Neurology

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.

Measles has sickened 59 children in an outbreak that began in November and now spans four Ohio counties.

None of the children had been fully vaccinated against measles, and 23 of them have been hospitalized, local officials report.

“Measles can be very serious, especially for children under age 5,” Columbus Public Health spokesperson Kelli Newman told CNN.

Nearly all of the infected children are under age 5, with 12 of them being under 1 year old. 

“Many children are hospitalized for dehydration,” Ms. Newman told CNN in an email. “Other serious complications also can include pneumonia and neurological conditions such as encephalitis. There’s no way of knowing which children will become so sick they have to be hospitalized. The safest way to protect children from measles is to make sure they are vaccinated with MMR.”

Of the 59 infected children, 56 were unvaccinated and three had been partially vaccinated. The MMR (measles, mumps, and rubella) vaccine is recommended for children beginning at 12 months old, according to the Centers for Disease Control and American Academy of Pediatrics. Two doses are needed to be considered fully vaccinated, and the second dose is usually given between 4 and 6 years old.

Measles “is one of the most infectious agents known to man,” the academy says.

It is so contagious that if one person has it, up to 9 out of 10 people around that person will also become infected if they are not protected, the CDC explains. Measles infection causes a rash and a fever that can spike beyond 104° F. Sometimes, the illness can lead to brain swelling, brain damage, or death.

Last month, the World Health Organization and CDC warned that 40 million children worldwide missed their measles vaccinations in 2021, partly due to pandemic disruptions. The American Academy of Pediatrics also notes that many parents choose not to vaccinate their children due to misinformation.

Infants are at heightened risk because they are too young to be vaccinated.

The academy offered several tips for protecting unvaccinated infants during a measles outbreak:

• Limit your baby’s exposure to crowds, other children, and people with cold symptoms.
• Disinfect objects and surfaces at home regularly, because the measles virus can live on surfaces or suspended in the air for 2 hours.
• If possible, feed your baby breast milk, because it has antibodies to prevent and fight infections.

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

Measles has sickened 59 children in an outbreak that began in November and now spans four Ohio counties.

None of the children had been fully vaccinated against measles, and 23 of them have been hospitalized, local officials report.

“Measles can be very serious, especially for children under age 5,” Columbus Public Health spokesperson Kelli Newman told CNN.

Nearly all of the infected children are under age 5, with 12 of them being under 1 year old. 

“Many children are hospitalized for dehydration,” Ms. Newman told CNN in an email. “Other serious complications also can include pneumonia and neurological conditions such as encephalitis. There’s no way of knowing which children will become so sick they have to be hospitalized. The safest way to protect children from measles is to make sure they are vaccinated with MMR.”

Of the 59 infected children, 56 were unvaccinated and three had been partially vaccinated. The MMR (measles, mumps, and rubella) vaccine is recommended for children beginning at 12 months old, according to the Centers for Disease Control and American Academy of Pediatrics. Two doses are needed to be considered fully vaccinated, and the second dose is usually given between 4 and 6 years old.

Measles “is one of the most infectious agents known to man,” the academy says.

It is so contagious that if one person has it, up to 9 out of 10 people around that person will also become infected if they are not protected, the CDC explains. Measles infection causes a rash and a fever that can spike beyond 104° F. Sometimes, the illness can lead to brain swelling, brain damage, or death.

Last month, the World Health Organization and CDC warned that 40 million children worldwide missed their measles vaccinations in 2021, partly due to pandemic disruptions. The American Academy of Pediatrics also notes that many parents choose not to vaccinate their children due to misinformation.

Infants are at heightened risk because they are too young to be vaccinated.

The academy offered several tips for protecting unvaccinated infants during a measles outbreak:

• Limit your baby’s exposure to crowds, other children, and people with cold symptoms.
• Disinfect objects and surfaces at home regularly, because the measles virus can live on surfaces or suspended in the air for 2 hours.
• If possible, feed your baby breast milk, because it has antibodies to prevent and fight infections.

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

Measles has sickened 59 children in an outbreak that began in November and now spans four Ohio counties.

None of the children had been fully vaccinated against measles, and 23 of them have been hospitalized, local officials report.

“Measles can be very serious, especially for children under age 5,” Columbus Public Health spokesperson Kelli Newman told CNN.

Nearly all of the infected children are under age 5, with 12 of them being under 1 year old. 

“Many children are hospitalized for dehydration,” Ms. Newman told CNN in an email. “Other serious complications also can include pneumonia and neurological conditions such as encephalitis. There’s no way of knowing which children will become so sick they have to be hospitalized. The safest way to protect children from measles is to make sure they are vaccinated with MMR.”

Of the 59 infected children, 56 were unvaccinated and three had been partially vaccinated. The MMR (measles, mumps, and rubella) vaccine is recommended for children beginning at 12 months old, according to the Centers for Disease Control and American Academy of Pediatrics. Two doses are needed to be considered fully vaccinated, and the second dose is usually given between 4 and 6 years old.

Measles “is one of the most infectious agents known to man,” the academy says.

It is so contagious that if one person has it, up to 9 out of 10 people around that person will also become infected if they are not protected, the CDC explains. Measles infection causes a rash and a fever that can spike beyond 104° F. Sometimes, the illness can lead to brain swelling, brain damage, or death.

Last month, the World Health Organization and CDC warned that 40 million children worldwide missed their measles vaccinations in 2021, partly due to pandemic disruptions. The American Academy of Pediatrics also notes that many parents choose not to vaccinate their children due to misinformation.

Infants are at heightened risk because they are too young to be vaccinated.

The academy offered several tips for protecting unvaccinated infants during a measles outbreak:

• Limit your baby’s exposure to crowds, other children, and people with cold symptoms.
• Disinfect objects and surfaces at home regularly, because the measles virus can live on surfaces or suspended in the air for 2 hours.
• If possible, feed your baby breast milk, because it has antibodies to prevent and fight infections.

A version of this article first appeared on WebMD.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.

A large Danish study supports a robust and long-term bidirectional relationship between epilepsy and depression, with implications for diagnosis and patient care. The findings “strongly support previous observations of a bidirectional association between these two brain disorders,” said Eva Bølling-Ladegaard, MD, a PhD student, department of clinical medicine (Neurology), Aarhus (Denmark) University.

“We add to the existing evidence in temporal range, showing that the increased risks of depression following epilepsy, and vice versa, are sustained over a much more extended time period than previously shown; that is, 20 years on both sides of receiving a diagnosis of the index disorder,” Ms. Bølling-Ladegaard said.

The study was published online in Neurology.
 

Epilepsy then depression

The researchers examined the magnitude and long-term temporal association between epilepsy and depression. They compared the risk of the two brain disorders following another chronic disorder (asthma) in a nationwide, register-based, matched cohort study.

In a population of more than 8.7 million people, they identified 139,014 persons with epilepsy (54% males; median age at diagnosis, 43 years), 219,990 with depression (37% males; median age at diagnosis, 43 years), and 358,821 with asthma (49% males; median age at diagnosis, 29 years).

The rate of developing depression was increased nearly twofold among people with epilepsy compared with the matched population who did not have epilepsy (adjusted hazard ratio, 1.88; 95% confidence interval, 1.82-1.95).

The rate of depression was highest during the first months and years after epilepsy diagnosis. It declined over time, yet remained significantly elevated throughout the 20+ years of observation.

The cumulative incidence of depression at 5 and 35 years’ follow-up in the epilepsy cohort was 1.37% and 6.05%, respectively, compared with 0.59% and 3.92% in the reference population.

The highest rate of depression after epilepsy was among individuals aged 40-59 years, and the lowest was among those aged 0-19 years at first epilepsy diagnosis.
 

Depression then epilepsy

The rate of developing epilepsy was increased more than twofold among patients with incident depression compared with the matched population who were without depression (aHR, 2.35; 95% CI, 2.25-2.44).

As in the opposite analysis, the rate of epilepsy was highest during the first months and years after depression diagnosis and declined over time.

The cumulative incidence of epilepsy at 5 and 35 years after depression diagnosis was 1.10% and 4.19%, respectively, compared with 0.32% and 2.06% in the reference population.

The rate of epilepsy was highest among those aged 0-19 years at time of first depression diagnosis and was lowest among those aged 80+ at first depression diagnosis.

For comparison, after asthma diagnosis, rates of depression and epilepsy were increased 1.63-fold (95% CI, 1.59-1.67) and 1.48-fold (95% CI, 1.44-1.53), respectively, compared with matched individuals without asthma.

Using admission with seizures as a proxy for treatment failure, the researchers observed an increased risk of treatment failure among people with epilepsy who were diagnosed with depression.

“Our results support previous findings indicating worse seizure outcomes in people with epilepsy and coexisting depression,” said Ms. Bølling-Ladegaard.

“Increased clinical awareness of the association between epilepsy and depression is therefore needed in order to increase the proportion of patients that receive appropriate treatment and improve outcomes for these patient groups,” she said.
 

Clinical implications

Reached for comment, Zulfi Haneef, MBBS, MD, associate professor of neurology, Baylor College of Medicine, Houston, noted that the link between epilepsy and depression is “well-known.”

“However, typically one thinks of epilepsy as leading to depression, not vice versa. Here they show the risk of epilepsy following depression to be high (highest of the risks given), which is thought provoking. However, association does not imply causation,” Dr. Haneef said.

“Prima facie, there is no biological rationale for depression to lead to epilepsy,” he said. He noted that some antidepressants can reduce the seizure threshold.

The findings do have implications for care, he said.

“For neurologists, this is another study that exhorts them to screen for depression and treat adequately in all patients with epilepsy,” Dr. Haneef said.

“For psychiatrists, this study may give guidance to watch more carefully for seizures in patients with depression, especially when using antidepressant medications that induce seizures.

“For the general public with either epilepsy or depression, it would help them be aware about this bidirectional association,” Dr. Haneef said.

The study was funded by the Lundbeck Foundation, the Danish Epilepsy Association, and the Novo Nordisk Foundation. Ms. Bølling-Ladegaard and Dr. Haneef have disclosed no relevant financial relationships.

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

A large Danish study supports a robust and long-term bidirectional relationship between epilepsy and depression, with implications for diagnosis and patient care. The findings “strongly support previous observations of a bidirectional association between these two brain disorders,” said Eva Bølling-Ladegaard, MD, a PhD student, department of clinical medicine (Neurology), Aarhus (Denmark) University.

“We add to the existing evidence in temporal range, showing that the increased risks of depression following epilepsy, and vice versa, are sustained over a much more extended time period than previously shown; that is, 20 years on both sides of receiving a diagnosis of the index disorder,” Ms. Bølling-Ladegaard said.

The study was published online in Neurology.
 

Epilepsy then depression

The researchers examined the magnitude and long-term temporal association between epilepsy and depression. They compared the risk of the two brain disorders following another chronic disorder (asthma) in a nationwide, register-based, matched cohort study.

In a population of more than 8.7 million people, they identified 139,014 persons with epilepsy (54% males; median age at diagnosis, 43 years), 219,990 with depression (37% males; median age at diagnosis, 43 years), and 358,821 with asthma (49% males; median age at diagnosis, 29 years).

The rate of developing depression was increased nearly twofold among people with epilepsy compared with the matched population who did not have epilepsy (adjusted hazard ratio, 1.88; 95% confidence interval, 1.82-1.95).

The rate of depression was highest during the first months and years after epilepsy diagnosis. It declined over time, yet remained significantly elevated throughout the 20+ years of observation.

The cumulative incidence of depression at 5 and 35 years’ follow-up in the epilepsy cohort was 1.37% and 6.05%, respectively, compared with 0.59% and 3.92% in the reference population.

The highest rate of depression after epilepsy was among individuals aged 40-59 years, and the lowest was among those aged 0-19 years at first epilepsy diagnosis.
 

Depression then epilepsy

The rate of developing epilepsy was increased more than twofold among patients with incident depression compared with the matched population who were without depression (aHR, 2.35; 95% CI, 2.25-2.44).

As in the opposite analysis, the rate of epilepsy was highest during the first months and years after depression diagnosis and declined over time.

The cumulative incidence of epilepsy at 5 and 35 years after depression diagnosis was 1.10% and 4.19%, respectively, compared with 0.32% and 2.06% in the reference population.

The rate of epilepsy was highest among those aged 0-19 years at time of first depression diagnosis and was lowest among those aged 80+ at first depression diagnosis.

For comparison, after asthma diagnosis, rates of depression and epilepsy were increased 1.63-fold (95% CI, 1.59-1.67) and 1.48-fold (95% CI, 1.44-1.53), respectively, compared with matched individuals without asthma.

Using admission with seizures as a proxy for treatment failure, the researchers observed an increased risk of treatment failure among people with epilepsy who were diagnosed with depression.

“Our results support previous findings indicating worse seizure outcomes in people with epilepsy and coexisting depression,” said Ms. Bølling-Ladegaard.

“Increased clinical awareness of the association between epilepsy and depression is therefore needed in order to increase the proportion of patients that receive appropriate treatment and improve outcomes for these patient groups,” she said.
 

Clinical implications

Reached for comment, Zulfi Haneef, MBBS, MD, associate professor of neurology, Baylor College of Medicine, Houston, noted that the link between epilepsy and depression is “well-known.”

“However, typically one thinks of epilepsy as leading to depression, not vice versa. Here they show the risk of epilepsy following depression to be high (highest of the risks given), which is thought provoking. However, association does not imply causation,” Dr. Haneef said.

“Prima facie, there is no biological rationale for depression to lead to epilepsy,” he said. He noted that some antidepressants can reduce the seizure threshold.

The findings do have implications for care, he said.

“For neurologists, this is another study that exhorts them to screen for depression and treat adequately in all patients with epilepsy,” Dr. Haneef said.

“For psychiatrists, this study may give guidance to watch more carefully for seizures in patients with depression, especially when using antidepressant medications that induce seizures.

“For the general public with either epilepsy or depression, it would help them be aware about this bidirectional association,” Dr. Haneef said.

The study was funded by the Lundbeck Foundation, the Danish Epilepsy Association, and the Novo Nordisk Foundation. Ms. Bølling-Ladegaard and Dr. Haneef have disclosed no relevant financial relationships.

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

A large Danish study supports a robust and long-term bidirectional relationship between epilepsy and depression, with implications for diagnosis and patient care. The findings “strongly support previous observations of a bidirectional association between these two brain disorders,” said Eva Bølling-Ladegaard, MD, a PhD student, department of clinical medicine (Neurology), Aarhus (Denmark) University.

“We add to the existing evidence in temporal range, showing that the increased risks of depression following epilepsy, and vice versa, are sustained over a much more extended time period than previously shown; that is, 20 years on both sides of receiving a diagnosis of the index disorder,” Ms. Bølling-Ladegaard said.

The study was published online in Neurology.
 

Epilepsy then depression

The researchers examined the magnitude and long-term temporal association between epilepsy and depression. They compared the risk of the two brain disorders following another chronic disorder (asthma) in a nationwide, register-based, matched cohort study.

In a population of more than 8.7 million people, they identified 139,014 persons with epilepsy (54% males; median age at diagnosis, 43 years), 219,990 with depression (37% males; median age at diagnosis, 43 years), and 358,821 with asthma (49% males; median age at diagnosis, 29 years).

The rate of developing depression was increased nearly twofold among people with epilepsy compared with the matched population who did not have epilepsy (adjusted hazard ratio, 1.88; 95% confidence interval, 1.82-1.95).

The rate of depression was highest during the first months and years after epilepsy diagnosis. It declined over time, yet remained significantly elevated throughout the 20+ years of observation.

The cumulative incidence of depression at 5 and 35 years’ follow-up in the epilepsy cohort was 1.37% and 6.05%, respectively, compared with 0.59% and 3.92% in the reference population.

The highest rate of depression after epilepsy was among individuals aged 40-59 years, and the lowest was among those aged 0-19 years at first epilepsy diagnosis.
 

Depression then epilepsy

The rate of developing epilepsy was increased more than twofold among patients with incident depression compared with the matched population who were without depression (aHR, 2.35; 95% CI, 2.25-2.44).

As in the opposite analysis, the rate of epilepsy was highest during the first months and years after depression diagnosis and declined over time.

The cumulative incidence of epilepsy at 5 and 35 years after depression diagnosis was 1.10% and 4.19%, respectively, compared with 0.32% and 2.06% in the reference population.

The rate of epilepsy was highest among those aged 0-19 years at time of first depression diagnosis and was lowest among those aged 80+ at first depression diagnosis.

For comparison, after asthma diagnosis, rates of depression and epilepsy were increased 1.63-fold (95% CI, 1.59-1.67) and 1.48-fold (95% CI, 1.44-1.53), respectively, compared with matched individuals without asthma.

Using admission with seizures as a proxy for treatment failure, the researchers observed an increased risk of treatment failure among people with epilepsy who were diagnosed with depression.

“Our results support previous findings indicating worse seizure outcomes in people with epilepsy and coexisting depression,” said Ms. Bølling-Ladegaard.

“Increased clinical awareness of the association between epilepsy and depression is therefore needed in order to increase the proportion of patients that receive appropriate treatment and improve outcomes for these patient groups,” she said.
 

Clinical implications

Reached for comment, Zulfi Haneef, MBBS, MD, associate professor of neurology, Baylor College of Medicine, Houston, noted that the link between epilepsy and depression is “well-known.”

“However, typically one thinks of epilepsy as leading to depression, not vice versa. Here they show the risk of epilepsy following depression to be high (highest of the risks given), which is thought provoking. However, association does not imply causation,” Dr. Haneef said.

“Prima facie, there is no biological rationale for depression to lead to epilepsy,” he said. He noted that some antidepressants can reduce the seizure threshold.

The findings do have implications for care, he said.

“For neurologists, this is another study that exhorts them to screen for depression and treat adequately in all patients with epilepsy,” Dr. Haneef said.

“For psychiatrists, this study may give guidance to watch more carefully for seizures in patients with depression, especially when using antidepressant medications that induce seizures.

“For the general public with either epilepsy or depression, it would help them be aware about this bidirectional association,” Dr. Haneef said.

The study was funded by the Lundbeck Foundation, the Danish Epilepsy Association, and the Novo Nordisk Foundation. Ms. Bølling-Ladegaard and Dr. Haneef have disclosed no relevant financial relationships.

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

The American Academy of Pediatrics is cautioning physicians and parents to be on the lookout for unnecessary diagnostic testing associated with several common pediatric conditions.

Children seen for these conditions in emergency settings and even in primary care offices could experience avoidable pain, exposure to harmful radiation, and other harms, according to the group.

“The emergency department has the ability to rapidly perform myriad diagnostic tests and receive results quickly,” said Paul Mullan, MD, MPH, chair of the AAP’s Section of Emergency Medicine’s Choosing Wisely task force. “However, this comes with the danger of diagnostic overtesting.”

The five recommendations are as follows:

• Radiographs should not be obtained for children with bronchiolitis, croup, asthma, or first-time wheezing.
• Laboratory tests for screening should not be undertaken in the medical clearance process of children who require inpatient psychiatric admission unless clinically indicated.
• Laboratory testing or a CT scan of the head should not be ordered for a child with an unprovoked, generalized seizure or a simple febrile seizure whose mental status has returned to baseline.
• Abdominal radiographs should not be obtained for suspected constipation.
• Comprehensive viral panel testing should not be undertaken for children who are suspected of having respiratory viral illnesses.

The AAP task force partnered with Choosing Wisely Canada to create the recommendations. The list is the first of its kind to be published jointly by two countries, according to the release.

“We hope this Choosing Wisely list will encourage clinicians to rely on their clinical skills and avoid unnecessary tests,” said Dr. Mullan, who is also a physician at Children’s Hospital of the King’s Daughters and professor of pediatrics at Eastern Virginia Medical School, Norfolk.

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

The American Academy of Pediatrics is cautioning physicians and parents to be on the lookout for unnecessary diagnostic testing associated with several common pediatric conditions.

Children seen for these conditions in emergency settings and even in primary care offices could experience avoidable pain, exposure to harmful radiation, and other harms, according to the group.

“The emergency department has the ability to rapidly perform myriad diagnostic tests and receive results quickly,” said Paul Mullan, MD, MPH, chair of the AAP’s Section of Emergency Medicine’s Choosing Wisely task force. “However, this comes with the danger of diagnostic overtesting.”

The five recommendations are as follows:

• Radiographs should not be obtained for children with bronchiolitis, croup, asthma, or first-time wheezing.
• Laboratory tests for screening should not be undertaken in the medical clearance process of children who require inpatient psychiatric admission unless clinically indicated.
• Laboratory testing or a CT scan of the head should not be ordered for a child with an unprovoked, generalized seizure or a simple febrile seizure whose mental status has returned to baseline.
• Abdominal radiographs should not be obtained for suspected constipation.
• Comprehensive viral panel testing should not be undertaken for children who are suspected of having respiratory viral illnesses.

The AAP task force partnered with Choosing Wisely Canada to create the recommendations. The list is the first of its kind to be published jointly by two countries, according to the release.

“We hope this Choosing Wisely list will encourage clinicians to rely on their clinical skills and avoid unnecessary tests,” said Dr. Mullan, who is also a physician at Children’s Hospital of the King’s Daughters and professor of pediatrics at Eastern Virginia Medical School, Norfolk.

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

The American Academy of Pediatrics is cautioning physicians and parents to be on the lookout for unnecessary diagnostic testing associated with several common pediatric conditions.

Children seen for these conditions in emergency settings and even in primary care offices could experience avoidable pain, exposure to harmful radiation, and other harms, according to the group.

“The emergency department has the ability to rapidly perform myriad diagnostic tests and receive results quickly,” said Paul Mullan, MD, MPH, chair of the AAP’s Section of Emergency Medicine’s Choosing Wisely task force. “However, this comes with the danger of diagnostic overtesting.”

The five recommendations are as follows:

• Radiographs should not be obtained for children with bronchiolitis, croup, asthma, or first-time wheezing.
• Laboratory tests for screening should not be undertaken in the medical clearance process of children who require inpatient psychiatric admission unless clinically indicated.
• Laboratory testing or a CT scan of the head should not be ordered for a child with an unprovoked, generalized seizure or a simple febrile seizure whose mental status has returned to baseline.
• Abdominal radiographs should not be obtained for suspected constipation.
• Comprehensive viral panel testing should not be undertaken for children who are suspected of having respiratory viral illnesses.

The AAP task force partnered with Choosing Wisely Canada to create the recommendations. The list is the first of its kind to be published jointly by two countries, according to the release.

“We hope this Choosing Wisely list will encourage clinicians to rely on their clinical skills and avoid unnecessary tests,” said Dr. Mullan, who is also a physician at Children’s Hospital of the King’s Daughters and professor of pediatrics at Eastern Virginia Medical School, Norfolk.

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

The offspring of mothers who sustain unintentional injuries during pregnancy appear to have a modest 33% increased risk of developing cerebral palsy (CP) – higher when injuries are more severe, multiple, or lead to delivery soon afterward, a Canadian birth cohort study found.

Such children may benefit from long-term monitoring for neurodevelpmental issues, wrote a group led by Asma Ahmed, MD, PhD, MPH, a pediatric epidemiologist at the Hospital for Sick Children Research Institute in Toronto in JAMA Pediatrics.

“We need to provide better support for babies whose mothers have been injured in pregnancy, especially after severe injuries,” Dr. Ahmed said in a press release. “As well, these findings suggest the need for early monitoring of babies’ development, regular check-ups, and longer-term neurodevelopmental assessments.” Future studies should directly measure injury severity and its possible link to CP.

Current guidelines, however, focus on monitoring fetal condition immediately after injury with little attention to its long-term effects.

In their findings from the population-based linkage study of 2,110,177 children born in Ontario’s public health system during 2002-2017 and followed to 2018 with a median follow-up of 8 years:

• A total of 81,281 fetuses were exposed in utero to unintentional maternal injury.
• Overall, 0.3% children were diagnosed with CP, and the mean CP incidence rates were 4.36 per 10,000 child-years for the exposed versus 2.93 for the unexposed.
• In those exposed, the hazard ratio was 1.33 (95% confidence interval, 1.18-1.50) after adjusting for maternal sociodemographic and clinical characteristics.
• Injuries resulting in hospitalization or delivery within 1 week were linked to higher adjusted hazard ratios of 2.18 (95% CI, 1.29-3.68) and 3.40 (95% CI, 1.93-6.00), respectively.
• Injuries most frequently resulted from transportation mishaps, falls, and being struck by a person or object. They were most commonly associated with age younger than 20 years, substance use disorder, residence in rural and under-resourced areas, and lower socioeconomic status.

The authors noted that complications after maternal injuries – which affect 6%-8% of pregnant women – include uterine rupture, preterm delivery, and placental abruption and are linked to fetal complications such as asphyxia. The association with an offspring’s neurodevelopment has been rarely investigated. One U.K. population study, however, suggested a link between vehicular crashes and higher CP risk in preterm infants.

A related editorial on the study noted that while CP affects about two to four children per 1,000 live births each year in high-income countries, the etiological causes of most cases remain unknown. “This large population-based cohort study ... should inspire more research into preventing and mitigating factors for maternal injuries and offspring CP development,” wrote Zeyan Liew, PhD, MPH, and Haoran Zhuo, MPH, of Yale University School of Public Health in New Haven, Conn.

This study was supported by Santé-Québec and ICES, a research institute funded by the Ontario Ministry of Health and the Ministry of Long-Term Care.

Dr. Ahmed and coauthor Seungmi Yang, PhD, reported research funding from Santé-Québec during the conduct of the study.

The offspring of mothers who sustain unintentional injuries during pregnancy appear to have a modest 33% increased risk of developing cerebral palsy (CP) – higher when injuries are more severe, multiple, or lead to delivery soon afterward, a Canadian birth cohort study found.

Such children may benefit from long-term monitoring for neurodevelpmental issues, wrote a group led by Asma Ahmed, MD, PhD, MPH, a pediatric epidemiologist at the Hospital for Sick Children Research Institute in Toronto in JAMA Pediatrics.

“We need to provide better support for babies whose mothers have been injured in pregnancy, especially after severe injuries,” Dr. Ahmed said in a press release. “As well, these findings suggest the need for early monitoring of babies’ development, regular check-ups, and longer-term neurodevelopmental assessments.” Future studies should directly measure injury severity and its possible link to CP.

Current guidelines, however, focus on monitoring fetal condition immediately after injury with little attention to its long-term effects.

In their findings from the population-based linkage study of 2,110,177 children born in Ontario’s public health system during 2002-2017 and followed to 2018 with a median follow-up of 8 years:

• A total of 81,281 fetuses were exposed in utero to unintentional maternal injury.
• Overall, 0.3% children were diagnosed with CP, and the mean CP incidence rates were 4.36 per 10,000 child-years for the exposed versus 2.93 for the unexposed.
• In those exposed, the hazard ratio was 1.33 (95% confidence interval, 1.18-1.50) after adjusting for maternal sociodemographic and clinical characteristics.
• Injuries resulting in hospitalization or delivery within 1 week were linked to higher adjusted hazard ratios of 2.18 (95% CI, 1.29-3.68) and 3.40 (95% CI, 1.93-6.00), respectively.
• Injuries most frequently resulted from transportation mishaps, falls, and being struck by a person or object. They were most commonly associated with age younger than 20 years, substance use disorder, residence in rural and under-resourced areas, and lower socioeconomic status.

The authors noted that complications after maternal injuries – which affect 6%-8% of pregnant women – include uterine rupture, preterm delivery, and placental abruption and are linked to fetal complications such as asphyxia. The association with an offspring’s neurodevelopment has been rarely investigated. One U.K. population study, however, suggested a link between vehicular crashes and higher CP risk in preterm infants.

A related editorial on the study noted that while CP affects about two to four children per 1,000 live births each year in high-income countries, the etiological causes of most cases remain unknown. “This large population-based cohort study ... should inspire more research into preventing and mitigating factors for maternal injuries and offspring CP development,” wrote Zeyan Liew, PhD, MPH, and Haoran Zhuo, MPH, of Yale University School of Public Health in New Haven, Conn.

This study was supported by Santé-Québec and ICES, a research institute funded by the Ontario Ministry of Health and the Ministry of Long-Term Care.

Dr. Ahmed and coauthor Seungmi Yang, PhD, reported research funding from Santé-Québec during the conduct of the study.

The offspring of mothers who sustain unintentional injuries during pregnancy appear to have a modest 33% increased risk of developing cerebral palsy (CP) – higher when injuries are more severe, multiple, or lead to delivery soon afterward, a Canadian birth cohort study found.

Such children may benefit from long-term monitoring for neurodevelpmental issues, wrote a group led by Asma Ahmed, MD, PhD, MPH, a pediatric epidemiologist at the Hospital for Sick Children Research Institute in Toronto in JAMA Pediatrics.

“We need to provide better support for babies whose mothers have been injured in pregnancy, especially after severe injuries,” Dr. Ahmed said in a press release. “As well, these findings suggest the need for early monitoring of babies’ development, regular check-ups, and longer-term neurodevelopmental assessments.” Future studies should directly measure injury severity and its possible link to CP.

Current guidelines, however, focus on monitoring fetal condition immediately after injury with little attention to its long-term effects.

In their findings from the population-based linkage study of 2,110,177 children born in Ontario’s public health system during 2002-2017 and followed to 2018 with a median follow-up of 8 years:

• A total of 81,281 fetuses were exposed in utero to unintentional maternal injury.
• Overall, 0.3% children were diagnosed with CP, and the mean CP incidence rates were 4.36 per 10,000 child-years for the exposed versus 2.93 for the unexposed.
• In those exposed, the hazard ratio was 1.33 (95% confidence interval, 1.18-1.50) after adjusting for maternal sociodemographic and clinical characteristics.
• Injuries resulting in hospitalization or delivery within 1 week were linked to higher adjusted hazard ratios of 2.18 (95% CI, 1.29-3.68) and 3.40 (95% CI, 1.93-6.00), respectively.
• Injuries most frequently resulted from transportation mishaps, falls, and being struck by a person or object. They were most commonly associated with age younger than 20 years, substance use disorder, residence in rural and under-resourced areas, and lower socioeconomic status.

The authors noted that complications after maternal injuries – which affect 6%-8% of pregnant women – include uterine rupture, preterm delivery, and placental abruption and are linked to fetal complications such as asphyxia. The association with an offspring’s neurodevelopment has been rarely investigated. One U.K. population study, however, suggested a link between vehicular crashes and higher CP risk in preterm infants.

A related editorial on the study noted that while CP affects about two to four children per 1,000 live births each year in high-income countries, the etiological causes of most cases remain unknown. “This large population-based cohort study ... should inspire more research into preventing and mitigating factors for maternal injuries and offspring CP development,” wrote Zeyan Liew, PhD, MPH, and Haoran Zhuo, MPH, of Yale University School of Public Health in New Haven, Conn.

This study was supported by Santé-Québec and ICES, a research institute funded by the Ontario Ministry of Health and the Ministry of Long-Term Care.

Dr. Ahmed and coauthor Seungmi Yang, PhD, reported research funding from Santé-Québec during the conduct of the study.

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.

CHICAGO – A single chest x-ray could predict a patient’s 10-year risk of dying from a heart attack or stroke, say researchers who presented the results of their deep-learning model at the annual meeting of the Radiological Society of North America.

Current American College of Cardiologists and American Heart Association guidelines recommend estimating 10-year risk of major adverse cardiovascular events (MACE) to determine whether a patient should receive statins to help prevent atherosclerotic cardiovascular disease (ASCVD). Statins are recommended for patients with a 10-year risk of 7.5% or higher, the authors noted.

The current ASCVD risk score is determined with nine factors: age, sex, race, systolic blood pressure, hypertension treatment, smoking, type 2 diabetes, and a lipid panel.
 

Not all data points available in EHR

But not all of those data points may be available through the electronic health record, “which makes novel and easier approaches for population-wide screening desirable,” said lead researcher Jakob Weiss, MD, a radiologist affiliated with the Cardiovascular Imaging Research Center at Massachusetts General Hospital and the AI in medicine program at the Brigham and Women’s Hospital in Boston.

Chest x-ray images, on the other hand, are commonly available. The images carry rich information beyond diagnostic data but have not been used in this type of prediction model because AI models have been lacking, Dr. Weiss said.

The researchers trained a deep-learning model with single chest x-rays only.

They used 147,497 chest x-rays from 40,643 participants in the Prostate, Lung, Colorectal, and Ovarian Cancer (PLCO) Screening Trial, a multicenter, randomized controlled trial designed and sponsored by the National Cancer Institute.

Dr. Weiss acknowledged that the population used to train the model was heavily White and that should be a consideration in validating the model.

They compared their model’s ability to predict 10-year ASCVD risk with the standard ACC/AHA model.

“Based on a single chest radiograph image, deep learning can predict the risk of future cardiovascular events independent of cardiovascular risk factors and with similar performance to the established and guideline-recommended ASCVD risk score,” Dr. Weiss said.
 

Tested against independent group

They tested the model against an independent group of 11,430 outpatients (average age, 60 years; 42.9% male) who underwent a routine outpatient chest x-ray at Mass General Brigham and were potentially eligible to receive statins.

Of those 11,430 patients, 1,096 (9.6%) had a major adverse cardiac event over the median follow-up of 10.3 years.

There was a significant association of CXR-CVD risk and MACE among patients eligible to receive statins, the researchers found (hazard ratio, 2.03; 95% confidence interval, 1.81-2.30; P < .001), which remained significant after adjusting for cardiovascular risk factors (adjusted HR, 1.63; 95% CI, 1.43-1.86; P < .001).

Some of the variables were missing in the standard model, but in a subgroup of 2,401 patients, all the variables were available.

They calculated ASCVD risk in that subgroup using the standard model and the CXR model and found that the performance was similar (c-statistic, 0.64 vs. 0.65; P = .48) to the ASCVD risk score (aHR, 1.58; 95% CI, 1.20-2.09; P = .001).

Ritu R. Gill MD, MPH, associate professor of radiology at Harvard Medical School in Boston, who was not part of the study, said in an interview that “the predictive algorithm is promising and potentially translatable and could enhance the annual medical checkup in a select population.

“The algorithm was developed using the PLCO cohort with radiographs, which are likely subjects in the lung cancer screening arm,” she said. “This cohort would be at high risk of cardiovascular diseases, as smoking is a known risk factor for atherosclerotic disease, and therefore the results are expected.

“The algorithm needs to be validated in an independent database with inclusion of subjects with younger age groups and adjusted for gender and racial diversity,” Gill said.

David Cho, MD, a cardiologist at the University of California, Los Angeles, who also was not part of the study, said in an interview that “this work is a great example of AI being able to detect clinically relevant outcomes with a widely used and low-cost screening test.

“The volume of data needed to train these models is already out there,” Dr. Cho said. “It just needs to be mined.”

He noted that this tool, if validated in randomized trials, could help determine risk among patients living in places where access to specialized cardiac care is limited.

Dr. Weiss and Dr. Cho disclosed no relevant financial relationships. Dr. Gill has received research support from Cannon Inc and consultant fees from Imbio and WorldCare.

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

CHICAGO – A single chest x-ray could predict a patient’s 10-year risk of dying from a heart attack or stroke, say researchers who presented the results of their deep-learning model at the annual meeting of the Radiological Society of North America.

Current American College of Cardiologists and American Heart Association guidelines recommend estimating 10-year risk of major adverse cardiovascular events (MACE) to determine whether a patient should receive statins to help prevent atherosclerotic cardiovascular disease (ASCVD). Statins are recommended for patients with a 10-year risk of 7.5% or higher, the authors noted.

The current ASCVD risk score is determined with nine factors: age, sex, race, systolic blood pressure, hypertension treatment, smoking, type 2 diabetes, and a lipid panel.
 

Not all data points available in EHR

But not all of those data points may be available through the electronic health record, “which makes novel and easier approaches for population-wide screening desirable,” said lead researcher Jakob Weiss, MD, a radiologist affiliated with the Cardiovascular Imaging Research Center at Massachusetts General Hospital and the AI in medicine program at the Brigham and Women’s Hospital in Boston.

Chest x-ray images, on the other hand, are commonly available. The images carry rich information beyond diagnostic data but have not been used in this type of prediction model because AI models have been lacking, Dr. Weiss said.

The researchers trained a deep-learning model with single chest x-rays only.

They used 147,497 chest x-rays from 40,643 participants in the Prostate, Lung, Colorectal, and Ovarian Cancer (PLCO) Screening Trial, a multicenter, randomized controlled trial designed and sponsored by the National Cancer Institute.

Dr. Weiss acknowledged that the population used to train the model was heavily White and that should be a consideration in validating the model.

They compared their model’s ability to predict 10-year ASCVD risk with the standard ACC/AHA model.

“Based on a single chest radiograph image, deep learning can predict the risk of future cardiovascular events independent of cardiovascular risk factors and with similar performance to the established and guideline-recommended ASCVD risk score,” Dr. Weiss said.
 

Tested against independent group

They tested the model against an independent group of 11,430 outpatients (average age, 60 years; 42.9% male) who underwent a routine outpatient chest x-ray at Mass General Brigham and were potentially eligible to receive statins.

Of those 11,430 patients, 1,096 (9.6%) had a major adverse cardiac event over the median follow-up of 10.3 years.

There was a significant association of CXR-CVD risk and MACE among patients eligible to receive statins, the researchers found (hazard ratio, 2.03; 95% confidence interval, 1.81-2.30; P < .001), which remained significant after adjusting for cardiovascular risk factors (adjusted HR, 1.63; 95% CI, 1.43-1.86; P < .001).

Some of the variables were missing in the standard model, but in a subgroup of 2,401 patients, all the variables were available.

They calculated ASCVD risk in that subgroup using the standard model and the CXR model and found that the performance was similar (c-statistic, 0.64 vs. 0.65; P = .48) to the ASCVD risk score (aHR, 1.58; 95% CI, 1.20-2.09; P = .001).

Ritu R. Gill MD, MPH, associate professor of radiology at Harvard Medical School in Boston, who was not part of the study, said in an interview that “the predictive algorithm is promising and potentially translatable and could enhance the annual medical checkup in a select population.

“The algorithm was developed using the PLCO cohort with radiographs, which are likely subjects in the lung cancer screening arm,” she said. “This cohort would be at high risk of cardiovascular diseases, as smoking is a known risk factor for atherosclerotic disease, and therefore the results are expected.

“The algorithm needs to be validated in an independent database with inclusion of subjects with younger age groups and adjusted for gender and racial diversity,” Gill said.

David Cho, MD, a cardiologist at the University of California, Los Angeles, who also was not part of the study, said in an interview that “this work is a great example of AI being able to detect clinically relevant outcomes with a widely used and low-cost screening test.

“The volume of data needed to train these models is already out there,” Dr. Cho said. “It just needs to be mined.”

He noted that this tool, if validated in randomized trials, could help determine risk among patients living in places where access to specialized cardiac care is limited.

Dr. Weiss and Dr. Cho disclosed no relevant financial relationships. Dr. Gill has received research support from Cannon Inc and consultant fees from Imbio and WorldCare.

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

CHICAGO – A single chest x-ray could predict a patient’s 10-year risk of dying from a heart attack or stroke, say researchers who presented the results of their deep-learning model at the annual meeting of the Radiological Society of North America.

Current American College of Cardiologists and American Heart Association guidelines recommend estimating 10-year risk of major adverse cardiovascular events (MACE) to determine whether a patient should receive statins to help prevent atherosclerotic cardiovascular disease (ASCVD). Statins are recommended for patients with a 10-year risk of 7.5% or higher, the authors noted.

The current ASCVD risk score is determined with nine factors: age, sex, race, systolic blood pressure, hypertension treatment, smoking, type 2 diabetes, and a lipid panel.
 

Not all data points available in EHR

But not all of those data points may be available through the electronic health record, “which makes novel and easier approaches for population-wide screening desirable,” said lead researcher Jakob Weiss, MD, a radiologist affiliated with the Cardiovascular Imaging Research Center at Massachusetts General Hospital and the AI in medicine program at the Brigham and Women’s Hospital in Boston.

Chest x-ray images, on the other hand, are commonly available. The images carry rich information beyond diagnostic data but have not been used in this type of prediction model because AI models have been lacking, Dr. Weiss said.

The researchers trained a deep-learning model with single chest x-rays only.

They used 147,497 chest x-rays from 40,643 participants in the Prostate, Lung, Colorectal, and Ovarian Cancer (PLCO) Screening Trial, a multicenter, randomized controlled trial designed and sponsored by the National Cancer Institute.

Dr. Weiss acknowledged that the population used to train the model was heavily White and that should be a consideration in validating the model.

They compared their model’s ability to predict 10-year ASCVD risk with the standard ACC/AHA model.

“Based on a single chest radiograph image, deep learning can predict the risk of future cardiovascular events independent of cardiovascular risk factors and with similar performance to the established and guideline-recommended ASCVD risk score,” Dr. Weiss said.
 

Tested against independent group

They tested the model against an independent group of 11,430 outpatients (average age, 60 years; 42.9% male) who underwent a routine outpatient chest x-ray at Mass General Brigham and were potentially eligible to receive statins.

Of those 11,430 patients, 1,096 (9.6%) had a major adverse cardiac event over the median follow-up of 10.3 years.

There was a significant association of CXR-CVD risk and MACE among patients eligible to receive statins, the researchers found (hazard ratio, 2.03; 95% confidence interval, 1.81-2.30; P < .001), which remained significant after adjusting for cardiovascular risk factors (adjusted HR, 1.63; 95% CI, 1.43-1.86; P < .001).

Some of the variables were missing in the standard model, but in a subgroup of 2,401 patients, all the variables were available.

They calculated ASCVD risk in that subgroup using the standard model and the CXR model and found that the performance was similar (c-statistic, 0.64 vs. 0.65; P = .48) to the ASCVD risk score (aHR, 1.58; 95% CI, 1.20-2.09; P = .001).

Ritu R. Gill MD, MPH, associate professor of radiology at Harvard Medical School in Boston, who was not part of the study, said in an interview that “the predictive algorithm is promising and potentially translatable and could enhance the annual medical checkup in a select population.

“The algorithm was developed using the PLCO cohort with radiographs, which are likely subjects in the lung cancer screening arm,” she said. “This cohort would be at high risk of cardiovascular diseases, as smoking is a known risk factor for atherosclerotic disease, and therefore the results are expected.

“The algorithm needs to be validated in an independent database with inclusion of subjects with younger age groups and adjusted for gender and racial diversity,” Gill said.

David Cho, MD, a cardiologist at the University of California, Los Angeles, who also was not part of the study, said in an interview that “this work is a great example of AI being able to detect clinically relevant outcomes with a widely used and low-cost screening test.

“The volume of data needed to train these models is already out there,” Dr. Cho said. “It just needs to be mined.”

He noted that this tool, if validated in randomized trials, could help determine risk among patients living in places where access to specialized cardiac care is limited.

Dr. Weiss and Dr. Cho disclosed no relevant financial relationships. Dr. Gill has received research support from Cannon Inc and consultant fees from Imbio and WorldCare.

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

By the time Mira Halker started high school, hardly a day passed that she wasn’t either getting a migraine attack or recovering from one. She missed volleyball team practice. She missed classes. She missed social events. And few people understood. After all, she looked healthy.

“A lot of times, people think I’m faking it,” said Mira, now 16, who lives in Phoenix. Friends called her flaky; her volleyball coaches questioned her dedication to the team. “I’m like, ‘I’m not trying to get out of this. This is not what this is about,’ ” she said.

Her mother, Rashmi B. Halker Singh, MD, is a neurologist at Mayo Clinic who happens to specialize in migraine. Even so, finding a solution was not easy. Neither ibuprofen nor triptans, nor various preventive measures such as a daily prescription for topiramate controlled the pain and associated symptoms. Mira was barely making it through her school day and had to quit volleyball. Then, in the spring of 10th grade, Mira told her mother that she couldn’t go to prom because the loud noises and lights could give her a migraine attack.

Mother and daughter decided it was time to get even more aggressive. “There are these key moments in life that you can’t get back,” Dr. Singh said. “Migraine steals so much from you.”
 

Diagnosis

One of the challenges Mira’s physicians faced was deciding which medications and other therapies to prescribe to a teenager. Drug companies have been releasing a steady stream of new treatments for migraine headaches, and researchers promise more are on the way soon. Here’s what works for children, what hasn’t yet been approved for use with minors, and how to diagnose migraines in the first place, from experts at some of the nation’s leading pediatric headache centers.

Migraine affects about 10% of children, according to the American Migraine Foundation. The headaches can strike children as early as age 3 or 4 years, said Robert Little, MD, a pediatric neurologist at Phoenix Children’s Hospital.

Before puberty, boys report more migraine attacks than girls, according to the American Academy of Pediatrics. But that reverses in adolescence: By age 17, as many as 8% of boys and 23% of girls have had migraine. To diagnose migraine, Juliana H. VanderPluym, MD, associate professor of neurology at Mayo Clinic in Phoenix, said she uses the criteria published in the latest edition of the International Classification of Headache Disorders (ICHD): A patient must have had at least five attacks in their life; and in children and adolescents, the attacks must last no less than 2 hours.

In addition, the headaches should exhibit at least two out of four features:

1. Occur more on one side of the head than the other (although Dr. VanderPluym said in children and adolescents headaches often are bilateral).

2. Be of moderate to severe intensity.

3. Have a pounding or throbbing quality.

4. Grow worse with activity or cause an avoidance of activity.

If the attacks meet those criteria, clinicians should check to see if they meet at least one out of the two following:

1. Are sensitive to light and sounds.

2. Are associated with nausea and/or vomiting.

A clinician should consider whether the headaches are not better accounted for by another diagnosis, according to the ICHD criteria. But, Dr. VanderPluym warned that does not necessarily mean running a slew of tests.

“In the absence of red flag features, it is more than likely going to be migraine headache,” she said. That’s especially true if a child has a family history of migraine, as the condition is often passed down from parent to child.

Ultimately, the diagnosis is fairly simple and can be made in a minute or less, said Jack Gladstein, MD, a pediatrician at the University of Maryland whose research focuses on the clinical care of children and adolescents with headache.

“Migraine is acute,” Dr. Gladstein said. “It’s really bad. And it’s recurrent.”
 

First line of treatment

Whatever a patient takes to treat a migraine, they should hit it early and hard, Dr. Gladstein said.

“The first thing you say, as a primary care physician, is treat your migraine at first twinge, whatever you use. Don’t wait, don’t wish it away,” he said. “The longer you wait, the less chance anything will work.”

The second piece of advice, Dr. Gladstein said, is that whatever drug a patient is taking, they should be on the highest feasible dose. “Work as fast as you can to treat them. You want the brain to reset as quickly as you can,” he said.

Patients should begin with over-the-counter pain relievers, Dr. Little said. If those prove insufficient, they can try a triptan. Rizatriptan is the only such agent that the Food and Drug Administration has approved for children aged 6-17 years. Other drugs in the class – sumatriptan/naproxen, almotriptan, and zolmitriptan – are approved for children 12 and older.

Another migraine therapy recently approved for children aged 12 and older is the use of neurostimulators. “It’s helpful to be aware of them,” Dr. VanderPluym said.

However, if neurostimulators and acute medications prove insufficient, clinicians should warn patients not to up their doses of triptans. Rebound headaches can occur if patients take triptans more than twice a week, or a maximum 10 days per month.

Another possibility is to add a preventive therapy. One mild, first option is nutraceuticals, like riboflavin (vitamin B₂) or magnesium, said Anisa F. Kelley, MD, a neurologist and associate director of the headache program at the Ann and Robert H. Lurie Children’s Hospital of Chicago.

“We don’t have definitive evidence, but they’re probably doing more benefit than they are harm,” Dr. Kelley said of these therapies. “In patients who have anywhere from 4 to 8 migraine days a month, where you’re in that in-between period where you don’t necessarily need a [prescription] prophylactic, I will often start with a nutraceutical,” Dr. Kelley said.

For those patients who don’t respond to nutraceuticals, or who need more support, clinicians can prescribe amitriptyline or topiramate. Dr. VanderPluym said.

A 2017 study found such prophylactics to be no more effective than placebo in pediatric migraine patients, but experts caution the results should not be considered definitive.

For one thing, the study enrolled a highly selective group of participants, with milder forms of migraine who may have improved anyway, Dr. VanderPluym said. All participants also received lifestyle counseling.

Every time participants came in for a follow-up, they were asked questions such as how much water were they drinking and how much sleep were they getting, Dr. Kelley noted. The takeaway, she said: “Pediatric and adolescent migraine [management] is very, very much reliant on lifestyle factors.”
 

Lifestyle triggers

Clinicians should counsel their migraine patients about lifestyle changes, experts said. Getting adequate sleep, staying hydrated, and managing stress can help reduce the intensity and frequency of attacks.

Migraine patients should also be mindful of their screen time, Dr. Kelley added.

“I’ve had lots and lots of patients who find excessive screen time will trigger or worsen migraine,” she said.

As for other potential triggers of attacks, the evidence is mixed.

“There’s clearly an association with disrupted sleep and migraine, and that has been very well established,” Dr. Little said. “And there is some modest amount of evidence that regular exercise can be helpful.” But for reported food triggers, he said, there have been very inconclusive results.

Commonly reported triggers include MSG, red wine, chocolate, and aged cheese. When Dr. Little’s patients keep headache diaries, tracking their meals alongside when they got migraine attacks, they often discover individualized triggers – strawberries, for instance, in one case, he said.

Scientists believe migraines result from the inappropriate activation of the trigeminal ganglion. “The question is, what causes it to get triggered? And how does it get triggered?” Dr. Gladstein said. “And that’s where there’s a lot of difference of opinion and no conclusive evidence.” Clinicians also should make sure that something else – usually depression, anxiety, insomnia, and dizziness – is not hindering effective migraine management. “If someone has terrible insomnia, until you treat the insomnia, the headaches aren’t going to get better,” he said.

As for Mira, her migraine attacks did not significantly improve, despite trying triptans, prophylactics, lifestyle changes, and shots to block nerve pain. When the headaches threatened Mira’s chance to go to her prom, her neurologist suggested trying something different. The physician persuaded the family’s insurance to cover a calcitonin gene-related peptide antagonist, an injectable monoclonal antibody treatment for migraine that the FDA has currently approved only for use in adults.

The difference for Mira has been extraordinary.

“I can do so much more than I was able to do,” said Mira, who attended the dance migraine free. “I feel liberated.”

It’s only migraine

One of the greatest challenges in diagnosing migraine can be reassuring the patient, the parents, even clinicians themselves that migraine really is the cause of all this pain and discomfort, experts said.

“A lot of migraine treatment actually comes down to migraine education,” Dr. VanderPluym said.

Patients and their parents often wonder how they can be sure that this pain is not resulting from something more dangerous than migraine, Dr. Little said. In these cases, he cites practice guidelines published by the American Academy of Neurology.

“The gist of those guidelines is that most pediatric patients do not need further workup,” he said. “But I think that there’s always a fear that you’re missing something because we don’t have a test that we can do” for migraine.

Some warning signs that further tests might be warranted, Dr. Kelley said, include:

• Headaches that wake a patient up in the middle of the night.
• Headaches that start first thing in the morning, especially those that include vomiting.
• A headache pattern that suddenly gets much worse.
• Certain symptoms that accompany the headache, such as tingling, numbness or double vision.

Although all of these signs can still stem from migraines – tingling or numbness, for instance, can be signs of migraine aura – running additional tests can rule out more serious concerns, she said.

By the time Mira Halker started high school, hardly a day passed that she wasn’t either getting a migraine attack or recovering from one. She missed volleyball team practice. She missed classes. She missed social events. And few people understood. After all, she looked healthy.

“A lot of times, people think I’m faking it,” said Mira, now 16, who lives in Phoenix. Friends called her flaky; her volleyball coaches questioned her dedication to the team. “I’m like, ‘I’m not trying to get out of this. This is not what this is about,’ ” she said.

Her mother, Rashmi B. Halker Singh, MD, is a neurologist at Mayo Clinic who happens to specialize in migraine. Even so, finding a solution was not easy. Neither ibuprofen nor triptans, nor various preventive measures such as a daily prescription for topiramate controlled the pain and associated symptoms. Mira was barely making it through her school day and had to quit volleyball. Then, in the spring of 10th grade, Mira told her mother that she couldn’t go to prom because the loud noises and lights could give her a migraine attack.

Mother and daughter decided it was time to get even more aggressive. “There are these key moments in life that you can’t get back,” Dr. Singh said. “Migraine steals so much from you.”
 

Diagnosis

One of the challenges Mira’s physicians faced was deciding which medications and other therapies to prescribe to a teenager. Drug companies have been releasing a steady stream of new treatments for migraine headaches, and researchers promise more are on the way soon. Here’s what works for children, what hasn’t yet been approved for use with minors, and how to diagnose migraines in the first place, from experts at some of the nation’s leading pediatric headache centers.

Migraine affects about 10% of children, according to the American Migraine Foundation. The headaches can strike children as early as age 3 or 4 years, said Robert Little, MD, a pediatric neurologist at Phoenix Children’s Hospital.

Before puberty, boys report more migraine attacks than girls, according to the American Academy of Pediatrics. But that reverses in adolescence: By age 17, as many as 8% of boys and 23% of girls have had migraine. To diagnose migraine, Juliana H. VanderPluym, MD, associate professor of neurology at Mayo Clinic in Phoenix, said she uses the criteria published in the latest edition of the International Classification of Headache Disorders (ICHD): A patient must have had at least five attacks in their life; and in children and adolescents, the attacks must last no less than 2 hours.

In addition, the headaches should exhibit at least two out of four features:

1. Occur more on one side of the head than the other (although Dr. VanderPluym said in children and adolescents headaches often are bilateral).

2. Be of moderate to severe intensity.

3. Have a pounding or throbbing quality.

4. Grow worse with activity or cause an avoidance of activity.

If the attacks meet those criteria, clinicians should check to see if they meet at least one out of the two following:

1. Are sensitive to light and sounds.

2. Are associated with nausea and/or vomiting.

A clinician should consider whether the headaches are not better accounted for by another diagnosis, according to the ICHD criteria. But, Dr. VanderPluym warned that does not necessarily mean running a slew of tests.

“In the absence of red flag features, it is more than likely going to be migraine headache,” she said. That’s especially true if a child has a family history of migraine, as the condition is often passed down from parent to child.

Ultimately, the diagnosis is fairly simple and can be made in a minute or less, said Jack Gladstein, MD, a pediatrician at the University of Maryland whose research focuses on the clinical care of children and adolescents with headache.

“Migraine is acute,” Dr. Gladstein said. “It’s really bad. And it’s recurrent.”
 

First line of treatment

Whatever a patient takes to treat a migraine, they should hit it early and hard, Dr. Gladstein said.

“The first thing you say, as a primary care physician, is treat your migraine at first twinge, whatever you use. Don’t wait, don’t wish it away,” he said. “The longer you wait, the less chance anything will work.”

The second piece of advice, Dr. Gladstein said, is that whatever drug a patient is taking, they should be on the highest feasible dose. “Work as fast as you can to treat them. You want the brain to reset as quickly as you can,” he said.

Patients should begin with over-the-counter pain relievers, Dr. Little said. If those prove insufficient, they can try a triptan. Rizatriptan is the only such agent that the Food and Drug Administration has approved for children aged 6-17 years. Other drugs in the class – sumatriptan/naproxen, almotriptan, and zolmitriptan – are approved for children 12 and older.

Another migraine therapy recently approved for children aged 12 and older is the use of neurostimulators. “It’s helpful to be aware of them,” Dr. VanderPluym said.

However, if neurostimulators and acute medications prove insufficient, clinicians should warn patients not to up their doses of triptans. Rebound headaches can occur if patients take triptans more than twice a week, or a maximum 10 days per month.

Another possibility is to add a preventive therapy. One mild, first option is nutraceuticals, like riboflavin (vitamin B₂) or magnesium, said Anisa F. Kelley, MD, a neurologist and associate director of the headache program at the Ann and Robert H. Lurie Children’s Hospital of Chicago.

“We don’t have definitive evidence, but they’re probably doing more benefit than they are harm,” Dr. Kelley said of these therapies. “In patients who have anywhere from 4 to 8 migraine days a month, where you’re in that in-between period where you don’t necessarily need a [prescription] prophylactic, I will often start with a nutraceutical,” Dr. Kelley said.

For those patients who don’t respond to nutraceuticals, or who need more support, clinicians can prescribe amitriptyline or topiramate. Dr. VanderPluym said.

A 2017 study found such prophylactics to be no more effective than placebo in pediatric migraine patients, but experts caution the results should not be considered definitive.

For one thing, the study enrolled a highly selective group of participants, with milder forms of migraine who may have improved anyway, Dr. VanderPluym said. All participants also received lifestyle counseling.

Every time participants came in for a follow-up, they were asked questions such as how much water were they drinking and how much sleep were they getting, Dr. Kelley noted. The takeaway, she said: “Pediatric and adolescent migraine [management] is very, very much reliant on lifestyle factors.”
 

Lifestyle triggers

Clinicians should counsel their migraine patients about lifestyle changes, experts said. Getting adequate sleep, staying hydrated, and managing stress can help reduce the intensity and frequency of attacks.

Migraine patients should also be mindful of their screen time, Dr. Kelley added.

“I’ve had lots and lots of patients who find excessive screen time will trigger or worsen migraine,” she said.

As for other potential triggers of attacks, the evidence is mixed.

“There’s clearly an association with disrupted sleep and migraine, and that has been very well established,” Dr. Little said. “And there is some modest amount of evidence that regular exercise can be helpful.” But for reported food triggers, he said, there have been very inconclusive results.

Commonly reported triggers include MSG, red wine, chocolate, and aged cheese. When Dr. Little’s patients keep headache diaries, tracking their meals alongside when they got migraine attacks, they often discover individualized triggers – strawberries, for instance, in one case, he said.

Scientists believe migraines result from the inappropriate activation of the trigeminal ganglion. “The question is, what causes it to get triggered? And how does it get triggered?” Dr. Gladstein said. “And that’s where there’s a lot of difference of opinion and no conclusive evidence.” Clinicians also should make sure that something else – usually depression, anxiety, insomnia, and dizziness – is not hindering effective migraine management. “If someone has terrible insomnia, until you treat the insomnia, the headaches aren’t going to get better,” he said.

As for Mira, her migraine attacks did not significantly improve, despite trying triptans, prophylactics, lifestyle changes, and shots to block nerve pain. When the headaches threatened Mira’s chance to go to her prom, her neurologist suggested trying something different. The physician persuaded the family’s insurance to cover a calcitonin gene-related peptide antagonist, an injectable monoclonal antibody treatment for migraine that the FDA has currently approved only for use in adults.

The difference for Mira has been extraordinary.

“I can do so much more than I was able to do,” said Mira, who attended the dance migraine free. “I feel liberated.”

It’s only migraine

One of the greatest challenges in diagnosing migraine can be reassuring the patient, the parents, even clinicians themselves that migraine really is the cause of all this pain and discomfort, experts said.

“A lot of migraine treatment actually comes down to migraine education,” Dr. VanderPluym said.

Patients and their parents often wonder how they can be sure that this pain is not resulting from something more dangerous than migraine, Dr. Little said. In these cases, he cites practice guidelines published by the American Academy of Neurology.

“The gist of those guidelines is that most pediatric patients do not need further workup,” he said. “But I think that there’s always a fear that you’re missing something because we don’t have a test that we can do” for migraine.

Some warning signs that further tests might be warranted, Dr. Kelley said, include:

• Headaches that wake a patient up in the middle of the night.
• Headaches that start first thing in the morning, especially those that include vomiting.
• A headache pattern that suddenly gets much worse.
• Certain symptoms that accompany the headache, such as tingling, numbness or double vision.

Although all of these signs can still stem from migraines – tingling or numbness, for instance, can be signs of migraine aura – running additional tests can rule out more serious concerns, she said.

By the time Mira Halker started high school, hardly a day passed that she wasn’t either getting a migraine attack or recovering from one. She missed volleyball team practice. She missed classes. She missed social events. And few people understood. After all, she looked healthy.

“A lot of times, people think I’m faking it,” said Mira, now 16, who lives in Phoenix. Friends called her flaky; her volleyball coaches questioned her dedication to the team. “I’m like, ‘I’m not trying to get out of this. This is not what this is about,’ ” she said.

Her mother, Rashmi B. Halker Singh, MD, is a neurologist at Mayo Clinic who happens to specialize in migraine. Even so, finding a solution was not easy. Neither ibuprofen nor triptans, nor various preventive measures such as a daily prescription for topiramate controlled the pain and associated symptoms. Mira was barely making it through her school day and had to quit volleyball. Then, in the spring of 10th grade, Mira told her mother that she couldn’t go to prom because the loud noises and lights could give her a migraine attack.

Mother and daughter decided it was time to get even more aggressive. “There are these key moments in life that you can’t get back,” Dr. Singh said. “Migraine steals so much from you.”
 

Diagnosis

One of the challenges Mira’s physicians faced was deciding which medications and other therapies to prescribe to a teenager. Drug companies have been releasing a steady stream of new treatments for migraine headaches, and researchers promise more are on the way soon. Here’s what works for children, what hasn’t yet been approved for use with minors, and how to diagnose migraines in the first place, from experts at some of the nation’s leading pediatric headache centers.

Migraine affects about 10% of children, according to the American Migraine Foundation. The headaches can strike children as early as age 3 or 4 years, said Robert Little, MD, a pediatric neurologist at Phoenix Children’s Hospital.

Before puberty, boys report more migraine attacks than girls, according to the American Academy of Pediatrics. But that reverses in adolescence: By age 17, as many as 8% of boys and 23% of girls have had migraine. To diagnose migraine, Juliana H. VanderPluym, MD, associate professor of neurology at Mayo Clinic in Phoenix, said she uses the criteria published in the latest edition of the International Classification of Headache Disorders (ICHD): A patient must have had at least five attacks in their life; and in children and adolescents, the attacks must last no less than 2 hours.

In addition, the headaches should exhibit at least two out of four features:

1. Occur more on one side of the head than the other (although Dr. VanderPluym said in children and adolescents headaches often are bilateral).

2. Be of moderate to severe intensity.

3. Have a pounding or throbbing quality.

4. Grow worse with activity or cause an avoidance of activity.

If the attacks meet those criteria, clinicians should check to see if they meet at least one out of the two following:

1. Are sensitive to light and sounds.

2. Are associated with nausea and/or vomiting.

A clinician should consider whether the headaches are not better accounted for by another diagnosis, according to the ICHD criteria. But, Dr. VanderPluym warned that does not necessarily mean running a slew of tests.

“In the absence of red flag features, it is more than likely going to be migraine headache,” she said. That’s especially true if a child has a family history of migraine, as the condition is often passed down from parent to child.

Ultimately, the diagnosis is fairly simple and can be made in a minute or less, said Jack Gladstein, MD, a pediatrician at the University of Maryland whose research focuses on the clinical care of children and adolescents with headache.

“Migraine is acute,” Dr. Gladstein said. “It’s really bad. And it’s recurrent.”
 

First line of treatment

Whatever a patient takes to treat a migraine, they should hit it early and hard, Dr. Gladstein said.

“The first thing you say, as a primary care physician, is treat your migraine at first twinge, whatever you use. Don’t wait, don’t wish it away,” he said. “The longer you wait, the less chance anything will work.”

The second piece of advice, Dr. Gladstein said, is that whatever drug a patient is taking, they should be on the highest feasible dose. “Work as fast as you can to treat them. You want the brain to reset as quickly as you can,” he said.

Patients should begin with over-the-counter pain relievers, Dr. Little said. If those prove insufficient, they can try a triptan. Rizatriptan is the only such agent that the Food and Drug Administration has approved for children aged 6-17 years. Other drugs in the class – sumatriptan/naproxen, almotriptan, and zolmitriptan – are approved for children 12 and older.

Another migraine therapy recently approved for children aged 12 and older is the use of neurostimulators. “It’s helpful to be aware of them,” Dr. VanderPluym said.

However, if neurostimulators and acute medications prove insufficient, clinicians should warn patients not to up their doses of triptans. Rebound headaches can occur if patients take triptans more than twice a week, or a maximum 10 days per month.

Another possibility is to add a preventive therapy. One mild, first option is nutraceuticals, like riboflavin (vitamin B₂) or magnesium, said Anisa F. Kelley, MD, a neurologist and associate director of the headache program at the Ann and Robert H. Lurie Children’s Hospital of Chicago.

“We don’t have definitive evidence, but they’re probably doing more benefit than they are harm,” Dr. Kelley said of these therapies. “In patients who have anywhere from 4 to 8 migraine days a month, where you’re in that in-between period where you don’t necessarily need a [prescription] prophylactic, I will often start with a nutraceutical,” Dr. Kelley said.

For those patients who don’t respond to nutraceuticals, or who need more support, clinicians can prescribe amitriptyline or topiramate. Dr. VanderPluym said.

A 2017 study found such prophylactics to be no more effective than placebo in pediatric migraine patients, but experts caution the results should not be considered definitive.

For one thing, the study enrolled a highly selective group of participants, with milder forms of migraine who may have improved anyway, Dr. VanderPluym said. All participants also received lifestyle counseling.

Every time participants came in for a follow-up, they were asked questions such as how much water were they drinking and how much sleep were they getting, Dr. Kelley noted. The takeaway, she said: “Pediatric and adolescent migraine [management] is very, very much reliant on lifestyle factors.”
 

Lifestyle triggers

Clinicians should counsel their migraine patients about lifestyle changes, experts said. Getting adequate sleep, staying hydrated, and managing stress can help reduce the intensity and frequency of attacks.

Migraine patients should also be mindful of their screen time, Dr. Kelley added.

“I’ve had lots and lots of patients who find excessive screen time will trigger or worsen migraine,” she said.

As for other potential triggers of attacks, the evidence is mixed.

“There’s clearly an association with disrupted sleep and migraine, and that has been very well established,” Dr. Little said. “And there is some modest amount of evidence that regular exercise can be helpful.” But for reported food triggers, he said, there have been very inconclusive results.

Commonly reported triggers include MSG, red wine, chocolate, and aged cheese. When Dr. Little’s patients keep headache diaries, tracking their meals alongside when they got migraine attacks, they often discover individualized triggers – strawberries, for instance, in one case, he said.

Scientists believe migraines result from the inappropriate activation of the trigeminal ganglion. “The question is, what causes it to get triggered? And how does it get triggered?” Dr. Gladstein said. “And that’s where there’s a lot of difference of opinion and no conclusive evidence.” Clinicians also should make sure that something else – usually depression, anxiety, insomnia, and dizziness – is not hindering effective migraine management. “If someone has terrible insomnia, until you treat the insomnia, the headaches aren’t going to get better,” he said.

As for Mira, her migraine attacks did not significantly improve, despite trying triptans, prophylactics, lifestyle changes, and shots to block nerve pain. When the headaches threatened Mira’s chance to go to her prom, her neurologist suggested trying something different. The physician persuaded the family’s insurance to cover a calcitonin gene-related peptide antagonist, an injectable monoclonal antibody treatment for migraine that the FDA has currently approved only for use in adults.

The difference for Mira has been extraordinary.

“I can do so much more than I was able to do,” said Mira, who attended the dance migraine free. “I feel liberated.”

It’s only migraine

One of the greatest challenges in diagnosing migraine can be reassuring the patient, the parents, even clinicians themselves that migraine really is the cause of all this pain and discomfort, experts said.

“A lot of migraine treatment actually comes down to migraine education,” Dr. VanderPluym said.

Patients and their parents often wonder how they can be sure that this pain is not resulting from something more dangerous than migraine, Dr. Little said. In these cases, he cites practice guidelines published by the American Academy of Neurology.

“The gist of those guidelines is that most pediatric patients do not need further workup,” he said. “But I think that there’s always a fear that you’re missing something because we don’t have a test that we can do” for migraine.

Some warning signs that further tests might be warranted, Dr. Kelley said, include:

• Headaches that wake a patient up in the middle of the night.
• Headaches that start first thing in the morning, especially those that include vomiting.
• A headache pattern that suddenly gets much worse.
• Certain symptoms that accompany the headache, such as tingling, numbness or double vision.

Although all of these signs can still stem from migraines – tingling or numbness, for instance, can be signs of migraine aura – running additional tests can rule out more serious concerns, she said.

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.