicare beneficiaries – are progressing each day from mild to moderate disease stages, where treatment may no longer be an option,” Biogen said.

Drug makers had been worried about CMS opting for CED even before the draft decision was unveiled.
 

Others weigh in

BIO, the trade group for biotechnology companies, urged the CMS to provide access to aducanumab without excess restrictions.

There already are concerns among drug makers about CMS efforts “to impose new coverage barriers – and, in particular, coverage with evidence development,” Crystal Kuntz, vice president of policy and research at BIO, and Andy Cosgrove, the organization’s senior director for policy and research, noted in a July 2021 comment about the aducanumab review.

Medicare should instead continue to provide access to medicines for indications that the FDA has approved, with additional flexibility for off-label indications of cancer drugs, they noted. “We believe this should continue to be the case, to ensure that vulnerable Medicare beneficiaries have necessary access to life-altering and lifesaving medications,” the BIO officials wrote.

However, the CMS also received many pleas from physicians asking the agency to limit use of aducanumab at least until there is evidence that it produces a significant clinical benefit.

In a press release, Howard Fillit, MD, cofounder and chief science officer of the Alzheimer’s Drug Discovery Foundation, applauded the decision, describing it as “the right call.

“This decision supports conducting additional clinical trials, which are needed to obtain further insights into the clinical efficacy and safety profile of this drug in real-world populations. This decision has implications for other drugs in this class in late-stage development. If these trials show more clear and robust clinical efficacy, then it is possible the FDA will give these amyloid monoclonal antibodies full approval, and Medicare would be likely to provide full payment,” he added.

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

Medicare intends to limit coverage of the controversial Alzheimer’s drug aducanumab (Aduhelm, Biogen) via a special program intended to help assess how well this exorbitantly expensive medication works, federal officials announced Jan. 11.

On Dec. 20, 2021, Biogen announced a plan to reduce the annual U.S. cost of the drug by 50% – from $56,000 to $28,200 – as Centers for Medicare & Medicaid Services officials were deciding on Medicare’s coverage policy for the medication.

In making its proposed coverage decision, the CMS announced it will pay for aducanumab, a monoclonal antibody, under its coverage-with-evidence-development (CED) mechanism. In making its decision, the CMS approached aducanumab as the first of a potential new class of monoclonal antibodies for the treatment of Alzheimer’s disease. Food and Drug Administration–approved drugs in this class would be covered for those with Medicare only if they are enrolled in qualifying clinical trials, the CMS said. The agency will accept public comments on this decision for 30 days.  

In a statement, CMS Administrator Chiquita Brooks-LaSure said the agency is “committed to providing the American public with a clear, trusted, evidence-based decision that is made only after a thorough analysis of public feedback on the benefits and risks of coverage for Medicare patients.”

As previously reported, the FDA approved aducanumab on June 7, 2021, via an accelerated approval process. The approval, which set off a firestorm of controversy that included resignations of three FDA Peripheral and Central Nervous System Drugs Advisory Committee panel members, was granted based on the medication’s ability to reduce beta-amyloid plaque.

Under the accelerated approval mechanism, Biogen still must deliver solid scientific proof that aducanumab has clinically significant disease-modifying effects. However, the final evidence won’t be in any time soon. In its approval letter, the FDA set a 2030 deadline for a final report on this research.

 

‘Unusual but appropriate’ step

The Medicare decision marks something of a shift in the agency’s approach to paying for medications. On a call with reporters, Tamara Syrek Jensen, JD, director of CMS’ Coverage and Analysis Group, admitted that the agency had taken an “unusual but appropriate” step in trying to set a national policy regarding payment for a drug.

On the same call, Lee Fleisher, MD, CMS’ chief medical officer, addressed the challenges presented by aducanumab, given the serious need for treatments for Alzheimer’s disease. “As a practicing physician, I cannot overemphasize the need to understand the risks and benefits of a given treatment in order to better inform patients and their families,” Dr. Fleisher said. “We do know based on some of the evidence that there may be potential promise with this treatment. That’s why it is critical for us to pursue additional scientific evidence.”

The coverage-with-evidence program will allow Medicare to aid in gathering data, while protecting patients, Dr. Fleisher noted.

“CMS is using its authority provided by Congress to determine if the drug is considered reasonable and necessary, meaning that the benefits of improvement of cognition outweigh the harms in the Medicare population,” Dr. Fleisher said.
 

Biogen disappointed

Cambridge, Mass.–based Biogen urged the CMS to reconsider its approach to payment for aducanumab. In a statement, the company said Medicare should cover “the class of amyloid-directed therapies with the populations studied in the respective clinical trials and guided by expert recommendations for appropriate use.

“We believe Alzheimer’s patients should have access consistent with other therapies with FDA accelerated approval,” Biogen said in the release.

In the company’s view, the CED approach will “significantly limit patient access to an FDA-approved treatment, especially for underserved patients as evidenced in other CED determinations.

“CEDs can take months to years to initiate, and hundreds of Alzheimer’s patients – the majority of whom are Medicare beneficiaries – are progressing each day from mild to moderate disease stages, where treatment may no longer be an option,” Biogen said.

Drug makers had been worried about CMS opting for CED even before the draft decision was unveiled.
 

Others weigh in

BIO, the trade group for biotechnology companies, urged the CMS to provide access to aducanumab without excess restrictions.

There already are concerns among drug makers about CMS efforts “to impose new coverage barriers – and, in particular, coverage with evidence development,” Crystal Kuntz, vice president of policy and research at BIO, and Andy Cosgrove, the organization’s senior director for policy and research, noted in a July 2021 comment about the aducanumab review.

Medicare should instead continue to provide access to medicines for indications that the FDA has approved, with additional flexibility for off-label indications of cancer drugs, they noted. “We believe this should continue to be the case, to ensure that vulnerable Medicare beneficiaries have necessary access to life-altering and lifesaving medications,” the BIO officials wrote.

However, the CMS also received many pleas from physicians asking the agency to limit use of aducanumab at least until there is evidence that it produces a significant clinical benefit.

In a press release, Howard Fillit, MD, cofounder and chief science officer of the Alzheimer’s Drug Discovery Foundation, applauded the decision, describing it as “the right call.

“This decision supports conducting additional clinical trials, which are needed to obtain further insights into the clinical efficacy and safety profile of this drug in real-world populations. This decision has implications for other drugs in this class in late-stage development. If these trials show more clear and robust clinical efficacy, then it is possible the FDA will give these amyloid monoclonal antibodies full approval, and Medicare would be likely to provide full payment,” he added.

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

A new, augmented autism-screening strategy boosted the number of boys diagnosed with the condition, especially Spanish speakers, a new study finds. The research was published in JAMA Pediatrics

The number of diagnoses in girls didn’t budge significantly, however, surprising researchers. Still, the findings suggest that “multistage screening and appropriate access to diagnostic services can really move the needle on the early detection of autism and reducing disparities in autism diagnosis and detection,” said lead author R. Christopher Sheldrick, PhD, a Boston University research associate professor of health law, policy, and management, in an interview.

While early intervention is considered crucial, U.S. research suggests that several groups of children – the poor, racial and ethnic minorities, and non-English speakers – are more likely to be diagnosed with autism spectrum disorder (ASD) later in life. “They have much lower access to appropriate services, both to get kids diagnosed and to get the kinds of interventions that can be helpful for families,” Dr. Sheldrick said. “Our study is about trying to close the gap around diagnosis, the first step.”

For the new study, the researchers implemented an intervention strategy in Massachusetts at three Early Intervention (EI) programs, which provide autism screening to children who are referred by pediatricians or parents. The researchers then tracked the programs, all in Boston, and nine comparison programs from the greater Boston area from 2012 to 2018.

Overall, 33,326 children were assessed, all aged 14-36 months. Those at the intervention programs were chosen because they had high levels of poverty. Children at those programs were more likely to be Black than those at the comparison programs (30.7% vs. 12.2%), to be Spanish speakers (28.9% vs. 12.5%), and to be in the lowest household income bracket (66.9% vs. 54.2%). In both groups, about 64% of the children were male.

The intervention strategy aimed to reduce the reliance on screening tests. Instead, the study authors write, “our protocol emphasizes ASD screening as a process that includes clinician and parent decision-making.”

As Dr. Sheldrick explained, parents and specialists observe children together “and then decide whether it’s worth taking the next step, which is a full diagnostic assessment with a licensed professional.” According to the study, either the parent(s) or the specialists could make the referral for a full, university-based assessment.

The goal was to help specialists use their professional judgment more, he said, and refer children who don’t show signs of ASD via a screening instrument but still spark concern, he said. “We’re really trying to create a system in which the screening tools support professional judgment, but don’t really replace it.”

After weighting, the researchers found that diagnoses of ASD were more common in the intervention sites vs. comparison sites (incidence rate ratio, 1.6; 95% confidence interval, 1.3-2.1, P < .001), accounting for an extra 8.1 diagnoses per 1,000 per quarter. Among Spanish-speaking families only, diagnoses grew even more in the intervention sites vs. comparison sites (IRR, 2.6; 95% CI, 1.6-4.3; P < .001), representing 15.4 additional diagnoses per 1,000 children per quarter.

There was also an increase in diagnoses among boys in the intervention sites vs. comparison sites (IRR, 1.8; 95% CI, 1.4-2.3; P < .001), accounting for 14.8 additional diagnoses per 1,000 children per quarter. However, there was no statistically significant increase in diagnosis among girls (IRR, 1.1; 95% CI, 0.6-1.7; P = .84).

The finding about girls surprised the researchers. “The program was highly effective for boys, but really didn’t have any effect for girls,” Dr. Sheldrick said. “Even though autism is considered to be more common in boys, there are questions about whether it’s underidentified in girls. These data would be consistent with that view. So there’s work to do to be able to recognize how a young girl with autism might present and how you might note that in a sensitive way and then respond appropriately.”

The overall message of the study is “that screening with appropriate supports can make a difference,” he said. However, he acknowledged that the extra cost of the program is unclear. “We did not systematically collect data on cost,” he said, noting that the funding for the study paid for both the intervention and the analysis.

For now, he said, researchers are following the children in the study to see if they were able to access treatment services. Some of the investigators are also taking part in a randomized study to evaluate an intervention in children with social communication disorders, he said.

In an accompanying commentary, three pediatric specialists noted that the study is the first to analyze ASD screening in EI. “This study supports the notion of ASD screening as an iterative, multistep process that optimally involves multiple community stakeholders with varying levels of developmental expertise who have done the work to build trust with families,” write pediatrician Kate E. Wallis, MD, MPH, of Children’s Hospital of Philadelphia, graduate student Monica M. Abdul-Chani, MA, of the University of Alabama at Birmingham, and pediatrician Katharine E. Zuckerman, MD, MPH, of Oregon Health & Science University, Portland.

In regard to disparities in diagnosis in Spanish-speaking families, the commentary authors write that “locating a greater proportion of the ASD identification process in EI, which families are already familiar with, has no to low cost for families, and is likely geographically closer for families, can reduce structural barriers to identification.”

They add that the emphasis within Latino families on the “building of warm and caring relationships with others based on mutual trust and respect” can allow EI specialists to “develop relationships with families who may be afraid or skeptical of sharing what could be considered personal details of their family life.”

The commentary authors also note that “it remains all too common for language delays to be attributed to child exposure to two languages, even though data do not support this attribution. Bilingual EI staff can help to demystify this perpetual myth and better estimate a child’s communication and social skills in both languages as they communicate and play.”

The study was funded by grants from the Health Resources Services Administration and the National Institute of Mental Health. Dr. Sheldrick is cocreator of the Parent’s Observations of Social Interaction (POSI), which is one of the two first-stage screeners used in this study. He conducts research related to this instrument but receives no royalties. He reports grants from the National Institutes of Health. Coauthor Alice S. Carter, PhD, is cocreator of the POSI but receives no royalties. She is also cocreator of the Brief Infant Toddler Social Emotional Assessment, which is one of the two first-stage screeners used in this study, and receives royalties on the sale of the instrument. She reports grants from the National Institutes of Health and the Health Resources and Services Administration. Study coauthor Thomas I. Mackie, PhD, MPH, reports grants from the National Institute of Mental Health. Study coauthor Noah Hoch reports grants from the Health Resources Services Administration and the National Institute of Mental Health. No other disclosures from study authors are reported. Dr. Zuckerman reported grants from the National Institutes of Health and National Institute of Mental Health and consulting fees from H2N related to autism. The other commentary authors report no disclosures.

A new, augmented autism-screening strategy boosted the number of boys diagnosed with the condition, especially Spanish speakers, a new study finds. The research was published in JAMA Pediatrics

The number of diagnoses in girls didn’t budge significantly, however, surprising researchers. Still, the findings suggest that “multistage screening and appropriate access to diagnostic services can really move the needle on the early detection of autism and reducing disparities in autism diagnosis and detection,” said lead author R. Christopher Sheldrick, PhD, a Boston University research associate professor of health law, policy, and management, in an interview.

While early intervention is considered crucial, U.S. research suggests that several groups of children – the poor, racial and ethnic minorities, and non-English speakers – are more likely to be diagnosed with autism spectrum disorder (ASD) later in life. “They have much lower access to appropriate services, both to get kids diagnosed and to get the kinds of interventions that can be helpful for families,” Dr. Sheldrick said. “Our study is about trying to close the gap around diagnosis, the first step.”

For the new study, the researchers implemented an intervention strategy in Massachusetts at three Early Intervention (EI) programs, which provide autism screening to children who are referred by pediatricians or parents. The researchers then tracked the programs, all in Boston, and nine comparison programs from the greater Boston area from 2012 to 2018.

Overall, 33,326 children were assessed, all aged 14-36 months. Those at the intervention programs were chosen because they had high levels of poverty. Children at those programs were more likely to be Black than those at the comparison programs (30.7% vs. 12.2%), to be Spanish speakers (28.9% vs. 12.5%), and to be in the lowest household income bracket (66.9% vs. 54.2%). In both groups, about 64% of the children were male.

The intervention strategy aimed to reduce the reliance on screening tests. Instead, the study authors write, “our protocol emphasizes ASD screening as a process that includes clinician and parent decision-making.”

As Dr. Sheldrick explained, parents and specialists observe children together “and then decide whether it’s worth taking the next step, which is a full diagnostic assessment with a licensed professional.” According to the study, either the parent(s) or the specialists could make the referral for a full, university-based assessment.

The goal was to help specialists use their professional judgment more, he said, and refer children who don’t show signs of ASD via a screening instrument but still spark concern, he said. “We’re really trying to create a system in which the screening tools support professional judgment, but don’t really replace it.”

After weighting, the researchers found that diagnoses of ASD were more common in the intervention sites vs. comparison sites (incidence rate ratio, 1.6; 95% confidence interval, 1.3-2.1, P < .001), accounting for an extra 8.1 diagnoses per 1,000 per quarter. Among Spanish-speaking families only, diagnoses grew even more in the intervention sites vs. comparison sites (IRR, 2.6; 95% CI, 1.6-4.3; P < .001), representing 15.4 additional diagnoses per 1,000 children per quarter.

There was also an increase in diagnoses among boys in the intervention sites vs. comparison sites (IRR, 1.8; 95% CI, 1.4-2.3; P < .001), accounting for 14.8 additional diagnoses per 1,000 children per quarter. However, there was no statistically significant increase in diagnosis among girls (IRR, 1.1; 95% CI, 0.6-1.7; P = .84).

The finding about girls surprised the researchers. “The program was highly effective for boys, but really didn’t have any effect for girls,” Dr. Sheldrick said. “Even though autism is considered to be more common in boys, there are questions about whether it’s underidentified in girls. These data would be consistent with that view. So there’s work to do to be able to recognize how a young girl with autism might present and how you might note that in a sensitive way and then respond appropriately.”

The overall message of the study is “that screening with appropriate supports can make a difference,” he said. However, he acknowledged that the extra cost of the program is unclear. “We did not systematically collect data on cost,” he said, noting that the funding for the study paid for both the intervention and the analysis.

For now, he said, researchers are following the children in the study to see if they were able to access treatment services. Some of the investigators are also taking part in a randomized study to evaluate an intervention in children with social communication disorders, he said.

In an accompanying commentary, three pediatric specialists noted that the study is the first to analyze ASD screening in EI. “This study supports the notion of ASD screening as an iterative, multistep process that optimally involves multiple community stakeholders with varying levels of developmental expertise who have done the work to build trust with families,” write pediatrician Kate E. Wallis, MD, MPH, of Children’s Hospital of Philadelphia, graduate student Monica M. Abdul-Chani, MA, of the University of Alabama at Birmingham, and pediatrician Katharine E. Zuckerman, MD, MPH, of Oregon Health & Science University, Portland.

In regard to disparities in diagnosis in Spanish-speaking families, the commentary authors write that “locating a greater proportion of the ASD identification process in EI, which families are already familiar with, has no to low cost for families, and is likely geographically closer for families, can reduce structural barriers to identification.”

They add that the emphasis within Latino families on the “building of warm and caring relationships with others based on mutual trust and respect” can allow EI specialists to “develop relationships with families who may be afraid or skeptical of sharing what could be considered personal details of their family life.”

The commentary authors also note that “it remains all too common for language delays to be attributed to child exposure to two languages, even though data do not support this attribution. Bilingual EI staff can help to demystify this perpetual myth and better estimate a child’s communication and social skills in both languages as they communicate and play.”

The study was funded by grants from the Health Resources Services Administration and the National Institute of Mental Health. Dr. Sheldrick is cocreator of the Parent’s Observations of Social Interaction (POSI), which is one of the two first-stage screeners used in this study. He conducts research related to this instrument but receives no royalties. He reports grants from the National Institutes of Health. Coauthor Alice S. Carter, PhD, is cocreator of the POSI but receives no royalties. She is also cocreator of the Brief Infant Toddler Social Emotional Assessment, which is one of the two first-stage screeners used in this study, and receives royalties on the sale of the instrument. She reports grants from the National Institutes of Health and the Health Resources and Services Administration. Study coauthor Thomas I. Mackie, PhD, MPH, reports grants from the National Institute of Mental Health. Study coauthor Noah Hoch reports grants from the Health Resources Services Administration and the National Institute of Mental Health. No other disclosures from study authors are reported. Dr. Zuckerman reported grants from the National Institutes of Health and National Institute of Mental Health and consulting fees from H2N related to autism. The other commentary authors report no disclosures.

A new, augmented autism-screening strategy boosted the number of boys diagnosed with the condition, especially Spanish speakers, a new study finds. The research was published in JAMA Pediatrics

The number of diagnoses in girls didn’t budge significantly, however, surprising researchers. Still, the findings suggest that “multistage screening and appropriate access to diagnostic services can really move the needle on the early detection of autism and reducing disparities in autism diagnosis and detection,” said lead author R. Christopher Sheldrick, PhD, a Boston University research associate professor of health law, policy, and management, in an interview.

While early intervention is considered crucial, U.S. research suggests that several groups of children – the poor, racial and ethnic minorities, and non-English speakers – are more likely to be diagnosed with autism spectrum disorder (ASD) later in life. “They have much lower access to appropriate services, both to get kids diagnosed and to get the kinds of interventions that can be helpful for families,” Dr. Sheldrick said. “Our study is about trying to close the gap around diagnosis, the first step.”

For the new study, the researchers implemented an intervention strategy in Massachusetts at three Early Intervention (EI) programs, which provide autism screening to children who are referred by pediatricians or parents. The researchers then tracked the programs, all in Boston, and nine comparison programs from the greater Boston area from 2012 to 2018.

Overall, 33,326 children were assessed, all aged 14-36 months. Those at the intervention programs were chosen because they had high levels of poverty. Children at those programs were more likely to be Black than those at the comparison programs (30.7% vs. 12.2%), to be Spanish speakers (28.9% vs. 12.5%), and to be in the lowest household income bracket (66.9% vs. 54.2%). In both groups, about 64% of the children were male.

The intervention strategy aimed to reduce the reliance on screening tests. Instead, the study authors write, “our protocol emphasizes ASD screening as a process that includes clinician and parent decision-making.”

As Dr. Sheldrick explained, parents and specialists observe children together “and then decide whether it’s worth taking the next step, which is a full diagnostic assessment with a licensed professional.” According to the study, either the parent(s) or the specialists could make the referral for a full, university-based assessment.

The goal was to help specialists use their professional judgment more, he said, and refer children who don’t show signs of ASD via a screening instrument but still spark concern, he said. “We’re really trying to create a system in which the screening tools support professional judgment, but don’t really replace it.”

After weighting, the researchers found that diagnoses of ASD were more common in the intervention sites vs. comparison sites (incidence rate ratio, 1.6; 95% confidence interval, 1.3-2.1, P < .001), accounting for an extra 8.1 diagnoses per 1,000 per quarter. Among Spanish-speaking families only, diagnoses grew even more in the intervention sites vs. comparison sites (IRR, 2.6; 95% CI, 1.6-4.3; P < .001), representing 15.4 additional diagnoses per 1,000 children per quarter.

There was also an increase in diagnoses among boys in the intervention sites vs. comparison sites (IRR, 1.8; 95% CI, 1.4-2.3; P < .001), accounting for 14.8 additional diagnoses per 1,000 children per quarter. However, there was no statistically significant increase in diagnosis among girls (IRR, 1.1; 95% CI, 0.6-1.7; P = .84).

The finding about girls surprised the researchers. “The program was highly effective for boys, but really didn’t have any effect for girls,” Dr. Sheldrick said. “Even though autism is considered to be more common in boys, there are questions about whether it’s underidentified in girls. These data would be consistent with that view. So there’s work to do to be able to recognize how a young girl with autism might present and how you might note that in a sensitive way and then respond appropriately.”

The overall message of the study is “that screening with appropriate supports can make a difference,” he said. However, he acknowledged that the extra cost of the program is unclear. “We did not systematically collect data on cost,” he said, noting that the funding for the study paid for both the intervention and the analysis.

For now, he said, researchers are following the children in the study to see if they were able to access treatment services. Some of the investigators are also taking part in a randomized study to evaluate an intervention in children with social communication disorders, he said.

In an accompanying commentary, three pediatric specialists noted that the study is the first to analyze ASD screening in EI. “This study supports the notion of ASD screening as an iterative, multistep process that optimally involves multiple community stakeholders with varying levels of developmental expertise who have done the work to build trust with families,” write pediatrician Kate E. Wallis, MD, MPH, of Children’s Hospital of Philadelphia, graduate student Monica M. Abdul-Chani, MA, of the University of Alabama at Birmingham, and pediatrician Katharine E. Zuckerman, MD, MPH, of Oregon Health & Science University, Portland.

In regard to disparities in diagnosis in Spanish-speaking families, the commentary authors write that “locating a greater proportion of the ASD identification process in EI, which families are already familiar with, has no to low cost for families, and is likely geographically closer for families, can reduce structural barriers to identification.”

They add that the emphasis within Latino families on the “building of warm and caring relationships with others based on mutual trust and respect” can allow EI specialists to “develop relationships with families who may be afraid or skeptical of sharing what could be considered personal details of their family life.”

The commentary authors also note that “it remains all too common for language delays to be attributed to child exposure to two languages, even though data do not support this attribution. Bilingual EI staff can help to demystify this perpetual myth and better estimate a child’s communication and social skills in both languages as they communicate and play.”

The study was funded by grants from the Health Resources Services Administration and the National Institute of Mental Health. Dr. Sheldrick is cocreator of the Parent’s Observations of Social Interaction (POSI), which is one of the two first-stage screeners used in this study. He conducts research related to this instrument but receives no royalties. He reports grants from the National Institutes of Health. Coauthor Alice S. Carter, PhD, is cocreator of the POSI but receives no royalties. She is also cocreator of the Brief Infant Toddler Social Emotional Assessment, which is one of the two first-stage screeners used in this study, and receives royalties on the sale of the instrument. She reports grants from the National Institutes of Health and the Health Resources and Services Administration. Study coauthor Thomas I. Mackie, PhD, MPH, reports grants from the National Institute of Mental Health. Study coauthor Noah Hoch reports grants from the Health Resources Services Administration and the National Institute of Mental Health. No other disclosures from study authors are reported. Dr. Zuckerman reported grants from the National Institutes of Health and National Institute of Mental Health and consulting fees from H2N related to autism. The other commentary authors report no disclosures.

The number of individuals older than 40 with dementia will nearly triple worldwide and double in the United States by 2050 unless steps are taken to address risk factors, new research suggests.

Results from a study of 195 countries and territories estimates that by 2050, 153 million people are expected to have dementia worldwide – up from 57 million in 2019. In the United States, the number is expected to increase 100%, from an estimated 5.3 million in 2019 to 10.5 million in 2050.

The increase is largely driven by population growth and population aging, but researchers noted that expanding access to education and addressing risk factors such as obesity, high blood sugar, and smoking could blunt the rise in cases.

The study predicts increases in dementia in every country included in the analysis. The sharpest rise is expected in north Africa and the Middle East (367%) and sub-Saharan Africa (357%). The smallest increases will be in high-income countries in Asia Pacific (53%) and western Europe (74%).

Although the United States had the 37th lowest percentage increase across all countries considered, “this expected increase is still large and requires attention from policy and decision-makers,” said coinvestigator Emma Nichols, MPH, a researcher with the Institute for Health Metrics and Evaluation at the University of Washington, Seattle.

The findings were published online Jan. 6, 2022, in The Lancet Public Health (doi: 10.1016/S2468-2667[21]00249-8).
 

Dementia prevalence

For the study, researchers used country-specific estimates of dementia prevalence from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 study to project dementia prevalence globally, by world region, and at the country level.

They also used information on projected trends in four important dementia risk factors (high body mass index, high fasting plasma glucose, smoking, and education) to estimate how changes in these risk factors might impact dementia prevalence between 2019 and 2050.

Despite large increases in the projected number of people living with dementia, age-standardized both-sex prevalence remained stable between 2019 and 2050, with a global percentage change of 0.1% (95% uncertainty interval, –7.5 to 10.8).

Dementia prevalence was higher in women than in men and increased with age, doubling about every 5 years until 85 years of age in both 2019 and 2050 (female-to-male ratio, 1.67; 95% UI, 1.52-1.85).

Projected increases in cases could largely be attributed to population growth and population aging, although their relative importance varied by world region. Population growth contributed most to the increases in sub-Saharan Africa and population aging contributed most to the increases in east Asia.

The countries with the highest expected percentage change in total number of dementia cases between 2019 and 2050 were: Qatar (1,926%), United Arab Emirates (1,795%), Bahrain (1,084%), Oman (943%), Saudi Arabia (898%), Kuwait (850%), Iraq (559%), Maldives (554%), Jordan (522%), and Equatorial Guinea (498%).

The countries with the lowest expected percentage change in total number of dementia cases between 2019 and 2050 were Japan (27%), Bulgaria (37%), Serbia (38%), Lithuania (44%), Greece (45%), Latvia (47%), Croatia (55%), Ukraine (55%), Italy (56%), and Finland (58%).
 

Modifiable risk factors

Researchers also calculated how changes in risk factors might affect dementia prevalence. They found that improvements in global education access would reduce dementia prevalence by an estimated 6.2 million cases worldwide by 2050. However, that decrease would be offset by expected increases in obesity, high blood sugar, and smoking, which investigators estimate will result in an additional 6.8 million dementia cases.

The projections are based on expected trends in population aging, population growth, and risk factor trajectories, but “projections could change if effective interventions for modifiable risk factors are developed and deployed,” Ms. Nichols said.

In 2020, the Lancet Commission on Dementia Prevention, Intervention, and Care issued an update of its 2017 report, identifying 12 modifiable risk factors that could delay or prevent 40% of dementia cases. The risk factors were low education, hypertension, hearing impairment, smoking, midlife obesity, depression, physical inactivity, diabetes, social isolation, excessive alcohol consumption, head injury, and air pollution.

“Countries, including the U.S., should look to develop effective interventions for modifiable risk factors, but also should invest in the resources needed to support those with dementia and their caregivers,” Ms. Nichols said. She added that additional support for research and resources to develop therapeutic interventions is also warranted.
 

Oversimplifying mechanisms?

In an accompanying commentary, Michaël Schwarzinger, MD, and Carole Dufouil, PhD, of Bordeaux (France) University Hospital, noted that the authors’ efforts to build on GBD 2019 oversimplify the underlying mechanisms that cause dementia. The authors “provide somehow apocalyptic projections that do not factor in advisable changes in lifestyle over the lifetime,” they wrote.

“There is a considerable and urgent need to reinforce a public health approach towards dementia to better inform the people and decision-makers about the appropriate means to delay or avoid these dire projections,” the editorialists added.

The study was funded by the Bill and Melinda Gates Foundation and Gates Ventures. Ms. Nichols and the editorialists disclosed no relevant financial relationships.

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

The number of individuals older than 40 with dementia will nearly triple worldwide and double in the United States by 2050 unless steps are taken to address risk factors, new research suggests.

Results from a study of 195 countries and territories estimates that by 2050, 153 million people are expected to have dementia worldwide – up from 57 million in 2019. In the United States, the number is expected to increase 100%, from an estimated 5.3 million in 2019 to 10.5 million in 2050.

The increase is largely driven by population growth and population aging, but researchers noted that expanding access to education and addressing risk factors such as obesity, high blood sugar, and smoking could blunt the rise in cases.

The study predicts increases in dementia in every country included in the analysis. The sharpest rise is expected in north Africa and the Middle East (367%) and sub-Saharan Africa (357%). The smallest increases will be in high-income countries in Asia Pacific (53%) and western Europe (74%).

Although the United States had the 37th lowest percentage increase across all countries considered, “this expected increase is still large and requires attention from policy and decision-makers,” said coinvestigator Emma Nichols, MPH, a researcher with the Institute for Health Metrics and Evaluation at the University of Washington, Seattle.

The findings were published online Jan. 6, 2022, in The Lancet Public Health (doi: 10.1016/S2468-2667[21]00249-8).
 

Dementia prevalence

For the study, researchers used country-specific estimates of dementia prevalence from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 study to project dementia prevalence globally, by world region, and at the country level.

They also used information on projected trends in four important dementia risk factors (high body mass index, high fasting plasma glucose, smoking, and education) to estimate how changes in these risk factors might impact dementia prevalence between 2019 and 2050.

Despite large increases in the projected number of people living with dementia, age-standardized both-sex prevalence remained stable between 2019 and 2050, with a global percentage change of 0.1% (95% uncertainty interval, –7.5 to 10.8).

Dementia prevalence was higher in women than in men and increased with age, doubling about every 5 years until 85 years of age in both 2019 and 2050 (female-to-male ratio, 1.67; 95% UI, 1.52-1.85).

Projected increases in cases could largely be attributed to population growth and population aging, although their relative importance varied by world region. Population growth contributed most to the increases in sub-Saharan Africa and population aging contributed most to the increases in east Asia.

The countries with the highest expected percentage change in total number of dementia cases between 2019 and 2050 were: Qatar (1,926%), United Arab Emirates (1,795%), Bahrain (1,084%), Oman (943%), Saudi Arabia (898%), Kuwait (850%), Iraq (559%), Maldives (554%), Jordan (522%), and Equatorial Guinea (498%).

The countries with the lowest expected percentage change in total number of dementia cases between 2019 and 2050 were Japan (27%), Bulgaria (37%), Serbia (38%), Lithuania (44%), Greece (45%), Latvia (47%), Croatia (55%), Ukraine (55%), Italy (56%), and Finland (58%).
 

Modifiable risk factors

Researchers also calculated how changes in risk factors might affect dementia prevalence. They found that improvements in global education access would reduce dementia prevalence by an estimated 6.2 million cases worldwide by 2050. However, that decrease would be offset by expected increases in obesity, high blood sugar, and smoking, which investigators estimate will result in an additional 6.8 million dementia cases.

The projections are based on expected trends in population aging, population growth, and risk factor trajectories, but “projections could change if effective interventions for modifiable risk factors are developed and deployed,” Ms. Nichols said.

In 2020, the Lancet Commission on Dementia Prevention, Intervention, and Care issued an update of its 2017 report, identifying 12 modifiable risk factors that could delay or prevent 40% of dementia cases. The risk factors were low education, hypertension, hearing impairment, smoking, midlife obesity, depression, physical inactivity, diabetes, social isolation, excessive alcohol consumption, head injury, and air pollution.

“Countries, including the U.S., should look to develop effective interventions for modifiable risk factors, but also should invest in the resources needed to support those with dementia and their caregivers,” Ms. Nichols said. She added that additional support for research and resources to develop therapeutic interventions is also warranted.
 

Oversimplifying mechanisms?

In an accompanying commentary, Michaël Schwarzinger, MD, and Carole Dufouil, PhD, of Bordeaux (France) University Hospital, noted that the authors’ efforts to build on GBD 2019 oversimplify the underlying mechanisms that cause dementia. The authors “provide somehow apocalyptic projections that do not factor in advisable changes in lifestyle over the lifetime,” they wrote.

“There is a considerable and urgent need to reinforce a public health approach towards dementia to better inform the people and decision-makers about the appropriate means to delay or avoid these dire projections,” the editorialists added.

The study was funded by the Bill and Melinda Gates Foundation and Gates Ventures. Ms. Nichols and the editorialists disclosed no relevant financial relationships.

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

The number of individuals older than 40 with dementia will nearly triple worldwide and double in the United States by 2050 unless steps are taken to address risk factors, new research suggests.

Results from a study of 195 countries and territories estimates that by 2050, 153 million people are expected to have dementia worldwide – up from 57 million in 2019. In the United States, the number is expected to increase 100%, from an estimated 5.3 million in 2019 to 10.5 million in 2050.

The increase is largely driven by population growth and population aging, but researchers noted that expanding access to education and addressing risk factors such as obesity, high blood sugar, and smoking could blunt the rise in cases.

The study predicts increases in dementia in every country included in the analysis. The sharpest rise is expected in north Africa and the Middle East (367%) and sub-Saharan Africa (357%). The smallest increases will be in high-income countries in Asia Pacific (53%) and western Europe (74%).

Although the United States had the 37th lowest percentage increase across all countries considered, “this expected increase is still large and requires attention from policy and decision-makers,” said coinvestigator Emma Nichols, MPH, a researcher with the Institute for Health Metrics and Evaluation at the University of Washington, Seattle.

The findings were published online Jan. 6, 2022, in The Lancet Public Health (doi: 10.1016/S2468-2667[21]00249-8).
 

Dementia prevalence

For the study, researchers used country-specific estimates of dementia prevalence from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 study to project dementia prevalence globally, by world region, and at the country level.

They also used information on projected trends in four important dementia risk factors (high body mass index, high fasting plasma glucose, smoking, and education) to estimate how changes in these risk factors might impact dementia prevalence between 2019 and 2050.

Despite large increases in the projected number of people living with dementia, age-standardized both-sex prevalence remained stable between 2019 and 2050, with a global percentage change of 0.1% (95% uncertainty interval, –7.5 to 10.8).

Dementia prevalence was higher in women than in men and increased with age, doubling about every 5 years until 85 years of age in both 2019 and 2050 (female-to-male ratio, 1.67; 95% UI, 1.52-1.85).

Projected increases in cases could largely be attributed to population growth and population aging, although their relative importance varied by world region. Population growth contributed most to the increases in sub-Saharan Africa and population aging contributed most to the increases in east Asia.

The countries with the highest expected percentage change in total number of dementia cases between 2019 and 2050 were: Qatar (1,926%), United Arab Emirates (1,795%), Bahrain (1,084%), Oman (943%), Saudi Arabia (898%), Kuwait (850%), Iraq (559%), Maldives (554%), Jordan (522%), and Equatorial Guinea (498%).

The countries with the lowest expected percentage change in total number of dementia cases between 2019 and 2050 were Japan (27%), Bulgaria (37%), Serbia (38%), Lithuania (44%), Greece (45%), Latvia (47%), Croatia (55%), Ukraine (55%), Italy (56%), and Finland (58%).
 

Modifiable risk factors

Researchers also calculated how changes in risk factors might affect dementia prevalence. They found that improvements in global education access would reduce dementia prevalence by an estimated 6.2 million cases worldwide by 2050. However, that decrease would be offset by expected increases in obesity, high blood sugar, and smoking, which investigators estimate will result in an additional 6.8 million dementia cases.

The projections are based on expected trends in population aging, population growth, and risk factor trajectories, but “projections could change if effective interventions for modifiable risk factors are developed and deployed,” Ms. Nichols said.

In 2020, the Lancet Commission on Dementia Prevention, Intervention, and Care issued an update of its 2017 report, identifying 12 modifiable risk factors that could delay or prevent 40% of dementia cases. The risk factors were low education, hypertension, hearing impairment, smoking, midlife obesity, depression, physical inactivity, diabetes, social isolation, excessive alcohol consumption, head injury, and air pollution.

“Countries, including the U.S., should look to develop effective interventions for modifiable risk factors, but also should invest in the resources needed to support those with dementia and their caregivers,” Ms. Nichols said. She added that additional support for research and resources to develop therapeutic interventions is also warranted.
 

Oversimplifying mechanisms?

In an accompanying commentary, Michaël Schwarzinger, MD, and Carole Dufouil, PhD, of Bordeaux (France) University Hospital, noted that the authors’ efforts to build on GBD 2019 oversimplify the underlying mechanisms that cause dementia. The authors “provide somehow apocalyptic projections that do not factor in advisable changes in lifestyle over the lifetime,” they wrote.

“There is a considerable and urgent need to reinforce a public health approach towards dementia to better inform the people and decision-makers about the appropriate means to delay or avoid these dire projections,” the editorialists added.

The study was funded by the Bill and Melinda Gates Foundation and Gates Ventures. Ms. Nichols and the editorialists disclosed no relevant financial relationships.

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

Inpatient and outpatient treatments of transient ischemic attack (TIA) or minor ischemic stroke (mIS) yield comparable safety outcomes, new research suggests. In a meta-analysis of more than 200,000 patients with TIA or mIS, risk for subsequent stroke within 90 days was 2.1% for those treated in a TIA clinic versus 2.8% for patients treated in inpatient settings, which was not significantly different. The risk for patients treated in an emergency department was higher, at 3.5%.

“The message is that if you do the correct risk stratification and then triage patients based on their risk profile, you can safely discharge and have a timely follow-up for the patients who have low risk for a subsequent event,” said coinvestigator Ramin Zand, MD, vascular neurologist and stroke attending physician at Geisinger Health System, Danville, Pennsylvania.

The findings were published online Jan. 5 in JAMA Network Open.
 

Higher risk in EDs

There is currently no consensus on the care protocol for patients with TIA or mIS, and the rate at which these patients are hospitalized varies by region, hospital, and practitioner, the investigators noted.

Previous studies have indicated that outpatient management of certain individuals with TIA can be safe and cost-effective.

The current researchers searched for retrospective and prospective studies of adult patients that provided information about ischemic stroke after TIA or mIS. Studies that used time- and tissue-based definitions of TIA were included, as well as studies that used various definitions of mIS.

The investigators examined care provided at TIA clinics, inpatient settings (such as medical-surgical units, stroke units, or observation units), EDs, and unspecified settings. Their main aim was to compare outcomes between TIA clinics and inpatient settings.

In all, 226,683 patients (recruited between 1981 and 2018) from 71 studies were included in the meta-analysis. The studies examined 101 cohorts, 24 of which were studied prospectively. Among the 5,636 patients who received care in TIA clinics, the mean age was 65.7 years, and 50.8% of this group were men. Among the 130,139 inpatients, the mean age was 78.3 years, and 61.6% of the group were women.

Results showed no significant difference in risk for subsequent stroke between patients treated in the inpatient and outpatient settings.

Among patients treated in a TIA clinic, risk for subsequent stroke following a TIA or mIS was 0.3% within 2 days, 1.0% within 7 days, 1.3% within 30 days, and 2.1% within 90 days. Among those treated as inpatients, risk for subsequent stroke was 0.5% within 2 days, 1.2% within 7 days, 1.6% within 30 days, and 2.8% within 90 days.

Risk for subsequent stroke was higher among patients treated in the ED and in unspecified settings. At the EDs, the risk was 1.9% within 2 days, 3.4% within 7 days, 3.5% within 30 days, and 3.5% within 90 days. Among those treated in unspecified settings, the risk was 2.2% within 2 days, 3.4% within 7 days, 4.2% within 30 days, and 6.0% within 90 days.

Patients treated in the ED also had a significantly higher risk for subsequent stroke at 2 and 7 days, compared with those treated in inpatient settings and a significantly higher risk for subsequent stroke at 2, 7, and 90 days, compared with those treated in TIA clinics.
 

‘Most comprehensive look’

“This is the most comprehensive look at all the studies to try and answer this research question,” said Dr. Zand. The results were similar to what was expected, he added.

The infrastructure and resources differed among the sites at which the various studies were conducted, and the investigators adjusted for these differences as much as possible, Dr. Zand noted. A certain amount of selection bias may remain, but it does not affect the overall conclusion, he added.

“Timely outpatient care among low-risk TIA patients is both feasible and safe,” he said.

Dr. Zand noted that the findings have implications not only for patient management but also for the management of the health system. “It’s not feasible nor desirable to admit all the TIA patients, especially with the lessons that we learned from COVID, the burden on the health systems, and the fact that many hospitals are operating at full capacity right now,” he said.

The recommendation is to hospitalize high-risk patients and provide outpatient evaluation and workup to low-risk patients, he added. “This is exactly what we saw in this study,” Dr. Zand said.
 

Selection bias?

Commenting on the research, Louis R. Caplan, MD, professor of neurology at Harvard Medical School, Boston, noted that evaluation of patients with TIA or mIS “can be done very well as an outpatient” if clinicians have experienced personnel, the outpatient facilities to do the studies necessary, and criteria in place for deciding who to admit or not admit.

However, the decision on whether to choose an inpatient or outpatient approach for a particular patient is complicated, said Dr. Caplan, who was not involved with the research.

Clinicians must consider factors such as whether the patient is mobile, has a car, or has a significant other. The patient’s symptoms and past illnesses also influence the decision, he added.

Dr. Caplan noted that in the meta-analysis, far fewer patients were seen in the TIA clinics than were seen in the inpatient setting. In addition, none of the studies used uniform criteria to determine which patients should undergo workup as outpatients and which as inpatients. “There was a lot of selection bias that may have had nothing to do with how sick the person was,” Dr. Caplan said.

In addition, few hospitals in the United States have an outpatient TIA clinic, he noted. Most of the studies of TIA clinics that the researchers examined were conducted in Europe. “It’s easier to do [that] in Europe because of their socialized medicine,” said Dr. Caplan.

But TIA clinics should be more widespread in the U.S., he added. “Insurance companies should be willing to pay for comparable facilities, inpatient and outpatient,” he said.

The study was conducted without external funding. Dr. Zand reported no relevant financial relationships. Dr. Caplan was an investigator for TIAregistry.org, which analyzed the outcomes of treatment in TIA clinics in Europe.

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

Inpatient and outpatient treatments of transient ischemic attack (TIA) or minor ischemic stroke (mIS) yield comparable safety outcomes, new research suggests. In a meta-analysis of more than 200,000 patients with TIA or mIS, risk for subsequent stroke within 90 days was 2.1% for those treated in a TIA clinic versus 2.8% for patients treated in inpatient settings, which was not significantly different. The risk for patients treated in an emergency department was higher, at 3.5%.

“The message is that if you do the correct risk stratification and then triage patients based on their risk profile, you can safely discharge and have a timely follow-up for the patients who have low risk for a subsequent event,” said coinvestigator Ramin Zand, MD, vascular neurologist and stroke attending physician at Geisinger Health System, Danville, Pennsylvania.

The findings were published online Jan. 5 in JAMA Network Open.
 

Higher risk in EDs

There is currently no consensus on the care protocol for patients with TIA or mIS, and the rate at which these patients are hospitalized varies by region, hospital, and practitioner, the investigators noted.

Previous studies have indicated that outpatient management of certain individuals with TIA can be safe and cost-effective.

The current researchers searched for retrospective and prospective studies of adult patients that provided information about ischemic stroke after TIA or mIS. Studies that used time- and tissue-based definitions of TIA were included, as well as studies that used various definitions of mIS.

The investigators examined care provided at TIA clinics, inpatient settings (such as medical-surgical units, stroke units, or observation units), EDs, and unspecified settings. Their main aim was to compare outcomes between TIA clinics and inpatient settings.

In all, 226,683 patients (recruited between 1981 and 2018) from 71 studies were included in the meta-analysis. The studies examined 101 cohorts, 24 of which were studied prospectively. Among the 5,636 patients who received care in TIA clinics, the mean age was 65.7 years, and 50.8% of this group were men. Among the 130,139 inpatients, the mean age was 78.3 years, and 61.6% of the group were women.

Results showed no significant difference in risk for subsequent stroke between patients treated in the inpatient and outpatient settings.

Among patients treated in a TIA clinic, risk for subsequent stroke following a TIA or mIS was 0.3% within 2 days, 1.0% within 7 days, 1.3% within 30 days, and 2.1% within 90 days. Among those treated as inpatients, risk for subsequent stroke was 0.5% within 2 days, 1.2% within 7 days, 1.6% within 30 days, and 2.8% within 90 days.

Risk for subsequent stroke was higher among patients treated in the ED and in unspecified settings. At the EDs, the risk was 1.9% within 2 days, 3.4% within 7 days, 3.5% within 30 days, and 3.5% within 90 days. Among those treated in unspecified settings, the risk was 2.2% within 2 days, 3.4% within 7 days, 4.2% within 30 days, and 6.0% within 90 days.

Patients treated in the ED also had a significantly higher risk for subsequent stroke at 2 and 7 days, compared with those treated in inpatient settings and a significantly higher risk for subsequent stroke at 2, 7, and 90 days, compared with those treated in TIA clinics.
 

‘Most comprehensive look’

“This is the most comprehensive look at all the studies to try and answer this research question,” said Dr. Zand. The results were similar to what was expected, he added.

The infrastructure and resources differed among the sites at which the various studies were conducted, and the investigators adjusted for these differences as much as possible, Dr. Zand noted. A certain amount of selection bias may remain, but it does not affect the overall conclusion, he added.

“Timely outpatient care among low-risk TIA patients is both feasible and safe,” he said.

Dr. Zand noted that the findings have implications not only for patient management but also for the management of the health system. “It’s not feasible nor desirable to admit all the TIA patients, especially with the lessons that we learned from COVID, the burden on the health systems, and the fact that many hospitals are operating at full capacity right now,” he said.

The recommendation is to hospitalize high-risk patients and provide outpatient evaluation and workup to low-risk patients, he added. “This is exactly what we saw in this study,” Dr. Zand said.
 

Selection bias?

Commenting on the research, Louis R. Caplan, MD, professor of neurology at Harvard Medical School, Boston, noted that evaluation of patients with TIA or mIS “can be done very well as an outpatient” if clinicians have experienced personnel, the outpatient facilities to do the studies necessary, and criteria in place for deciding who to admit or not admit.

However, the decision on whether to choose an inpatient or outpatient approach for a particular patient is complicated, said Dr. Caplan, who was not involved with the research.

Clinicians must consider factors such as whether the patient is mobile, has a car, or has a significant other. The patient’s symptoms and past illnesses also influence the decision, he added.

Dr. Caplan noted that in the meta-analysis, far fewer patients were seen in the TIA clinics than were seen in the inpatient setting. In addition, none of the studies used uniform criteria to determine which patients should undergo workup as outpatients and which as inpatients. “There was a lot of selection bias that may have had nothing to do with how sick the person was,” Dr. Caplan said.

In addition, few hospitals in the United States have an outpatient TIA clinic, he noted. Most of the studies of TIA clinics that the researchers examined were conducted in Europe. “It’s easier to do [that] in Europe because of their socialized medicine,” said Dr. Caplan.

But TIA clinics should be more widespread in the U.S., he added. “Insurance companies should be willing to pay for comparable facilities, inpatient and outpatient,” he said.

The study was conducted without external funding. Dr. Zand reported no relevant financial relationships. Dr. Caplan was an investigator for TIAregistry.org, which analyzed the outcomes of treatment in TIA clinics in Europe.

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

Inpatient and outpatient treatments of transient ischemic attack (TIA) or minor ischemic stroke (mIS) yield comparable safety outcomes, new research suggests. In a meta-analysis of more than 200,000 patients with TIA or mIS, risk for subsequent stroke within 90 days was 2.1% for those treated in a TIA clinic versus 2.8% for patients treated in inpatient settings, which was not significantly different. The risk for patients treated in an emergency department was higher, at 3.5%.

“The message is that if you do the correct risk stratification and then triage patients based on their risk profile, you can safely discharge and have a timely follow-up for the patients who have low risk for a subsequent event,” said coinvestigator Ramin Zand, MD, vascular neurologist and stroke attending physician at Geisinger Health System, Danville, Pennsylvania.

The findings were published online Jan. 5 in JAMA Network Open.
 

Higher risk in EDs

There is currently no consensus on the care protocol for patients with TIA or mIS, and the rate at which these patients are hospitalized varies by region, hospital, and practitioner, the investigators noted.

Previous studies have indicated that outpatient management of certain individuals with TIA can be safe and cost-effective.

The current researchers searched for retrospective and prospective studies of adult patients that provided information about ischemic stroke after TIA or mIS. Studies that used time- and tissue-based definitions of TIA were included, as well as studies that used various definitions of mIS.

The investigators examined care provided at TIA clinics, inpatient settings (such as medical-surgical units, stroke units, or observation units), EDs, and unspecified settings. Their main aim was to compare outcomes between TIA clinics and inpatient settings.

In all, 226,683 patients (recruited between 1981 and 2018) from 71 studies were included in the meta-analysis. The studies examined 101 cohorts, 24 of which were studied prospectively. Among the 5,636 patients who received care in TIA clinics, the mean age was 65.7 years, and 50.8% of this group were men. Among the 130,139 inpatients, the mean age was 78.3 years, and 61.6% of the group were women.

Results showed no significant difference in risk for subsequent stroke between patients treated in the inpatient and outpatient settings.

Among patients treated in a TIA clinic, risk for subsequent stroke following a TIA or mIS was 0.3% within 2 days, 1.0% within 7 days, 1.3% within 30 days, and 2.1% within 90 days. Among those treated as inpatients, risk for subsequent stroke was 0.5% within 2 days, 1.2% within 7 days, 1.6% within 30 days, and 2.8% within 90 days.

Risk for subsequent stroke was higher among patients treated in the ED and in unspecified settings. At the EDs, the risk was 1.9% within 2 days, 3.4% within 7 days, 3.5% within 30 days, and 3.5% within 90 days. Among those treated in unspecified settings, the risk was 2.2% within 2 days, 3.4% within 7 days, 4.2% within 30 days, and 6.0% within 90 days.

Patients treated in the ED also had a significantly higher risk for subsequent stroke at 2 and 7 days, compared with those treated in inpatient settings and a significantly higher risk for subsequent stroke at 2, 7, and 90 days, compared with those treated in TIA clinics.
 

‘Most comprehensive look’

“This is the most comprehensive look at all the studies to try and answer this research question,” said Dr. Zand. The results were similar to what was expected, he added.

The infrastructure and resources differed among the sites at which the various studies were conducted, and the investigators adjusted for these differences as much as possible, Dr. Zand noted. A certain amount of selection bias may remain, but it does not affect the overall conclusion, he added.

“Timely outpatient care among low-risk TIA patients is both feasible and safe,” he said.

Dr. Zand noted that the findings have implications not only for patient management but also for the management of the health system. “It’s not feasible nor desirable to admit all the TIA patients, especially with the lessons that we learned from COVID, the burden on the health systems, and the fact that many hospitals are operating at full capacity right now,” he said.

The recommendation is to hospitalize high-risk patients and provide outpatient evaluation and workup to low-risk patients, he added. “This is exactly what we saw in this study,” Dr. Zand said.
 

Selection bias?

Commenting on the research, Louis R. Caplan, MD, professor of neurology at Harvard Medical School, Boston, noted that evaluation of patients with TIA or mIS “can be done very well as an outpatient” if clinicians have experienced personnel, the outpatient facilities to do the studies necessary, and criteria in place for deciding who to admit or not admit.

However, the decision on whether to choose an inpatient or outpatient approach for a particular patient is complicated, said Dr. Caplan, who was not involved with the research.

Clinicians must consider factors such as whether the patient is mobile, has a car, or has a significant other. The patient’s symptoms and past illnesses also influence the decision, he added.

Dr. Caplan noted that in the meta-analysis, far fewer patients were seen in the TIA clinics than were seen in the inpatient setting. In addition, none of the studies used uniform criteria to determine which patients should undergo workup as outpatients and which as inpatients. “There was a lot of selection bias that may have had nothing to do with how sick the person was,” Dr. Caplan said.

In addition, few hospitals in the United States have an outpatient TIA clinic, he noted. Most of the studies of TIA clinics that the researchers examined were conducted in Europe. “It’s easier to do [that] in Europe because of their socialized medicine,” said Dr. Caplan.

But TIA clinics should be more widespread in the U.S., he added. “Insurance companies should be willing to pay for comparable facilities, inpatient and outpatient,” he said.

The study was conducted without external funding. Dr. Zand reported no relevant financial relationships. Dr. Caplan was an investigator for TIAregistry.org, which analyzed the outcomes of treatment in TIA clinics in Europe.

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