Alzheimer's & Cognition

These should be the best of times for geriatric medicine.

The baby boom has become a senior surge, bringing in a rapidly growing pool of aging patients for geriatricians to treat. According to the U.S. Census Bureau, more than 56 million adults aged 65 and older live in the United States. They account for about 17% of the nation’s population. That number is expected to hit 73 million by 2030 and 86 million by 2050.

The American Geriatrics Society estimates that 30% of older people require the attention of geriatricians. These clinicians excel in managing complex cases – patients with multiple comorbidities, such as coronary artery disease, dementia, and osteoporosis, who are taking a half dozen, and often more, medications.

But instead of thriving, geriatrics as a medical specialty appears to be hobbling. In the 2010s, geriatricians called for “25,000 [such specialists] by 2025.” As of 2021, 7123 certified geriatricians were practicing in the United States, according to the American Board of Medical Specialties.

The Health Resources and Services Administration, a federal agency that addresses medical workforce shortages, estimates that there will be 6,230 geriatricians by 2025, or approximately 1 for every 3,000 older adults requiring geriatric care. HRSA projects a shortage of 27,000 geriatricians by 2025.

The specialty has faced an uphill battle to attract fellows. This year, only 43% of the nation’s 177 geriatrics fellowship slots were filled, according to November’s National Resident Match Program report. Family medicine–based geriatrics achieved only a 32% fill rate, while internal medicine–based programs saw a rate of 45%.

“Our numbers are shrinking so we need another approach to make sure older adults get the care they need and deserve,” said G. Michael Harper, MD, president of the 6,000-member AGS.

But Dr. Harper, who practices at the University of California, San Francisco, and the San Francisco VA Medical Center, added a positive note: “We may be struggling to increase the number of board-certified geriatricians, but the field itself has made a lot of progress in terms of improving clinical care through advancements in science and in the ways we deliver care.”

Dr. Harper cited the Hospital Elder Life Program, a hospital model developed at the Harvard-affiliated Marcus Institute for Aging Research, which uses an interprofessional team and trained volunteers to prevent delirium and functional decline. HELP has been adopted by more than 200 hospitals worldwide and has been successful at returning older adults to their homes or previous living situations with maintained or improved ability to function, he said.

Mark Supiano, MD, professor and chief of geriatrics at the University of Utah, Salt Lake City, said the specialty has been in shortage mode since ABMS recognized it in 1988. He was in the initial cohort of fellowship-trained geriatricians, sitting for the first certifying exam in geriatrics offered that year.

“Back then, the demographic imperative of the aging of our society was on the horizon. We’re living it now. I knew enough to recognize it was coming and saw an opportunity,” Dr. Supiano said in an interview. “There was so much then that we didn’t know about how to understand aging or how to care for older adults that there really was such a knowledge gap.”

Dr. Supiano is an associate editor of Hazzard’s Geriatric Medicine and Gerontology (McGraw-Hill Education), which has more than doubled in pages and word count during his career.
 

Unfavorable finances

Katherine Thompson, MD, director of the geriatrics fellowship program at the University of Chicago and codirector of UChicago’s Successful Aging and Frailty Evaluation Clinic, said money is a major reason for the struggle. “I think probably the biggest driver is financial,” she said. “A lot of people are graduating medical school with really astronomical amounts of medical school loans.”

Geriatricians, like other doctors, carry a large debt – $200,000, on average, not counting undergraduate debt, according to the Association of American Medical Colleges.

But the typical geriatrician earns less than an internist or family medicine doctor who doesn’t undergo the additional year of training, Dr. Thompson said. “There’s not a lot of financial motivation to do this fellowship,” she said.

The jobs website Zippia reports that geriatricians earned roughly $165,000 per year on average in 2022. The average annual incomes in 2022 were $191,000 for pediatricians, $215,000 for family physicians, and $223,000 for internists, according to the site.

In other words, Dr. Harper said, “geriatrics is one of the few professions where you can actually do additional training and make less money.”

The reason for the pay issue is simple: Geriatricians treat patients covered by Medicare, whose reimbursement schedules lag behind those of commercial insurers. The Kaiser Family Foundation reported in 2020 that private insurance paid 143% of Medicare rates on average for physician services.

Dr. Harper said overall compensation for geriatricians has “not gained a lot of traction,” but they can earn comfortable livings.

Still, representation of the specialty on the American Medical Association’s Relative Value Scale Update Committee has led to approval by the Centers for Medicare & Medicaid Services of billing codes that pay geriatricians “for what they do. Examples include chronic care management, advance care planning, and dementia evaluation,” he said.

But the geriatrician gap goes beyond money.

Ageism, too, may play a role in residents not choosing geriatrics.

“Our culture is ageist. It definitely focuses on youth and looks at aging as being loss rather than just a change in what works well and what doesn’t work well,” said Mary Tinetti, MD, a geriatrician and researcher at Yale University, New Haven, Conn. “Ageism happens among physicians, just because they’re part of the broader society.”
 

Time for a new goal?

Dr. Tinetti said she’s optimistic that new ideas about geriatricians teaching other primary care clinicians about the tenets of geriatric medicine, which offer a wholistic approach to comorbidities, such as diabetes, atrial fibrillation, dementia, hypertension, hyperlipidemia, and polypharmacy problems faced by this population, especially those 85 and older.

She has called on her profession to abandon the goal of increasing the numbers of board-certified geriatricians – whom she refers to as big “G” geriatricians. She instead wants to develop a “small, elite workforce” that discovers and tests geriatrics principles through research, teaches these principles to all healthcare professions and to the public, and disseminates and implements the policies.

“We need a cadre of geriatricians who train all other clinicians in the care of older adults,” Dr. Tinetti said. “The goal is not more geriatricians but rather the preparation of all clinicians in the care of older adults.”

Dr. Thompson said geriatricians are teaching primary care specialists, nurses, social workers, and other health care providers the principles of age-friendly care. AGS has for the past 20 years led a program called the Geriatrics for Specialists Initiative to increase geriatrics knowledge and expertise of surgical and medical specialists.

Some specialties have taken the cue and have added geriatrics-related hyphens through additional training: geriatric-emergency, geriatric-general surgery, geriatric-hospitalists, and more.

HRSA runs programs to encourage physicians to train as geriatricians and geriatrics faculty, and it encourages the geriatrics interdisciplinary team approach.

Richard Olague, director of public affairs for HRSA, said his agency has invested over $160 million over the past 4 years in the education and training of geriatricians and other health care professionals who care for the elderly through its Geriatrics Workforce Enhancement Program and Geriatrics Academic Career Awards Program. In the academic year 2020-2021, the two programs trained 109 geriatricians; 456 other geriatric/gerontology providers and students; 44,450 other healthcare workforce professionals and students; and served 17,666 patients and 5,409 caregivers.

Dr. Harper, like his fellow geriatricians, tells young doctors that geriatrics is a fulfilling specialty.

“I get to care for the whole person and sometimes their families, too, and in the process form rich and meaningful relationships. And while I’m rarely in the position to cure, I always have the ability to care,” he said. “Sometimes that can mean being an advocate trying to make sure my patients receive the care they need, and other times it might mean protecting them from burdensome care that is unlikely to lead to any meaningful benefit. There is great reward in all of that.”

Dr. Supiano said geriatric patients are being helped by the Age-Friendly Health System initiative of the John A. Hartford Foundation and the Institute for Healthcare Improvement in partnership with the American Hospital Association and the Catholic Health Association of the United States. This is sort of a seal of approval for facilities committed to age-friendly care.

“When you go to your hospital, if they don’t have this age-friendly health system banner on the front door ... you either ask why that is not there, or you vote with your feet and go to another health system that is age friendly,” he said. “Geriatricians are eternal optimists.”

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

These should be the best of times for geriatric medicine.

The baby boom has become a senior surge, bringing in a rapidly growing pool of aging patients for geriatricians to treat. According to the U.S. Census Bureau, more than 56 million adults aged 65 and older live in the United States. They account for about 17% of the nation’s population. That number is expected to hit 73 million by 2030 and 86 million by 2050.

The American Geriatrics Society estimates that 30% of older people require the attention of geriatricians. These clinicians excel in managing complex cases – patients with multiple comorbidities, such as coronary artery disease, dementia, and osteoporosis, who are taking a half dozen, and often more, medications.

But instead of thriving, geriatrics as a medical specialty appears to be hobbling. In the 2010s, geriatricians called for “25,000 [such specialists] by 2025.” As of 2021, 7123 certified geriatricians were practicing in the United States, according to the American Board of Medical Specialties.

The Health Resources and Services Administration, a federal agency that addresses medical workforce shortages, estimates that there will be 6,230 geriatricians by 2025, or approximately 1 for every 3,000 older adults requiring geriatric care. HRSA projects a shortage of 27,000 geriatricians by 2025.

The specialty has faced an uphill battle to attract fellows. This year, only 43% of the nation’s 177 geriatrics fellowship slots were filled, according to November’s National Resident Match Program report. Family medicine–based geriatrics achieved only a 32% fill rate, while internal medicine–based programs saw a rate of 45%.

“Our numbers are shrinking so we need another approach to make sure older adults get the care they need and deserve,” said G. Michael Harper, MD, president of the 6,000-member AGS.

But Dr. Harper, who practices at the University of California, San Francisco, and the San Francisco VA Medical Center, added a positive note: “We may be struggling to increase the number of board-certified geriatricians, but the field itself has made a lot of progress in terms of improving clinical care through advancements in science and in the ways we deliver care.”

Dr. Harper cited the Hospital Elder Life Program, a hospital model developed at the Harvard-affiliated Marcus Institute for Aging Research, which uses an interprofessional team and trained volunteers to prevent delirium and functional decline. HELP has been adopted by more than 200 hospitals worldwide and has been successful at returning older adults to their homes or previous living situations with maintained or improved ability to function, he said.

Mark Supiano, MD, professor and chief of geriatrics at the University of Utah, Salt Lake City, said the specialty has been in shortage mode since ABMS recognized it in 1988. He was in the initial cohort of fellowship-trained geriatricians, sitting for the first certifying exam in geriatrics offered that year.

“Back then, the demographic imperative of the aging of our society was on the horizon. We’re living it now. I knew enough to recognize it was coming and saw an opportunity,” Dr. Supiano said in an interview. “There was so much then that we didn’t know about how to understand aging or how to care for older adults that there really was such a knowledge gap.”

Dr. Supiano is an associate editor of Hazzard’s Geriatric Medicine and Gerontology (McGraw-Hill Education), which has more than doubled in pages and word count during his career.
 

Unfavorable finances

Katherine Thompson, MD, director of the geriatrics fellowship program at the University of Chicago and codirector of UChicago’s Successful Aging and Frailty Evaluation Clinic, said money is a major reason for the struggle. “I think probably the biggest driver is financial,” she said. “A lot of people are graduating medical school with really astronomical amounts of medical school loans.”

Geriatricians, like other doctors, carry a large debt – $200,000, on average, not counting undergraduate debt, according to the Association of American Medical Colleges.

But the typical geriatrician earns less than an internist or family medicine doctor who doesn’t undergo the additional year of training, Dr. Thompson said. “There’s not a lot of financial motivation to do this fellowship,” she said.

The jobs website Zippia reports that geriatricians earned roughly $165,000 per year on average in 2022. The average annual incomes in 2022 were $191,000 for pediatricians, $215,000 for family physicians, and $223,000 for internists, according to the site.

In other words, Dr. Harper said, “geriatrics is one of the few professions where you can actually do additional training and make less money.”

The reason for the pay issue is simple: Geriatricians treat patients covered by Medicare, whose reimbursement schedules lag behind those of commercial insurers. The Kaiser Family Foundation reported in 2020 that private insurance paid 143% of Medicare rates on average for physician services.

Dr. Harper said overall compensation for geriatricians has “not gained a lot of traction,” but they can earn comfortable livings.

Still, representation of the specialty on the American Medical Association’s Relative Value Scale Update Committee has led to approval by the Centers for Medicare & Medicaid Services of billing codes that pay geriatricians “for what they do. Examples include chronic care management, advance care planning, and dementia evaluation,” he said.

But the geriatrician gap goes beyond money.

Ageism, too, may play a role in residents not choosing geriatrics.

“Our culture is ageist. It definitely focuses on youth and looks at aging as being loss rather than just a change in what works well and what doesn’t work well,” said Mary Tinetti, MD, a geriatrician and researcher at Yale University, New Haven, Conn. “Ageism happens among physicians, just because they’re part of the broader society.”
 

Time for a new goal?

Dr. Tinetti said she’s optimistic that new ideas about geriatricians teaching other primary care clinicians about the tenets of geriatric medicine, which offer a wholistic approach to comorbidities, such as diabetes, atrial fibrillation, dementia, hypertension, hyperlipidemia, and polypharmacy problems faced by this population, especially those 85 and older.

She has called on her profession to abandon the goal of increasing the numbers of board-certified geriatricians – whom she refers to as big “G” geriatricians. She instead wants to develop a “small, elite workforce” that discovers and tests geriatrics principles through research, teaches these principles to all healthcare professions and to the public, and disseminates and implements the policies.

“We need a cadre of geriatricians who train all other clinicians in the care of older adults,” Dr. Tinetti said. “The goal is not more geriatricians but rather the preparation of all clinicians in the care of older adults.”

Dr. Thompson said geriatricians are teaching primary care specialists, nurses, social workers, and other health care providers the principles of age-friendly care. AGS has for the past 20 years led a program called the Geriatrics for Specialists Initiative to increase geriatrics knowledge and expertise of surgical and medical specialists.

Some specialties have taken the cue and have added geriatrics-related hyphens through additional training: geriatric-emergency, geriatric-general surgery, geriatric-hospitalists, and more.

HRSA runs programs to encourage physicians to train as geriatricians and geriatrics faculty, and it encourages the geriatrics interdisciplinary team approach.

Richard Olague, director of public affairs for HRSA, said his agency has invested over $160 million over the past 4 years in the education and training of geriatricians and other health care professionals who care for the elderly through its Geriatrics Workforce Enhancement Program and Geriatrics Academic Career Awards Program. In the academic year 2020-2021, the two programs trained 109 geriatricians; 456 other geriatric/gerontology providers and students; 44,450 other healthcare workforce professionals and students; and served 17,666 patients and 5,409 caregivers.

Dr. Harper, like his fellow geriatricians, tells young doctors that geriatrics is a fulfilling specialty.

“I get to care for the whole person and sometimes their families, too, and in the process form rich and meaningful relationships. And while I’m rarely in the position to cure, I always have the ability to care,” he said. “Sometimes that can mean being an advocate trying to make sure my patients receive the care they need, and other times it might mean protecting them from burdensome care that is unlikely to lead to any meaningful benefit. There is great reward in all of that.”

Dr. Supiano said geriatric patients are being helped by the Age-Friendly Health System initiative of the John A. Hartford Foundation and the Institute for Healthcare Improvement in partnership with the American Hospital Association and the Catholic Health Association of the United States. This is sort of a seal of approval for facilities committed to age-friendly care.

“When you go to your hospital, if they don’t have this age-friendly health system banner on the front door ... you either ask why that is not there, or you vote with your feet and go to another health system that is age friendly,” he said. “Geriatricians are eternal optimists.”

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

These should be the best of times for geriatric medicine.

The baby boom has become a senior surge, bringing in a rapidly growing pool of aging patients for geriatricians to treat. According to the U.S. Census Bureau, more than 56 million adults aged 65 and older live in the United States. They account for about 17% of the nation’s population. That number is expected to hit 73 million by 2030 and 86 million by 2050.

The American Geriatrics Society estimates that 30% of older people require the attention of geriatricians. These clinicians excel in managing complex cases – patients with multiple comorbidities, such as coronary artery disease, dementia, and osteoporosis, who are taking a half dozen, and often more, medications.

But instead of thriving, geriatrics as a medical specialty appears to be hobbling. In the 2010s, geriatricians called for “25,000 [such specialists] by 2025.” As of 2021, 7123 certified geriatricians were practicing in the United States, according to the American Board of Medical Specialties.

The Health Resources and Services Administration, a federal agency that addresses medical workforce shortages, estimates that there will be 6,230 geriatricians by 2025, or approximately 1 for every 3,000 older adults requiring geriatric care. HRSA projects a shortage of 27,000 geriatricians by 2025.

The specialty has faced an uphill battle to attract fellows. This year, only 43% of the nation’s 177 geriatrics fellowship slots were filled, according to November’s National Resident Match Program report. Family medicine–based geriatrics achieved only a 32% fill rate, while internal medicine–based programs saw a rate of 45%.

“Our numbers are shrinking so we need another approach to make sure older adults get the care they need and deserve,” said G. Michael Harper, MD, president of the 6,000-member AGS.

But Dr. Harper, who practices at the University of California, San Francisco, and the San Francisco VA Medical Center, added a positive note: “We may be struggling to increase the number of board-certified geriatricians, but the field itself has made a lot of progress in terms of improving clinical care through advancements in science and in the ways we deliver care.”

Dr. Harper cited the Hospital Elder Life Program, a hospital model developed at the Harvard-affiliated Marcus Institute for Aging Research, which uses an interprofessional team and trained volunteers to prevent delirium and functional decline. HELP has been adopted by more than 200 hospitals worldwide and has been successful at returning older adults to their homes or previous living situations with maintained or improved ability to function, he said.

Mark Supiano, MD, professor and chief of geriatrics at the University of Utah, Salt Lake City, said the specialty has been in shortage mode since ABMS recognized it in 1988. He was in the initial cohort of fellowship-trained geriatricians, sitting for the first certifying exam in geriatrics offered that year.

“Back then, the demographic imperative of the aging of our society was on the horizon. We’re living it now. I knew enough to recognize it was coming and saw an opportunity,” Dr. Supiano said in an interview. “There was so much then that we didn’t know about how to understand aging or how to care for older adults that there really was such a knowledge gap.”

Dr. Supiano is an associate editor of Hazzard’s Geriatric Medicine and Gerontology (McGraw-Hill Education), which has more than doubled in pages and word count during his career.
 

Unfavorable finances

Katherine Thompson, MD, director of the geriatrics fellowship program at the University of Chicago and codirector of UChicago’s Successful Aging and Frailty Evaluation Clinic, said money is a major reason for the struggle. “I think probably the biggest driver is financial,” she said. “A lot of people are graduating medical school with really astronomical amounts of medical school loans.”

Geriatricians, like other doctors, carry a large debt – $200,000, on average, not counting undergraduate debt, according to the Association of American Medical Colleges.

But the typical geriatrician earns less than an internist or family medicine doctor who doesn’t undergo the additional year of training, Dr. Thompson said. “There’s not a lot of financial motivation to do this fellowship,” she said.

The jobs website Zippia reports that geriatricians earned roughly $165,000 per year on average in 2022. The average annual incomes in 2022 were $191,000 for pediatricians, $215,000 for family physicians, and $223,000 for internists, according to the site.

In other words, Dr. Harper said, “geriatrics is one of the few professions where you can actually do additional training and make less money.”

The reason for the pay issue is simple: Geriatricians treat patients covered by Medicare, whose reimbursement schedules lag behind those of commercial insurers. The Kaiser Family Foundation reported in 2020 that private insurance paid 143% of Medicare rates on average for physician services.

Dr. Harper said overall compensation for geriatricians has “not gained a lot of traction,” but they can earn comfortable livings.

Still, representation of the specialty on the American Medical Association’s Relative Value Scale Update Committee has led to approval by the Centers for Medicare & Medicaid Services of billing codes that pay geriatricians “for what they do. Examples include chronic care management, advance care planning, and dementia evaluation,” he said.

But the geriatrician gap goes beyond money.

Ageism, too, may play a role in residents not choosing geriatrics.

“Our culture is ageist. It definitely focuses on youth and looks at aging as being loss rather than just a change in what works well and what doesn’t work well,” said Mary Tinetti, MD, a geriatrician and researcher at Yale University, New Haven, Conn. “Ageism happens among physicians, just because they’re part of the broader society.”
 

Time for a new goal?

Dr. Tinetti said she’s optimistic that new ideas about geriatricians teaching other primary care clinicians about the tenets of geriatric medicine, which offer a wholistic approach to comorbidities, such as diabetes, atrial fibrillation, dementia, hypertension, hyperlipidemia, and polypharmacy problems faced by this population, especially those 85 and older.

She has called on her profession to abandon the goal of increasing the numbers of board-certified geriatricians – whom she refers to as big “G” geriatricians. She instead wants to develop a “small, elite workforce” that discovers and tests geriatrics principles through research, teaches these principles to all healthcare professions and to the public, and disseminates and implements the policies.

“We need a cadre of geriatricians who train all other clinicians in the care of older adults,” Dr. Tinetti said. “The goal is not more geriatricians but rather the preparation of all clinicians in the care of older adults.”

Dr. Thompson said geriatricians are teaching primary care specialists, nurses, social workers, and other health care providers the principles of age-friendly care. AGS has for the past 20 years led a program called the Geriatrics for Specialists Initiative to increase geriatrics knowledge and expertise of surgical and medical specialists.

Some specialties have taken the cue and have added geriatrics-related hyphens through additional training: geriatric-emergency, geriatric-general surgery, geriatric-hospitalists, and more.

HRSA runs programs to encourage physicians to train as geriatricians and geriatrics faculty, and it encourages the geriatrics interdisciplinary team approach.

Richard Olague, director of public affairs for HRSA, said his agency has invested over $160 million over the past 4 years in the education and training of geriatricians and other health care professionals who care for the elderly through its Geriatrics Workforce Enhancement Program and Geriatrics Academic Career Awards Program. In the academic year 2020-2021, the two programs trained 109 geriatricians; 456 other geriatric/gerontology providers and students; 44,450 other healthcare workforce professionals and students; and served 17,666 patients and 5,409 caregivers.

Dr. Harper, like his fellow geriatricians, tells young doctors that geriatrics is a fulfilling specialty.

“I get to care for the whole person and sometimes their families, too, and in the process form rich and meaningful relationships. And while I’m rarely in the position to cure, I always have the ability to care,” he said. “Sometimes that can mean being an advocate trying to make sure my patients receive the care they need, and other times it might mean protecting them from burdensome care that is unlikely to lead to any meaningful benefit. There is great reward in all of that.”

Dr. Supiano said geriatric patients are being helped by the Age-Friendly Health System initiative of the John A. Hartford Foundation and the Institute for Healthcare Improvement in partnership with the American Hospital Association and the Catholic Health Association of the United States. This is sort of a seal of approval for facilities committed to age-friendly care.

“When you go to your hospital, if they don’t have this age-friendly health system banner on the front door ... you either ask why that is not there, or you vote with your feet and go to another health system that is age friendly,” he said. “Geriatricians are eternal optimists.”

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

New research supports the benefit of maintaining a diet low in ultraprocessed foods (UPFs) to protect the aging brain.

Results from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil), which included more than 10,000 people aged 35 and older, showed that higher intake of UPF was significantly associated with a faster rate of decline in executive and global cognitive function.

“These findings show that lifestyle choices, particularly high intake of ultraprocessed foods, can influence our cognitive health many years later,” coinvestigator Natalia Goncalves, PhD, University of São Paulo, Brazil, said in an interview.

The study was published online in JAMA Neurology.

The study’s findings were presented in August at the Alzheimer’s Association International Conference (AAIC) 2022 and were reported by this news organization at that time.
 

High sugar, salt, fat

The new results align with another recent study linking a diet high in UPFs to an increased risk for dementia.

UPFs are highly manipulated, are packed with added ingredients, including sugar, fat, and salt, and are low in protein and fiber. Examples of UPFs are soft drinks, chips, chocolate, candy, ice cream, sweetened breakfast cereals, packaged soups, chicken nuggets, hot dogs, and fries.

The ELSA-Brasil study comprised 10,775 adults (mean age, 50.6 years at baseline; 55% women; 53% White) who were evaluated in three waves approximately 4 years apart from 2008 to 2017.

Information on diet was obtained via food frequency questionnaires and included details regarding consumption of unprocessed foods, minimally processed foods, and UPFs.

Participants were grouped according to UPF consumption quartiles (lowest to highest). Cognitive performance was evaluated by use of a standardized battery of tests.

During median follow-up of 8 years, people who consumed more than 20% of daily calories from UPFs (quartiles 2-4) experienced a 28% faster rate of decline in global cognition (beta = –0.004; 95% confidence interval [CI], –0.006 to –0.001; P = .003) and a 25% faster rate of decline in executive function (beta = –0.003, 95% CI, –0.005 to 0.000; P = .01) compared to peers in quartile 1 who consumed less than 20% of daily calories from UPFs.

The researchers did not investigate individual groups of UPFs.

However, Dr. Goncalves noted that some studies have linked the consumption of sugar-sweetened beverages with lower cognitive performance, lower brain volume, and poorer memory performance. Another group of ultraprocessed foods, processed meats, has been associated with increased all-cause dementia and Alzheimer’s disease.

Other limitations include the fact that self-reported diet habits were assessed only at baseline using a food frequency questionnaire that was not designed to assess the degree of processing.

While analyses were adjusted for several sociodemographic and clinical confounders, the researchers said they could not exclude the possibility of residual confounding.

Also, since neuroimaging is not available in the ELSA-Brasil study, they were not able to investigate potential mechanisms that could explain the association between higher UPF consumption and cognitive decline.

Despite these limitations, the researchers said their findings suggest that “limiting UPF consumption, particularly in middle-aged adults, may be an efficient form to prevent cognitive decline.”
 

Weighing the evidence

Several experts weighed in on the results in a statement from the UK nonprofit organization, Science Media Centre.

Kevin McConway, PhD, with Open University, Milton Keynes, England, said it’s important to note that the study suggests “an association, a correlation, and that doesn’t necessarily mean that the cognitive decline was caused by eating more ultra-processed foods.”

He also noted that some types of cognitive decline that are associated with aging occurred in participants in all four quartiles, which were defined by the percentage of their daily energy that came from consuming UPFs.

“That’s hardly surprising – it’s a sad fact of life that pretty well all of us gradually lose some of our cognitive functions as we go through middle and older age,” Dr. McConway said.

“The study doesn’t establish that differences in speed of cognitive decline are caused by ultra-processed food consumption anyway. That’s because it’s an observational study. If the consumption of ultra-processed food causes the differences in rate of cognitive decline, then eating less of it might slow cognitive decline, but if the cause is something else, then that won’t happen,” Dr. McConway added.

Gunter Kuhnle, PhD, professor of nutrition and food science, University of Reading, England, noted that UPFs have become a “fashionable term to explain associations between diet and ill health, and many studies have attempted to show associations.

“Most studies have been observational and had a key limitation: It is very difficult to determine ultra-processed food intake using methods that are not designed to do so, and so authors need to make a lot of assumptions. Bread and meat products are often classed as ‘ultra-processed,’ even though this is often wrong,” Dr. Kuhnle noted.

“The same applies to this study – the method used to measure ultra-processed food intake was not designed for that task and relied on assumptions. This makes it virtually impossible to draw any conclusions,” Dr. Kuhnle said.

Duane Mellor, PhD, RD, RNutr, registered dietitian and senior teaching fellow, Aston University, Birmingham, England, said the study does not change how we should try to eat to maintain good brain function and cognition.

“We should try to eat less foods which are high in added sugar, salt, and fat, which would include many of the foods classified as being ultra-processed, while eating more in terms of both quantity and variety of vegetables, fruit, nuts, seeds, and pulses, which are known to be beneficial for both our cognitive and overall health,” Dr. Mellor said.

The ELSA-Brasil study was supported by the Brazilian Ministry of Health, the Ministry of Science, Technology and Innovation, and the National Council for Scientific and Technological Development. The authors as well as Dr. McConway, Dr. Mellor, and Dr. Kuhnle have disclosed no relevant financial relationships.

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

New research supports the benefit of maintaining a diet low in ultraprocessed foods (UPFs) to protect the aging brain.

Results from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil), which included more than 10,000 people aged 35 and older, showed that higher intake of UPF was significantly associated with a faster rate of decline in executive and global cognitive function.

“These findings show that lifestyle choices, particularly high intake of ultraprocessed foods, can influence our cognitive health many years later,” coinvestigator Natalia Goncalves, PhD, University of São Paulo, Brazil, said in an interview.

The study was published online in JAMA Neurology.

The study’s findings were presented in August at the Alzheimer’s Association International Conference (AAIC) 2022 and were reported by this news organization at that time.
 

High sugar, salt, fat

The new results align with another recent study linking a diet high in UPFs to an increased risk for dementia.

UPFs are highly manipulated, are packed with added ingredients, including sugar, fat, and salt, and are low in protein and fiber. Examples of UPFs are soft drinks, chips, chocolate, candy, ice cream, sweetened breakfast cereals, packaged soups, chicken nuggets, hot dogs, and fries.

The ELSA-Brasil study comprised 10,775 adults (mean age, 50.6 years at baseline; 55% women; 53% White) who were evaluated in three waves approximately 4 years apart from 2008 to 2017.

Information on diet was obtained via food frequency questionnaires and included details regarding consumption of unprocessed foods, minimally processed foods, and UPFs.

Participants were grouped according to UPF consumption quartiles (lowest to highest). Cognitive performance was evaluated by use of a standardized battery of tests.

During median follow-up of 8 years, people who consumed more than 20% of daily calories from UPFs (quartiles 2-4) experienced a 28% faster rate of decline in global cognition (beta = –0.004; 95% confidence interval [CI], –0.006 to –0.001; P = .003) and a 25% faster rate of decline in executive function (beta = –0.003, 95% CI, –0.005 to 0.000; P = .01) compared to peers in quartile 1 who consumed less than 20% of daily calories from UPFs.

The researchers did not investigate individual groups of UPFs.

However, Dr. Goncalves noted that some studies have linked the consumption of sugar-sweetened beverages with lower cognitive performance, lower brain volume, and poorer memory performance. Another group of ultraprocessed foods, processed meats, has been associated with increased all-cause dementia and Alzheimer’s disease.

Other limitations include the fact that self-reported diet habits were assessed only at baseline using a food frequency questionnaire that was not designed to assess the degree of processing.

While analyses were adjusted for several sociodemographic and clinical confounders, the researchers said they could not exclude the possibility of residual confounding.

Also, since neuroimaging is not available in the ELSA-Brasil study, they were not able to investigate potential mechanisms that could explain the association between higher UPF consumption and cognitive decline.

Despite these limitations, the researchers said their findings suggest that “limiting UPF consumption, particularly in middle-aged adults, may be an efficient form to prevent cognitive decline.”
 

Weighing the evidence

Several experts weighed in on the results in a statement from the UK nonprofit organization, Science Media Centre.

Kevin McConway, PhD, with Open University, Milton Keynes, England, said it’s important to note that the study suggests “an association, a correlation, and that doesn’t necessarily mean that the cognitive decline was caused by eating more ultra-processed foods.”

He also noted that some types of cognitive decline that are associated with aging occurred in participants in all four quartiles, which were defined by the percentage of their daily energy that came from consuming UPFs.

“That’s hardly surprising – it’s a sad fact of life that pretty well all of us gradually lose some of our cognitive functions as we go through middle and older age,” Dr. McConway said.

“The study doesn’t establish that differences in speed of cognitive decline are caused by ultra-processed food consumption anyway. That’s because it’s an observational study. If the consumption of ultra-processed food causes the differences in rate of cognitive decline, then eating less of it might slow cognitive decline, but if the cause is something else, then that won’t happen,” Dr. McConway added.

Gunter Kuhnle, PhD, professor of nutrition and food science, University of Reading, England, noted that UPFs have become a “fashionable term to explain associations between diet and ill health, and many studies have attempted to show associations.

“Most studies have been observational and had a key limitation: It is very difficult to determine ultra-processed food intake using methods that are not designed to do so, and so authors need to make a lot of assumptions. Bread and meat products are often classed as ‘ultra-processed,’ even though this is often wrong,” Dr. Kuhnle noted.

“The same applies to this study – the method used to measure ultra-processed food intake was not designed for that task and relied on assumptions. This makes it virtually impossible to draw any conclusions,” Dr. Kuhnle said.

Duane Mellor, PhD, RD, RNutr, registered dietitian and senior teaching fellow, Aston University, Birmingham, England, said the study does not change how we should try to eat to maintain good brain function and cognition.

“We should try to eat less foods which are high in added sugar, salt, and fat, which would include many of the foods classified as being ultra-processed, while eating more in terms of both quantity and variety of vegetables, fruit, nuts, seeds, and pulses, which are known to be beneficial for both our cognitive and overall health,” Dr. Mellor said.

The ELSA-Brasil study was supported by the Brazilian Ministry of Health, the Ministry of Science, Technology and Innovation, and the National Council for Scientific and Technological Development. The authors as well as Dr. McConway, Dr. Mellor, and Dr. Kuhnle have disclosed no relevant financial relationships.

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

New research supports the benefit of maintaining a diet low in ultraprocessed foods (UPFs) to protect the aging brain.

Results from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil), which included more than 10,000 people aged 35 and older, showed that higher intake of UPF was significantly associated with a faster rate of decline in executive and global cognitive function.

“These findings show that lifestyle choices, particularly high intake of ultraprocessed foods, can influence our cognitive health many years later,” coinvestigator Natalia Goncalves, PhD, University of São Paulo, Brazil, said in an interview.

The study was published online in JAMA Neurology.

The study’s findings were presented in August at the Alzheimer’s Association International Conference (AAIC) 2022 and were reported by this news organization at that time.
 

High sugar, salt, fat

The new results align with another recent study linking a diet high in UPFs to an increased risk for dementia.

UPFs are highly manipulated, are packed with added ingredients, including sugar, fat, and salt, and are low in protein and fiber. Examples of UPFs are soft drinks, chips, chocolate, candy, ice cream, sweetened breakfast cereals, packaged soups, chicken nuggets, hot dogs, and fries.

The ELSA-Brasil study comprised 10,775 adults (mean age, 50.6 years at baseline; 55% women; 53% White) who were evaluated in three waves approximately 4 years apart from 2008 to 2017.

Information on diet was obtained via food frequency questionnaires and included details regarding consumption of unprocessed foods, minimally processed foods, and UPFs.

Participants were grouped according to UPF consumption quartiles (lowest to highest). Cognitive performance was evaluated by use of a standardized battery of tests.

During median follow-up of 8 years, people who consumed more than 20% of daily calories from UPFs (quartiles 2-4) experienced a 28% faster rate of decline in global cognition (beta = –0.004; 95% confidence interval [CI], –0.006 to –0.001; P = .003) and a 25% faster rate of decline in executive function (beta = –0.003, 95% CI, –0.005 to 0.000; P = .01) compared to peers in quartile 1 who consumed less than 20% of daily calories from UPFs.

The researchers did not investigate individual groups of UPFs.

However, Dr. Goncalves noted that some studies have linked the consumption of sugar-sweetened beverages with lower cognitive performance, lower brain volume, and poorer memory performance. Another group of ultraprocessed foods, processed meats, has been associated with increased all-cause dementia and Alzheimer’s disease.

Other limitations include the fact that self-reported diet habits were assessed only at baseline using a food frequency questionnaire that was not designed to assess the degree of processing.

While analyses were adjusted for several sociodemographic and clinical confounders, the researchers said they could not exclude the possibility of residual confounding.

Also, since neuroimaging is not available in the ELSA-Brasil study, they were not able to investigate potential mechanisms that could explain the association between higher UPF consumption and cognitive decline.

Despite these limitations, the researchers said their findings suggest that “limiting UPF consumption, particularly in middle-aged adults, may be an efficient form to prevent cognitive decline.”
 

Weighing the evidence

Several experts weighed in on the results in a statement from the UK nonprofit organization, Science Media Centre.

Kevin McConway, PhD, with Open University, Milton Keynes, England, said it’s important to note that the study suggests “an association, a correlation, and that doesn’t necessarily mean that the cognitive decline was caused by eating more ultra-processed foods.”

He also noted that some types of cognitive decline that are associated with aging occurred in participants in all four quartiles, which were defined by the percentage of their daily energy that came from consuming UPFs.

“That’s hardly surprising – it’s a sad fact of life that pretty well all of us gradually lose some of our cognitive functions as we go through middle and older age,” Dr. McConway said.

“The study doesn’t establish that differences in speed of cognitive decline are caused by ultra-processed food consumption anyway. That’s because it’s an observational study. If the consumption of ultra-processed food causes the differences in rate of cognitive decline, then eating less of it might slow cognitive decline, but if the cause is something else, then that won’t happen,” Dr. McConway added.

Gunter Kuhnle, PhD, professor of nutrition and food science, University of Reading, England, noted that UPFs have become a “fashionable term to explain associations between diet and ill health, and many studies have attempted to show associations.

“Most studies have been observational and had a key limitation: It is very difficult to determine ultra-processed food intake using methods that are not designed to do so, and so authors need to make a lot of assumptions. Bread and meat products are often classed as ‘ultra-processed,’ even though this is often wrong,” Dr. Kuhnle noted.

“The same applies to this study – the method used to measure ultra-processed food intake was not designed for that task and relied on assumptions. This makes it virtually impossible to draw any conclusions,” Dr. Kuhnle said.

Duane Mellor, PhD, RD, RNutr, registered dietitian and senior teaching fellow, Aston University, Birmingham, England, said the study does not change how we should try to eat to maintain good brain function and cognition.

“We should try to eat less foods which are high in added sugar, salt, and fat, which would include many of the foods classified as being ultra-processed, while eating more in terms of both quantity and variety of vegetables, fruit, nuts, seeds, and pulses, which are known to be beneficial for both our cognitive and overall health,” Dr. Mellor said.

The ELSA-Brasil study was supported by the Brazilian Ministry of Health, the Ministry of Science, Technology and Innovation, and the National Council for Scientific and Technological Development. The authors as well as Dr. McConway, Dr. Mellor, and Dr. Kuhnle have disclosed no relevant financial relationships.

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

Because of the high out-of-pocket costs of new-to-market neurologic drugs that are of similar benefit as older agents, only a small percentage of patients with neurologic disorders have access to these cutting-edge medications, new research shows.

“Our study of people with neurologic conditions found that fewer than 20% were being treated with new medications,” study author Brian C. Callaghan, MD, with University of Michigan Health in Ann Arbor, said in a statement.

“For new, high-cost medications that have similar effectiveness to older drugs, limited use is likely appropriate. However, future studies are needed to look into whether the high costs are barriers to those new medications that can really make a difference for people living with neurologic disease,” Dr. Callaghan said.

The study was published online in Neurology.
 

Most expensive drugs

Using insurance claims data, the investigators compared the utilization and costs of new-to-market drugs from 2014 to 2018 with those for existing guideline-supported medications for treating 11 neurologic conditions.

The new drugs included:

• erenumab, fremanezumab, and galcanezumab for migraine.
• ocrelizumab and peginterferon beta-1a for multiple sclerosis (MS).
• pimavanserin and safinamide for Parkinson’s disease.
• droxidopa for orthostatic hypertension.
• eculizumab for myasthenia gravis (MG).
• edaravone for amyotrophic lateral sclerosis (ALS).
• deutetrabenazine and valbenazine for Huntington’s disease and tardive dyskinesia.
• patisiran and inotersen for transthyretin amyloidosis (ATTR).
• eteplirsen and deflazacort for Duchenne disease.
• nusinersen for spinal muscular atrophy (SMA).

Utilization of new drugs was modest – they accounted for one in five prescriptions for every condition except tardive dyskinesia (32% for valbenazine), the researchers noted.

Mean out-of-pocket costs were significantly higher for the new medications, although there was large variability among individual drugs.

The two most expensive drugs were edaravone, for ALS, with a mean out-of-pocket cost of $713 for a 30-day supply, and eculizumab, for MG, which costs $91 per month.

“For new-to-market medications, the distribution of out-of-pocket costs were highly variable and the trends over time were unpredictable compared with existing guideline-supported medications,” the authors reported.

They noted that potential reasons for low utilization of newer agents include delay in provider uptake and prescriber and/or patient avoidance because of high cost.

Given that most of the new neurologic agents offer little advantage compared with existing treatments – exceptions being new drugs for SMA and ATTR – drug costs should be a key consideration in prescribing decisions, Dr. Callaghan and colleagues concluded.

One limitation of the study is that follow-up time was short for some of the recently approved medications. Another limitation is that the number of people in the study who had rare diseases was small.
 

Revolution in neurotherapeutics

“We are living in a time when new treatments bring hope to people with neurologic diseases and disorders,” Orly Avitzur, MD, president of the American Academy of Neurology, said in a statement.

“However, even existing prescription medication can be expensive and drug prices continue to rise. In order for neurologists to provide people with the highest quality care, it is imperative that new drugs are accessible and affordable to the people who need them,” Dr. Avitzur added.

Writing in a linked editorial, A. Gordon Smith, MD, professor and chair, department of neurology, Virginia Commonwealth University, Richmond, said there is a revolution in neurotherapeutics, with particularly robust growth in new drug approvals for orphan diseases (those affecting < 200,000 Americans).

“This study adds to a growing literature indicating rising drug prices are a threat to the health care system. No matter how effective a disease-modifying therapy may be, if a patient cannot afford the cost, it doesn’t work,” Dr. Smith wrote.

He added that neurologists must be “diligent in assessing for financial toxicity and appropriately tailor individual treatment recommendations. We must insist on development of point-of-care tools to accurately estimate each patient’s potential financial toxicity including RTBT [real-time benefit tools].

“Neurologists’ primary obligation is to the individual patient, but we are also compelled to support access to high-quality care for all people, which requires advocacy for appropriate policy reforms to ensure value based and fair drug pricing and treatment success,” Dr. Smith added.

The study was funded by the American Academy of Neurology Health Services Research Subcommittee. Dr. Callaghan consults for a PCORI grant, DynaMed, receives research support from the American Academy of Neurology, and performs medical/legal consultations, including consultations for the Vaccine Injury Compensation Program. Dr. Smith has disclosed no relevant financial relationships.

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

Because of the high out-of-pocket costs of new-to-market neurologic drugs that are of similar benefit as older agents, only a small percentage of patients with neurologic disorders have access to these cutting-edge medications, new research shows.

“Our study of people with neurologic conditions found that fewer than 20% were being treated with new medications,” study author Brian C. Callaghan, MD, with University of Michigan Health in Ann Arbor, said in a statement.

“For new, high-cost medications that have similar effectiveness to older drugs, limited use is likely appropriate. However, future studies are needed to look into whether the high costs are barriers to those new medications that can really make a difference for people living with neurologic disease,” Dr. Callaghan said.

The study was published online in Neurology.
 

Most expensive drugs

Using insurance claims data, the investigators compared the utilization and costs of new-to-market drugs from 2014 to 2018 with those for existing guideline-supported medications for treating 11 neurologic conditions.

The new drugs included:

• erenumab, fremanezumab, and galcanezumab for migraine.
• ocrelizumab and peginterferon beta-1a for multiple sclerosis (MS).
• pimavanserin and safinamide for Parkinson’s disease.
• droxidopa for orthostatic hypertension.
• eculizumab for myasthenia gravis (MG).
• edaravone for amyotrophic lateral sclerosis (ALS).
• deutetrabenazine and valbenazine for Huntington’s disease and tardive dyskinesia.
• patisiran and inotersen for transthyretin amyloidosis (ATTR).
• eteplirsen and deflazacort for Duchenne disease.
• nusinersen for spinal muscular atrophy (SMA).

Utilization of new drugs was modest – they accounted for one in five prescriptions for every condition except tardive dyskinesia (32% for valbenazine), the researchers noted.

Mean out-of-pocket costs were significantly higher for the new medications, although there was large variability among individual drugs.

The two most expensive drugs were edaravone, for ALS, with a mean out-of-pocket cost of $713 for a 30-day supply, and eculizumab, for MG, which costs $91 per month.

“For new-to-market medications, the distribution of out-of-pocket costs were highly variable and the trends over time were unpredictable compared with existing guideline-supported medications,” the authors reported.

They noted that potential reasons for low utilization of newer agents include delay in provider uptake and prescriber and/or patient avoidance because of high cost.

Given that most of the new neurologic agents offer little advantage compared with existing treatments – exceptions being new drugs for SMA and ATTR – drug costs should be a key consideration in prescribing decisions, Dr. Callaghan and colleagues concluded.

One limitation of the study is that follow-up time was short for some of the recently approved medications. Another limitation is that the number of people in the study who had rare diseases was small.
 

Revolution in neurotherapeutics

“We are living in a time when new treatments bring hope to people with neurologic diseases and disorders,” Orly Avitzur, MD, president of the American Academy of Neurology, said in a statement.

“However, even existing prescription medication can be expensive and drug prices continue to rise. In order for neurologists to provide people with the highest quality care, it is imperative that new drugs are accessible and affordable to the people who need them,” Dr. Avitzur added.

Writing in a linked editorial, A. Gordon Smith, MD, professor and chair, department of neurology, Virginia Commonwealth University, Richmond, said there is a revolution in neurotherapeutics, with particularly robust growth in new drug approvals for orphan diseases (those affecting < 200,000 Americans).

“This study adds to a growing literature indicating rising drug prices are a threat to the health care system. No matter how effective a disease-modifying therapy may be, if a patient cannot afford the cost, it doesn’t work,” Dr. Smith wrote.

He added that neurologists must be “diligent in assessing for financial toxicity and appropriately tailor individual treatment recommendations. We must insist on development of point-of-care tools to accurately estimate each patient’s potential financial toxicity including RTBT [real-time benefit tools].

“Neurologists’ primary obligation is to the individual patient, but we are also compelled to support access to high-quality care for all people, which requires advocacy for appropriate policy reforms to ensure value based and fair drug pricing and treatment success,” Dr. Smith added.

The study was funded by the American Academy of Neurology Health Services Research Subcommittee. Dr. Callaghan consults for a PCORI grant, DynaMed, receives research support from the American Academy of Neurology, and performs medical/legal consultations, including consultations for the Vaccine Injury Compensation Program. Dr. Smith has disclosed no relevant financial relationships.

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

Because of the high out-of-pocket costs of new-to-market neurologic drugs that are of similar benefit as older agents, only a small percentage of patients with neurologic disorders have access to these cutting-edge medications, new research shows.

“Our study of people with neurologic conditions found that fewer than 20% were being treated with new medications,” study author Brian C. Callaghan, MD, with University of Michigan Health in Ann Arbor, said in a statement.

“For new, high-cost medications that have similar effectiveness to older drugs, limited use is likely appropriate. However, future studies are needed to look into whether the high costs are barriers to those new medications that can really make a difference for people living with neurologic disease,” Dr. Callaghan said.

The study was published online in Neurology.
 

Most expensive drugs

Using insurance claims data, the investigators compared the utilization and costs of new-to-market drugs from 2014 to 2018 with those for existing guideline-supported medications for treating 11 neurologic conditions.

The new drugs included:

• erenumab, fremanezumab, and galcanezumab for migraine.
• ocrelizumab and peginterferon beta-1a for multiple sclerosis (MS).
• pimavanserin and safinamide for Parkinson’s disease.
• droxidopa for orthostatic hypertension.
• eculizumab for myasthenia gravis (MG).
• edaravone for amyotrophic lateral sclerosis (ALS).
• deutetrabenazine and valbenazine for Huntington’s disease and tardive dyskinesia.
• patisiran and inotersen for transthyretin amyloidosis (ATTR).
• eteplirsen and deflazacort for Duchenne disease.
• nusinersen for spinal muscular atrophy (SMA).

Utilization of new drugs was modest – they accounted for one in five prescriptions for every condition except tardive dyskinesia (32% for valbenazine), the researchers noted.

Mean out-of-pocket costs were significantly higher for the new medications, although there was large variability among individual drugs.

The two most expensive drugs were edaravone, for ALS, with a mean out-of-pocket cost of $713 for a 30-day supply, and eculizumab, for MG, which costs $91 per month.

“For new-to-market medications, the distribution of out-of-pocket costs were highly variable and the trends over time were unpredictable compared with existing guideline-supported medications,” the authors reported.

They noted that potential reasons for low utilization of newer agents include delay in provider uptake and prescriber and/or patient avoidance because of high cost.

Given that most of the new neurologic agents offer little advantage compared with existing treatments – exceptions being new drugs for SMA and ATTR – drug costs should be a key consideration in prescribing decisions, Dr. Callaghan and colleagues concluded.

One limitation of the study is that follow-up time was short for some of the recently approved medications. Another limitation is that the number of people in the study who had rare diseases was small.
 

Revolution in neurotherapeutics

“We are living in a time when new treatments bring hope to people with neurologic diseases and disorders,” Orly Avitzur, MD, president of the American Academy of Neurology, said in a statement.

“However, even existing prescription medication can be expensive and drug prices continue to rise. In order for neurologists to provide people with the highest quality care, it is imperative that new drugs are accessible and affordable to the people who need them,” Dr. Avitzur added.

Writing in a linked editorial, A. Gordon Smith, MD, professor and chair, department of neurology, Virginia Commonwealth University, Richmond, said there is a revolution in neurotherapeutics, with particularly robust growth in new drug approvals for orphan diseases (those affecting < 200,000 Americans).

“This study adds to a growing literature indicating rising drug prices are a threat to the health care system. No matter how effective a disease-modifying therapy may be, if a patient cannot afford the cost, it doesn’t work,” Dr. Smith wrote.

He added that neurologists must be “diligent in assessing for financial toxicity and appropriately tailor individual treatment recommendations. We must insist on development of point-of-care tools to accurately estimate each patient’s potential financial toxicity including RTBT [real-time benefit tools].

“Neurologists’ primary obligation is to the individual patient, but we are also compelled to support access to high-quality care for all people, which requires advocacy for appropriate policy reforms to ensure value based and fair drug pricing and treatment success,” Dr. Smith added.

The study was funded by the American Academy of Neurology Health Services Research Subcommittee. Dr. Callaghan consults for a PCORI grant, DynaMed, receives research support from the American Academy of Neurology, and performs medical/legal consultations, including consultations for the Vaccine Injury Compensation Program. Dr. Smith has disclosed no relevant financial relationships.

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

A new study supports the hypothesis that changes in levels of amyloid and tau occur many years before the emergence of clinical symptoms of Alzheimer’s disease (AD).

“Our results confirm accelerated biomarker changes during preclinical AD and highlight the important role of amyloid levels in tau accelerations,” the investigators note.

“These data may suggest that there is a short therapeutic window for slowing AD pathogenesis prior to the emergence of clinical symptoms – and that this window may occur after amyloid accumulation begins but before amyloid has substantial impacts on tau accumulation,” study investigator Corinne Pettigrew, PhD, department of neurology, Johns Hopkins University School of Medicine, Baltimore, told this news organization.

The study was published online in Alzheimer’s and Dementia.
 

Novel long-term CSF data

The study builds on previous research by examining changes in cerebrospinal fluid (CSF) biomarkers over longer periods than had been done previously, particularly among largely middle-aged and cognitively normal at baseline individuals.

The researchers examined changes in amyloid beta (Aβ) 42/Aβ40, phosphorylated tau181 (p-tau181), and total tau (t-tau) in CSF over an average of 10.7 years (and up to 23 years) among 278 individuals who were largely middle-aged persons who were cognitively normal at baseline.

“To our knowledge, no prior study among initially cognitively normal, primarily middle-aged individuals has described CSF AD biomarker changes over this duration of follow-up,” the researchers write.

During follow-up, 94 individuals who initially had normal cognition developed mild cognitive impairment (MCI).

Lower baseline levels of amyloid were associated with greater increases in tau (more strongly in men than women), while accelerations in tau were more closely linked to onset of MCI, the researchers report.

Among individuals who developed MCI, biomarker levels were more abnormal and tau increased to a greater extent prior to the onset of MCI symptoms, they found.
 

Clear impact of APOE4

The findings also suggest that among APOE4 carriers, amyloid onset occurs at an earlier age and rates of amyloid positivity are higher, but there are no differences in rates of change in amyloid over time.

“APOE4 genetic status was not related to changes in CSF beta-amyloid after accounting for the fact that APOE4 carriers have higher rates of amyloid positivity,” said Dr. Pettigrew.

“These findings suggest that APOE4 genetic status shifts the age of onset of amyloid accumulation (with APOE4 carriers having an earlier age of onset compared to non-carriers), but that APOE4 is not related to rates of change in CSF beta-amyloid over time,” she added.

“Thus, cognitively normal APOE4 carriers may be in more advanced preclinical AD stages at younger ages than individuals who are not APOE4 carriers, which is likely relevant for optimizing clinical trial recruitment strategies,” she said.

Funding for the study was provided by the National Institutes of Health. Dr. Pettigrew has disclosed no relevant financial relationships. The original article contains a complete list of author disclosures.

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

A new study supports the hypothesis that changes in levels of amyloid and tau occur many years before the emergence of clinical symptoms of Alzheimer’s disease (AD).

“Our results confirm accelerated biomarker changes during preclinical AD and highlight the important role of amyloid levels in tau accelerations,” the investigators note.

“These data may suggest that there is a short therapeutic window for slowing AD pathogenesis prior to the emergence of clinical symptoms – and that this window may occur after amyloid accumulation begins but before amyloid has substantial impacts on tau accumulation,” study investigator Corinne Pettigrew, PhD, department of neurology, Johns Hopkins University School of Medicine, Baltimore, told this news organization.

The study was published online in Alzheimer’s and Dementia.
 

Novel long-term CSF data

The study builds on previous research by examining changes in cerebrospinal fluid (CSF) biomarkers over longer periods than had been done previously, particularly among largely middle-aged and cognitively normal at baseline individuals.

The researchers examined changes in amyloid beta (Aβ) 42/Aβ40, phosphorylated tau181 (p-tau181), and total tau (t-tau) in CSF over an average of 10.7 years (and up to 23 years) among 278 individuals who were largely middle-aged persons who were cognitively normal at baseline.

“To our knowledge, no prior study among initially cognitively normal, primarily middle-aged individuals has described CSF AD biomarker changes over this duration of follow-up,” the researchers write.

During follow-up, 94 individuals who initially had normal cognition developed mild cognitive impairment (MCI).

Lower baseline levels of amyloid were associated with greater increases in tau (more strongly in men than women), while accelerations in tau were more closely linked to onset of MCI, the researchers report.

Among individuals who developed MCI, biomarker levels were more abnormal and tau increased to a greater extent prior to the onset of MCI symptoms, they found.
 

Clear impact of APOE4

The findings also suggest that among APOE4 carriers, amyloid onset occurs at an earlier age and rates of amyloid positivity are higher, but there are no differences in rates of change in amyloid over time.

“APOE4 genetic status was not related to changes in CSF beta-amyloid after accounting for the fact that APOE4 carriers have higher rates of amyloid positivity,” said Dr. Pettigrew.

“These findings suggest that APOE4 genetic status shifts the age of onset of amyloid accumulation (with APOE4 carriers having an earlier age of onset compared to non-carriers), but that APOE4 is not related to rates of change in CSF beta-amyloid over time,” she added.

“Thus, cognitively normal APOE4 carriers may be in more advanced preclinical AD stages at younger ages than individuals who are not APOE4 carriers, which is likely relevant for optimizing clinical trial recruitment strategies,” she said.

Funding for the study was provided by the National Institutes of Health. Dr. Pettigrew has disclosed no relevant financial relationships. The original article contains a complete list of author disclosures.

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

A new study supports the hypothesis that changes in levels of amyloid and tau occur many years before the emergence of clinical symptoms of Alzheimer’s disease (AD).

“Our results confirm accelerated biomarker changes during preclinical AD and highlight the important role of amyloid levels in tau accelerations,” the investigators note.

“These data may suggest that there is a short therapeutic window for slowing AD pathogenesis prior to the emergence of clinical symptoms – and that this window may occur after amyloid accumulation begins but before amyloid has substantial impacts on tau accumulation,” study investigator Corinne Pettigrew, PhD, department of neurology, Johns Hopkins University School of Medicine, Baltimore, told this news organization.

The study was published online in Alzheimer’s and Dementia.
 

Novel long-term CSF data

The study builds on previous research by examining changes in cerebrospinal fluid (CSF) biomarkers over longer periods than had been done previously, particularly among largely middle-aged and cognitively normal at baseline individuals.

The researchers examined changes in amyloid beta (Aβ) 42/Aβ40, phosphorylated tau181 (p-tau181), and total tau (t-tau) in CSF over an average of 10.7 years (and up to 23 years) among 278 individuals who were largely middle-aged persons who were cognitively normal at baseline.

“To our knowledge, no prior study among initially cognitively normal, primarily middle-aged individuals has described CSF AD biomarker changes over this duration of follow-up,” the researchers write.

During follow-up, 94 individuals who initially had normal cognition developed mild cognitive impairment (MCI).

Lower baseline levels of amyloid were associated with greater increases in tau (more strongly in men than women), while accelerations in tau were more closely linked to onset of MCI, the researchers report.

Among individuals who developed MCI, biomarker levels were more abnormal and tau increased to a greater extent prior to the onset of MCI symptoms, they found.
 

Clear impact of APOE4

The findings also suggest that among APOE4 carriers, amyloid onset occurs at an earlier age and rates of amyloid positivity are higher, but there are no differences in rates of change in amyloid over time.

“APOE4 genetic status was not related to changes in CSF beta-amyloid after accounting for the fact that APOE4 carriers have higher rates of amyloid positivity,” said Dr. Pettigrew.

“These findings suggest that APOE4 genetic status shifts the age of onset of amyloid accumulation (with APOE4 carriers having an earlier age of onset compared to non-carriers), but that APOE4 is not related to rates of change in CSF beta-amyloid over time,” she added.

“Thus, cognitively normal APOE4 carriers may be in more advanced preclinical AD stages at younger ages than individuals who are not APOE4 carriers, which is likely relevant for optimizing clinical trial recruitment strategies,” she said.

Funding for the study was provided by the National Institutes of Health. Dr. Pettigrew has disclosed no relevant financial relationships. The original article contains a complete list of author disclosures.

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

SAN FRANCISCO – Widely anticipated data from a phase 3 trial of the monoclonal antibody lecanemab suggest the drug “modestly” relieved cognitive impairment in patients with early Alzheimer’s disease (AD) – but at a cost.

In the CLARITY AD trial, adverse events (AEs) were common compared with placebo, including amyloid-related edema and effusions; and a recent news report linked a second death to the drug.

Moving forward, “longer trials are warranted to determine the efficacy and safety of lecanemab in early Alzheimer’s disease,” wrote Christopher H. van Dyck, MD, Yale University, New Haven, Conn., and colleagues.

The full trial findings were presented at the Clinical Trials on Alzheimer’s Disease (CTAD) conference, with simultaneous publication on Nov. 29 in the New England Journal of Medicine.
 

Complications in the field

The phase 3 trial of lecanemab has been closely watched in AD circles, especially considering positive early data released in September and reported by this news organization at that time.

The Food and Drug Administration is expected to make a decision about possible approval of the drug in January 2023. Only one other antiamyloid treatment, the highly controversial and expensive aducanumab (Aduhelm), is currently approved by the FDA.

For the new 18-month, randomized, double-blind CLARITY AD trial, researchers enrolled 1,795 patients aged 50-90 years (average age, 71 years) with early AD. All were randomly assigned to receive either a placebo (n = 898) or intravenous lecanemab, a humanized immunoglobulin G1 (IgG1) monoclonal antibody that selectively targets amyloid beta (A-beta) protofibrils, at 10 mg/kg of body weight every 2 weeks (n = 897).

The study ran from 2019 to 2021. The participants (52% women, 20% non-White) were recruited in North America, Europe, and Asia. Safety data included all participants, and the modified intention-to-treat group included 1,734 participants, with 859 receiving lecanemab and 875 receiving placebo.

The primary endpoint was the Clinical Dementia Rating–Sum of Boxes (CDR-SB). Scores from 0.5 to 6 are signs of early AD, according to the study. The mean baseline score for both groups was 3.2. The adjusted mean change at 18 months was 1.21 for lecanemab versus 1.66 for placebo (difference, –0.45; 95% confidence interval [CI], –0.67 to –0.23; P < .001).

As Dr. van Dyck noted in his presentation at the CTAD meting, this represents a 27% slowing of the decline in the lecanemab group.

The published findings do not speculate about how this difference would affect the day-to-day life of participants who took the drug, although it does refer to “modestly less decline” of cognition/function in the lecanemab group.

Other measurements that suggest cognitive improvements in the lecanemab group versus placebo include the Alzheimer’s Disease Assessment Scale–Cognitive Subscale score (mean difference, –1.44; 95% CI, –2.27 to –0.61), the Alzheimer’s Disease Composite Score (mean difference, –0.05; 95% CI, –.074 to –.027,), and the Alzheimer’s Disease Cooperative Study–Activities of Daily Living Scale for Mild Cognitive Impairment score (mean difference, 2.0; 95% CI, 1.2-2.8; all, P < .001).

Overall, Dr. van Dyck said, “Lecanemab met the primary and secondary endpoints versus placebo at 18 months, with highly significant differences starting at 6 months.”

In a substudy of 698 participants, results showed that amyloid burden fell at a higher rate in the lecanemab group than in the placebo group (difference, –59.1 centiloids; 95% CI, –62.6 to –55.6).

“Lecanemab has high selectivity for soluble aggregated species of A-beta as compared with monomeric amyloid, with moderate selectivity for fibrillar amyloid; this profile is considered to target the most toxic pathologic amyloid species,” the researchers wrote.
 

Concerning AE data

With respect to AEs, deaths occurred in both groups (0.7% in those who took lecanemab and 0.8% in those who took the placebo). The researchers did not attribute any deaths to the drug. However, according to a report in the journal Science published Nov. 27, a 65-year-old woman who was taking the drug as part of a clinical trial “recently died from a massive brain hemorrhage that some researchers link to the drug.”

The woman, the second person “whose death was linked to lecanemab,” died after suffering a stroke. Researchers summarized a case report as saying that the drug “contributed to her brain hemorrhage after biweekly infusions of lecanemab inflamed and weakened the blood vessels.”

Eisai, which sponsored the new trial, told Science that “all the available safety information indicates that lecanemab therapy is not associated with an increased risk of death overall or from any specific cause.”

In a CTAD presentation, study coauthor Marwan Sabbagh, MD, Barrow Neurological Institute, Phoenix, said two hemorrhage-related deaths occurred in an open-label extension. One was in the context of a tissue plasminogen activator treatment for a stroke, which fits with the description of the case in the Science report. “Causality with lecanemab is a little difficult ...,” he said. “Patients on anticoagulation might need further consideration.”

In the CLARITY AD Trial, serious AEs occurred in 14% of the lecanemab group, leading to discontinuation 6.9% of the time, and in 11.3% of the placebo group, leading to discontinuation 2.9% of the time, the investigators reported.

They added that, in the lecanemab group, the most common AEs, defined as affecting more than 10% of participants, were infusion-related reactions (26.4% vs. 7.4% for placebo); amyloid-related imaging abnormalities with cerebral microhemorrhages, cerebral macrohemorrhages, or superficial siderosis (17.3% vs. 9%, respectively); amyloid-related imaging abnormalities with edema or effusions (12.6% vs. 1.7%); headache (11.1% vs. 8.1%); and falls (10.4% vs. 9.6%).

In addition, macrohemorrhage was reported in 0.6% of the lecanemab group and 0.1% of the placebo group.
 

Cautious optimism

In separate interviews, two Alzheimer’s specialists who weren’t involved in the study praised the trial and described the findings as “exciting.” But they also highlighted its limitations.

Alvaro Pascual-Leone, MD, PhD, professor of neurology at Harvard Medical School and chief medical officer of Linus Health, said the study represents impressive progress after 60-plus trials examining anti-amyloid monoclonal antibodies. “This is the first trial that shows a clinical benefit that can be measured,” he said.

However, it’s unclear whether the changes “are really going to make a difference in people’s lives,” he said. The drug is likely to be expensive, owing to the large investment needed for research, he added, and patients will have to undergo costly testing, such as PET scans and spinal taps.

Still, “this could be a valuable adjunct to the armamentarium we have,” which includes interventions such as lifestyle changes, he said.

Howard Fillit, MD, cofounder and chief science officer at the Alzheimer’s Drug Discovery Foundation, noted that the trial reached its primary and secondary endpoints and that the drug had what he called a “modest” effect on cognition.

However, the drugmaker will need to explore the adverse effects, he said, especially among patients with atrial fibrillation who take anticoagulants. And, he said, medicine is still far from the ultimate goal – fully reversing cognitive decline.

Michael Weiner, MD, president of the CTAD22 Scientific Committee, noted in a press release that there is “growing evidence” that some antiamyloid therapies, “especially lecanemab and donanemab” have shown promising results.

“Unfortunately, these treatments are also associated with abnormal differences seen in imaging, including brain swelling and bleeding in the brain,” said Dr. Weiner, professor of radiology, medicine, and neurology at the University of California, San Francisco.

“There is considerable controversy concerning the significance and impact of these findings, including whether or not governments and medical insurance will provide financial coverage for such treatments,” he added.
 

Rave reviews from the Alzheimer’s Association

In a statement, the Alzheimer’s Association raved about lecanemab and declared that the FDA should approve lecanemab on an accelerated basis. The study “confirms this treatment can meaningfully change the course of the disease for people in the earliest stages of Alzheimer’s disease ...” the association said, adding that “it could mean many months more of recognizing their spouse, children and grandchildren.”

The association, which is a staunch supporter of aducanumab, called on the Centers for Medicare & Medicaid Services to cover the drug if the FDA approves it. The association’s statement did not address the drug’s potential high cost, the adverse effects, or the two reported deaths.

The trial was supported by Eisai (regulatory sponsor) with partial funding from Biogen. Dr. van Dyck reports having received research grants from Biogen, Eisai, Biohaven, Cerevel Therapeutics, Eli Lilly, Genentech, Janssen, Novartis, and UCB. He has been a consultant to Cerevel, Eisai, Ono Pharmaceutical, and Roche. Relevant financial relationships for the other investigators are fully listed in the original article.

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

SAN FRANCISCO – Widely anticipated data from a phase 3 trial of the monoclonal antibody lecanemab suggest the drug “modestly” relieved cognitive impairment in patients with early Alzheimer’s disease (AD) – but at a cost.

In the CLARITY AD trial, adverse events (AEs) were common compared with placebo, including amyloid-related edema and effusions; and a recent news report linked a second death to the drug.

Moving forward, “longer trials are warranted to determine the efficacy and safety of lecanemab in early Alzheimer’s disease,” wrote Christopher H. van Dyck, MD, Yale University, New Haven, Conn., and colleagues.

The full trial findings were presented at the Clinical Trials on Alzheimer’s Disease (CTAD) conference, with simultaneous publication on Nov. 29 in the New England Journal of Medicine.
 

Complications in the field

The phase 3 trial of lecanemab has been closely watched in AD circles, especially considering positive early data released in September and reported by this news organization at that time.

The Food and Drug Administration is expected to make a decision about possible approval of the drug in January 2023. Only one other antiamyloid treatment, the highly controversial and expensive aducanumab (Aduhelm), is currently approved by the FDA.

For the new 18-month, randomized, double-blind CLARITY AD trial, researchers enrolled 1,795 patients aged 50-90 years (average age, 71 years) with early AD. All were randomly assigned to receive either a placebo (n = 898) or intravenous lecanemab, a humanized immunoglobulin G1 (IgG1) monoclonal antibody that selectively targets amyloid beta (A-beta) protofibrils, at 10 mg/kg of body weight every 2 weeks (n = 897).

The study ran from 2019 to 2021. The participants (52% women, 20% non-White) were recruited in North America, Europe, and Asia. Safety data included all participants, and the modified intention-to-treat group included 1,734 participants, with 859 receiving lecanemab and 875 receiving placebo.

The primary endpoint was the Clinical Dementia Rating–Sum of Boxes (CDR-SB). Scores from 0.5 to 6 are signs of early AD, according to the study. The mean baseline score for both groups was 3.2. The adjusted mean change at 18 months was 1.21 for lecanemab versus 1.66 for placebo (difference, –0.45; 95% confidence interval [CI], –0.67 to –0.23; P < .001).

As Dr. van Dyck noted in his presentation at the CTAD meting, this represents a 27% slowing of the decline in the lecanemab group.

The published findings do not speculate about how this difference would affect the day-to-day life of participants who took the drug, although it does refer to “modestly less decline” of cognition/function in the lecanemab group.

Other measurements that suggest cognitive improvements in the lecanemab group versus placebo include the Alzheimer’s Disease Assessment Scale–Cognitive Subscale score (mean difference, –1.44; 95% CI, –2.27 to –0.61), the Alzheimer’s Disease Composite Score (mean difference, –0.05; 95% CI, –.074 to –.027,), and the Alzheimer’s Disease Cooperative Study–Activities of Daily Living Scale for Mild Cognitive Impairment score (mean difference, 2.0; 95% CI, 1.2-2.8; all, P < .001).

Overall, Dr. van Dyck said, “Lecanemab met the primary and secondary endpoints versus placebo at 18 months, with highly significant differences starting at 6 months.”

In a substudy of 698 participants, results showed that amyloid burden fell at a higher rate in the lecanemab group than in the placebo group (difference, –59.1 centiloids; 95% CI, –62.6 to –55.6).

“Lecanemab has high selectivity for soluble aggregated species of A-beta as compared with monomeric amyloid, with moderate selectivity for fibrillar amyloid; this profile is considered to target the most toxic pathologic amyloid species,” the researchers wrote.
 

Concerning AE data

With respect to AEs, deaths occurred in both groups (0.7% in those who took lecanemab and 0.8% in those who took the placebo). The researchers did not attribute any deaths to the drug. However, according to a report in the journal Science published Nov. 27, a 65-year-old woman who was taking the drug as part of a clinical trial “recently died from a massive brain hemorrhage that some researchers link to the drug.”

The woman, the second person “whose death was linked to lecanemab,” died after suffering a stroke. Researchers summarized a case report as saying that the drug “contributed to her brain hemorrhage after biweekly infusions of lecanemab inflamed and weakened the blood vessels.”

Eisai, which sponsored the new trial, told Science that “all the available safety information indicates that lecanemab therapy is not associated with an increased risk of death overall or from any specific cause.”

In a CTAD presentation, study coauthor Marwan Sabbagh, MD, Barrow Neurological Institute, Phoenix, said two hemorrhage-related deaths occurred in an open-label extension. One was in the context of a tissue plasminogen activator treatment for a stroke, which fits with the description of the case in the Science report. “Causality with lecanemab is a little difficult ...,” he said. “Patients on anticoagulation might need further consideration.”

In the CLARITY AD Trial, serious AEs occurred in 14% of the lecanemab group, leading to discontinuation 6.9% of the time, and in 11.3% of the placebo group, leading to discontinuation 2.9% of the time, the investigators reported.

They added that, in the lecanemab group, the most common AEs, defined as affecting more than 10% of participants, were infusion-related reactions (26.4% vs. 7.4% for placebo); amyloid-related imaging abnormalities with cerebral microhemorrhages, cerebral macrohemorrhages, or superficial siderosis (17.3% vs. 9%, respectively); amyloid-related imaging abnormalities with edema or effusions (12.6% vs. 1.7%); headache (11.1% vs. 8.1%); and falls (10.4% vs. 9.6%).

In addition, macrohemorrhage was reported in 0.6% of the lecanemab group and 0.1% of the placebo group.
 

Cautious optimism

In separate interviews, two Alzheimer’s specialists who weren’t involved in the study praised the trial and described the findings as “exciting.” But they also highlighted its limitations.

Alvaro Pascual-Leone, MD, PhD, professor of neurology at Harvard Medical School and chief medical officer of Linus Health, said the study represents impressive progress after 60-plus trials examining anti-amyloid monoclonal antibodies. “This is the first trial that shows a clinical benefit that can be measured,” he said.

However, it’s unclear whether the changes “are really going to make a difference in people’s lives,” he said. The drug is likely to be expensive, owing to the large investment needed for research, he added, and patients will have to undergo costly testing, such as PET scans and spinal taps.

Still, “this could be a valuable adjunct to the armamentarium we have,” which includes interventions such as lifestyle changes, he said.

Howard Fillit, MD, cofounder and chief science officer at the Alzheimer’s Drug Discovery Foundation, noted that the trial reached its primary and secondary endpoints and that the drug had what he called a “modest” effect on cognition.

However, the drugmaker will need to explore the adverse effects, he said, especially among patients with atrial fibrillation who take anticoagulants. And, he said, medicine is still far from the ultimate goal – fully reversing cognitive decline.

Michael Weiner, MD, president of the CTAD22 Scientific Committee, noted in a press release that there is “growing evidence” that some antiamyloid therapies, “especially lecanemab and donanemab” have shown promising results.

“Unfortunately, these treatments are also associated with abnormal differences seen in imaging, including brain swelling and bleeding in the brain,” said Dr. Weiner, professor of radiology, medicine, and neurology at the University of California, San Francisco.

“There is considerable controversy concerning the significance and impact of these findings, including whether or not governments and medical insurance will provide financial coverage for such treatments,” he added.
 

Rave reviews from the Alzheimer’s Association

In a statement, the Alzheimer’s Association raved about lecanemab and declared that the FDA should approve lecanemab on an accelerated basis. The study “confirms this treatment can meaningfully change the course of the disease for people in the earliest stages of Alzheimer’s disease ...” the association said, adding that “it could mean many months more of recognizing their spouse, children and grandchildren.”

The association, which is a staunch supporter of aducanumab, called on the Centers for Medicare & Medicaid Services to cover the drug if the FDA approves it. The association’s statement did not address the drug’s potential high cost, the adverse effects, or the two reported deaths.

The trial was supported by Eisai (regulatory sponsor) with partial funding from Biogen. Dr. van Dyck reports having received research grants from Biogen, Eisai, Biohaven, Cerevel Therapeutics, Eli Lilly, Genentech, Janssen, Novartis, and UCB. He has been a consultant to Cerevel, Eisai, Ono Pharmaceutical, and Roche. Relevant financial relationships for the other investigators are fully listed in the original article.

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

SAN FRANCISCO – Widely anticipated data from a phase 3 trial of the monoclonal antibody lecanemab suggest the drug “modestly” relieved cognitive impairment in patients with early Alzheimer’s disease (AD) – but at a cost.

In the CLARITY AD trial, adverse events (AEs) were common compared with placebo, including amyloid-related edema and effusions; and a recent news report linked a second death to the drug.

Moving forward, “longer trials are warranted to determine the efficacy and safety of lecanemab in early Alzheimer’s disease,” wrote Christopher H. van Dyck, MD, Yale University, New Haven, Conn., and colleagues.

The full trial findings were presented at the Clinical Trials on Alzheimer’s Disease (CTAD) conference, with simultaneous publication on Nov. 29 in the New England Journal of Medicine.
 

Complications in the field

The phase 3 trial of lecanemab has been closely watched in AD circles, especially considering positive early data released in September and reported by this news organization at that time.

The Food and Drug Administration is expected to make a decision about possible approval of the drug in January 2023. Only one other antiamyloid treatment, the highly controversial and expensive aducanumab (Aduhelm), is currently approved by the FDA.

For the new 18-month, randomized, double-blind CLARITY AD trial, researchers enrolled 1,795 patients aged 50-90 years (average age, 71 years) with early AD. All were randomly assigned to receive either a placebo (n = 898) or intravenous lecanemab, a humanized immunoglobulin G1 (IgG1) monoclonal antibody that selectively targets amyloid beta (A-beta) protofibrils, at 10 mg/kg of body weight every 2 weeks (n = 897).

The study ran from 2019 to 2021. The participants (52% women, 20% non-White) were recruited in North America, Europe, and Asia. Safety data included all participants, and the modified intention-to-treat group included 1,734 participants, with 859 receiving lecanemab and 875 receiving placebo.

The primary endpoint was the Clinical Dementia Rating–Sum of Boxes (CDR-SB). Scores from 0.5 to 6 are signs of early AD, according to the study. The mean baseline score for both groups was 3.2. The adjusted mean change at 18 months was 1.21 for lecanemab versus 1.66 for placebo (difference, –0.45; 95% confidence interval [CI], –0.67 to –0.23; P < .001).

As Dr. van Dyck noted in his presentation at the CTAD meting, this represents a 27% slowing of the decline in the lecanemab group.

The published findings do not speculate about how this difference would affect the day-to-day life of participants who took the drug, although it does refer to “modestly less decline” of cognition/function in the lecanemab group.

Other measurements that suggest cognitive improvements in the lecanemab group versus placebo include the Alzheimer’s Disease Assessment Scale–Cognitive Subscale score (mean difference, –1.44; 95% CI, –2.27 to –0.61), the Alzheimer’s Disease Composite Score (mean difference, –0.05; 95% CI, –.074 to –.027,), and the Alzheimer’s Disease Cooperative Study–Activities of Daily Living Scale for Mild Cognitive Impairment score (mean difference, 2.0; 95% CI, 1.2-2.8; all, P < .001).

Overall, Dr. van Dyck said, “Lecanemab met the primary and secondary endpoints versus placebo at 18 months, with highly significant differences starting at 6 months.”

In a substudy of 698 participants, results showed that amyloid burden fell at a higher rate in the lecanemab group than in the placebo group (difference, –59.1 centiloids; 95% CI, –62.6 to –55.6).

“Lecanemab has high selectivity for soluble aggregated species of A-beta as compared with monomeric amyloid, with moderate selectivity for fibrillar amyloid; this profile is considered to target the most toxic pathologic amyloid species,” the researchers wrote.
 

Concerning AE data

With respect to AEs, deaths occurred in both groups (0.7% in those who took lecanemab and 0.8% in those who took the placebo). The researchers did not attribute any deaths to the drug. However, according to a report in the journal Science published Nov. 27, a 65-year-old woman who was taking the drug as part of a clinical trial “recently died from a massive brain hemorrhage that some researchers link to the drug.”

The woman, the second person “whose death was linked to lecanemab,” died after suffering a stroke. Researchers summarized a case report as saying that the drug “contributed to her brain hemorrhage after biweekly infusions of lecanemab inflamed and weakened the blood vessels.”

Eisai, which sponsored the new trial, told Science that “all the available safety information indicates that lecanemab therapy is not associated with an increased risk of death overall or from any specific cause.”

In a CTAD presentation, study coauthor Marwan Sabbagh, MD, Barrow Neurological Institute, Phoenix, said two hemorrhage-related deaths occurred in an open-label extension. One was in the context of a tissue plasminogen activator treatment for a stroke, which fits with the description of the case in the Science report. “Causality with lecanemab is a little difficult ...,” he said. “Patients on anticoagulation might need further consideration.”

In the CLARITY AD Trial, serious AEs occurred in 14% of the lecanemab group, leading to discontinuation 6.9% of the time, and in 11.3% of the placebo group, leading to discontinuation 2.9% of the time, the investigators reported.

They added that, in the lecanemab group, the most common AEs, defined as affecting more than 10% of participants, were infusion-related reactions (26.4% vs. 7.4% for placebo); amyloid-related imaging abnormalities with cerebral microhemorrhages, cerebral macrohemorrhages, or superficial siderosis (17.3% vs. 9%, respectively); amyloid-related imaging abnormalities with edema or effusions (12.6% vs. 1.7%); headache (11.1% vs. 8.1%); and falls (10.4% vs. 9.6%).

In addition, macrohemorrhage was reported in 0.6% of the lecanemab group and 0.1% of the placebo group.
 

Cautious optimism

In separate interviews, two Alzheimer’s specialists who weren’t involved in the study praised the trial and described the findings as “exciting.” But they also highlighted its limitations.

Alvaro Pascual-Leone, MD, PhD, professor of neurology at Harvard Medical School and chief medical officer of Linus Health, said the study represents impressive progress after 60-plus trials examining anti-amyloid monoclonal antibodies. “This is the first trial that shows a clinical benefit that can be measured,” he said.

However, it’s unclear whether the changes “are really going to make a difference in people’s lives,” he said. The drug is likely to be expensive, owing to the large investment needed for research, he added, and patients will have to undergo costly testing, such as PET scans and spinal taps.

Still, “this could be a valuable adjunct to the armamentarium we have,” which includes interventions such as lifestyle changes, he said.

Howard Fillit, MD, cofounder and chief science officer at the Alzheimer’s Drug Discovery Foundation, noted that the trial reached its primary and secondary endpoints and that the drug had what he called a “modest” effect on cognition.

However, the drugmaker will need to explore the adverse effects, he said, especially among patients with atrial fibrillation who take anticoagulants. And, he said, medicine is still far from the ultimate goal – fully reversing cognitive decline.

Michael Weiner, MD, president of the CTAD22 Scientific Committee, noted in a press release that there is “growing evidence” that some antiamyloid therapies, “especially lecanemab and donanemab” have shown promising results.

“Unfortunately, these treatments are also associated with abnormal differences seen in imaging, including brain swelling and bleeding in the brain,” said Dr. Weiner, professor of radiology, medicine, and neurology at the University of California, San Francisco.

“There is considerable controversy concerning the significance and impact of these findings, including whether or not governments and medical insurance will provide financial coverage for such treatments,” he added.
 

Rave reviews from the Alzheimer’s Association

In a statement, the Alzheimer’s Association raved about lecanemab and declared that the FDA should approve lecanemab on an accelerated basis. The study “confirms this treatment can meaningfully change the course of the disease for people in the earliest stages of Alzheimer’s disease ...” the association said, adding that “it could mean many months more of recognizing their spouse, children and grandchildren.”

The association, which is a staunch supporter of aducanumab, called on the Centers for Medicare & Medicaid Services to cover the drug if the FDA approves it. The association’s statement did not address the drug’s potential high cost, the adverse effects, or the two reported deaths.

The trial was supported by Eisai (regulatory sponsor) with partial funding from Biogen. Dr. van Dyck reports having received research grants from Biogen, Eisai, Biohaven, Cerevel Therapeutics, Eli Lilly, Genentech, Janssen, Novartis, and UCB. He has been a consultant to Cerevel, Eisai, Ono Pharmaceutical, and Roche. Relevant financial relationships for the other investigators are fully listed in the original article.

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

Black and Latinx older adults are up to three times as likely to develop Alzheimer’s disease than non-Latinx White adults and tend to experience onset at a younger age with more severe symptoms, according to Monica Rivera-Mindt, PhD, a professor of psychology at Fordham University and the Icahn School of Medicine at Mount Sinai, New York. Looking ahead, that means by 2030, nearly 40% of the 8.4 million Americans affected by Alzheimer’s disease will be Black and/or Latinx, she said. These facts were among the stark disparities in health care outcomes Dr. Rivera-Mindt discussed in her presentation on brain health equity at the 2022 annual meeting of the American Neurological Association.

Dr. Rivera-Mindt’s presentation opened the ANA’s plenary session on health disparities and inequities. The plenary, “Advancing Neurologic Equity: Challenges and Paths Forward,” did not simply enumerate racial and ethnic disparities that exist with various neurological conditions. Rather it went beyond the discussion of what disparities exist into understanding the roots of them as well as tips, tools, and resources that can aid clinicians in addressing or ameliorating them.

“Our most prevalent, most burdensome diseases in neurology disproportionately affect persons from minoritized and marginalized backgrounds,” Roy Hamilton, MD, an associate professor of neurology and physical medicine and rehabilitation at the University of Pennsylvania, Philadelphia, said. “If clinicians are unaware of these disparities or don’t have any sense of how to start to address or think about them, then they’re really missing out on an important component of their education as persons who take care of patients with brain disorders.”

Dr. Hamilton, who organized the plenary, noted that awareness of these disparities is crucial to comprehensively caring for patients.
 

Missed opportunities

“We’re talking about disadvantages that are structural and large scale, but those disadvantages play themselves out in the individual encounter,” Dr. Hamilton said. “When physicians see patients, they have to treat the whole patient in front of them,” which means being aware of the risks and factors that could affect a patient’s clinical presentation. “Being aware of disparities has practical impacts on physician judgment,” he said.

For example, recent research in multiple sclerosis (MS) has highlighted how clinicians may be missing diagnosis of this condition in non-White populations because the condition has been regarded for so long as a “White person’s” disease, Dr. Hamilton said. In non-White patients exhibiting MS symptoms, then, clinicians may have been less likely to consider MS as a possibility, thereby delaying diagnosis and treatment.

Those patterns may partly explain why the mortality rate for MS is greater in Black patients, who also show more rapid neurodegeneration than White patients with MS, Lilyana Amezcua, MD, an associate professor of neurology at the University of Southern California, Los Angeles, reported in the plenary’s second presentation.
 

Transgender issues

The third session, presented by Nicole Rosendale, MD, an assistant professor of neurology at the University of California, San Francisco, and director of the San Francisco General Hospital neurology inpatient services, examined disparities in neurology within the LGBTQ+ community through representative case studies and then offered specific ways that neurologists could make their practices more inclusive and equitable for sexual and gender minorities.

Her first case study was a 52-year-old man who presented with new-onset seizures, right hemiparesis, and aphasia. A brain biopsy consistent with adenocarcinoma eventually led his physician to discover he had metastatic breast cancer. It turned out the man was transgender and, despite a family history of breast cancer, hadn’t been advised to get breast cancer screenings.

“Breast cancer was not initially on the differential as no one had identified that the patient was transmasculine,” Dr. Rosendale said. A major challenge to providing care to transgender patients is a dearth of data on risks and screening recommendations. Another barrier is low knowledge of LGBTQ+ health among neurologists, Dr. Rosendale said while sharing findings from her 2019 study on the topic and calling for more research in LGBTQ+ populations.

Dr. Rosendale’s second case study dealt with a nonbinary patient who suffered from debilitating headaches for decades, first because they lacked access to health insurance and then because negative experiences with providers dissuaded them from seeking care. In data from the Center for American Progress she shared, 8% of LGB respondents and 22% of transgender respondents said they had avoided or delayed care because of fear of discrimination or mistreatment.

“So it’s not only access but also what experiences people are having when they go in and whether they’re actually even getting access to care or being taken care of,” Dr. Rosendale said. Other findings from the CAP found that:

• 8% of LGB patients and 29% of transgender patients reported having a clinician refuse to see them.
• 6% of LGB patients and 12% of transgender patients reported that a clinician refused to give them health care.
• 9% of LGB patients and 21% of transgender patients experienced harsh or abusive language during a health care experience.
• 7% of LGB patients and nearly a third (29%) of transgender patients experienced unwanted physical contact, such as fondling or sexual assault.

Reducing the disparities

Adys Mendizabal, MD, an assistant professor of neurology at the Institute of Society and Genetics at the University of California, Los Angeles, who attended the presentation, was grateful to see how the various lectures enriched the discussion beyond stating the fact of racial/ethnic disparities and dug into the nuances on how to think about and address these disparities. She particularly appreciated discussion about the need to go out of the way to recruit diverse patient populations for clinical trials while also providing them care.

“It is definitely complicated, but it’s not impossible for an individual neurologist or an individual department to do something to reduce some of the disparities,” Dr. Mendizabal said. “It starts with just knowing that they exist and being aware of some of the things that may be impacting care for a particular patient.”
 

Tools to counter disparity

In the final presentation, Amy Kind, MD, PhD, the associate dean for social health sciences and programs at the University of Wisconsin–Madison, rounded out the discussion by exploring social determinants of health and their influence on outcomes.

“Social determinants impact brain health, and brain health is not distributed equally,” Dr. Kind told attendees. “We have known this for decades, yet disparities persist.”

Dr. Kind described the “exposome,” a “measure of all the exposures of an individual in a lifetime and how those exposures relate to health,” according to the CDC, and then introduced a tool clinicians can use to better understand social determinants of health in specific geographic areas. The Neighborhood Atlas, which Dr. Kind described in the New England Journal of Medicine in 2018, measures 17 social determinants across small population-sensitive areas and provides an area deprivation index. A high area deprivation index is linked to a range of negative outcomes, including reshopitalization, later diagnoses, less comprehensive diagnostic evaluation, increased risk of postsurgical complications, and decreased life expectancy.

“One of the things that really stood out to me about Dr. Kind’s discussion of the use of the area deprivation index was the fact that understanding and quantifying these kinds of risks and exposures is the vehicle for creating the kinds of social changes, including policy changes, that will actually lead to addressing and mitigating some of these lifelong risks and exposures,” Dr. Hamilton said. “It is implausible to think that a specific group of people would be genetically more susceptible to basically every disease that we know,” he added. “It makes much more sense to think that groups of individuals have been subjected systematically to conditions that impair health in a variety of ways.”
 

Not just race, ethnicity, sex, and gender

Following the four presentations from researchers in health inequities was an Emerging Scholar presentation in which Jay B. Lusk, an MD/MBA candidate at Duke University, Durham, N.C., shared new research findings on the role of neighborhood disadvantage in predicting mortality from coma, stroke, and other neurologic conditions. His findings revealed that living in a neighborhood with greater deprivation substantially increased risk of mortality even after accounting for individual wealth and demographics.

Maria Eugenia Diaz-Ortiz, PhD, of the department of neurology, University of Pennsylvania, Philadelphia, said she found the five presentations to be an excellent introduction to people like herself who are in the earlier stages of learning about health equity research.

“I think they introduced various important concepts and frameworks and provided tools for people who don’t know about them,” Dr. Diaz-Ortiz said. “Then they asked important questions and provided some solutions to them.”

Dr. Diaz-Ortiz also appreciated seemingly minor but actually important details in how the speakers presented themselves, such as Dr. Rivera-Mindt opening with a land acknowledgment and her disclosures of “positionality.” The former recognized the traditional Native American custodians of the land on which she lives and works, and the latter revealed details about her as an individual – such as being the Afro-Latinx daughter of immigrants yet being cisgender, able-bodied, and U.S.-born – that show where she falls on the axis of adversity and axis of privilege.
 

Implications for research

The biggest takeaway for Dr. Diaz-Ortiz, however, came from the first Q&A session when someone asked how to increase underrepresented populations in dementia research. Dr. Rivera-Mindt described her experience engaging these communities by employing “community-based participatory research practices, which involves making yourself a part of the community and making the community active participants in the research,” Dr. Diaz-Ortiz said. “It’s an evidence-based approach that has been shown to increase participation in research not only in her work but in the work of others.”

Preaching to the choir

Dr. Diaz-Ortiz was pleased overall with the plenary but disappointed in its placement at the end of the meeting, when attendance is always lower as attendees head home.

“The people who stayed were people who already know and recognize the value of health equity work, so I think that was a missed opportunity where the session could have been included on day one or two to boost attendance and also to educate like a broader group of neurologists,” Dr. Diaz-Ortiz said in an interview.

Dr. Mendizabal felt similarly, appreciating the plenary but noting it was “definitely overdue” and that it should not be the last session. Instead, sessions on health equity should be as easy as possible to attend to bring in larger audiences. “Perhaps having that session on a Saturday or Sunday would have a higher likelihood of greater attendance than on a Tuesday,” she said. That said, Dr. Mendizabal also noticed that greater attention to health care disparities was woven into many other sessions throughout the conference, which is “the best way of addressing health equity instead of trying to just designate a session,” she said.

Dr. Mendizabal hopes that plenaries like this one and the weaving of health equity issues into presentations throughout neurology conferences continue.

“After the racial reckoning in 2020, there was a big impetus and a big wave of energy in addressing health disparities in the field, and I hope that that momentum is not starting to wane,” Dr. Mendizabal said. “It’s important because not talking about is not going to make this issue go away.”

Dr. Hamilton agreed that it is important that the conversation continue and that physicians recognize the importance of understanding health care disparities and determinants of health, regardless of where they fall on the political spectrum or whether they choose to get involved in policy or advocacy.

“Irrespective of whether you think race or ethnicity or socioeconomic status are political issues or not, it is the case that you’re obligated to have an objective understanding of the factors that contribute to your patient’s health and as points of intervention,” Dr. Hamilton said. “So even if you don’t want to sit down and jot off that email to your senator, you still have to take these factors into account when you’re treating the person who’s sitting right in front of you, and that’s not political. That’s the promise of being a physician.”

Dr. Amezcua has received personal compensation for consulting, speaking, or serving on steering committees or advisory boards for Biogen Idec, Novartis, Genentech, and EMD Serono, and she has received research support from Biogen Idec and Bristol Myers Squibb Foundation. Dr. Kind reported support from the Alzheimer’s Association. Dr. Diaz-Ortiz is coinventor of a provisional patent submitted by the University of Pennsylvania that relates to a potential therapeutic in Parkinson’s disease. Mr. Lusk reported fellowship support from American Heart Association and travel support from the American Neurological Association. No other speakers or sources had relevant disclosures.
 

Black and Latinx older adults are up to three times as likely to develop Alzheimer’s disease than non-Latinx White adults and tend to experience onset at a younger age with more severe symptoms, according to Monica Rivera-Mindt, PhD, a professor of psychology at Fordham University and the Icahn School of Medicine at Mount Sinai, New York. Looking ahead, that means by 2030, nearly 40% of the 8.4 million Americans affected by Alzheimer’s disease will be Black and/or Latinx, she said. These facts were among the stark disparities in health care outcomes Dr. Rivera-Mindt discussed in her presentation on brain health equity at the 2022 annual meeting of the American Neurological Association.

Dr. Rivera-Mindt’s presentation opened the ANA’s plenary session on health disparities and inequities. The plenary, “Advancing Neurologic Equity: Challenges and Paths Forward,” did not simply enumerate racial and ethnic disparities that exist with various neurological conditions. Rather it went beyond the discussion of what disparities exist into understanding the roots of them as well as tips, tools, and resources that can aid clinicians in addressing or ameliorating them.

“Our most prevalent, most burdensome diseases in neurology disproportionately affect persons from minoritized and marginalized backgrounds,” Roy Hamilton, MD, an associate professor of neurology and physical medicine and rehabilitation at the University of Pennsylvania, Philadelphia, said. “If clinicians are unaware of these disparities or don’t have any sense of how to start to address or think about them, then they’re really missing out on an important component of their education as persons who take care of patients with brain disorders.”

Dr. Hamilton, who organized the plenary, noted that awareness of these disparities is crucial to comprehensively caring for patients.
 

Missed opportunities

“We’re talking about disadvantages that are structural and large scale, but those disadvantages play themselves out in the individual encounter,” Dr. Hamilton said. “When physicians see patients, they have to treat the whole patient in front of them,” which means being aware of the risks and factors that could affect a patient’s clinical presentation. “Being aware of disparities has practical impacts on physician judgment,” he said.

For example, recent research in multiple sclerosis (MS) has highlighted how clinicians may be missing diagnosis of this condition in non-White populations because the condition has been regarded for so long as a “White person’s” disease, Dr. Hamilton said. In non-White patients exhibiting MS symptoms, then, clinicians may have been less likely to consider MS as a possibility, thereby delaying diagnosis and treatment.

Those patterns may partly explain why the mortality rate for MS is greater in Black patients, who also show more rapid neurodegeneration than White patients with MS, Lilyana Amezcua, MD, an associate professor of neurology at the University of Southern California, Los Angeles, reported in the plenary’s second presentation.
 

Transgender issues

The third session, presented by Nicole Rosendale, MD, an assistant professor of neurology at the University of California, San Francisco, and director of the San Francisco General Hospital neurology inpatient services, examined disparities in neurology within the LGBTQ+ community through representative case studies and then offered specific ways that neurologists could make their practices more inclusive and equitable for sexual and gender minorities.

Her first case study was a 52-year-old man who presented with new-onset seizures, right hemiparesis, and aphasia. A brain biopsy consistent with adenocarcinoma eventually led his physician to discover he had metastatic breast cancer. It turned out the man was transgender and, despite a family history of breast cancer, hadn’t been advised to get breast cancer screenings.

“Breast cancer was not initially on the differential as no one had identified that the patient was transmasculine,” Dr. Rosendale said. A major challenge to providing care to transgender patients is a dearth of data on risks and screening recommendations. Another barrier is low knowledge of LGBTQ+ health among neurologists, Dr. Rosendale said while sharing findings from her 2019 study on the topic and calling for more research in LGBTQ+ populations.

Dr. Rosendale’s second case study dealt with a nonbinary patient who suffered from debilitating headaches for decades, first because they lacked access to health insurance and then because negative experiences with providers dissuaded them from seeking care. In data from the Center for American Progress she shared, 8% of LGB respondents and 22% of transgender respondents said they had avoided or delayed care because of fear of discrimination or mistreatment.

“So it’s not only access but also what experiences people are having when they go in and whether they’re actually even getting access to care or being taken care of,” Dr. Rosendale said. Other findings from the CAP found that:

• 8% of LGB patients and 29% of transgender patients reported having a clinician refuse to see them.
• 6% of LGB patients and 12% of transgender patients reported that a clinician refused to give them health care.
• 9% of LGB patients and 21% of transgender patients experienced harsh or abusive language during a health care experience.
• 7% of LGB patients and nearly a third (29%) of transgender patients experienced unwanted physical contact, such as fondling or sexual assault.

Reducing the disparities

Adys Mendizabal, MD, an assistant professor of neurology at the Institute of Society and Genetics at the University of California, Los Angeles, who attended the presentation, was grateful to see how the various lectures enriched the discussion beyond stating the fact of racial/ethnic disparities and dug into the nuances on how to think about and address these disparities. She particularly appreciated discussion about the need to go out of the way to recruit diverse patient populations for clinical trials while also providing them care.

“It is definitely complicated, but it’s not impossible for an individual neurologist or an individual department to do something to reduce some of the disparities,” Dr. Mendizabal said. “It starts with just knowing that they exist and being aware of some of the things that may be impacting care for a particular patient.”
 

Tools to counter disparity

In the final presentation, Amy Kind, MD, PhD, the associate dean for social health sciences and programs at the University of Wisconsin–Madison, rounded out the discussion by exploring social determinants of health and their influence on outcomes.

“Social determinants impact brain health, and brain health is not distributed equally,” Dr. Kind told attendees. “We have known this for decades, yet disparities persist.”

Dr. Kind described the “exposome,” a “measure of all the exposures of an individual in a lifetime and how those exposures relate to health,” according to the CDC, and then introduced a tool clinicians can use to better understand social determinants of health in specific geographic areas. The Neighborhood Atlas, which Dr. Kind described in the New England Journal of Medicine in 2018, measures 17 social determinants across small population-sensitive areas and provides an area deprivation index. A high area deprivation index is linked to a range of negative outcomes, including reshopitalization, later diagnoses, less comprehensive diagnostic evaluation, increased risk of postsurgical complications, and decreased life expectancy.

“One of the things that really stood out to me about Dr. Kind’s discussion of the use of the area deprivation index was the fact that understanding and quantifying these kinds of risks and exposures is the vehicle for creating the kinds of social changes, including policy changes, that will actually lead to addressing and mitigating some of these lifelong risks and exposures,” Dr. Hamilton said. “It is implausible to think that a specific group of people would be genetically more susceptible to basically every disease that we know,” he added. “It makes much more sense to think that groups of individuals have been subjected systematically to conditions that impair health in a variety of ways.”
 

Not just race, ethnicity, sex, and gender

Following the four presentations from researchers in health inequities was an Emerging Scholar presentation in which Jay B. Lusk, an MD/MBA candidate at Duke University, Durham, N.C., shared new research findings on the role of neighborhood disadvantage in predicting mortality from coma, stroke, and other neurologic conditions. His findings revealed that living in a neighborhood with greater deprivation substantially increased risk of mortality even after accounting for individual wealth and demographics.

Maria Eugenia Diaz-Ortiz, PhD, of the department of neurology, University of Pennsylvania, Philadelphia, said she found the five presentations to be an excellent introduction to people like herself who are in the earlier stages of learning about health equity research.

“I think they introduced various important concepts and frameworks and provided tools for people who don’t know about them,” Dr. Diaz-Ortiz said. “Then they asked important questions and provided some solutions to them.”

Dr. Diaz-Ortiz also appreciated seemingly minor but actually important details in how the speakers presented themselves, such as Dr. Rivera-Mindt opening with a land acknowledgment and her disclosures of “positionality.” The former recognized the traditional Native American custodians of the land on which she lives and works, and the latter revealed details about her as an individual – such as being the Afro-Latinx daughter of immigrants yet being cisgender, able-bodied, and U.S.-born – that show where she falls on the axis of adversity and axis of privilege.
 

Implications for research

The biggest takeaway for Dr. Diaz-Ortiz, however, came from the first Q&A session when someone asked how to increase underrepresented populations in dementia research. Dr. Rivera-Mindt described her experience engaging these communities by employing “community-based participatory research practices, which involves making yourself a part of the community and making the community active participants in the research,” Dr. Diaz-Ortiz said. “It’s an evidence-based approach that has been shown to increase participation in research not only in her work but in the work of others.”

Preaching to the choir

Dr. Diaz-Ortiz was pleased overall with the plenary but disappointed in its placement at the end of the meeting, when attendance is always lower as attendees head home.

“The people who stayed were people who already know and recognize the value of health equity work, so I think that was a missed opportunity where the session could have been included on day one or two to boost attendance and also to educate like a broader group of neurologists,” Dr. Diaz-Ortiz said in an interview.

Dr. Mendizabal felt similarly, appreciating the plenary but noting it was “definitely overdue” and that it should not be the last session. Instead, sessions on health equity should be as easy as possible to attend to bring in larger audiences. “Perhaps having that session on a Saturday or Sunday would have a higher likelihood of greater attendance than on a Tuesday,” she said. That said, Dr. Mendizabal also noticed that greater attention to health care disparities was woven into many other sessions throughout the conference, which is “the best way of addressing health equity instead of trying to just designate a session,” she said.

Dr. Mendizabal hopes that plenaries like this one and the weaving of health equity issues into presentations throughout neurology conferences continue.

“After the racial reckoning in 2020, there was a big impetus and a big wave of energy in addressing health disparities in the field, and I hope that that momentum is not starting to wane,” Dr. Mendizabal said. “It’s important because not talking about is not going to make this issue go away.”

Dr. Hamilton agreed that it is important that the conversation continue and that physicians recognize the importance of understanding health care disparities and determinants of health, regardless of where they fall on the political spectrum or whether they choose to get involved in policy or advocacy.

“Irrespective of whether you think race or ethnicity or socioeconomic status are political issues or not, it is the case that you’re obligated to have an objective understanding of the factors that contribute to your patient’s health and as points of intervention,” Dr. Hamilton said. “So even if you don’t want to sit down and jot off that email to your senator, you still have to take these factors into account when you’re treating the person who’s sitting right in front of you, and that’s not political. That’s the promise of being a physician.”

Dr. Amezcua has received personal compensation for consulting, speaking, or serving on steering committees or advisory boards for Biogen Idec, Novartis, Genentech, and EMD Serono, and she has received research support from Biogen Idec and Bristol Myers Squibb Foundation. Dr. Kind reported support from the Alzheimer’s Association. Dr. Diaz-Ortiz is coinventor of a provisional patent submitted by the University of Pennsylvania that relates to a potential therapeutic in Parkinson’s disease. Mr. Lusk reported fellowship support from American Heart Association and travel support from the American Neurological Association. No other speakers or sources had relevant disclosures.
 

Black and Latinx older adults are up to three times as likely to develop Alzheimer’s disease than non-Latinx White adults and tend to experience onset at a younger age with more severe symptoms, according to Monica Rivera-Mindt, PhD, a professor of psychology at Fordham University and the Icahn School of Medicine at Mount Sinai, New York. Looking ahead, that means by 2030, nearly 40% of the 8.4 million Americans affected by Alzheimer’s disease will be Black and/or Latinx, she said. These facts were among the stark disparities in health care outcomes Dr. Rivera-Mindt discussed in her presentation on brain health equity at the 2022 annual meeting of the American Neurological Association.

Dr. Rivera-Mindt’s presentation opened the ANA’s plenary session on health disparities and inequities. The plenary, “Advancing Neurologic Equity: Challenges and Paths Forward,” did not simply enumerate racial and ethnic disparities that exist with various neurological conditions. Rather it went beyond the discussion of what disparities exist into understanding the roots of them as well as tips, tools, and resources that can aid clinicians in addressing or ameliorating them.

“Our most prevalent, most burdensome diseases in neurology disproportionately affect persons from minoritized and marginalized backgrounds,” Roy Hamilton, MD, an associate professor of neurology and physical medicine and rehabilitation at the University of Pennsylvania, Philadelphia, said. “If clinicians are unaware of these disparities or don’t have any sense of how to start to address or think about them, then they’re really missing out on an important component of their education as persons who take care of patients with brain disorders.”

Dr. Hamilton, who organized the plenary, noted that awareness of these disparities is crucial to comprehensively caring for patients.
 

Missed opportunities

“We’re talking about disadvantages that are structural and large scale, but those disadvantages play themselves out in the individual encounter,” Dr. Hamilton said. “When physicians see patients, they have to treat the whole patient in front of them,” which means being aware of the risks and factors that could affect a patient’s clinical presentation. “Being aware of disparities has practical impacts on physician judgment,” he said.

For example, recent research in multiple sclerosis (MS) has highlighted how clinicians may be missing diagnosis of this condition in non-White populations because the condition has been regarded for so long as a “White person’s” disease, Dr. Hamilton said. In non-White patients exhibiting MS symptoms, then, clinicians may have been less likely to consider MS as a possibility, thereby delaying diagnosis and treatment.

Those patterns may partly explain why the mortality rate for MS is greater in Black patients, who also show more rapid neurodegeneration than White patients with MS, Lilyana Amezcua, MD, an associate professor of neurology at the University of Southern California, Los Angeles, reported in the plenary’s second presentation.
 

Transgender issues

The third session, presented by Nicole Rosendale, MD, an assistant professor of neurology at the University of California, San Francisco, and director of the San Francisco General Hospital neurology inpatient services, examined disparities in neurology within the LGBTQ+ community through representative case studies and then offered specific ways that neurologists could make their practices more inclusive and equitable for sexual and gender minorities.

Her first case study was a 52-year-old man who presented with new-onset seizures, right hemiparesis, and aphasia. A brain biopsy consistent with adenocarcinoma eventually led his physician to discover he had metastatic breast cancer. It turned out the man was transgender and, despite a family history of breast cancer, hadn’t been advised to get breast cancer screenings.

“Breast cancer was not initially on the differential as no one had identified that the patient was transmasculine,” Dr. Rosendale said. A major challenge to providing care to transgender patients is a dearth of data on risks and screening recommendations. Another barrier is low knowledge of LGBTQ+ health among neurologists, Dr. Rosendale said while sharing findings from her 2019 study on the topic and calling for more research in LGBTQ+ populations.

Dr. Rosendale’s second case study dealt with a nonbinary patient who suffered from debilitating headaches for decades, first because they lacked access to health insurance and then because negative experiences with providers dissuaded them from seeking care. In data from the Center for American Progress she shared, 8% of LGB respondents and 22% of transgender respondents said they had avoided or delayed care because of fear of discrimination or mistreatment.

“So it’s not only access but also what experiences people are having when they go in and whether they’re actually even getting access to care or being taken care of,” Dr. Rosendale said. Other findings from the CAP found that:

• 8% of LGB patients and 29% of transgender patients reported having a clinician refuse to see them.
• 6% of LGB patients and 12% of transgender patients reported that a clinician refused to give them health care.
• 9% of LGB patients and 21% of transgender patients experienced harsh or abusive language during a health care experience.
• 7% of LGB patients and nearly a third (29%) of transgender patients experienced unwanted physical contact, such as fondling or sexual assault.

Reducing the disparities

Adys Mendizabal, MD, an assistant professor of neurology at the Institute of Society and Genetics at the University of California, Los Angeles, who attended the presentation, was grateful to see how the various lectures enriched the discussion beyond stating the fact of racial/ethnic disparities and dug into the nuances on how to think about and address these disparities. She particularly appreciated discussion about the need to go out of the way to recruit diverse patient populations for clinical trials while also providing them care.

“It is definitely complicated, but it’s not impossible for an individual neurologist or an individual department to do something to reduce some of the disparities,” Dr. Mendizabal said. “It starts with just knowing that they exist and being aware of some of the things that may be impacting care for a particular patient.”
 

Tools to counter disparity

In the final presentation, Amy Kind, MD, PhD, the associate dean for social health sciences and programs at the University of Wisconsin–Madison, rounded out the discussion by exploring social determinants of health and their influence on outcomes.

“Social determinants impact brain health, and brain health is not distributed equally,” Dr. Kind told attendees. “We have known this for decades, yet disparities persist.”

Dr. Kind described the “exposome,” a “measure of all the exposures of an individual in a lifetime and how those exposures relate to health,” according to the CDC, and then introduced a tool clinicians can use to better understand social determinants of health in specific geographic areas. The Neighborhood Atlas, which Dr. Kind described in the New England Journal of Medicine in 2018, measures 17 social determinants across small population-sensitive areas and provides an area deprivation index. A high area deprivation index is linked to a range of negative outcomes, including reshopitalization, later diagnoses, less comprehensive diagnostic evaluation, increased risk of postsurgical complications, and decreased life expectancy.

“One of the things that really stood out to me about Dr. Kind’s discussion of the use of the area deprivation index was the fact that understanding and quantifying these kinds of risks and exposures is the vehicle for creating the kinds of social changes, including policy changes, that will actually lead to addressing and mitigating some of these lifelong risks and exposures,” Dr. Hamilton said. “It is implausible to think that a specific group of people would be genetically more susceptible to basically every disease that we know,” he added. “It makes much more sense to think that groups of individuals have been subjected systematically to conditions that impair health in a variety of ways.”
 

Not just race, ethnicity, sex, and gender

Following the four presentations from researchers in health inequities was an Emerging Scholar presentation in which Jay B. Lusk, an MD/MBA candidate at Duke University, Durham, N.C., shared new research findings on the role of neighborhood disadvantage in predicting mortality from coma, stroke, and other neurologic conditions. His findings revealed that living in a neighborhood with greater deprivation substantially increased risk of mortality even after accounting for individual wealth and demographics.

Maria Eugenia Diaz-Ortiz, PhD, of the department of neurology, University of Pennsylvania, Philadelphia, said she found the five presentations to be an excellent introduction to people like herself who are in the earlier stages of learning about health equity research.

“I think they introduced various important concepts and frameworks and provided tools for people who don’t know about them,” Dr. Diaz-Ortiz said. “Then they asked important questions and provided some solutions to them.”

Dr. Diaz-Ortiz also appreciated seemingly minor but actually important details in how the speakers presented themselves, such as Dr. Rivera-Mindt opening with a land acknowledgment and her disclosures of “positionality.” The former recognized the traditional Native American custodians of the land on which she lives and works, and the latter revealed details about her as an individual – such as being the Afro-Latinx daughter of immigrants yet being cisgender, able-bodied, and U.S.-born – that show where she falls on the axis of adversity and axis of privilege.
 

Implications for research

The biggest takeaway for Dr. Diaz-Ortiz, however, came from the first Q&A session when someone asked how to increase underrepresented populations in dementia research. Dr. Rivera-Mindt described her experience engaging these communities by employing “community-based participatory research practices, which involves making yourself a part of the community and making the community active participants in the research,” Dr. Diaz-Ortiz said. “It’s an evidence-based approach that has been shown to increase participation in research not only in her work but in the work of others.”

Preaching to the choir

Dr. Diaz-Ortiz was pleased overall with the plenary but disappointed in its placement at the end of the meeting, when attendance is always lower as attendees head home.

“The people who stayed were people who already know and recognize the value of health equity work, so I think that was a missed opportunity where the session could have been included on day one or two to boost attendance and also to educate like a broader group of neurologists,” Dr. Diaz-Ortiz said in an interview.

Dr. Mendizabal felt similarly, appreciating the plenary but noting it was “definitely overdue” and that it should not be the last session. Instead, sessions on health equity should be as easy as possible to attend to bring in larger audiences. “Perhaps having that session on a Saturday or Sunday would have a higher likelihood of greater attendance than on a Tuesday,” she said. That said, Dr. Mendizabal also noticed that greater attention to health care disparities was woven into many other sessions throughout the conference, which is “the best way of addressing health equity instead of trying to just designate a session,” she said.

Dr. Mendizabal hopes that plenaries like this one and the weaving of health equity issues into presentations throughout neurology conferences continue.

“After the racial reckoning in 2020, there was a big impetus and a big wave of energy in addressing health disparities in the field, and I hope that that momentum is not starting to wane,” Dr. Mendizabal said. “It’s important because not talking about is not going to make this issue go away.”

Dr. Hamilton agreed that it is important that the conversation continue and that physicians recognize the importance of understanding health care disparities and determinants of health, regardless of where they fall on the political spectrum or whether they choose to get involved in policy or advocacy.

“Irrespective of whether you think race or ethnicity or socioeconomic status are political issues or not, it is the case that you’re obligated to have an objective understanding of the factors that contribute to your patient’s health and as points of intervention,” Dr. Hamilton said. “So even if you don’t want to sit down and jot off that email to your senator, you still have to take these factors into account when you’re treating the person who’s sitting right in front of you, and that’s not political. That’s the promise of being a physician.”

Dr. Amezcua has received personal compensation for consulting, speaking, or serving on steering committees or advisory boards for Biogen Idec, Novartis, Genentech, and EMD Serono, and she has received research support from Biogen Idec and Bristol Myers Squibb Foundation. Dr. Kind reported support from the Alzheimer’s Association. Dr. Diaz-Ortiz is coinventor of a provisional patent submitted by the University of Pennsylvania that relates to a potential therapeutic in Parkinson’s disease. Mr. Lusk reported fellowship support from American Heart Association and travel support from the American Neurological Association. No other speakers or sources had relevant disclosures.
 

In the October 2022 issue of JAMA Neurology was a research article and accompanying editorial on the ATN (amyloid/tau/neurodegeneration) framework for diagnosing and treating Alzheimer’s disease.

There are valid concerns with any system centered on early dementia diagnosis. If the new generation of Alzheimer’s treatments can reverse pathology before the symptoms are apparent, it certainly makes sense to treat people as early as possible. In a terrible disease with only partially effective treatments now, this is encouraging news.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

In the October 2022 issue of JAMA Neurology was a research article and accompanying editorial on the ATN (amyloid/tau/neurodegeneration) framework for diagnosing and treating Alzheimer’s disease.

There are valid concerns with any system centered on early dementia diagnosis. If the new generation of Alzheimer’s treatments can reverse pathology before the symptoms are apparent, it certainly makes sense to treat people as early as possible. In a terrible disease with only partially effective treatments now, this is encouraging news.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

In the October 2022 issue of JAMA Neurology was a research article and accompanying editorial on the ATN (amyloid/tau/neurodegeneration) framework for diagnosing and treating Alzheimer’s disease.

There are valid concerns with any system centered on early dementia diagnosis. If the new generation of Alzheimer’s treatments can reverse pathology before the symptoms are apparent, it certainly makes sense to treat people as early as possible. In a terrible disease with only partially effective treatments now, this is encouraging news.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

Of the more than 6 million patients with Alzheimer’s disease in the United States aged 65 or older, nearly two-thirds are women. A new study published online in Cell may help explain the gender gap – and offer clues to new treatments for helping patients of both sexes fight back.

Researchers zeroed in on a gene named USP11, found on the X chromosome. People assigned female at birth have two X chromosomes, while people assigned male at birth have one X and one Y. So while all males have one copy of USP11, females have two.
 

The body’s trash collection system

In the normal course of events, the brain creates waste that must be removed lest it becomes toxic. One waste product is the protein tau. Too little tau can damage nerve cells, explained researchers David Kang, PhD, and Jung-A “Alexa” Woo, PhD, who led the study. But too much becomes toxic and can lead to neurodegenerative diseases such as Alzheimer’s disease. In fact, new research suggests that testing for changes in tau may someday help doctors diagnose Alzheimer’s disease earlier.

To manage tau, the brain uses a regulatory protein called ubiquitin to “tag” or signal the body that extra tau should be removed.

USP11’s job is to give instructions to make an enzyme that removes the ubiquitin tag to maintain balance. But if too much of the enzyme is present, too much tau gets untagged – and not enough of it gets cleared.

“Our study showed USP11 is higher in females than males in both humans and in mice,” Dr. Kang said. “That’s already true before the onset of dementia. But once someone has Alzheimer’s disease, USP11 is much higher – regardless of sex.”

The study adds to a growing body of evidence that shows that women may be more vulnerable than men to higher levels of tau, possibly explaining why women are affected by the disease more often than men.

But what if there was a way to “turn off” or deactivate the USP11 gene? Might that help prevent Alzheimer’s disease? And could it be done safely?
 

What happened when the gene was eliminated?

To examine these questions, researchers used a method of gene manipulation to completely delete the USP11 gene in mice. They then examined the mice for changes. The result? The mice seemed fine.

“The mice bred well. Their brains looked fine,” Dr. Woo said.

It would not be possible – or ethical – to remove a gene from humans. But when a medical condition makes a certain gene unhelpful, that gene can be partially blocked or expression of the gene can be reduced with medication. In fact, medications targeting enzymes are common. Examples include statins for cardiovascular disease or HIV treatments that inhibit protease enzymes.

“If we are able to identify some type of medicine that would inhibit USP11, our study suggests it would be well tolerated and benefit women,” Dr. Woo said.

Dr. Kang also cautions that the process for creating such a therapy takes at least 10-15 years. The researchers said they’d like to shorten the timeline and plan to study currently approved FDA medications to see if any might work to target USP11 gene activity – and hopefully bring forth a new treatment for Alzheimer’s disease sooner.

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

Of the more than 6 million patients with Alzheimer’s disease in the United States aged 65 or older, nearly two-thirds are women. A new study published online in Cell may help explain the gender gap – and offer clues to new treatments for helping patients of both sexes fight back.

Researchers zeroed in on a gene named USP11, found on the X chromosome. People assigned female at birth have two X chromosomes, while people assigned male at birth have one X and one Y. So while all males have one copy of USP11, females have two.
 

The body’s trash collection system

In the normal course of events, the brain creates waste that must be removed lest it becomes toxic. One waste product is the protein tau. Too little tau can damage nerve cells, explained researchers David Kang, PhD, and Jung-A “Alexa” Woo, PhD, who led the study. But too much becomes toxic and can lead to neurodegenerative diseases such as Alzheimer’s disease. In fact, new research suggests that testing for changes in tau may someday help doctors diagnose Alzheimer’s disease earlier.

To manage tau, the brain uses a regulatory protein called ubiquitin to “tag” or signal the body that extra tau should be removed.

USP11’s job is to give instructions to make an enzyme that removes the ubiquitin tag to maintain balance. But if too much of the enzyme is present, too much tau gets untagged – and not enough of it gets cleared.

“Our study showed USP11 is higher in females than males in both humans and in mice,” Dr. Kang said. “That’s already true before the onset of dementia. But once someone has Alzheimer’s disease, USP11 is much higher – regardless of sex.”

The study adds to a growing body of evidence that shows that women may be more vulnerable than men to higher levels of tau, possibly explaining why women are affected by the disease more often than men.

But what if there was a way to “turn off” or deactivate the USP11 gene? Might that help prevent Alzheimer’s disease? And could it be done safely?
 

What happened when the gene was eliminated?

To examine these questions, researchers used a method of gene manipulation to completely delete the USP11 gene in mice. They then examined the mice for changes. The result? The mice seemed fine.

“The mice bred well. Their brains looked fine,” Dr. Woo said.

It would not be possible – or ethical – to remove a gene from humans. But when a medical condition makes a certain gene unhelpful, that gene can be partially blocked or expression of the gene can be reduced with medication. In fact, medications targeting enzymes are common. Examples include statins for cardiovascular disease or HIV treatments that inhibit protease enzymes.

“If we are able to identify some type of medicine that would inhibit USP11, our study suggests it would be well tolerated and benefit women,” Dr. Woo said.

Dr. Kang also cautions that the process for creating such a therapy takes at least 10-15 years. The researchers said they’d like to shorten the timeline and plan to study currently approved FDA medications to see if any might work to target USP11 gene activity – and hopefully bring forth a new treatment for Alzheimer’s disease sooner.

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

Of the more than 6 million patients with Alzheimer’s disease in the United States aged 65 or older, nearly two-thirds are women. A new study published online in Cell may help explain the gender gap – and offer clues to new treatments for helping patients of both sexes fight back.

Researchers zeroed in on a gene named USP11, found on the X chromosome. People assigned female at birth have two X chromosomes, while people assigned male at birth have one X and one Y. So while all males have one copy of USP11, females have two.
 

The body’s trash collection system

In the normal course of events, the brain creates waste that must be removed lest it becomes toxic. One waste product is the protein tau. Too little tau can damage nerve cells, explained researchers David Kang, PhD, and Jung-A “Alexa” Woo, PhD, who led the study. But too much becomes toxic and can lead to neurodegenerative diseases such as Alzheimer’s disease. In fact, new research suggests that testing for changes in tau may someday help doctors diagnose Alzheimer’s disease earlier.

To manage tau, the brain uses a regulatory protein called ubiquitin to “tag” or signal the body that extra tau should be removed.

USP11’s job is to give instructions to make an enzyme that removes the ubiquitin tag to maintain balance. But if too much of the enzyme is present, too much tau gets untagged – and not enough of it gets cleared.

“Our study showed USP11 is higher in females than males in both humans and in mice,” Dr. Kang said. “That’s already true before the onset of dementia. But once someone has Alzheimer’s disease, USP11 is much higher – regardless of sex.”

The study adds to a growing body of evidence that shows that women may be more vulnerable than men to higher levels of tau, possibly explaining why women are affected by the disease more often than men.

But what if there was a way to “turn off” or deactivate the USP11 gene? Might that help prevent Alzheimer’s disease? And could it be done safely?
 

What happened when the gene was eliminated?

To examine these questions, researchers used a method of gene manipulation to completely delete the USP11 gene in mice. They then examined the mice for changes. The result? The mice seemed fine.

“The mice bred well. Their brains looked fine,” Dr. Woo said.

It would not be possible – or ethical – to remove a gene from humans. But when a medical condition makes a certain gene unhelpful, that gene can be partially blocked or expression of the gene can be reduced with medication. In fact, medications targeting enzymes are common. Examples include statins for cardiovascular disease or HIV treatments that inhibit protease enzymes.

“If we are able to identify some type of medicine that would inhibit USP11, our study suggests it would be well tolerated and benefit women,” Dr. Woo said.

Dr. Kang also cautions that the process for creating such a therapy takes at least 10-15 years. The researchers said they’d like to shorten the timeline and plan to study currently approved FDA medications to see if any might work to target USP11 gene activity – and hopefully bring forth a new treatment for Alzheimer’s disease sooner.

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

Brain indicators of motor impairment were distinct among children with autism spectrum disorder (ASD), those with developmental coordination disorder (DCD), and controls, in a new study.

Previous research suggests that individuals with ASD overlap in motor impairment with those with DCD. But these two conditions may differ significantly in some areas, as children with ASD tend to show weaker skills in social motor tasks such as imitation, wrote Emil Kilroy, PhD, of the University of Southern California, Los Angeles, and colleagues.

The neurobiological basis of autism remains unknown, despite many research efforts, in part because of the heterogeneity of the disease, said corresponding author Lisa Aziz-Zadeh, PhD, also of the University of Southern California, in an interview.

Comorbidity with other disorders is a strong contributing factor to heterogeneity, and approximately 80% of autistic individuals have motor impairments and meet criteria for a diagnosis of DCD, said Dr. Aziz-Zadeh. “Controlling for other comorbidities, such as developmental coordination disorder, when trying to understand the neural basis of autism is important, so that we can understand which neural circuits are related to [core symptoms of autism] and which ones are related to motor impairments that are comorbid with autism, but not necessarily part of the core symptomology,” she explained. “We focused on white matter pathways here because many researchers now think the underlying basis of autism, besides genetics, is brain connectivity differences.”

In their study published in Scientific Reports, the researchers reviewed data from whole-brain correlational tractography for 22 individuals with autism spectrum disorder, 16 with developmental coordination disorder, and 21 normally developing individuals, who served as the control group. The mean age of the participants was approximately 11 years; the age range was 8-17 years.

Overall, patterns of brain diffusion (movement of fluid, mainly water molecules, in the brain) were significantly different in ASD children, compared with typically developing children.

The ASD group showed significantly reduced diffusivity in the bilateral fronto-parietal cingulum and the left parolfactory cingulum. This finding reflects previous studies suggesting an association between brain patterns in the cingulum area and ASD. But the current study is “the first to identify the fronto-parietal and the parolfactory portions of the cingulum as well as the anterior caudal u-fibers as specific to core ASD symptomatology and not related to motor-related comorbidity,” the researchers wrote.

Differences in brain diffusivity were associated with worse performance on motor skills and behavioral measures for children with ASD and children with DCD, compared with controls.

Motor development was assessed using the Total Movement Assessment Battery for Children-2 (MABC-2) and the Florida Apraxia Battery modified for children (FAB-M). The MABC-2 is among the most common tools for measuring motor skills and identifying clinically relevant motor deficits in children and teens aged 3-16 years. The test includes three subtest scores (manual dexterity, gross-motor aiming and catching, and balance) and a total score. Scores are based on a child’s best performance on each component, and higher scores indicate better functioning. In the new study, The MABC-2 total scores averaged 10.57 for controls, compared with 5.76 in the ASD group, and 4.31 in the DCD group.

Children with ASD differed from the other groups in social measures. Social skills were measured using several tools, including the Social Responsivity Scale (SRS Total), which is a parent-completed survey that includes a total score designed to reflect the severity of social deficits in ASD. It is divided into five subscales for parents to assess a child’s social skill impairment: social awareness, social cognition, social communication, social motivation, and mannerisms. Scores for the SRS are calculated in T-scores, in which a score of 50 represents the mean. T-scores of 59 and below are generally not associated with ASD, and patients with these scores are considered to have low to no symptomatology. Scores on the SRS Total in the new study were 45.95, 77.45, and 55.81 for the controls, ASD group, and DCD group, respectively.
 

Results should raise awareness

“The results were largely predicted in our hypotheses – that we would find specific white matter pathways in autism that would differ from [what we saw in typically developing patients and those with DCD], and that diffusivity in ASD would be related to socioemotional differences,” Dr. Aziz-Zadeh said, in an interview.

“What was surprising was that some pathways that had previously been thought to be different in autism were also compromised in DCD, indicating that they were common to motor deficits which both groups shared, not to core autism symptomology,” she noted.

A message for clinicians from the study is that a dual diagnosis of DCD is often missing in ASD practice, said Dr. Aziz-Zadeh. “Given that approximately 80% of children with ASD have DCD, testing for DCD and addressing potential motor issues should be more common practice,” she said.

Dr. Aziz-Zadeh and colleagues are now investigating relationships between the brain, behavior, and the gut microbiome. “We think that understanding autism from a full-body perspective, examining interactions between the brain and the body, will be an important step in this field,” she emphasized.

The study was limited by several factors, including the small sample size, the use of only right-handed participants, and the use of self-reports by children and parents, the researchers noted. Additionally, they noted that white matter develops at different rates in different age groups, and future studies might consider age as a factor, as well as further behavioral assessments, they said.
 

Small sample size limits conclusions

“Understanding the neuroanatomic differences that may contribute to the core symptoms of ASD is a very important goal for the field, particularly how they relate to other comorbid symptoms and neurodevelopmental disorders,” said Michael Gandal, MD, of the department of psychiatry at the University of Pennsylvania, Philadelphia, and a member of the Lifespan Brain Institute at the Children’s Hospital of Philadelphia, in an interview.

“While this study provides some clues into how structural connectivity may relate to motor coordination in ASD, it will be important to replicate these findings in a much larger sample before we can really appreciate how robust these findings are and how well they generalize to the broader ASD population,” Dr. Gandal emphasized.

The study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development. The researchers had no financial conflicts to disclose. Dr. Gandal had no financial conflicts to disclose.

Brain indicators of motor impairment were distinct among children with autism spectrum disorder (ASD), those with developmental coordination disorder (DCD), and controls, in a new study.

Previous research suggests that individuals with ASD overlap in motor impairment with those with DCD. But these two conditions may differ significantly in some areas, as children with ASD tend to show weaker skills in social motor tasks such as imitation, wrote Emil Kilroy, PhD, of the University of Southern California, Los Angeles, and colleagues.

The neurobiological basis of autism remains unknown, despite many research efforts, in part because of the heterogeneity of the disease, said corresponding author Lisa Aziz-Zadeh, PhD, also of the University of Southern California, in an interview.

Comorbidity with other disorders is a strong contributing factor to heterogeneity, and approximately 80% of autistic individuals have motor impairments and meet criteria for a diagnosis of DCD, said Dr. Aziz-Zadeh. “Controlling for other comorbidities, such as developmental coordination disorder, when trying to understand the neural basis of autism is important, so that we can understand which neural circuits are related to [core symptoms of autism] and which ones are related to motor impairments that are comorbid with autism, but not necessarily part of the core symptomology,” she explained. “We focused on white matter pathways here because many researchers now think the underlying basis of autism, besides genetics, is brain connectivity differences.”

In their study published in Scientific Reports, the researchers reviewed data from whole-brain correlational tractography for 22 individuals with autism spectrum disorder, 16 with developmental coordination disorder, and 21 normally developing individuals, who served as the control group. The mean age of the participants was approximately 11 years; the age range was 8-17 years.

Overall, patterns of brain diffusion (movement of fluid, mainly water molecules, in the brain) were significantly different in ASD children, compared with typically developing children.

The ASD group showed significantly reduced diffusivity in the bilateral fronto-parietal cingulum and the left parolfactory cingulum. This finding reflects previous studies suggesting an association between brain patterns in the cingulum area and ASD. But the current study is “the first to identify the fronto-parietal and the parolfactory portions of the cingulum as well as the anterior caudal u-fibers as specific to core ASD symptomatology and not related to motor-related comorbidity,” the researchers wrote.

Differences in brain diffusivity were associated with worse performance on motor skills and behavioral measures for children with ASD and children with DCD, compared with controls.

Motor development was assessed using the Total Movement Assessment Battery for Children-2 (MABC-2) and the Florida Apraxia Battery modified for children (FAB-M). The MABC-2 is among the most common tools for measuring motor skills and identifying clinically relevant motor deficits in children and teens aged 3-16 years. The test includes three subtest scores (manual dexterity, gross-motor aiming and catching, and balance) and a total score. Scores are based on a child’s best performance on each component, and higher scores indicate better functioning. In the new study, The MABC-2 total scores averaged 10.57 for controls, compared with 5.76 in the ASD group, and 4.31 in the DCD group.

Children with ASD differed from the other groups in social measures. Social skills were measured using several tools, including the Social Responsivity Scale (SRS Total), which is a parent-completed survey that includes a total score designed to reflect the severity of social deficits in ASD. It is divided into five subscales for parents to assess a child’s social skill impairment: social awareness, social cognition, social communication, social motivation, and mannerisms. Scores for the SRS are calculated in T-scores, in which a score of 50 represents the mean. T-scores of 59 and below are generally not associated with ASD, and patients with these scores are considered to have low to no symptomatology. Scores on the SRS Total in the new study were 45.95, 77.45, and 55.81 for the controls, ASD group, and DCD group, respectively.
 

Results should raise awareness

“The results were largely predicted in our hypotheses – that we would find specific white matter pathways in autism that would differ from [what we saw in typically developing patients and those with DCD], and that diffusivity in ASD would be related to socioemotional differences,” Dr. Aziz-Zadeh said, in an interview.

“What was surprising was that some pathways that had previously been thought to be different in autism were also compromised in DCD, indicating that they were common to motor deficits which both groups shared, not to core autism symptomology,” she noted.

A message for clinicians from the study is that a dual diagnosis of DCD is often missing in ASD practice, said Dr. Aziz-Zadeh. “Given that approximately 80% of children with ASD have DCD, testing for DCD and addressing potential motor issues should be more common practice,” she said.

Dr. Aziz-Zadeh and colleagues are now investigating relationships between the brain, behavior, and the gut microbiome. “We think that understanding autism from a full-body perspective, examining interactions between the brain and the body, will be an important step in this field,” she emphasized.

The study was limited by several factors, including the small sample size, the use of only right-handed participants, and the use of self-reports by children and parents, the researchers noted. Additionally, they noted that white matter develops at different rates in different age groups, and future studies might consider age as a factor, as well as further behavioral assessments, they said.
 

Small sample size limits conclusions

“Understanding the neuroanatomic differences that may contribute to the core symptoms of ASD is a very important goal for the field, particularly how they relate to other comorbid symptoms and neurodevelopmental disorders,” said Michael Gandal, MD, of the department of psychiatry at the University of Pennsylvania, Philadelphia, and a member of the Lifespan Brain Institute at the Children’s Hospital of Philadelphia, in an interview.

“While this study provides some clues into how structural connectivity may relate to motor coordination in ASD, it will be important to replicate these findings in a much larger sample before we can really appreciate how robust these findings are and how well they generalize to the broader ASD population,” Dr. Gandal emphasized.

The study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development. The researchers had no financial conflicts to disclose. Dr. Gandal had no financial conflicts to disclose.

Brain indicators of motor impairment were distinct among children with autism spectrum disorder (ASD), those with developmental coordination disorder (DCD), and controls, in a new study.

Previous research suggests that individuals with ASD overlap in motor impairment with those with DCD. But these two conditions may differ significantly in some areas, as children with ASD tend to show weaker skills in social motor tasks such as imitation, wrote Emil Kilroy, PhD, of the University of Southern California, Los Angeles, and colleagues.

The neurobiological basis of autism remains unknown, despite many research efforts, in part because of the heterogeneity of the disease, said corresponding author Lisa Aziz-Zadeh, PhD, also of the University of Southern California, in an interview.

Comorbidity with other disorders is a strong contributing factor to heterogeneity, and approximately 80% of autistic individuals have motor impairments and meet criteria for a diagnosis of DCD, said Dr. Aziz-Zadeh. “Controlling for other comorbidities, such as developmental coordination disorder, when trying to understand the neural basis of autism is important, so that we can understand which neural circuits are related to [core symptoms of autism] and which ones are related to motor impairments that are comorbid with autism, but not necessarily part of the core symptomology,” she explained. “We focused on white matter pathways here because many researchers now think the underlying basis of autism, besides genetics, is brain connectivity differences.”

In their study published in Scientific Reports, the researchers reviewed data from whole-brain correlational tractography for 22 individuals with autism spectrum disorder, 16 with developmental coordination disorder, and 21 normally developing individuals, who served as the control group. The mean age of the participants was approximately 11 years; the age range was 8-17 years.

Overall, patterns of brain diffusion (movement of fluid, mainly water molecules, in the brain) were significantly different in ASD children, compared with typically developing children.

The ASD group showed significantly reduced diffusivity in the bilateral fronto-parietal cingulum and the left parolfactory cingulum. This finding reflects previous studies suggesting an association between brain patterns in the cingulum area and ASD. But the current study is “the first to identify the fronto-parietal and the parolfactory portions of the cingulum as well as the anterior caudal u-fibers as specific to core ASD symptomatology and not related to motor-related comorbidity,” the researchers wrote.

Differences in brain diffusivity were associated with worse performance on motor skills and behavioral measures for children with ASD and children with DCD, compared with controls.

Motor development was assessed using the Total Movement Assessment Battery for Children-2 (MABC-2) and the Florida Apraxia Battery modified for children (FAB-M). The MABC-2 is among the most common tools for measuring motor skills and identifying clinically relevant motor deficits in children and teens aged 3-16 years. The test includes three subtest scores (manual dexterity, gross-motor aiming and catching, and balance) and a total score. Scores are based on a child’s best performance on each component, and higher scores indicate better functioning. In the new study, The MABC-2 total scores averaged 10.57 for controls, compared with 5.76 in the ASD group, and 4.31 in the DCD group.

Children with ASD differed from the other groups in social measures. Social skills were measured using several tools, including the Social Responsivity Scale (SRS Total), which is a parent-completed survey that includes a total score designed to reflect the severity of social deficits in ASD. It is divided into five subscales for parents to assess a child’s social skill impairment: social awareness, social cognition, social communication, social motivation, and mannerisms. Scores for the SRS are calculated in T-scores, in which a score of 50 represents the mean. T-scores of 59 and below are generally not associated with ASD, and patients with these scores are considered to have low to no symptomatology. Scores on the SRS Total in the new study were 45.95, 77.45, and 55.81 for the controls, ASD group, and DCD group, respectively.
 

Results should raise awareness

“The results were largely predicted in our hypotheses – that we would find specific white matter pathways in autism that would differ from [what we saw in typically developing patients and those with DCD], and that diffusivity in ASD would be related to socioemotional differences,” Dr. Aziz-Zadeh said, in an interview.

“What was surprising was that some pathways that had previously been thought to be different in autism were also compromised in DCD, indicating that they were common to motor deficits which both groups shared, not to core autism symptomology,” she noted.

A message for clinicians from the study is that a dual diagnosis of DCD is often missing in ASD practice, said Dr. Aziz-Zadeh. “Given that approximately 80% of children with ASD have DCD, testing for DCD and addressing potential motor issues should be more common practice,” she said.

Dr. Aziz-Zadeh and colleagues are now investigating relationships between the brain, behavior, and the gut microbiome. “We think that understanding autism from a full-body perspective, examining interactions between the brain and the body, will be an important step in this field,” she emphasized.

The study was limited by several factors, including the small sample size, the use of only right-handed participants, and the use of self-reports by children and parents, the researchers noted. Additionally, they noted that white matter develops at different rates in different age groups, and future studies might consider age as a factor, as well as further behavioral assessments, they said.
 

Small sample size limits conclusions

“Understanding the neuroanatomic differences that may contribute to the core symptoms of ASD is a very important goal for the field, particularly how they relate to other comorbid symptoms and neurodevelopmental disorders,” said Michael Gandal, MD, of the department of psychiatry at the University of Pennsylvania, Philadelphia, and a member of the Lifespan Brain Institute at the Children’s Hospital of Philadelphia, in an interview.

“While this study provides some clues into how structural connectivity may relate to motor coordination in ASD, it will be important to replicate these findings in a much larger sample before we can really appreciate how robust these findings are and how well they generalize to the broader ASD population,” Dr. Gandal emphasized.

The study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development. The researchers had no financial conflicts to disclose. Dr. Gandal had no financial conflicts to disclose.

Roughly 7% of all adult Americans may currently have had long COVID, with symptoms that have lasted 3 months or longer, according to the latest U.S. government survey done in October. More than a quarter say their condition is severe enough to significantly limit their day-to-day activities – yet the problem is only barely starting to get the attention of employers, the health care system, and policymakers.

With no cure or treatment in sight, long COVID is already burdening not only the health care system, but also the economy – and that burden is set to grow. Many experts worry about the possible long-term ripple effects, from increased spending on medical care costs to lost wages due to not being able to work, as well as the policy implications that come with addressing these issues.

“At this point, anyone who’s looking at this seriously would say this is a huge deal,” says senior Brookings Institution fellow Katie Bach, the author of a study that analyzed long COVID’s impact on the labor market.

“We need a real concerted focus on treating these people, which means both research and the clinical side, and figuring out how to build a labor market that is more inclusive of people with disabilities,” she said.

It’s not only that many people are affected. It’s that they are often affected for months and possibly even years.

The U.S. government figures suggest more than 18 million people could have symptoms of long COVID right now. The latest Household Pulse Survey by the Census Bureau and the National Center for Health Statistics takes data from 41,415 people.

A preprint of a study by researchers from City University of New York, posted on medRxiv in September and based on a similar population survey done between June 30 and July 2, drew comparable results. The study has not been peer reviewed.

More than 7% of all those who answered said they had long COVID at the time of the survey, which the researchers said corresponded to approximately 18.5 million U.S. adults. The same study found that a quarter of those, or an estimated 4.7 million adults, said their daily activities were impacted “a lot.”

This can translate into pain not only for the patients, but for governments and employers, too.

In high-income countries around the world, government surveys and other studies are shedding light on the extent to which post-COVID-19 symptoms – commonly known as long COVID – are affecting populations. While results vary, they generally fall within similar ranges.

The World Health Organization estimates that between 10% and 20% of those with COVID-19 go on to have an array of medium- to long-term post-COVID-19 symptoms that range from mild to debilitating. The U.S. Government Accountability Office puts that estimate at 10% to 30%; one of the latest studies published at the end of October in The Journal of the American Medical Association found that 15% of U.S. adults who had tested positive for COVID-19 reported current long COVID symptoms. Elsewhere, a study from the Netherlands published in The Lancet in August found that one in eight COVID-19 cases, or 12.7%, were likely to become long COVID.

“It’s very clear that the condition is devastating people’s lives and livelihoods,” WHO Director-General Tedros Adhanom Ghebreyesus wrote in an article for The Guardian newspaper in October.

“The world has already lost a significant number of the workforce to illness, death, fatigue, unplanned retirement due to an increase in long-term disability, which not only impacts the health system, but is a hit to the overarching economy … the impact of long COVID for all countries is very serious and needs immediate and sustained action equivalent to its scale.”
 

Global snapshot: Lasting symptoms, impact on activities

Patients describe a spectrum of persistent issues, with extreme fatigue, brain fog or cognitive problems, and shortness of breath among the most common complaints. Many also have manageable symptoms that worsen significantly after even mild physical or mental exertion.

Women appear almost twice as likely as men to get long COVID. Many patients have other medical conditions and disabilities that make them more vulnerable to the condition. Those who face greater obstacles accessing health care due to discrimination or socioeconomic inequity are at higher risk as well. 

While many are older, a large number are also in their prime working age. The Census Bureau data show that people ages 40-49 are more likely than any other group to get long COVID, which has broader implications for labor markets and the global economy. Already, experts have estimated that long COVID is likely to cost the U.S. trillions of dollars and affect multiple industries.

“Whether they’re in the financial world, the medical system, lawyers, they’re telling me they’re sitting at the computer screen and they’re unable to process the data,” said Zachary Schwartz, MD, medical director for Vancouver General Hospital’s Post-COVID-19 Recovery Clinic.

“That is what’s most distressing for people, in that they’re not working, they’re not making money, and they don’t know when, or if, they’re going to get better.”

Nearly a third of respondents in the Census Bureau’s Household Pulse Survey who said they have had COVID-19 reported symptoms that lasted 3 months or longer. People between the ages of 30 and 59 were the most affected, with about 32% reporting symptoms. Across the entire adult U.S. population, the survey found that 1 in 7 adults have had long COVID at some point during the pandemic, with about 1 in 18 saying it limited their activity to some degree, and 1 in 50 saying they have faced “a lot” of limits on their activities. Any way these numbers are dissected, long COVID has impacted a large swath of the population.

Yet research into the causes and possible treatments of long COVID is just getting underway.

“The amount of energy and time devoted to it is way, way less than it should, given how many people are likely affected,” said David Cutler, PhD, professor of economics at Harvard University, Cambridge, Mass., who has written about the economic cost of long COVID. “We’re way, way underdoing it here. And I think that’s really a terrible thing.”

Population surveys and studies from around the world show that long COVID lives up to its name, with people reporting serious symptoms for months on end.

In October, Statistics Canada and the Public Health Agency of Canada published early results from a questionnaire done between spring and summer 2022 that found just under 15% of adults who had a confirmed or suspected case of COVID-19 went on to have new or continuing symptoms 3 or more months later. Nearly half, or 47.3%, dealt with symptoms that lasted a year or more. More than one in five said their symptoms “often or always” limited their day-to-day activities, which included routine tasks such as preparing meals, doing errands and chores, and basic functions such as personal care and moving around in their homes.

Nearly three-quarters of workers or students said they missed an average of 20 days of work or school. 

“We haven’t yet been able to determine exactly when symptoms resolve,” said Rainu Kaushal, MD, the senior associate dean for clinical research at Weill Cornell Medicine in New York. She is co-leading a national study on long COVID in adults and children, funded by the National Institutes of Health RECOVER Initiative.

“But there does seem to be, for many of the milder symptoms, resolution at about 4-6 weeks. There seems to be a second point of resolution around 6 months for certain symptoms, and then some symptoms do seem to be permanent, and those tend to be patients who have underlying conditions,” she said.
 

Reducing the risk

Given all the data so far, experts recommend urgent policy changes to help people with long COVID.

“The population needs to be prepared, that understanding long COVID is going to be a very long and difficult process,” said Alexander Charney, MD, PhD, associate professor and the lead principal investigator of the RECOVER adult cohort at Icahn School of Medicine at Mount Sinai in New York. He said the government can do a great deal to help, including setting up a network of connected clinics treating long COVID, standardizing best practices, and sharing information.

“That would go a long way towards making sure that every person feels like they’re not too far away from a clinic where they can get treated for this particular condition,” he said.

But the only known way to prevent long COVID is to prevent COVID-19 infections in the first place, experts say. That means equitable access to tests, therapeutics, and vaccines.

“I will say that avoiding COVID remains the best treatment in the arsenal right now,” said Dr. Kaushal. This means masking, avoiding crowded places with poor ventilation and high exposure risk, and being up to date on vaccinations, she said.

A number of papers – including a large U.K. study published in May 2022, another one from July, and the JAMA study from October – all suggest that vaccinations can help reduce the risk of long COVID.

“I am absolutely of the belief that vaccination has reduced the incidence and overall amount of long COVID … [and is] still by far the best thing the public can do,” said Dr. Schwartz.

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

Roughly 7% of all adult Americans may currently have had long COVID, with symptoms that have lasted 3 months or longer, according to the latest U.S. government survey done in October. More than a quarter say their condition is severe enough to significantly limit their day-to-day activities – yet the problem is only barely starting to get the attention of employers, the health care system, and policymakers.

With no cure or treatment in sight, long COVID is already burdening not only the health care system, but also the economy – and that burden is set to grow. Many experts worry about the possible long-term ripple effects, from increased spending on medical care costs to lost wages due to not being able to work, as well as the policy implications that come with addressing these issues.

“At this point, anyone who’s looking at this seriously would say this is a huge deal,” says senior Brookings Institution fellow Katie Bach, the author of a study that analyzed long COVID’s impact on the labor market.

“We need a real concerted focus on treating these people, which means both research and the clinical side, and figuring out how to build a labor market that is more inclusive of people with disabilities,” she said.

It’s not only that many people are affected. It’s that they are often affected for months and possibly even years.

The U.S. government figures suggest more than 18 million people could have symptoms of long COVID right now. The latest Household Pulse Survey by the Census Bureau and the National Center for Health Statistics takes data from 41,415 people.

A preprint of a study by researchers from City University of New York, posted on medRxiv in September and based on a similar population survey done between June 30 and July 2, drew comparable results. The study has not been peer reviewed.

More than 7% of all those who answered said they had long COVID at the time of the survey, which the researchers said corresponded to approximately 18.5 million U.S. adults. The same study found that a quarter of those, or an estimated 4.7 million adults, said their daily activities were impacted “a lot.”

This can translate into pain not only for the patients, but for governments and employers, too.

In high-income countries around the world, government surveys and other studies are shedding light on the extent to which post-COVID-19 symptoms – commonly known as long COVID – are affecting populations. While results vary, they generally fall within similar ranges.

The World Health Organization estimates that between 10% and 20% of those with COVID-19 go on to have an array of medium- to long-term post-COVID-19 symptoms that range from mild to debilitating. The U.S. Government Accountability Office puts that estimate at 10% to 30%; one of the latest studies published at the end of October in The Journal of the American Medical Association found that 15% of U.S. adults who had tested positive for COVID-19 reported current long COVID symptoms. Elsewhere, a study from the Netherlands published in The Lancet in August found that one in eight COVID-19 cases, or 12.7%, were likely to become long COVID.

“It’s very clear that the condition is devastating people’s lives and livelihoods,” WHO Director-General Tedros Adhanom Ghebreyesus wrote in an article for The Guardian newspaper in October.

“The world has already lost a significant number of the workforce to illness, death, fatigue, unplanned retirement due to an increase in long-term disability, which not only impacts the health system, but is a hit to the overarching economy … the impact of long COVID for all countries is very serious and needs immediate and sustained action equivalent to its scale.”
 

Global snapshot: Lasting symptoms, impact on activities

Patients describe a spectrum of persistent issues, with extreme fatigue, brain fog or cognitive problems, and shortness of breath among the most common complaints. Many also have manageable symptoms that worsen significantly after even mild physical or mental exertion.

Women appear almost twice as likely as men to get long COVID. Many patients have other medical conditions and disabilities that make them more vulnerable to the condition. Those who face greater obstacles accessing health care due to discrimination or socioeconomic inequity are at higher risk as well. 

While many are older, a large number are also in their prime working age. The Census Bureau data show that people ages 40-49 are more likely than any other group to get long COVID, which has broader implications for labor markets and the global economy. Already, experts have estimated that long COVID is likely to cost the U.S. trillions of dollars and affect multiple industries.

“Whether they’re in the financial world, the medical system, lawyers, they’re telling me they’re sitting at the computer screen and they’re unable to process the data,” said Zachary Schwartz, MD, medical director for Vancouver General Hospital’s Post-COVID-19 Recovery Clinic.

“That is what’s most distressing for people, in that they’re not working, they’re not making money, and they don’t know when, or if, they’re going to get better.”

Nearly a third of respondents in the Census Bureau’s Household Pulse Survey who said they have had COVID-19 reported symptoms that lasted 3 months or longer. People between the ages of 30 and 59 were the most affected, with about 32% reporting symptoms. Across the entire adult U.S. population, the survey found that 1 in 7 adults have had long COVID at some point during the pandemic, with about 1 in 18 saying it limited their activity to some degree, and 1 in 50 saying they have faced “a lot” of limits on their activities. Any way these numbers are dissected, long COVID has impacted a large swath of the population.

Yet research into the causes and possible treatments of long COVID is just getting underway.

“The amount of energy and time devoted to it is way, way less than it should, given how many people are likely affected,” said David Cutler, PhD, professor of economics at Harvard University, Cambridge, Mass., who has written about the economic cost of long COVID. “We’re way, way underdoing it here. And I think that’s really a terrible thing.”

Population surveys and studies from around the world show that long COVID lives up to its name, with people reporting serious symptoms for months on end.

In October, Statistics Canada and the Public Health Agency of Canada published early results from a questionnaire done between spring and summer 2022 that found just under 15% of adults who had a confirmed or suspected case of COVID-19 went on to have new or continuing symptoms 3 or more months later. Nearly half, or 47.3%, dealt with symptoms that lasted a year or more. More than one in five said their symptoms “often or always” limited their day-to-day activities, which included routine tasks such as preparing meals, doing errands and chores, and basic functions such as personal care and moving around in their homes.

Nearly three-quarters of workers or students said they missed an average of 20 days of work or school. 

“We haven’t yet been able to determine exactly when symptoms resolve,” said Rainu Kaushal, MD, the senior associate dean for clinical research at Weill Cornell Medicine in New York. She is co-leading a national study on long COVID in adults and children, funded by the National Institutes of Health RECOVER Initiative.

“But there does seem to be, for many of the milder symptoms, resolution at about 4-6 weeks. There seems to be a second point of resolution around 6 months for certain symptoms, and then some symptoms do seem to be permanent, and those tend to be patients who have underlying conditions,” she said.
 

Reducing the risk

Given all the data so far, experts recommend urgent policy changes to help people with long COVID.

“The population needs to be prepared, that understanding long COVID is going to be a very long and difficult process,” said Alexander Charney, MD, PhD, associate professor and the lead principal investigator of the RECOVER adult cohort at Icahn School of Medicine at Mount Sinai in New York. He said the government can do a great deal to help, including setting up a network of connected clinics treating long COVID, standardizing best practices, and sharing information.

“That would go a long way towards making sure that every person feels like they’re not too far away from a clinic where they can get treated for this particular condition,” he said.

But the only known way to prevent long COVID is to prevent COVID-19 infections in the first place, experts say. That means equitable access to tests, therapeutics, and vaccines.

“I will say that avoiding COVID remains the best treatment in the arsenal right now,” said Dr. Kaushal. This means masking, avoiding crowded places with poor ventilation and high exposure risk, and being up to date on vaccinations, she said.

A number of papers – including a large U.K. study published in May 2022, another one from July, and the JAMA study from October – all suggest that vaccinations can help reduce the risk of long COVID.

“I am absolutely of the belief that vaccination has reduced the incidence and overall amount of long COVID … [and is] still by far the best thing the public can do,” said Dr. Schwartz.

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

Roughly 7% of all adult Americans may currently have had long COVID, with symptoms that have lasted 3 months or longer, according to the latest U.S. government survey done in October. More than a quarter say their condition is severe enough to significantly limit their day-to-day activities – yet the problem is only barely starting to get the attention of employers, the health care system, and policymakers.

With no cure or treatment in sight, long COVID is already burdening not only the health care system, but also the economy – and that burden is set to grow. Many experts worry about the possible long-term ripple effects, from increased spending on medical care costs to lost wages due to not being able to work, as well as the policy implications that come with addressing these issues.

“At this point, anyone who’s looking at this seriously would say this is a huge deal,” says senior Brookings Institution fellow Katie Bach, the author of a study that analyzed long COVID’s impact on the labor market.

“We need a real concerted focus on treating these people, which means both research and the clinical side, and figuring out how to build a labor market that is more inclusive of people with disabilities,” she said.

It’s not only that many people are affected. It’s that they are often affected for months and possibly even years.

The U.S. government figures suggest more than 18 million people could have symptoms of long COVID right now. The latest Household Pulse Survey by the Census Bureau and the National Center for Health Statistics takes data from 41,415 people.

A preprint of a study by researchers from City University of New York, posted on medRxiv in September and based on a similar population survey done between June 30 and July 2, drew comparable results. The study has not been peer reviewed.

More than 7% of all those who answered said they had long COVID at the time of the survey, which the researchers said corresponded to approximately 18.5 million U.S. adults. The same study found that a quarter of those, or an estimated 4.7 million adults, said their daily activities were impacted “a lot.”

This can translate into pain not only for the patients, but for governments and employers, too.

In high-income countries around the world, government surveys and other studies are shedding light on the extent to which post-COVID-19 symptoms – commonly known as long COVID – are affecting populations. While results vary, they generally fall within similar ranges.

The World Health Organization estimates that between 10% and 20% of those with COVID-19 go on to have an array of medium- to long-term post-COVID-19 symptoms that range from mild to debilitating. The U.S. Government Accountability Office puts that estimate at 10% to 30%; one of the latest studies published at the end of October in The Journal of the American Medical Association found that 15% of U.S. adults who had tested positive for COVID-19 reported current long COVID symptoms. Elsewhere, a study from the Netherlands published in The Lancet in August found that one in eight COVID-19 cases, or 12.7%, were likely to become long COVID.

“It’s very clear that the condition is devastating people’s lives and livelihoods,” WHO Director-General Tedros Adhanom Ghebreyesus wrote in an article for The Guardian newspaper in October.

“The world has already lost a significant number of the workforce to illness, death, fatigue, unplanned retirement due to an increase in long-term disability, which not only impacts the health system, but is a hit to the overarching economy … the impact of long COVID for all countries is very serious and needs immediate and sustained action equivalent to its scale.”
 

Global snapshot: Lasting symptoms, impact on activities

Patients describe a spectrum of persistent issues, with extreme fatigue, brain fog or cognitive problems, and shortness of breath among the most common complaints. Many also have manageable symptoms that worsen significantly after even mild physical or mental exertion.

Women appear almost twice as likely as men to get long COVID. Many patients have other medical conditions and disabilities that make them more vulnerable to the condition. Those who face greater obstacles accessing health care due to discrimination or socioeconomic inequity are at higher risk as well. 

While many are older, a large number are also in their prime working age. The Census Bureau data show that people ages 40-49 are more likely than any other group to get long COVID, which has broader implications for labor markets and the global economy. Already, experts have estimated that long COVID is likely to cost the U.S. trillions of dollars and affect multiple industries.

“Whether they’re in the financial world, the medical system, lawyers, they’re telling me they’re sitting at the computer screen and they’re unable to process the data,” said Zachary Schwartz, MD, medical director for Vancouver General Hospital’s Post-COVID-19 Recovery Clinic.

“That is what’s most distressing for people, in that they’re not working, they’re not making money, and they don’t know when, or if, they’re going to get better.”

Nearly a third of respondents in the Census Bureau’s Household Pulse Survey who said they have had COVID-19 reported symptoms that lasted 3 months or longer. People between the ages of 30 and 59 were the most affected, with about 32% reporting symptoms. Across the entire adult U.S. population, the survey found that 1 in 7 adults have had long COVID at some point during the pandemic, with about 1 in 18 saying it limited their activity to some degree, and 1 in 50 saying they have faced “a lot” of limits on their activities. Any way these numbers are dissected, long COVID has impacted a large swath of the population.

Yet research into the causes and possible treatments of long COVID is just getting underway.

“The amount of energy and time devoted to it is way, way less than it should, given how many people are likely affected,” said David Cutler, PhD, professor of economics at Harvard University, Cambridge, Mass., who has written about the economic cost of long COVID. “We’re way, way underdoing it here. And I think that’s really a terrible thing.”

Population surveys and studies from around the world show that long COVID lives up to its name, with people reporting serious symptoms for months on end.

In October, Statistics Canada and the Public Health Agency of Canada published early results from a questionnaire done between spring and summer 2022 that found just under 15% of adults who had a confirmed or suspected case of COVID-19 went on to have new or continuing symptoms 3 or more months later. Nearly half, or 47.3%, dealt with symptoms that lasted a year or more. More than one in five said their symptoms “often or always” limited their day-to-day activities, which included routine tasks such as preparing meals, doing errands and chores, and basic functions such as personal care and moving around in their homes.

Nearly three-quarters of workers or students said they missed an average of 20 days of work or school. 

“We haven’t yet been able to determine exactly when symptoms resolve,” said Rainu Kaushal, MD, the senior associate dean for clinical research at Weill Cornell Medicine in New York. She is co-leading a national study on long COVID in adults and children, funded by the National Institutes of Health RECOVER Initiative.

“But there does seem to be, for many of the milder symptoms, resolution at about 4-6 weeks. There seems to be a second point of resolution around 6 months for certain symptoms, and then some symptoms do seem to be permanent, and those tend to be patients who have underlying conditions,” she said.
 

Reducing the risk

Given all the data so far, experts recommend urgent policy changes to help people with long COVID.

“The population needs to be prepared, that understanding long COVID is going to be a very long and difficult process,” said Alexander Charney, MD, PhD, associate professor and the lead principal investigator of the RECOVER adult cohort at Icahn School of Medicine at Mount Sinai in New York. He said the government can do a great deal to help, including setting up a network of connected clinics treating long COVID, standardizing best practices, and sharing information.

“That would go a long way towards making sure that every person feels like they’re not too far away from a clinic where they can get treated for this particular condition,” he said.

But the only known way to prevent long COVID is to prevent COVID-19 infections in the first place, experts say. That means equitable access to tests, therapeutics, and vaccines.

“I will say that avoiding COVID remains the best treatment in the arsenal right now,” said Dr. Kaushal. This means masking, avoiding crowded places with poor ventilation and high exposure risk, and being up to date on vaccinations, she said.

A number of papers – including a large U.K. study published in May 2022, another one from July, and the JAMA study from October – all suggest that vaccinations can help reduce the risk of long COVID.

“I am absolutely of the belief that vaccination has reduced the incidence and overall amount of long COVID … [and is] still by far the best thing the public can do,” said Dr. Schwartz.

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