User login
Time is of the essence: DST up for debate again
Seasonal time change is now up for consideration in the U.S. Congress, prompting sleep medicine specialists to weigh in on the health impact of a major policy change.
As lawmakers in Washington propose an end to seasonal time changes by permanently establishing daylight saving time (DST), the American Academy of Sleep Medicine (AASM) is pushing for a Congressional hearing so scientists can present evidence in favor of converse legislation – to make standard time the new norm.
According to the AASM, ; however, the switch from standard time to DST incurs more risk.
“Current evidence best supports the adoption of year-round standard time, which aligns best with human circadian biology and provides distinct benefits for public health and safety,” the AASM noted in a 2020 position statement on DST.
The statement cites a number of studies that have reported associations between the switch to DST and acute, negative health outcomes, including higher rates of hospital admission, cardiovascular morbidity, atrial fibrillation, and stroke. The time shift has been associated with a spectrum of cellular, metabolic, and circadian derangements, from increased production of inflammatory markers, to higher blood pressure, and loss of sleep. These biological effects may have far-reaching consequences, including increased rates of fatal motor accidents in the days following the time change, and even increased volatility in the stock market, which may stem from cognitive deficits.
U.S. Senator Marco Rubio (R-Fla.) and others in the U.S. Congress have reintroduced the 2019 Sunshine Protection Act, legislation that would make DST permanent across the country. According to a statement on Sen. Rubio’s website, “The bill reflects the Florida legislature’s 2018 enactment of year-round DST; however, for Florida’s change to apply, a change in the federal statute is required. Fifteen other states – Arkansas, Alabama, California, Delaware, Georgia, Idaho, Louisiana, Maine, Ohio, Oregon, South Carolina, Tennessee, Utah, Washington, and Wyoming – have passed similar laws, resolutions, or voter initiatives, and dozens more are looking. The legislation, if enacted, would apply to those states [that] currently participate in DST, which most states observe for eight months out of the year.”
A stitch in time
“The sudden change in clock time disrupts sleep/wake patterns, decreasing total sleep time and sleep quality, leading to decrements in daytime cognition,” said Kannan Ramar, MBBS, MD, president of the AASM and a sleep medicine specialist at Mayo Clinic, Rochester, Minn.
Emphasizing this point, Dr. Ramar noted a recent study that reported an 18% increase in “patient safety-related incidents associated with human error” among health care workers within a week of the spring time change.
“Irregular bedtimes and wake times disrupt the timing of our circadian rhythms, which can lead to symptoms of insomnia or long-term, excessive daytime sleepiness. Lack of sleep can lead to numerous adverse effects on our minds, including decreased cognitive function, trouble concentrating, and general moodiness,” Dr. Ramar said.
He noted that these impacts may be more significant among certain individuals.
“The daylight saving time changes can be especially problematic for any populations that already experience chronic insufficient sleep or other sleep difficulties,” Dr. Ramar said. “Populations at greatest risk include teenagers, who tend to experience chronic sleep restriction during the school week, and night shift workers, who often struggle to sleep well during daytime hours.”
While fewer studies have evaluated the long-term effects of seasonal time changes, the AASM position statement cited evidence that “the body clock does not adjust to daylight saving time after several months,” possibly because “daylight saving time is less well-aligned with intrinsic human circadian physiology, and it disrupts the natural seasonal adjustment of the human clock due to the effect of late-evening light on the circadian rhythm.”
According to the AASM, permanent DST, as proposed by Sen. Rubio and colleagues, could “result in permanent phase delay, a condition that can also lead to a perpetual discrepancy between the innate biological clock and the extrinsic environmental clock, as well as chronic sleep loss due to early morning social demands that truncate the opportunity to sleep.” This mismatch between sleep/wake cycles and social demands, known as “social jet lag,” has been associated with chronic health risks, including metabolic syndrome, obesity, depression, and cardiovascular disease.
Cardiac impacts of seasonal time change
Muhammad Adeel Rishi, MD, a sleep specialist at Mayo Clinic, Eau Claire, Wis., and lead author of the AASM position statement, highlighted cardiovascular risks in a written statement for this article, noting increased rates of heart attack following the spring time change, and a higher risk of atrial fibrillation.
“Mayo Clinic has not taken a position on this issue,” Dr. Rishi noted. Still, he advocated for permanent standard time as the author of the AASM position statement and vice chair of the AASM public safety committee.
Jay Chudow, MD, and Andrew K. Krumerman, MD, of Montefiore Medical Center, New York, lead author and principal author, respectively, of a recent study that reported increased rates of atrial fibrillation admissions after DST transitions, had the same stance.
“We support elimination of seasonal time changes from a health perspective,” they wrote in a joint comment. “There is mounting evidence of a negative health impact with these seasonal time changes related to effects on sleep and circadian rhythm. Our work found the spring change was associated with more admissions for atrial fibrillation. This added to prior evidence of increased cardiovascular events related to these time changes. If physicians counsel patients on reducing risk factors for disease, shouldn’t we do the same as a society?”
Pros and cons
Not all sleep experts are convinced. Mary Jo Farmer, MD, PhD, FCCP, a sleep specialist and director of pulmonary hypertension services at Baystate Medical Center, and assistant professor of medicine at the University of Massachusetts, Springfield, considers perspectives from both sides of the issue.
“Daylight saving time promotes active lifestyles as people engage in more outdoor activities after work and school, [and] daylight saving time produces economic and safety benefits to society as retail revenues are higher and crimes are lower,” Dr. Farmer said. “Alternatively, moving the clocks forward is a cost burden to the U.S. economy when health issues, decreased productivity, and workplace injuries are considered.”
If one time system is permanently established, Dr. Farmer anticipates divided opinions from patients with sleep issues, regardless of which system is chosen.
“I can tell you, I have a cohort of sleep patients who prefer more evening light and look forward to the spring time change to daylight saving time,” she said. “However, they would not want the sun coming up at 9:00 a.m. in the winter months if we stayed on daylight saving time year-round. Similarly, patients would not want the sun coming up at 4:00 a.m. on the longest day of the year if we stayed on standard time all year round.”
Dr. Farmer called for more research before a decision is made.
“I suggest we need more information about the dangers of staying on daylight saving or standard time year-round because perhaps the current strategy of keeping morning light consistent is not so bad,” she said.
Time for a Congressional hearing?
According to Dr. Ramar, the time is now for a Congressional hearing, as lawmakers and the public need to be adequately informed when considering new legislation.
“There are public misconceptions about daylight saving time and standard time,” Dr. Ramar said. “People often like the idea of daylight saving time because they think it provides more light, and they dislike the concept of standard time because they think it provides more darkness. The reality is that neither time system provides more light or darkness than the other; it is only the timing that changes.”
Until new legislation is introduced, Dr. Ramar offered some practical advice for navigating seasonal time shifts.
“Beginning 2-3 days before the time change, it can be helpful to gradually adjust sleep and wake times, as well as other daily routines such as meal times,” he said. “After the time change, going outside for some morning light can help adjust the timing of your internal body clock.”
The investigators reported no conflicts of interest.
Seasonal time change is now up for consideration in the U.S. Congress, prompting sleep medicine specialists to weigh in on the health impact of a major policy change.
As lawmakers in Washington propose an end to seasonal time changes by permanently establishing daylight saving time (DST), the American Academy of Sleep Medicine (AASM) is pushing for a Congressional hearing so scientists can present evidence in favor of converse legislation – to make standard time the new norm.
According to the AASM, ; however, the switch from standard time to DST incurs more risk.
“Current evidence best supports the adoption of year-round standard time, which aligns best with human circadian biology and provides distinct benefits for public health and safety,” the AASM noted in a 2020 position statement on DST.
The statement cites a number of studies that have reported associations between the switch to DST and acute, negative health outcomes, including higher rates of hospital admission, cardiovascular morbidity, atrial fibrillation, and stroke. The time shift has been associated with a spectrum of cellular, metabolic, and circadian derangements, from increased production of inflammatory markers, to higher blood pressure, and loss of sleep. These biological effects may have far-reaching consequences, including increased rates of fatal motor accidents in the days following the time change, and even increased volatility in the stock market, which may stem from cognitive deficits.
U.S. Senator Marco Rubio (R-Fla.) and others in the U.S. Congress have reintroduced the 2019 Sunshine Protection Act, legislation that would make DST permanent across the country. According to a statement on Sen. Rubio’s website, “The bill reflects the Florida legislature’s 2018 enactment of year-round DST; however, for Florida’s change to apply, a change in the federal statute is required. Fifteen other states – Arkansas, Alabama, California, Delaware, Georgia, Idaho, Louisiana, Maine, Ohio, Oregon, South Carolina, Tennessee, Utah, Washington, and Wyoming – have passed similar laws, resolutions, or voter initiatives, and dozens more are looking. The legislation, if enacted, would apply to those states [that] currently participate in DST, which most states observe for eight months out of the year.”
A stitch in time
“The sudden change in clock time disrupts sleep/wake patterns, decreasing total sleep time and sleep quality, leading to decrements in daytime cognition,” said Kannan Ramar, MBBS, MD, president of the AASM and a sleep medicine specialist at Mayo Clinic, Rochester, Minn.
Emphasizing this point, Dr. Ramar noted a recent study that reported an 18% increase in “patient safety-related incidents associated with human error” among health care workers within a week of the spring time change.
“Irregular bedtimes and wake times disrupt the timing of our circadian rhythms, which can lead to symptoms of insomnia or long-term, excessive daytime sleepiness. Lack of sleep can lead to numerous adverse effects on our minds, including decreased cognitive function, trouble concentrating, and general moodiness,” Dr. Ramar said.
He noted that these impacts may be more significant among certain individuals.
“The daylight saving time changes can be especially problematic for any populations that already experience chronic insufficient sleep or other sleep difficulties,” Dr. Ramar said. “Populations at greatest risk include teenagers, who tend to experience chronic sleep restriction during the school week, and night shift workers, who often struggle to sleep well during daytime hours.”
While fewer studies have evaluated the long-term effects of seasonal time changes, the AASM position statement cited evidence that “the body clock does not adjust to daylight saving time after several months,” possibly because “daylight saving time is less well-aligned with intrinsic human circadian physiology, and it disrupts the natural seasonal adjustment of the human clock due to the effect of late-evening light on the circadian rhythm.”
According to the AASM, permanent DST, as proposed by Sen. Rubio and colleagues, could “result in permanent phase delay, a condition that can also lead to a perpetual discrepancy between the innate biological clock and the extrinsic environmental clock, as well as chronic sleep loss due to early morning social demands that truncate the opportunity to sleep.” This mismatch between sleep/wake cycles and social demands, known as “social jet lag,” has been associated with chronic health risks, including metabolic syndrome, obesity, depression, and cardiovascular disease.
Cardiac impacts of seasonal time change
Muhammad Adeel Rishi, MD, a sleep specialist at Mayo Clinic, Eau Claire, Wis., and lead author of the AASM position statement, highlighted cardiovascular risks in a written statement for this article, noting increased rates of heart attack following the spring time change, and a higher risk of atrial fibrillation.
“Mayo Clinic has not taken a position on this issue,” Dr. Rishi noted. Still, he advocated for permanent standard time as the author of the AASM position statement and vice chair of the AASM public safety committee.
Jay Chudow, MD, and Andrew K. Krumerman, MD, of Montefiore Medical Center, New York, lead author and principal author, respectively, of a recent study that reported increased rates of atrial fibrillation admissions after DST transitions, had the same stance.
“We support elimination of seasonal time changes from a health perspective,” they wrote in a joint comment. “There is mounting evidence of a negative health impact with these seasonal time changes related to effects on sleep and circadian rhythm. Our work found the spring change was associated with more admissions for atrial fibrillation. This added to prior evidence of increased cardiovascular events related to these time changes. If physicians counsel patients on reducing risk factors for disease, shouldn’t we do the same as a society?”
Pros and cons
Not all sleep experts are convinced. Mary Jo Farmer, MD, PhD, FCCP, a sleep specialist and director of pulmonary hypertension services at Baystate Medical Center, and assistant professor of medicine at the University of Massachusetts, Springfield, considers perspectives from both sides of the issue.
“Daylight saving time promotes active lifestyles as people engage in more outdoor activities after work and school, [and] daylight saving time produces economic and safety benefits to society as retail revenues are higher and crimes are lower,” Dr. Farmer said. “Alternatively, moving the clocks forward is a cost burden to the U.S. economy when health issues, decreased productivity, and workplace injuries are considered.”
If one time system is permanently established, Dr. Farmer anticipates divided opinions from patients with sleep issues, regardless of which system is chosen.
“I can tell you, I have a cohort of sleep patients who prefer more evening light and look forward to the spring time change to daylight saving time,” she said. “However, they would not want the sun coming up at 9:00 a.m. in the winter months if we stayed on daylight saving time year-round. Similarly, patients would not want the sun coming up at 4:00 a.m. on the longest day of the year if we stayed on standard time all year round.”
Dr. Farmer called for more research before a decision is made.
“I suggest we need more information about the dangers of staying on daylight saving or standard time year-round because perhaps the current strategy of keeping morning light consistent is not so bad,” she said.
Time for a Congressional hearing?
According to Dr. Ramar, the time is now for a Congressional hearing, as lawmakers and the public need to be adequately informed when considering new legislation.
“There are public misconceptions about daylight saving time and standard time,” Dr. Ramar said. “People often like the idea of daylight saving time because they think it provides more light, and they dislike the concept of standard time because they think it provides more darkness. The reality is that neither time system provides more light or darkness than the other; it is only the timing that changes.”
Until new legislation is introduced, Dr. Ramar offered some practical advice for navigating seasonal time shifts.
“Beginning 2-3 days before the time change, it can be helpful to gradually adjust sleep and wake times, as well as other daily routines such as meal times,” he said. “After the time change, going outside for some morning light can help adjust the timing of your internal body clock.”
The investigators reported no conflicts of interest.
Seasonal time change is now up for consideration in the U.S. Congress, prompting sleep medicine specialists to weigh in on the health impact of a major policy change.
As lawmakers in Washington propose an end to seasonal time changes by permanently establishing daylight saving time (DST), the American Academy of Sleep Medicine (AASM) is pushing for a Congressional hearing so scientists can present evidence in favor of converse legislation – to make standard time the new norm.
According to the AASM, ; however, the switch from standard time to DST incurs more risk.
“Current evidence best supports the adoption of year-round standard time, which aligns best with human circadian biology and provides distinct benefits for public health and safety,” the AASM noted in a 2020 position statement on DST.
The statement cites a number of studies that have reported associations between the switch to DST and acute, negative health outcomes, including higher rates of hospital admission, cardiovascular morbidity, atrial fibrillation, and stroke. The time shift has been associated with a spectrum of cellular, metabolic, and circadian derangements, from increased production of inflammatory markers, to higher blood pressure, and loss of sleep. These biological effects may have far-reaching consequences, including increased rates of fatal motor accidents in the days following the time change, and even increased volatility in the stock market, which may stem from cognitive deficits.
U.S. Senator Marco Rubio (R-Fla.) and others in the U.S. Congress have reintroduced the 2019 Sunshine Protection Act, legislation that would make DST permanent across the country. According to a statement on Sen. Rubio’s website, “The bill reflects the Florida legislature’s 2018 enactment of year-round DST; however, for Florida’s change to apply, a change in the federal statute is required. Fifteen other states – Arkansas, Alabama, California, Delaware, Georgia, Idaho, Louisiana, Maine, Ohio, Oregon, South Carolina, Tennessee, Utah, Washington, and Wyoming – have passed similar laws, resolutions, or voter initiatives, and dozens more are looking. The legislation, if enacted, would apply to those states [that] currently participate in DST, which most states observe for eight months out of the year.”
A stitch in time
“The sudden change in clock time disrupts sleep/wake patterns, decreasing total sleep time and sleep quality, leading to decrements in daytime cognition,” said Kannan Ramar, MBBS, MD, president of the AASM and a sleep medicine specialist at Mayo Clinic, Rochester, Minn.
Emphasizing this point, Dr. Ramar noted a recent study that reported an 18% increase in “patient safety-related incidents associated with human error” among health care workers within a week of the spring time change.
“Irregular bedtimes and wake times disrupt the timing of our circadian rhythms, which can lead to symptoms of insomnia or long-term, excessive daytime sleepiness. Lack of sleep can lead to numerous adverse effects on our minds, including decreased cognitive function, trouble concentrating, and general moodiness,” Dr. Ramar said.
He noted that these impacts may be more significant among certain individuals.
“The daylight saving time changes can be especially problematic for any populations that already experience chronic insufficient sleep or other sleep difficulties,” Dr. Ramar said. “Populations at greatest risk include teenagers, who tend to experience chronic sleep restriction during the school week, and night shift workers, who often struggle to sleep well during daytime hours.”
While fewer studies have evaluated the long-term effects of seasonal time changes, the AASM position statement cited evidence that “the body clock does not adjust to daylight saving time after several months,” possibly because “daylight saving time is less well-aligned with intrinsic human circadian physiology, and it disrupts the natural seasonal adjustment of the human clock due to the effect of late-evening light on the circadian rhythm.”
According to the AASM, permanent DST, as proposed by Sen. Rubio and colleagues, could “result in permanent phase delay, a condition that can also lead to a perpetual discrepancy between the innate biological clock and the extrinsic environmental clock, as well as chronic sleep loss due to early morning social demands that truncate the opportunity to sleep.” This mismatch between sleep/wake cycles and social demands, known as “social jet lag,” has been associated with chronic health risks, including metabolic syndrome, obesity, depression, and cardiovascular disease.
Cardiac impacts of seasonal time change
Muhammad Adeel Rishi, MD, a sleep specialist at Mayo Clinic, Eau Claire, Wis., and lead author of the AASM position statement, highlighted cardiovascular risks in a written statement for this article, noting increased rates of heart attack following the spring time change, and a higher risk of atrial fibrillation.
“Mayo Clinic has not taken a position on this issue,” Dr. Rishi noted. Still, he advocated for permanent standard time as the author of the AASM position statement and vice chair of the AASM public safety committee.
Jay Chudow, MD, and Andrew K. Krumerman, MD, of Montefiore Medical Center, New York, lead author and principal author, respectively, of a recent study that reported increased rates of atrial fibrillation admissions after DST transitions, had the same stance.
“We support elimination of seasonal time changes from a health perspective,” they wrote in a joint comment. “There is mounting evidence of a negative health impact with these seasonal time changes related to effects on sleep and circadian rhythm. Our work found the spring change was associated with more admissions for atrial fibrillation. This added to prior evidence of increased cardiovascular events related to these time changes. If physicians counsel patients on reducing risk factors for disease, shouldn’t we do the same as a society?”
Pros and cons
Not all sleep experts are convinced. Mary Jo Farmer, MD, PhD, FCCP, a sleep specialist and director of pulmonary hypertension services at Baystate Medical Center, and assistant professor of medicine at the University of Massachusetts, Springfield, considers perspectives from both sides of the issue.
“Daylight saving time promotes active lifestyles as people engage in more outdoor activities after work and school, [and] daylight saving time produces economic and safety benefits to society as retail revenues are higher and crimes are lower,” Dr. Farmer said. “Alternatively, moving the clocks forward is a cost burden to the U.S. economy when health issues, decreased productivity, and workplace injuries are considered.”
If one time system is permanently established, Dr. Farmer anticipates divided opinions from patients with sleep issues, regardless of which system is chosen.
“I can tell you, I have a cohort of sleep patients who prefer more evening light and look forward to the spring time change to daylight saving time,” she said. “However, they would not want the sun coming up at 9:00 a.m. in the winter months if we stayed on daylight saving time year-round. Similarly, patients would not want the sun coming up at 4:00 a.m. on the longest day of the year if we stayed on standard time all year round.”
Dr. Farmer called for more research before a decision is made.
“I suggest we need more information about the dangers of staying on daylight saving or standard time year-round because perhaps the current strategy of keeping morning light consistent is not so bad,” she said.
Time for a Congressional hearing?
According to Dr. Ramar, the time is now for a Congressional hearing, as lawmakers and the public need to be adequately informed when considering new legislation.
“There are public misconceptions about daylight saving time and standard time,” Dr. Ramar said. “People often like the idea of daylight saving time because they think it provides more light, and they dislike the concept of standard time because they think it provides more darkness. The reality is that neither time system provides more light or darkness than the other; it is only the timing that changes.”
Until new legislation is introduced, Dr. Ramar offered some practical advice for navigating seasonal time shifts.
“Beginning 2-3 days before the time change, it can be helpful to gradually adjust sleep and wake times, as well as other daily routines such as meal times,” he said. “After the time change, going outside for some morning light can help adjust the timing of your internal body clock.”
The investigators reported no conflicts of interest.
Prenatal dietary folate not enough to offset AEDs’ effect on kids’ cognition
New research underscores the importance of folic acid supplementation for pregnant women with epilepsy who are taking antiepileptic drugs (AEDs).
Dietary folate alone, even in the United States, where food is fortified with folic acid, is “not sufficient” to improve cognitive outcomes for children of women who take AEDs during pregnancy, the researchers report.
“We found that dietary folate was not related to outcomes,” study investigator Kimford Meador, MD, professor of neurology and neurologic sciences, Stanford (Calif.) University, told this news organization.
“Only when the mother was taking extra folate did we see an improvement in child outcomes,” he added.
The findings were published online Feb. 23 in Epilepsy and Behavior.
Cognitive boost
“Daily folate is recommended to women in the general populations to reduce congenital malformations,” Dr. Meador said. In addition, periconceptional use of folate has been shown in previous research to improve neurodevelopmental outcomes for children of mothers with epilepsy who are taking AEDs.
Whether folate-fortified food alone, without supplements, has any effect on cognitive outcomes in this population of children has not been examined previously.
To investigate, the researchers assessed 117 children from the Neurodevelopmental Effects of Antiepileptic Drugs (NEAD) study, a prospective, observational study of women with epilepsy who were taking one of four AEDs: carbamazepine, lamotrigine, phenytoin, or valproate.
Results showed that dietary folate from fortified food alone, without supplements, had no significant impact on IQ at age 6 years among children with prenatal exposure to AEDs.
In contrast, use of periconceptual folate supplements was significantly associated with a 10-point higher IQ at age 6 in the adjusted analyses (95% confidence interval, 5.2-15.0; P < .001).
These six other nutrients from food and supplements had no significant association with IQ at age 6 years: vitamins C, D, and E, omega-3, gamma tocopherol, and vitamin B12.
Optimal dose unclear
The findings indicate that folates, including natural folate and folic acid, in food do not have positive cognitive effects for children of women with epilepsy who take AEDs, the researchers write.
Dr. Meador noted that the optimal dose of folic acid supplementation to provide a cognitive benefit remains unclear.
The U.S. Centers for Disease Control recommends 0.4 mg/d for the general population of women of childbearing age. In Europe, the recommendation is 1 mg/d.
“Higher doses are recommended if there is a personal or family history of spina bifida in prior pregnancies, but there is some concern that very high doses of folate may be detrimental,” Dr. Meador said.
For women with epilepsy, he would recommend “at least 1 mg/d and not more than 4 mg/d.”
Proves a point?
Commenting on the study for this news organization, Derek Chong, MD, vice chair of neurology and director of epilepsy at Lenox Hill Hospital, New York, said the finding that folate fortification of food alone is not adequate for women with epilepsy is “not groundbreaking” but does prove something previously thought.
“Folic acid is important for all women, but it does seem like folic acid may be even more important in the epilepsy population,” said Dr. Chong, who was not involved with the research.
He cautioned that the current analysis included only four medications, three of which are not used very often anymore.
“Lamotrigine is probably the most commonly used one now. It’s unfortunate that this study did not include Keppra [levetiracetam], which probably is the number one medication that we use now,” Dr. Chong said.
The research was supported by the National Institutes of Health. Dr. Meador and Dr. Chong have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
New research underscores the importance of folic acid supplementation for pregnant women with epilepsy who are taking antiepileptic drugs (AEDs).
Dietary folate alone, even in the United States, where food is fortified with folic acid, is “not sufficient” to improve cognitive outcomes for children of women who take AEDs during pregnancy, the researchers report.
“We found that dietary folate was not related to outcomes,” study investigator Kimford Meador, MD, professor of neurology and neurologic sciences, Stanford (Calif.) University, told this news organization.
“Only when the mother was taking extra folate did we see an improvement in child outcomes,” he added.
The findings were published online Feb. 23 in Epilepsy and Behavior.
Cognitive boost
“Daily folate is recommended to women in the general populations to reduce congenital malformations,” Dr. Meador said. In addition, periconceptional use of folate has been shown in previous research to improve neurodevelopmental outcomes for children of mothers with epilepsy who are taking AEDs.
Whether folate-fortified food alone, without supplements, has any effect on cognitive outcomes in this population of children has not been examined previously.
To investigate, the researchers assessed 117 children from the Neurodevelopmental Effects of Antiepileptic Drugs (NEAD) study, a prospective, observational study of women with epilepsy who were taking one of four AEDs: carbamazepine, lamotrigine, phenytoin, or valproate.
Results showed that dietary folate from fortified food alone, without supplements, had no significant impact on IQ at age 6 years among children with prenatal exposure to AEDs.
In contrast, use of periconceptual folate supplements was significantly associated with a 10-point higher IQ at age 6 in the adjusted analyses (95% confidence interval, 5.2-15.0; P < .001).
These six other nutrients from food and supplements had no significant association with IQ at age 6 years: vitamins C, D, and E, omega-3, gamma tocopherol, and vitamin B12.
Optimal dose unclear
The findings indicate that folates, including natural folate and folic acid, in food do not have positive cognitive effects for children of women with epilepsy who take AEDs, the researchers write.
Dr. Meador noted that the optimal dose of folic acid supplementation to provide a cognitive benefit remains unclear.
The U.S. Centers for Disease Control recommends 0.4 mg/d for the general population of women of childbearing age. In Europe, the recommendation is 1 mg/d.
“Higher doses are recommended if there is a personal or family history of spina bifida in prior pregnancies, but there is some concern that very high doses of folate may be detrimental,” Dr. Meador said.
For women with epilepsy, he would recommend “at least 1 mg/d and not more than 4 mg/d.”
Proves a point?
Commenting on the study for this news organization, Derek Chong, MD, vice chair of neurology and director of epilepsy at Lenox Hill Hospital, New York, said the finding that folate fortification of food alone is not adequate for women with epilepsy is “not groundbreaking” but does prove something previously thought.
“Folic acid is important for all women, but it does seem like folic acid may be even more important in the epilepsy population,” said Dr. Chong, who was not involved with the research.
He cautioned that the current analysis included only four medications, three of which are not used very often anymore.
“Lamotrigine is probably the most commonly used one now. It’s unfortunate that this study did not include Keppra [levetiracetam], which probably is the number one medication that we use now,” Dr. Chong said.
The research was supported by the National Institutes of Health. Dr. Meador and Dr. Chong have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
New research underscores the importance of folic acid supplementation for pregnant women with epilepsy who are taking antiepileptic drugs (AEDs).
Dietary folate alone, even in the United States, where food is fortified with folic acid, is “not sufficient” to improve cognitive outcomes for children of women who take AEDs during pregnancy, the researchers report.
“We found that dietary folate was not related to outcomes,” study investigator Kimford Meador, MD, professor of neurology and neurologic sciences, Stanford (Calif.) University, told this news organization.
“Only when the mother was taking extra folate did we see an improvement in child outcomes,” he added.
The findings were published online Feb. 23 in Epilepsy and Behavior.
Cognitive boost
“Daily folate is recommended to women in the general populations to reduce congenital malformations,” Dr. Meador said. In addition, periconceptional use of folate has been shown in previous research to improve neurodevelopmental outcomes for children of mothers with epilepsy who are taking AEDs.
Whether folate-fortified food alone, without supplements, has any effect on cognitive outcomes in this population of children has not been examined previously.
To investigate, the researchers assessed 117 children from the Neurodevelopmental Effects of Antiepileptic Drugs (NEAD) study, a prospective, observational study of women with epilepsy who were taking one of four AEDs: carbamazepine, lamotrigine, phenytoin, or valproate.
Results showed that dietary folate from fortified food alone, without supplements, had no significant impact on IQ at age 6 years among children with prenatal exposure to AEDs.
In contrast, use of periconceptual folate supplements was significantly associated with a 10-point higher IQ at age 6 in the adjusted analyses (95% confidence interval, 5.2-15.0; P < .001).
These six other nutrients from food and supplements had no significant association with IQ at age 6 years: vitamins C, D, and E, omega-3, gamma tocopherol, and vitamin B12.
Optimal dose unclear
The findings indicate that folates, including natural folate and folic acid, in food do not have positive cognitive effects for children of women with epilepsy who take AEDs, the researchers write.
Dr. Meador noted that the optimal dose of folic acid supplementation to provide a cognitive benefit remains unclear.
The U.S. Centers for Disease Control recommends 0.4 mg/d for the general population of women of childbearing age. In Europe, the recommendation is 1 mg/d.
“Higher doses are recommended if there is a personal or family history of spina bifida in prior pregnancies, but there is some concern that very high doses of folate may be detrimental,” Dr. Meador said.
For women with epilepsy, he would recommend “at least 1 mg/d and not more than 4 mg/d.”
Proves a point?
Commenting on the study for this news organization, Derek Chong, MD, vice chair of neurology and director of epilepsy at Lenox Hill Hospital, New York, said the finding that folate fortification of food alone is not adequate for women with epilepsy is “not groundbreaking” but does prove something previously thought.
“Folic acid is important for all women, but it does seem like folic acid may be even more important in the epilepsy population,” said Dr. Chong, who was not involved with the research.
He cautioned that the current analysis included only four medications, three of which are not used very often anymore.
“Lamotrigine is probably the most commonly used one now. It’s unfortunate that this study did not include Keppra [levetiracetam], which probably is the number one medication that we use now,” Dr. Chong said.
The research was supported by the National Institutes of Health. Dr. Meador and Dr. Chong have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Cannabinoids promising for improving appetite, behavior in dementia
For patients with dementia, cannabinoids may be a promising intervention for treating neuropsychiatric symptoms (NPS) and the refusing of food, new research suggests.
Results of a systematic literature review, presented at the 2021 meeting of the American Association for Geriatric Psychiatry, showed that cannabinoids were associated with reduced agitation, longer sleep, and lower NPS. They were also linked to increased meal consumption and weight gain.
Refusing food is a common problem for patients with dementia, often resulting in worsening sleep, agitation, and mood, study investigator Niraj Asthana, MD, a second-year resident in the department of psychiatry, University of California, San Diego, said in an interview. Dr. Asthana noted that certain cannabinoid analogues are now used to stimulate appetite for patients undergoing chemotherapy.
Filling a treatment gap
After years of legal and other problems affecting cannabinoid research, there is renewed interest in investigating its use for patients with dementia. Early evidence suggests that cannabinoids may also be beneficial for pain, sleep, and aggression.
The researchers noted that cannabinoids may be especially valuable in areas where there are currently limited therapies, including food refusal and NPS.
“Unfortunately, there are limited treatments available for food refusal, so we’re left with appetite stimulants and electroconvulsive therapy, and although atypical antipsychotics are commonly used to treat NPS, they’re associated with an increased risk of serious adverse events and mortality in older patients,” said Dr. Asthana.
Dr. Asthana and colleague Dan Sewell, MD, carried out a systematic literature review of relevant studies of the use of cannabinoids for dementia patients.
“We found there are lot of studies, but they’re small scale; I’d say the largest was probably about 50 patients, with most studies having 10-50 patients,” said Dr. Asthana. In part, this may be because, until very recently, research on cannabinoids was controversial.
To review the current literature on the potential applications of cannabinoids in the treatment of food refusal and NPS in dementia patients, the researchers conducted a literature review.
They identified 23 relevant studies of the use of synthetic cannabinoids, including dronabinol and nabilone, for dementia patients. These products contain tetrahydrocannabinol (THC), the main psychoactive compound in cannabis.
More research coming
Several studies showed that cannabinoid use was associated with reduced nighttime motor activity, improved sleep duration, reduced agitation, and lower Neuropsychiatric Inventory scores.
One crossover placebo-controlled trial showed an overall increase in body weight among dementia patients who took dronabinol.
This suggests there might be something to the “colloquial cultural association between cannabinoids and the munchies,” said Dr. Asthana.
Possible mechanisms for the effects on appetite may be that cannabinoids increase levels of the hormone ghrelin, which is also known as the “hunger hormone,” and decrease leptin levels, a hormone that inhibits hunger. Dr. Asthana noted that, in these studies, the dose of THC was low and that overall, cannabinoids appeared to be safe.
“We found that, at least in these small-scale studies, cannabinoid analogues are well tolerated,” possibly because of the relatively low doses of THC, said Dr. Asthana. “They generally don’t seem to have a ton of side effects; they may make people a little sleepy, which is actually good, because these patents also have a lot of trouble sleeping.”
He noted that more recent research suggests cannabidiol oil may reduce agitation by up to 40%.
“Now that cannabis is losing a lot of its stigma, both culturally and in the scientific community, you’re seeing a lot of grant applications for clinical trials,” said Dr. Asthana. “I’m excited to see what we find in the next 5-10 years.”
In a comment, Kirsten Wilkins, MD, associate professor of psychiatry, Yale University, New Haven, Conn., who is also a geriatric psychiatrist at the Veterans Affairs Connecticut Health Care System, welcomed the new research in this area.
“With limited safe and effective treatments for food refusal and neuropsychiatric symptoms of dementia, Dr. Asthana and Dr. Sewell highlight the growing body of literature suggesting cannabinoids may be a novel treatment option,” she said.
A version of this article first appeared on Medscape.com.
For patients with dementia, cannabinoids may be a promising intervention for treating neuropsychiatric symptoms (NPS) and the refusing of food, new research suggests.
Results of a systematic literature review, presented at the 2021 meeting of the American Association for Geriatric Psychiatry, showed that cannabinoids were associated with reduced agitation, longer sleep, and lower NPS. They were also linked to increased meal consumption and weight gain.
Refusing food is a common problem for patients with dementia, often resulting in worsening sleep, agitation, and mood, study investigator Niraj Asthana, MD, a second-year resident in the department of psychiatry, University of California, San Diego, said in an interview. Dr. Asthana noted that certain cannabinoid analogues are now used to stimulate appetite for patients undergoing chemotherapy.
Filling a treatment gap
After years of legal and other problems affecting cannabinoid research, there is renewed interest in investigating its use for patients with dementia. Early evidence suggests that cannabinoids may also be beneficial for pain, sleep, and aggression.
The researchers noted that cannabinoids may be especially valuable in areas where there are currently limited therapies, including food refusal and NPS.
“Unfortunately, there are limited treatments available for food refusal, so we’re left with appetite stimulants and electroconvulsive therapy, and although atypical antipsychotics are commonly used to treat NPS, they’re associated with an increased risk of serious adverse events and mortality in older patients,” said Dr. Asthana.
Dr. Asthana and colleague Dan Sewell, MD, carried out a systematic literature review of relevant studies of the use of cannabinoids for dementia patients.
“We found there are lot of studies, but they’re small scale; I’d say the largest was probably about 50 patients, with most studies having 10-50 patients,” said Dr. Asthana. In part, this may be because, until very recently, research on cannabinoids was controversial.
To review the current literature on the potential applications of cannabinoids in the treatment of food refusal and NPS in dementia patients, the researchers conducted a literature review.
They identified 23 relevant studies of the use of synthetic cannabinoids, including dronabinol and nabilone, for dementia patients. These products contain tetrahydrocannabinol (THC), the main psychoactive compound in cannabis.
More research coming
Several studies showed that cannabinoid use was associated with reduced nighttime motor activity, improved sleep duration, reduced agitation, and lower Neuropsychiatric Inventory scores.
One crossover placebo-controlled trial showed an overall increase in body weight among dementia patients who took dronabinol.
This suggests there might be something to the “colloquial cultural association between cannabinoids and the munchies,” said Dr. Asthana.
Possible mechanisms for the effects on appetite may be that cannabinoids increase levels of the hormone ghrelin, which is also known as the “hunger hormone,” and decrease leptin levels, a hormone that inhibits hunger. Dr. Asthana noted that, in these studies, the dose of THC was low and that overall, cannabinoids appeared to be safe.
“We found that, at least in these small-scale studies, cannabinoid analogues are well tolerated,” possibly because of the relatively low doses of THC, said Dr. Asthana. “They generally don’t seem to have a ton of side effects; they may make people a little sleepy, which is actually good, because these patents also have a lot of trouble sleeping.”
He noted that more recent research suggests cannabidiol oil may reduce agitation by up to 40%.
“Now that cannabis is losing a lot of its stigma, both culturally and in the scientific community, you’re seeing a lot of grant applications for clinical trials,” said Dr. Asthana. “I’m excited to see what we find in the next 5-10 years.”
In a comment, Kirsten Wilkins, MD, associate professor of psychiatry, Yale University, New Haven, Conn., who is also a geriatric psychiatrist at the Veterans Affairs Connecticut Health Care System, welcomed the new research in this area.
“With limited safe and effective treatments for food refusal and neuropsychiatric symptoms of dementia, Dr. Asthana and Dr. Sewell highlight the growing body of literature suggesting cannabinoids may be a novel treatment option,” she said.
A version of this article first appeared on Medscape.com.
For patients with dementia, cannabinoids may be a promising intervention for treating neuropsychiatric symptoms (NPS) and the refusing of food, new research suggests.
Results of a systematic literature review, presented at the 2021 meeting of the American Association for Geriatric Psychiatry, showed that cannabinoids were associated with reduced agitation, longer sleep, and lower NPS. They were also linked to increased meal consumption and weight gain.
Refusing food is a common problem for patients with dementia, often resulting in worsening sleep, agitation, and mood, study investigator Niraj Asthana, MD, a second-year resident in the department of psychiatry, University of California, San Diego, said in an interview. Dr. Asthana noted that certain cannabinoid analogues are now used to stimulate appetite for patients undergoing chemotherapy.
Filling a treatment gap
After years of legal and other problems affecting cannabinoid research, there is renewed interest in investigating its use for patients with dementia. Early evidence suggests that cannabinoids may also be beneficial for pain, sleep, and aggression.
The researchers noted that cannabinoids may be especially valuable in areas where there are currently limited therapies, including food refusal and NPS.
“Unfortunately, there are limited treatments available for food refusal, so we’re left with appetite stimulants and electroconvulsive therapy, and although atypical antipsychotics are commonly used to treat NPS, they’re associated with an increased risk of serious adverse events and mortality in older patients,” said Dr. Asthana.
Dr. Asthana and colleague Dan Sewell, MD, carried out a systematic literature review of relevant studies of the use of cannabinoids for dementia patients.
“We found there are lot of studies, but they’re small scale; I’d say the largest was probably about 50 patients, with most studies having 10-50 patients,” said Dr. Asthana. In part, this may be because, until very recently, research on cannabinoids was controversial.
To review the current literature on the potential applications of cannabinoids in the treatment of food refusal and NPS in dementia patients, the researchers conducted a literature review.
They identified 23 relevant studies of the use of synthetic cannabinoids, including dronabinol and nabilone, for dementia patients. These products contain tetrahydrocannabinol (THC), the main psychoactive compound in cannabis.
More research coming
Several studies showed that cannabinoid use was associated with reduced nighttime motor activity, improved sleep duration, reduced agitation, and lower Neuropsychiatric Inventory scores.
One crossover placebo-controlled trial showed an overall increase in body weight among dementia patients who took dronabinol.
This suggests there might be something to the “colloquial cultural association between cannabinoids and the munchies,” said Dr. Asthana.
Possible mechanisms for the effects on appetite may be that cannabinoids increase levels of the hormone ghrelin, which is also known as the “hunger hormone,” and decrease leptin levels, a hormone that inhibits hunger. Dr. Asthana noted that, in these studies, the dose of THC was low and that overall, cannabinoids appeared to be safe.
“We found that, at least in these small-scale studies, cannabinoid analogues are well tolerated,” possibly because of the relatively low doses of THC, said Dr. Asthana. “They generally don’t seem to have a ton of side effects; they may make people a little sleepy, which is actually good, because these patents also have a lot of trouble sleeping.”
He noted that more recent research suggests cannabidiol oil may reduce agitation by up to 40%.
“Now that cannabis is losing a lot of its stigma, both culturally and in the scientific community, you’re seeing a lot of grant applications for clinical trials,” said Dr. Asthana. “I’m excited to see what we find in the next 5-10 years.”
In a comment, Kirsten Wilkins, MD, associate professor of psychiatry, Yale University, New Haven, Conn., who is also a geriatric psychiatrist at the Veterans Affairs Connecticut Health Care System, welcomed the new research in this area.
“With limited safe and effective treatments for food refusal and neuropsychiatric symptoms of dementia, Dr. Asthana and Dr. Sewell highlight the growing body of literature suggesting cannabinoids may be a novel treatment option,” she said.
A version of this article first appeared on Medscape.com.
Can supplementary estrogen relieve MS symptoms in menopausal women?
, a neurologist told colleagues at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
This kind of research should explore the effects of aging, including in the brain, and “focus on what is preventable – this dramatic and abrupt loss of estrogen in women with MS,” said Rhonda Voskuhl, MD, of the Brain Research Institute at the University of California, Los Angeles.
“This is a call to action. There’s a huge gap that needs to be filled,” she added in an interview. “Not enough attention has been paid to menopause and cognitive issues in MS and even in healthy women.”
Research has found that many women with MS experience a decline in function during menopause, she said. “They’re having a worsening of their preexisting disabilities,” she noted, due to neurodegeneration.
Dr. Voskuhl highlighted a 2016 study, for instance, that found postmenopausal women with MS on hormone replacement therapy reported better physical function and quality of life than did their counterparts after adjustment for covariates. She also pointed to a 2019 study that concluded that “natural menopause seems to be a turning point to a more progressive phase of MS.”
Estrogen appears to play a significant role. “It’s involved in synaptic plasticity,” she said. “That’s why the disabilities are worsening.”
Dr. Voskuhl supports a year-long, randomized and controlled study of estrogen supplementation in 150-200 participants. The goal, she said, is “not just to prevent loss and bad things from happening but also make improvements.”
In healthy patients, she said, outcomes should include cognitive decline in menopause, cognitive domain outcomes, and region-specific biomarkers in the frontal cortex and hippocampus instead of global cognition and global brain volume. In patients with MS, she said, the focus should be on worsening of disability with emphasis on specific disabilities such as walking and region-specific biomarkers for the motor cortex and spinal cord.
“We need to be looking at cortical gray matter, which we know is responsive to estrogen,” Dr. Voskuhl said. She led a 2018 placebo-controlled study that found women with MS who took estrogen supplements appeared to experience localized sparing of progressive gray matter, which the researchers linked to improved results in cognitive testing. The findings, the study authors wrote, suggest “a clinically relevant, disability-specific biomarker for clinical trials of candidate neuroprotective treatments in MS.”
What about men? Does hormone loss worsen their MS? Dr. Voskuhl said there seems to be a connection between lower levels of testosterone and more disability in men with MS. But their situation is different. Loss of testosterone in men is gradual and happens over decades instead of over the short period of menopause in women, she said.
Jennifer Graves, MD, a neurologist at the University of California, San Diego, agreed that it’s time for further research into estrogen supplementation in MS. As she noted, “we don’t know the exact biological mechanism that might link perimenopause with developing a more progressive type of MS.”
She added: “An overall decrease in estrogen may be at play but there are other biological changes around menopause. We must also take care in studies to try to separate out what might be due to ovarian aging versus other types of aging processes that might be happening at the same time.”
Dr. Voskuhl disclosed that she is an inventor on university patents for use of estriol and estrogen receptor–beta ligands as treatments. Dr. Graves reports no relevant disclosures.
, a neurologist told colleagues at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
This kind of research should explore the effects of aging, including in the brain, and “focus on what is preventable – this dramatic and abrupt loss of estrogen in women with MS,” said Rhonda Voskuhl, MD, of the Brain Research Institute at the University of California, Los Angeles.
“This is a call to action. There’s a huge gap that needs to be filled,” she added in an interview. “Not enough attention has been paid to menopause and cognitive issues in MS and even in healthy women.”
Research has found that many women with MS experience a decline in function during menopause, she said. “They’re having a worsening of their preexisting disabilities,” she noted, due to neurodegeneration.
Dr. Voskuhl highlighted a 2016 study, for instance, that found postmenopausal women with MS on hormone replacement therapy reported better physical function and quality of life than did their counterparts after adjustment for covariates. She also pointed to a 2019 study that concluded that “natural menopause seems to be a turning point to a more progressive phase of MS.”
Estrogen appears to play a significant role. “It’s involved in synaptic plasticity,” she said. “That’s why the disabilities are worsening.”
Dr. Voskuhl supports a year-long, randomized and controlled study of estrogen supplementation in 150-200 participants. The goal, she said, is “not just to prevent loss and bad things from happening but also make improvements.”
In healthy patients, she said, outcomes should include cognitive decline in menopause, cognitive domain outcomes, and region-specific biomarkers in the frontal cortex and hippocampus instead of global cognition and global brain volume. In patients with MS, she said, the focus should be on worsening of disability with emphasis on specific disabilities such as walking and region-specific biomarkers for the motor cortex and spinal cord.
“We need to be looking at cortical gray matter, which we know is responsive to estrogen,” Dr. Voskuhl said. She led a 2018 placebo-controlled study that found women with MS who took estrogen supplements appeared to experience localized sparing of progressive gray matter, which the researchers linked to improved results in cognitive testing. The findings, the study authors wrote, suggest “a clinically relevant, disability-specific biomarker for clinical trials of candidate neuroprotective treatments in MS.”
What about men? Does hormone loss worsen their MS? Dr. Voskuhl said there seems to be a connection between lower levels of testosterone and more disability in men with MS. But their situation is different. Loss of testosterone in men is gradual and happens over decades instead of over the short period of menopause in women, she said.
Jennifer Graves, MD, a neurologist at the University of California, San Diego, agreed that it’s time for further research into estrogen supplementation in MS. As she noted, “we don’t know the exact biological mechanism that might link perimenopause with developing a more progressive type of MS.”
She added: “An overall decrease in estrogen may be at play but there are other biological changes around menopause. We must also take care in studies to try to separate out what might be due to ovarian aging versus other types of aging processes that might be happening at the same time.”
Dr. Voskuhl disclosed that she is an inventor on university patents for use of estriol and estrogen receptor–beta ligands as treatments. Dr. Graves reports no relevant disclosures.
, a neurologist told colleagues at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
This kind of research should explore the effects of aging, including in the brain, and “focus on what is preventable – this dramatic and abrupt loss of estrogen in women with MS,” said Rhonda Voskuhl, MD, of the Brain Research Institute at the University of California, Los Angeles.
“This is a call to action. There’s a huge gap that needs to be filled,” she added in an interview. “Not enough attention has been paid to menopause and cognitive issues in MS and even in healthy women.”
Research has found that many women with MS experience a decline in function during menopause, she said. “They’re having a worsening of their preexisting disabilities,” she noted, due to neurodegeneration.
Dr. Voskuhl highlighted a 2016 study, for instance, that found postmenopausal women with MS on hormone replacement therapy reported better physical function and quality of life than did their counterparts after adjustment for covariates. She also pointed to a 2019 study that concluded that “natural menopause seems to be a turning point to a more progressive phase of MS.”
Estrogen appears to play a significant role. “It’s involved in synaptic plasticity,” she said. “That’s why the disabilities are worsening.”
Dr. Voskuhl supports a year-long, randomized and controlled study of estrogen supplementation in 150-200 participants. The goal, she said, is “not just to prevent loss and bad things from happening but also make improvements.”
In healthy patients, she said, outcomes should include cognitive decline in menopause, cognitive domain outcomes, and region-specific biomarkers in the frontal cortex and hippocampus instead of global cognition and global brain volume. In patients with MS, she said, the focus should be on worsening of disability with emphasis on specific disabilities such as walking and region-specific biomarkers for the motor cortex and spinal cord.
“We need to be looking at cortical gray matter, which we know is responsive to estrogen,” Dr. Voskuhl said. She led a 2018 placebo-controlled study that found women with MS who took estrogen supplements appeared to experience localized sparing of progressive gray matter, which the researchers linked to improved results in cognitive testing. The findings, the study authors wrote, suggest “a clinically relevant, disability-specific biomarker for clinical trials of candidate neuroprotective treatments in MS.”
What about men? Does hormone loss worsen their MS? Dr. Voskuhl said there seems to be a connection between lower levels of testosterone and more disability in men with MS. But their situation is different. Loss of testosterone in men is gradual and happens over decades instead of over the short period of menopause in women, she said.
Jennifer Graves, MD, a neurologist at the University of California, San Diego, agreed that it’s time for further research into estrogen supplementation in MS. As she noted, “we don’t know the exact biological mechanism that might link perimenopause with developing a more progressive type of MS.”
She added: “An overall decrease in estrogen may be at play but there are other biological changes around menopause. We must also take care in studies to try to separate out what might be due to ovarian aging versus other types of aging processes that might be happening at the same time.”
Dr. Voskuhl disclosed that she is an inventor on university patents for use of estriol and estrogen receptor–beta ligands as treatments. Dr. Graves reports no relevant disclosures.
FROM ACTRIMS FORUM 2021
Type 2 diabetes linked to increased risk for Parkinson’s
New analyses of both observational and genetic data have provided “convincing evidence” that type 2 diabetes is associated with an increased risk for Parkinson’s disease.
“The fact that we see the same effects in both types of analysis separately makes it more likely that these results are real – that type 2 diabetes really is a driver of Parkinson’s disease risk,” Alastair Noyce, PhD, senior author of the new studies, said in an interview.
The two analyses are reported in one paper published online March 8 in the journal Movement Disorders.
Dr. Noyce, clinical senior lecturer in the preventive neurology unit at the Wolfson Institute of Preventive Medicine, Queen Mary University of London, explained that his group is interested in risk factors for Parkinson’s disease, particularly those relevant at the population level and which might be modifiable.
“Several studies have looked at diabetes as a risk factor for Parkinson’s but very few have focused on type 2 diabetes, and, as this is such a growing health issue, we wanted to look at that in more detail,” he said.
The researchers performed two different analyses: a meta-analysis of observational studies investigating an association between type 2 diabetes and Parkinson’s; and a separate Mendelian randomization analysis of genetic data on the two conditions.
They found similar results in both studies, with the observational data suggesting type 2 diabetes was associated with a 21% increased risk for Parkinson’s disease and the genetic data suggesting an 8% increased risk. There were also hints that type 2 diabetes might also be associated with faster progression of Parkinson’s symptoms.
“I don’t think type 2 diabetes is a major cause of Parkinson’s, but it probably makes some contribution and may increase the risk of a more aggressive form of the condition,” Dr. Noyce said.
“I would say the increased risk of Parkinson’s disease attributable to type 2 diabetes may be similar to that of head injury or pesticide exposure, but it is important, as type 2 diabetes is very prevalent and is increasing,” he added. “As we see the growth in type 2 diabetes, this could lead to a later increase in Parkinson’s, which is already one of the fastest-growing diseases worldwide.”
For the meta-analysis of observational data, the researchers included nine studies that investigated preceding type 2 diabetes specifically and its effect on the risk for Parkinson’s disease and progression.
The pooled effect estimates showed that type 2 diabetes was associated with an increased risk for Parkinson’s disease (odds ratio, 1.21; 95% confidence interval, 1.07-1.36), and there was some evidence that type 2 diabetes was associated with faster progression of motor symptoms (standardized mean difference [SMD], 0.55) and cognitive decline (SMD, −0.92).
The observational meta-analysis included seven cohort studies and two case-control studies, and these different types of studies showed different results in regard to the association between diabetes and Parkinson’s. While the cohort studies showed a detrimental effect of diabetes on Parkinson’s risk (OR, 1.29), the case-control studies suggested protective effect (OR, 0.51).
Addressing this, Dr. Noyce noted that the case-control studies may be less reliable as they suffered more from survivor bias. “Diabetes may cause deaths in mid-life before people go on to develop Parkinson’s, and this would cause a protective effect to be seen, but we believe this to be a spurious result. Cohort studies are generally more reliable and are less susceptible to survivor bias,” he said.
For the genetic analysis, the researchers combined results from two large publicly available genome-wide association studies – one for type 2 diabetes and one for Parkinson’s disease to assess whether individuals with a genetic tendency to type 2 diabetes had a higher risk of developing Parkinson’s.
Results showed an increased risk for Parkinson’s in those individuals with genetic variants associated with type 2 diabetes, with an odds ratio of 1.08 (P = .010). There was also some evidence of an effect on motor progression (OR, 1.10; P = .032) but not on cognitive progression.
On the possible mechanism behind this observation, Dr. Noyce noted type 2 diabetes and Parkinson’s have some similarities in biology, including abnormal protein aggregation.
In the study, the authors also suggest that circulating insulin may have a neuroprotective role, whereas systemic and local insulin resistance can influence pathways known to be important in Parkinson’s pathogenesis, including those that relate to mitochondrial dysfunction, neuroinflammation, synaptic plasticity, and mitochondrial dysfunction.
Dr. Noyce further pointed out that several drugs used for the treatment of type 2 diabetes have been repurposed as possible treatments for Parkinson’s disease and are now being tested for this new indication. “Our results support that approach and raise the idea that some of these drugs may even prevent Parkinson’s in people at risk,” he said.
Most people who have type 2 diabetes won’t get Parkinson’s disease, he added. Other outcomes such as heart disease, kidney disease, and microvascular complications are far more likely, and the main aim of preventing and treating type 2 diabetes is to prevent these far more common outcomes. “But our data suggests that this could also have a possible benefit in reducing future Parkinson’s risk,” he said.
Not on the horizon at present is the possibility of screening patients with type 2 diabetes for signs of early Parkinson’s, Dr. Noyce said.
“There isn’t a test for identifying presymptomatic neurodegenerative diseases such as Parkinson’s yet, but perhaps in the future there will be, and type 2 diabetes may be one risk factor to take into account when considering such screening,” he added.
This work was financially supported by grants from The Michael J. Fox Foundation; the Canadian Consortium on Neurodegeneration in Aging (CCNA); the Canada First Research Excellence Fund (CFREF), awarded to McGill University for the Healthy Brains for Healthy Lives (HBHL) initiative; and Parkinson Canada, and the Intramural Research Program of the NIH, National Institute on Aging.
Dr. Noyce reports grants from the Barts Charity, Parkinson’s UK, Aligning Science Across Parkinson’s and Michael J. Fox Foundation, and the Virginia Keiley Benefaction; and personal fees/honoraria from Britannia, BIAL, AbbVie, Global Kinetics Corporation, Profile, Biogen, Roche, and UCB outside of the submitted work.
A version of this article first appeared on Medscape.com.
New analyses of both observational and genetic data have provided “convincing evidence” that type 2 diabetes is associated with an increased risk for Parkinson’s disease.
“The fact that we see the same effects in both types of analysis separately makes it more likely that these results are real – that type 2 diabetes really is a driver of Parkinson’s disease risk,” Alastair Noyce, PhD, senior author of the new studies, said in an interview.
The two analyses are reported in one paper published online March 8 in the journal Movement Disorders.
Dr. Noyce, clinical senior lecturer in the preventive neurology unit at the Wolfson Institute of Preventive Medicine, Queen Mary University of London, explained that his group is interested in risk factors for Parkinson’s disease, particularly those relevant at the population level and which might be modifiable.
“Several studies have looked at diabetes as a risk factor for Parkinson’s but very few have focused on type 2 diabetes, and, as this is such a growing health issue, we wanted to look at that in more detail,” he said.
The researchers performed two different analyses: a meta-analysis of observational studies investigating an association between type 2 diabetes and Parkinson’s; and a separate Mendelian randomization analysis of genetic data on the two conditions.
They found similar results in both studies, with the observational data suggesting type 2 diabetes was associated with a 21% increased risk for Parkinson’s disease and the genetic data suggesting an 8% increased risk. There were also hints that type 2 diabetes might also be associated with faster progression of Parkinson’s symptoms.
“I don’t think type 2 diabetes is a major cause of Parkinson’s, but it probably makes some contribution and may increase the risk of a more aggressive form of the condition,” Dr. Noyce said.
“I would say the increased risk of Parkinson’s disease attributable to type 2 diabetes may be similar to that of head injury or pesticide exposure, but it is important, as type 2 diabetes is very prevalent and is increasing,” he added. “As we see the growth in type 2 diabetes, this could lead to a later increase in Parkinson’s, which is already one of the fastest-growing diseases worldwide.”
For the meta-analysis of observational data, the researchers included nine studies that investigated preceding type 2 diabetes specifically and its effect on the risk for Parkinson’s disease and progression.
The pooled effect estimates showed that type 2 diabetes was associated with an increased risk for Parkinson’s disease (odds ratio, 1.21; 95% confidence interval, 1.07-1.36), and there was some evidence that type 2 diabetes was associated with faster progression of motor symptoms (standardized mean difference [SMD], 0.55) and cognitive decline (SMD, −0.92).
The observational meta-analysis included seven cohort studies and two case-control studies, and these different types of studies showed different results in regard to the association between diabetes and Parkinson’s. While the cohort studies showed a detrimental effect of diabetes on Parkinson’s risk (OR, 1.29), the case-control studies suggested protective effect (OR, 0.51).
Addressing this, Dr. Noyce noted that the case-control studies may be less reliable as they suffered more from survivor bias. “Diabetes may cause deaths in mid-life before people go on to develop Parkinson’s, and this would cause a protective effect to be seen, but we believe this to be a spurious result. Cohort studies are generally more reliable and are less susceptible to survivor bias,” he said.
For the genetic analysis, the researchers combined results from two large publicly available genome-wide association studies – one for type 2 diabetes and one for Parkinson’s disease to assess whether individuals with a genetic tendency to type 2 diabetes had a higher risk of developing Parkinson’s.
Results showed an increased risk for Parkinson’s in those individuals with genetic variants associated with type 2 diabetes, with an odds ratio of 1.08 (P = .010). There was also some evidence of an effect on motor progression (OR, 1.10; P = .032) but not on cognitive progression.
On the possible mechanism behind this observation, Dr. Noyce noted type 2 diabetes and Parkinson’s have some similarities in biology, including abnormal protein aggregation.
In the study, the authors also suggest that circulating insulin may have a neuroprotective role, whereas systemic and local insulin resistance can influence pathways known to be important in Parkinson’s pathogenesis, including those that relate to mitochondrial dysfunction, neuroinflammation, synaptic plasticity, and mitochondrial dysfunction.
Dr. Noyce further pointed out that several drugs used for the treatment of type 2 diabetes have been repurposed as possible treatments for Parkinson’s disease and are now being tested for this new indication. “Our results support that approach and raise the idea that some of these drugs may even prevent Parkinson’s in people at risk,” he said.
Most people who have type 2 diabetes won’t get Parkinson’s disease, he added. Other outcomes such as heart disease, kidney disease, and microvascular complications are far more likely, and the main aim of preventing and treating type 2 diabetes is to prevent these far more common outcomes. “But our data suggests that this could also have a possible benefit in reducing future Parkinson’s risk,” he said.
Not on the horizon at present is the possibility of screening patients with type 2 diabetes for signs of early Parkinson’s, Dr. Noyce said.
“There isn’t a test for identifying presymptomatic neurodegenerative diseases such as Parkinson’s yet, but perhaps in the future there will be, and type 2 diabetes may be one risk factor to take into account when considering such screening,” he added.
This work was financially supported by grants from The Michael J. Fox Foundation; the Canadian Consortium on Neurodegeneration in Aging (CCNA); the Canada First Research Excellence Fund (CFREF), awarded to McGill University for the Healthy Brains for Healthy Lives (HBHL) initiative; and Parkinson Canada, and the Intramural Research Program of the NIH, National Institute on Aging.
Dr. Noyce reports grants from the Barts Charity, Parkinson’s UK, Aligning Science Across Parkinson’s and Michael J. Fox Foundation, and the Virginia Keiley Benefaction; and personal fees/honoraria from Britannia, BIAL, AbbVie, Global Kinetics Corporation, Profile, Biogen, Roche, and UCB outside of the submitted work.
A version of this article first appeared on Medscape.com.
New analyses of both observational and genetic data have provided “convincing evidence” that type 2 diabetes is associated with an increased risk for Parkinson’s disease.
“The fact that we see the same effects in both types of analysis separately makes it more likely that these results are real – that type 2 diabetes really is a driver of Parkinson’s disease risk,” Alastair Noyce, PhD, senior author of the new studies, said in an interview.
The two analyses are reported in one paper published online March 8 in the journal Movement Disorders.
Dr. Noyce, clinical senior lecturer in the preventive neurology unit at the Wolfson Institute of Preventive Medicine, Queen Mary University of London, explained that his group is interested in risk factors for Parkinson’s disease, particularly those relevant at the population level and which might be modifiable.
“Several studies have looked at diabetes as a risk factor for Parkinson’s but very few have focused on type 2 diabetes, and, as this is such a growing health issue, we wanted to look at that in more detail,” he said.
The researchers performed two different analyses: a meta-analysis of observational studies investigating an association between type 2 diabetes and Parkinson’s; and a separate Mendelian randomization analysis of genetic data on the two conditions.
They found similar results in both studies, with the observational data suggesting type 2 diabetes was associated with a 21% increased risk for Parkinson’s disease and the genetic data suggesting an 8% increased risk. There were also hints that type 2 diabetes might also be associated with faster progression of Parkinson’s symptoms.
“I don’t think type 2 diabetes is a major cause of Parkinson’s, but it probably makes some contribution and may increase the risk of a more aggressive form of the condition,” Dr. Noyce said.
“I would say the increased risk of Parkinson’s disease attributable to type 2 diabetes may be similar to that of head injury or pesticide exposure, but it is important, as type 2 diabetes is very prevalent and is increasing,” he added. “As we see the growth in type 2 diabetes, this could lead to a later increase in Parkinson’s, which is already one of the fastest-growing diseases worldwide.”
For the meta-analysis of observational data, the researchers included nine studies that investigated preceding type 2 diabetes specifically and its effect on the risk for Parkinson’s disease and progression.
The pooled effect estimates showed that type 2 diabetes was associated with an increased risk for Parkinson’s disease (odds ratio, 1.21; 95% confidence interval, 1.07-1.36), and there was some evidence that type 2 diabetes was associated with faster progression of motor symptoms (standardized mean difference [SMD], 0.55) and cognitive decline (SMD, −0.92).
The observational meta-analysis included seven cohort studies and two case-control studies, and these different types of studies showed different results in regard to the association between diabetes and Parkinson’s. While the cohort studies showed a detrimental effect of diabetes on Parkinson’s risk (OR, 1.29), the case-control studies suggested protective effect (OR, 0.51).
Addressing this, Dr. Noyce noted that the case-control studies may be less reliable as they suffered more from survivor bias. “Diabetes may cause deaths in mid-life before people go on to develop Parkinson’s, and this would cause a protective effect to be seen, but we believe this to be a spurious result. Cohort studies are generally more reliable and are less susceptible to survivor bias,” he said.
For the genetic analysis, the researchers combined results from two large publicly available genome-wide association studies – one for type 2 diabetes and one for Parkinson’s disease to assess whether individuals with a genetic tendency to type 2 diabetes had a higher risk of developing Parkinson’s.
Results showed an increased risk for Parkinson’s in those individuals with genetic variants associated with type 2 diabetes, with an odds ratio of 1.08 (P = .010). There was also some evidence of an effect on motor progression (OR, 1.10; P = .032) but not on cognitive progression.
On the possible mechanism behind this observation, Dr. Noyce noted type 2 diabetes and Parkinson’s have some similarities in biology, including abnormal protein aggregation.
In the study, the authors also suggest that circulating insulin may have a neuroprotective role, whereas systemic and local insulin resistance can influence pathways known to be important in Parkinson’s pathogenesis, including those that relate to mitochondrial dysfunction, neuroinflammation, synaptic plasticity, and mitochondrial dysfunction.
Dr. Noyce further pointed out that several drugs used for the treatment of type 2 diabetes have been repurposed as possible treatments for Parkinson’s disease and are now being tested for this new indication. “Our results support that approach and raise the idea that some of these drugs may even prevent Parkinson’s in people at risk,” he said.
Most people who have type 2 diabetes won’t get Parkinson’s disease, he added. Other outcomes such as heart disease, kidney disease, and microvascular complications are far more likely, and the main aim of preventing and treating type 2 diabetes is to prevent these far more common outcomes. “But our data suggests that this could also have a possible benefit in reducing future Parkinson’s risk,” he said.
Not on the horizon at present is the possibility of screening patients with type 2 diabetes for signs of early Parkinson’s, Dr. Noyce said.
“There isn’t a test for identifying presymptomatic neurodegenerative diseases such as Parkinson’s yet, but perhaps in the future there will be, and type 2 diabetes may be one risk factor to take into account when considering such screening,” he added.
This work was financially supported by grants from The Michael J. Fox Foundation; the Canadian Consortium on Neurodegeneration in Aging (CCNA); the Canada First Research Excellence Fund (CFREF), awarded to McGill University for the Healthy Brains for Healthy Lives (HBHL) initiative; and Parkinson Canada, and the Intramural Research Program of the NIH, National Institute on Aging.
Dr. Noyce reports grants from the Barts Charity, Parkinson’s UK, Aligning Science Across Parkinson’s and Michael J. Fox Foundation, and the Virginia Keiley Benefaction; and personal fees/honoraria from Britannia, BIAL, AbbVie, Global Kinetics Corporation, Profile, Biogen, Roche, and UCB outside of the submitted work.
A version of this article first appeared on Medscape.com.
Neurologic drug prices jump 50% in five years
, new research shows. Results of the retrospective study also showed that most of the increased costs for these agents were due to rising costs for neuroimmunology drugs, mainly for those used to treat multiple sclerosis (MS).
“The same brand name medication in 2017 cost approximately 50% more than in 2013,” said Adam de Havenon, MD, assistant professor of neurology, University of Utah, Salt Lake City.
“An analogy would be if you bought an iPhone 5 in 2013 for $500, and then in 2017, you were asked to pay $750 for the exact same iPhone 5,” Dr. de Havenon added.
The study findings were published online March 10 in the journal Neurology.
$26 billion in payments
Both neurologists and patients are concerned about the high cost of prescription drugs for neurologic diseases, and Medicare Part D data indicate that these drugs are the most expensive component of neurologic care, the researchers noted. In addition, out-of-pocket costs have increased significantly for patients with neurologic disease such as Parkinson’s disease, epilepsy, and MS.
To understand trends in payments for neurologic drugs, Dr. de Havenon and colleagues analyzed Medicare Part D claims filed from 2013 to 2017. The payments include costs paid by Medicare, the patient, government subsidies, and other third-party payers.
In addition to examining more current Medicare Part D data than previous studies, the current analysis examined all medications prescribed by neurologists that consistently remained branded or generic during the 5-year study period, said Dr. de Havenon. This approach resulted in a large number of claims and a large total cost.
To calculate the percentage change in annual payment claims, the researchers used 2013 prices as a reference point. They identified drugs named in 2013 claims and classified them as generic, brand-name only, or brand-name with generic equivalent. Researchers also divided the drugs by neurologic subspecialty.
The analysis included 520 drugs, all of which were available in each year of the study period. Of these drugs, 322 were generic, 61 were brand-name only, and 137 were brand-name with a generic equivalent. There were 90.7 million total claims.
Results showed total payments amounted to $26.65 billion. Yearly total payments increased from $4.05 billion in 2013 to $6.09 billion in 2017, representing a 50.4% increase, even after adjusting for inflation. Total claims increased by 7.6% – from 17.1 million in 2013 to 18.4 million in 2017.
From 2013 to 2017, claim payments increased by 0.6% for generic drugs, 42.4% for brand-name only drugs, and 45% for brand-name drugs with generic equivalents. The proportion of claims increased from 81.9% to 88% for generic drugs and from 4.9% to 6.2% for brand-name only drugs.
However, the proportion of claims for brand-name drugs with generic equivalents decreased from 13.3% to 5.8%.
Treatment barrier
Neuroimmunologic drugs, most of which were prescribed for MS, had exceptional cost, the researchers noted. These drugs accounted for more than 50% of payments but only 4.3% of claims. Claim payment for these drugs increased by 46.9% during the study period, from $3,337 to $4,902.
When neuroimmunologic drugs were removed from the analysis there was still significant increase in claim payments for brand-name only drugs (50.4%) and brand-name drugs with generic equivalents (45.6%).
Although neuroimmunologic medicines, including monoclonal antibodies, are more expensive to produce, this factor alone does not explain their exceptional cost, said Dr. de Havenon. “The high cost of brand-name drugs in this speciality is likely because the market bears it,” he added. “In other words, MS is a disabling disease and the medications work, so historically the Centers for Medicare & Medicaid Services have been willing to tolerate the high cost of these primarily brand-name medications.”
Several countries have controlled drug costs by negotiating with pharmaceutical companies and through legislation, Dr. de Havenon noted.
“My intent with this article was to raise awareness on the topic, which I struggle with frequently as a clinician. I know I want my patients to have a medication, but the cost prevents it,” he said.
‘Unfettered’ price-setting
Commenting on the findings, Robert J. Fox, MD, vice chair for research at the Neurological Institute of the Cleveland Clinic, said the study “brings into clear light” what neurologists, particularly those who treat MS, have long suspected but did not really know. These neurologists “are typically distanced from the payment aspects of the medications they prescribe,” said Dr. Fox, who was not involved with the research.
Although a particular strength of the study was its comprehensiveness, the researchers excluded infusion claims – which account for a large portion of total patient care costs for many disorders, he noted.
Drugs for MS historically have been expensive, ostensibly because of their high cost of development. In addition, the large and continued price increase that occurs long after these drugs have been approved remains unexplained, said Dr. Fox.
He noted that the study findings might not directly affect clinical practice because neurologists will continue prescribing medications they think are best for their patients. “Instead, I think this is a lesson to lawmakers about the massive error in the Medicare Modernization Act of 2003, where the federal government was prohibited from negotiating drug prices. If the seller is unfettered in setting a price, then no one should be surprised when the price rises,” Dr. Fox said.
Because many new drugs and new generic formulations for treating MS have become available during the past year, “repeating these types of economic studies for the period 2020-2025 will help us understand if generic competition – as well as new laws if they are passed – alter price,” he concluded.
The study was funded by the American Academy of Neurology, which publishes Neurology. Dr. de Havenon has received clinical research funding from AMAG Pharmaceuticals and Regeneron Pharmaceuticals. Dr. Fox receives consulting fees from many pharmaceutical companies involved in the development of therapies for MS.
A version of this article first appeared on Medscape.com.
, new research shows. Results of the retrospective study also showed that most of the increased costs for these agents were due to rising costs for neuroimmunology drugs, mainly for those used to treat multiple sclerosis (MS).
“The same brand name medication in 2017 cost approximately 50% more than in 2013,” said Adam de Havenon, MD, assistant professor of neurology, University of Utah, Salt Lake City.
“An analogy would be if you bought an iPhone 5 in 2013 for $500, and then in 2017, you were asked to pay $750 for the exact same iPhone 5,” Dr. de Havenon added.
The study findings were published online March 10 in the journal Neurology.
$26 billion in payments
Both neurologists and patients are concerned about the high cost of prescription drugs for neurologic diseases, and Medicare Part D data indicate that these drugs are the most expensive component of neurologic care, the researchers noted. In addition, out-of-pocket costs have increased significantly for patients with neurologic disease such as Parkinson’s disease, epilepsy, and MS.
To understand trends in payments for neurologic drugs, Dr. de Havenon and colleagues analyzed Medicare Part D claims filed from 2013 to 2017. The payments include costs paid by Medicare, the patient, government subsidies, and other third-party payers.
In addition to examining more current Medicare Part D data than previous studies, the current analysis examined all medications prescribed by neurologists that consistently remained branded or generic during the 5-year study period, said Dr. de Havenon. This approach resulted in a large number of claims and a large total cost.
To calculate the percentage change in annual payment claims, the researchers used 2013 prices as a reference point. They identified drugs named in 2013 claims and classified them as generic, brand-name only, or brand-name with generic equivalent. Researchers also divided the drugs by neurologic subspecialty.
The analysis included 520 drugs, all of which were available in each year of the study period. Of these drugs, 322 were generic, 61 were brand-name only, and 137 were brand-name with a generic equivalent. There were 90.7 million total claims.
Results showed total payments amounted to $26.65 billion. Yearly total payments increased from $4.05 billion in 2013 to $6.09 billion in 2017, representing a 50.4% increase, even after adjusting for inflation. Total claims increased by 7.6% – from 17.1 million in 2013 to 18.4 million in 2017.
From 2013 to 2017, claim payments increased by 0.6% for generic drugs, 42.4% for brand-name only drugs, and 45% for brand-name drugs with generic equivalents. The proportion of claims increased from 81.9% to 88% for generic drugs and from 4.9% to 6.2% for brand-name only drugs.
However, the proportion of claims for brand-name drugs with generic equivalents decreased from 13.3% to 5.8%.
Treatment barrier
Neuroimmunologic drugs, most of which were prescribed for MS, had exceptional cost, the researchers noted. These drugs accounted for more than 50% of payments but only 4.3% of claims. Claim payment for these drugs increased by 46.9% during the study period, from $3,337 to $4,902.
When neuroimmunologic drugs were removed from the analysis there was still significant increase in claim payments for brand-name only drugs (50.4%) and brand-name drugs with generic equivalents (45.6%).
Although neuroimmunologic medicines, including monoclonal antibodies, are more expensive to produce, this factor alone does not explain their exceptional cost, said Dr. de Havenon. “The high cost of brand-name drugs in this speciality is likely because the market bears it,” he added. “In other words, MS is a disabling disease and the medications work, so historically the Centers for Medicare & Medicaid Services have been willing to tolerate the high cost of these primarily brand-name medications.”
Several countries have controlled drug costs by negotiating with pharmaceutical companies and through legislation, Dr. de Havenon noted.
“My intent with this article was to raise awareness on the topic, which I struggle with frequently as a clinician. I know I want my patients to have a medication, but the cost prevents it,” he said.
‘Unfettered’ price-setting
Commenting on the findings, Robert J. Fox, MD, vice chair for research at the Neurological Institute of the Cleveland Clinic, said the study “brings into clear light” what neurologists, particularly those who treat MS, have long suspected but did not really know. These neurologists “are typically distanced from the payment aspects of the medications they prescribe,” said Dr. Fox, who was not involved with the research.
Although a particular strength of the study was its comprehensiveness, the researchers excluded infusion claims – which account for a large portion of total patient care costs for many disorders, he noted.
Drugs for MS historically have been expensive, ostensibly because of their high cost of development. In addition, the large and continued price increase that occurs long after these drugs have been approved remains unexplained, said Dr. Fox.
He noted that the study findings might not directly affect clinical practice because neurologists will continue prescribing medications they think are best for their patients. “Instead, I think this is a lesson to lawmakers about the massive error in the Medicare Modernization Act of 2003, where the federal government was prohibited from negotiating drug prices. If the seller is unfettered in setting a price, then no one should be surprised when the price rises,” Dr. Fox said.
Because many new drugs and new generic formulations for treating MS have become available during the past year, “repeating these types of economic studies for the period 2020-2025 will help us understand if generic competition – as well as new laws if they are passed – alter price,” he concluded.
The study was funded by the American Academy of Neurology, which publishes Neurology. Dr. de Havenon has received clinical research funding from AMAG Pharmaceuticals and Regeneron Pharmaceuticals. Dr. Fox receives consulting fees from many pharmaceutical companies involved in the development of therapies for MS.
A version of this article first appeared on Medscape.com.
, new research shows. Results of the retrospective study also showed that most of the increased costs for these agents were due to rising costs for neuroimmunology drugs, mainly for those used to treat multiple sclerosis (MS).
“The same brand name medication in 2017 cost approximately 50% more than in 2013,” said Adam de Havenon, MD, assistant professor of neurology, University of Utah, Salt Lake City.
“An analogy would be if you bought an iPhone 5 in 2013 for $500, and then in 2017, you were asked to pay $750 for the exact same iPhone 5,” Dr. de Havenon added.
The study findings were published online March 10 in the journal Neurology.
$26 billion in payments
Both neurologists and patients are concerned about the high cost of prescription drugs for neurologic diseases, and Medicare Part D data indicate that these drugs are the most expensive component of neurologic care, the researchers noted. In addition, out-of-pocket costs have increased significantly for patients with neurologic disease such as Parkinson’s disease, epilepsy, and MS.
To understand trends in payments for neurologic drugs, Dr. de Havenon and colleagues analyzed Medicare Part D claims filed from 2013 to 2017. The payments include costs paid by Medicare, the patient, government subsidies, and other third-party payers.
In addition to examining more current Medicare Part D data than previous studies, the current analysis examined all medications prescribed by neurologists that consistently remained branded or generic during the 5-year study period, said Dr. de Havenon. This approach resulted in a large number of claims and a large total cost.
To calculate the percentage change in annual payment claims, the researchers used 2013 prices as a reference point. They identified drugs named in 2013 claims and classified them as generic, brand-name only, or brand-name with generic equivalent. Researchers also divided the drugs by neurologic subspecialty.
The analysis included 520 drugs, all of which were available in each year of the study period. Of these drugs, 322 were generic, 61 were brand-name only, and 137 were brand-name with a generic equivalent. There were 90.7 million total claims.
Results showed total payments amounted to $26.65 billion. Yearly total payments increased from $4.05 billion in 2013 to $6.09 billion in 2017, representing a 50.4% increase, even after adjusting for inflation. Total claims increased by 7.6% – from 17.1 million in 2013 to 18.4 million in 2017.
From 2013 to 2017, claim payments increased by 0.6% for generic drugs, 42.4% for brand-name only drugs, and 45% for brand-name drugs with generic equivalents. The proportion of claims increased from 81.9% to 88% for generic drugs and from 4.9% to 6.2% for brand-name only drugs.
However, the proportion of claims for brand-name drugs with generic equivalents decreased from 13.3% to 5.8%.
Treatment barrier
Neuroimmunologic drugs, most of which were prescribed for MS, had exceptional cost, the researchers noted. These drugs accounted for more than 50% of payments but only 4.3% of claims. Claim payment for these drugs increased by 46.9% during the study period, from $3,337 to $4,902.
When neuroimmunologic drugs were removed from the analysis there was still significant increase in claim payments for brand-name only drugs (50.4%) and brand-name drugs with generic equivalents (45.6%).
Although neuroimmunologic medicines, including monoclonal antibodies, are more expensive to produce, this factor alone does not explain their exceptional cost, said Dr. de Havenon. “The high cost of brand-name drugs in this speciality is likely because the market bears it,” he added. “In other words, MS is a disabling disease and the medications work, so historically the Centers for Medicare & Medicaid Services have been willing to tolerate the high cost of these primarily brand-name medications.”
Several countries have controlled drug costs by negotiating with pharmaceutical companies and through legislation, Dr. de Havenon noted.
“My intent with this article was to raise awareness on the topic, which I struggle with frequently as a clinician. I know I want my patients to have a medication, but the cost prevents it,” he said.
‘Unfettered’ price-setting
Commenting on the findings, Robert J. Fox, MD, vice chair for research at the Neurological Institute of the Cleveland Clinic, said the study “brings into clear light” what neurologists, particularly those who treat MS, have long suspected but did not really know. These neurologists “are typically distanced from the payment aspects of the medications they prescribe,” said Dr. Fox, who was not involved with the research.
Although a particular strength of the study was its comprehensiveness, the researchers excluded infusion claims – which account for a large portion of total patient care costs for many disorders, he noted.
Drugs for MS historically have been expensive, ostensibly because of their high cost of development. In addition, the large and continued price increase that occurs long after these drugs have been approved remains unexplained, said Dr. Fox.
He noted that the study findings might not directly affect clinical practice because neurologists will continue prescribing medications they think are best for their patients. “Instead, I think this is a lesson to lawmakers about the massive error in the Medicare Modernization Act of 2003, where the federal government was prohibited from negotiating drug prices. If the seller is unfettered in setting a price, then no one should be surprised when the price rises,” Dr. Fox said.
Because many new drugs and new generic formulations for treating MS have become available during the past year, “repeating these types of economic studies for the period 2020-2025 will help us understand if generic competition – as well as new laws if they are passed – alter price,” he concluded.
The study was funded by the American Academy of Neurology, which publishes Neurology. Dr. de Havenon has received clinical research funding from AMAG Pharmaceuticals and Regeneron Pharmaceuticals. Dr. Fox receives consulting fees from many pharmaceutical companies involved in the development of therapies for MS.
A version of this article first appeared on Medscape.com.
FROM NEUROLOGY
Despite risks and warnings, CNS polypharmacy is prevalent among patients with dementia
, new research suggests.
Investigators found that 14% of these individuals were receiving CNS-active polypharmacy, defined as combinations of multiple psychotropic and opioid medications taken for more than 30 days.
“For most patients, the risks of these medications, particularly in combination, are almost certainly greater than the potential benefits,” said Donovan Maust, MD, associate director of the geriatric psychiatry program, University of Michigan, Ann Arbor.
The study was published online March 9 in JAMA.
Serious risks
Memory impairment is the cardinal feature of dementia, but behavioral and psychological symptoms, which can include apathy, delusions, and agitation, are common during all stages of illness and cause significant caregiver distress, the researchers noted.
They noted that there is a dearth of high-quality evidence to support prescribing these medications in this patient population, yet “clinicians regularly prescribe psychotropic medications to community-dwelling persons with dementia in rates that far exceed use in the general older adult population.”
The Beers Criteria, from the American Geriatrics Society, advise against the practice of CNS polypharmacy because of the significant increase in risk for falls as well as impaired cognition, cardiac conduction abnormalities, respiratory suppression, and death when polypharmacy involves opioids.
They note that previous studies from Europe of polypharmacy for patients with dementia have not included antiepileptic medications or opioids, so the true extent of CNS-active polypharmacy may be “significantly” underestimated.
To determine the prevalence of polypharmacy with CNS-active medications among community-dwelling older adults with dementia, the researchers analyzed data on prescription fills for nearly 1.2 million community-dwelling Medicare patients with dementia.
The primary outcome was the prevalence of CNS-active polypharmacy in 2018. They defined CNS-active polypharmacy as exposure to three or more medications for more than 30 consecutive days from the following drug classes: antidepressants, antipsychotics, antiepileptics, benzodiazepines, nonbenzodiazepines, benzodiazepine receptor agonist hypnotics, and opioids.
They found that roughly one in seven (13.9%) patients met criteria for CNS-active polypharmacy. Of those receiving a CNS-active polypharmacy regimen, 57.8% had been doing so for longer than 180 days, and 6.8% had been doing so for a year. Nearly 30% of patients were exposed to five or more medications, and 5.2% were exposed to five or more medication classes.
Conservative approach warranted
Nearly all (92%) patients taking three or more CNS-active medications were taking an antidepressant, “consistent with their place as the psychotropic class most commonly prescribed both to older adults overall and those with dementia,” the investigators noted.
There is minimal high-quality evidence to support the efficacy of antidepressants for the treatment of depression for patients with dementia, they pointed out.
Nearly half (47%) of patients who were taking three or more CNS-active medications received at least one antipsychotic, most often quetiapine. Antipsychotics are not approved for people with dementia but are often prescribed off label for agitation, anxiety, and sleep problems, the researchers noted.
Nearly two thirds (62%) of patients with dementia who were taking three or more CNS drugs were taking an antiepileptic (most commonly, gabapentin); 41%, benzodiazepines; 32%, opioids; and 6%, Z-drugs.
The most common polypharmacy class combination included at least one antidepressant, one antiepileptic, and one antipsychotic. These accounted for 12.9% of polypharmacy days.
Despite limited high-quality evidence of efficacy, the prescribing of psychotropic medications and opioids is “pervasive” for adults with dementia in the United States, the investigators noted.
“Especially given that older adults with dementia might not be able to convey side effects they are experiencing, I think clinicians should be more conservative in how they are prescribing these medications and skeptical about the potential for benefit,” said Dr. Maust.
Regarding study limitations, the researchers noted that prescription medication claims may have led to an overestimation of the exposure to polypharmacy, insofar as the prescriptions may have been filled but not taken or were taken only on an as-needed basis.
In addition, the investigators were unable to determine the appropriateness of the particular combinations used or to examine the specific harms associated with CNS-active polypharmacy.
A major clinical challenge
Weighing in on the results, Howard Fillit, MD, founding executive director and chief science officer of the Alzheimer’s Drug Discovery Foundation, said the study is important because polypharmacy is one of the “geriatric giants, and the question is, what do you do about it?”
Dr. Fillit said it is important to conduct a careful medication review for all older patients, “making sure that the use of each drug is appropriate. The most important thing is to define what is the appropriate utilization of these kinds of drugs. That goes for both overutilization or misuse of these drugs and underutilization, where people are undertreated for symptoms that can’t be managed by behavioral management, for example,” Dr. Fillit said.
Dr. Fillit also said the finding that about 14% of dementia patients were receiving three or more of these drugs “may not be an outrageous number, because these patients, especially as they get into moderate and severe stages of disease, can be incredibly difficult to manage.
“Very often, dementia patients have depression, and up to 90% will have agitation and even psychosis during the course of dementia. And many of these patients need these types of drugs,” said Dr. Fillit.
Echoing the authors, Dr. Fillit said a key limitation of the study is not knowing whether the prescribing was appropriate or not.
The study was supported by a grant from the National Institute on Aging. Dr. Maust and Dr. Fillit have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, new research suggests.
Investigators found that 14% of these individuals were receiving CNS-active polypharmacy, defined as combinations of multiple psychotropic and opioid medications taken for more than 30 days.
“For most patients, the risks of these medications, particularly in combination, are almost certainly greater than the potential benefits,” said Donovan Maust, MD, associate director of the geriatric psychiatry program, University of Michigan, Ann Arbor.
The study was published online March 9 in JAMA.
Serious risks
Memory impairment is the cardinal feature of dementia, but behavioral and psychological symptoms, which can include apathy, delusions, and agitation, are common during all stages of illness and cause significant caregiver distress, the researchers noted.
They noted that there is a dearth of high-quality evidence to support prescribing these medications in this patient population, yet “clinicians regularly prescribe psychotropic medications to community-dwelling persons with dementia in rates that far exceed use in the general older adult population.”
The Beers Criteria, from the American Geriatrics Society, advise against the practice of CNS polypharmacy because of the significant increase in risk for falls as well as impaired cognition, cardiac conduction abnormalities, respiratory suppression, and death when polypharmacy involves opioids.
They note that previous studies from Europe of polypharmacy for patients with dementia have not included antiepileptic medications or opioids, so the true extent of CNS-active polypharmacy may be “significantly” underestimated.
To determine the prevalence of polypharmacy with CNS-active medications among community-dwelling older adults with dementia, the researchers analyzed data on prescription fills for nearly 1.2 million community-dwelling Medicare patients with dementia.
The primary outcome was the prevalence of CNS-active polypharmacy in 2018. They defined CNS-active polypharmacy as exposure to three or more medications for more than 30 consecutive days from the following drug classes: antidepressants, antipsychotics, antiepileptics, benzodiazepines, nonbenzodiazepines, benzodiazepine receptor agonist hypnotics, and opioids.
They found that roughly one in seven (13.9%) patients met criteria for CNS-active polypharmacy. Of those receiving a CNS-active polypharmacy regimen, 57.8% had been doing so for longer than 180 days, and 6.8% had been doing so for a year. Nearly 30% of patients were exposed to five or more medications, and 5.2% were exposed to five or more medication classes.
Conservative approach warranted
Nearly all (92%) patients taking three or more CNS-active medications were taking an antidepressant, “consistent with their place as the psychotropic class most commonly prescribed both to older adults overall and those with dementia,” the investigators noted.
There is minimal high-quality evidence to support the efficacy of antidepressants for the treatment of depression for patients with dementia, they pointed out.
Nearly half (47%) of patients who were taking three or more CNS-active medications received at least one antipsychotic, most often quetiapine. Antipsychotics are not approved for people with dementia but are often prescribed off label for agitation, anxiety, and sleep problems, the researchers noted.
Nearly two thirds (62%) of patients with dementia who were taking three or more CNS drugs were taking an antiepileptic (most commonly, gabapentin); 41%, benzodiazepines; 32%, opioids; and 6%, Z-drugs.
The most common polypharmacy class combination included at least one antidepressant, one antiepileptic, and one antipsychotic. These accounted for 12.9% of polypharmacy days.
Despite limited high-quality evidence of efficacy, the prescribing of psychotropic medications and opioids is “pervasive” for adults with dementia in the United States, the investigators noted.
“Especially given that older adults with dementia might not be able to convey side effects they are experiencing, I think clinicians should be more conservative in how they are prescribing these medications and skeptical about the potential for benefit,” said Dr. Maust.
Regarding study limitations, the researchers noted that prescription medication claims may have led to an overestimation of the exposure to polypharmacy, insofar as the prescriptions may have been filled but not taken or were taken only on an as-needed basis.
In addition, the investigators were unable to determine the appropriateness of the particular combinations used or to examine the specific harms associated with CNS-active polypharmacy.
A major clinical challenge
Weighing in on the results, Howard Fillit, MD, founding executive director and chief science officer of the Alzheimer’s Drug Discovery Foundation, said the study is important because polypharmacy is one of the “geriatric giants, and the question is, what do you do about it?”
Dr. Fillit said it is important to conduct a careful medication review for all older patients, “making sure that the use of each drug is appropriate. The most important thing is to define what is the appropriate utilization of these kinds of drugs. That goes for both overutilization or misuse of these drugs and underutilization, where people are undertreated for symptoms that can’t be managed by behavioral management, for example,” Dr. Fillit said.
Dr. Fillit also said the finding that about 14% of dementia patients were receiving three or more of these drugs “may not be an outrageous number, because these patients, especially as they get into moderate and severe stages of disease, can be incredibly difficult to manage.
“Very often, dementia patients have depression, and up to 90% will have agitation and even psychosis during the course of dementia. And many of these patients need these types of drugs,” said Dr. Fillit.
Echoing the authors, Dr. Fillit said a key limitation of the study is not knowing whether the prescribing was appropriate or not.
The study was supported by a grant from the National Institute on Aging. Dr. Maust and Dr. Fillit have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, new research suggests.
Investigators found that 14% of these individuals were receiving CNS-active polypharmacy, defined as combinations of multiple psychotropic and opioid medications taken for more than 30 days.
“For most patients, the risks of these medications, particularly in combination, are almost certainly greater than the potential benefits,” said Donovan Maust, MD, associate director of the geriatric psychiatry program, University of Michigan, Ann Arbor.
The study was published online March 9 in JAMA.
Serious risks
Memory impairment is the cardinal feature of dementia, but behavioral and psychological symptoms, which can include apathy, delusions, and agitation, are common during all stages of illness and cause significant caregiver distress, the researchers noted.
They noted that there is a dearth of high-quality evidence to support prescribing these medications in this patient population, yet “clinicians regularly prescribe psychotropic medications to community-dwelling persons with dementia in rates that far exceed use in the general older adult population.”
The Beers Criteria, from the American Geriatrics Society, advise against the practice of CNS polypharmacy because of the significant increase in risk for falls as well as impaired cognition, cardiac conduction abnormalities, respiratory suppression, and death when polypharmacy involves opioids.
They note that previous studies from Europe of polypharmacy for patients with dementia have not included antiepileptic medications or opioids, so the true extent of CNS-active polypharmacy may be “significantly” underestimated.
To determine the prevalence of polypharmacy with CNS-active medications among community-dwelling older adults with dementia, the researchers analyzed data on prescription fills for nearly 1.2 million community-dwelling Medicare patients with dementia.
The primary outcome was the prevalence of CNS-active polypharmacy in 2018. They defined CNS-active polypharmacy as exposure to three or more medications for more than 30 consecutive days from the following drug classes: antidepressants, antipsychotics, antiepileptics, benzodiazepines, nonbenzodiazepines, benzodiazepine receptor agonist hypnotics, and opioids.
They found that roughly one in seven (13.9%) patients met criteria for CNS-active polypharmacy. Of those receiving a CNS-active polypharmacy regimen, 57.8% had been doing so for longer than 180 days, and 6.8% had been doing so for a year. Nearly 30% of patients were exposed to five or more medications, and 5.2% were exposed to five or more medication classes.
Conservative approach warranted
Nearly all (92%) patients taking three or more CNS-active medications were taking an antidepressant, “consistent with their place as the psychotropic class most commonly prescribed both to older adults overall and those with dementia,” the investigators noted.
There is minimal high-quality evidence to support the efficacy of antidepressants for the treatment of depression for patients with dementia, they pointed out.
Nearly half (47%) of patients who were taking three or more CNS-active medications received at least one antipsychotic, most often quetiapine. Antipsychotics are not approved for people with dementia but are often prescribed off label for agitation, anxiety, and sleep problems, the researchers noted.
Nearly two thirds (62%) of patients with dementia who were taking three or more CNS drugs were taking an antiepileptic (most commonly, gabapentin); 41%, benzodiazepines; 32%, opioids; and 6%, Z-drugs.
The most common polypharmacy class combination included at least one antidepressant, one antiepileptic, and one antipsychotic. These accounted for 12.9% of polypharmacy days.
Despite limited high-quality evidence of efficacy, the prescribing of psychotropic medications and opioids is “pervasive” for adults with dementia in the United States, the investigators noted.
“Especially given that older adults with dementia might not be able to convey side effects they are experiencing, I think clinicians should be more conservative in how they are prescribing these medications and skeptical about the potential for benefit,” said Dr. Maust.
Regarding study limitations, the researchers noted that prescription medication claims may have led to an overestimation of the exposure to polypharmacy, insofar as the prescriptions may have been filled but not taken or were taken only on an as-needed basis.
In addition, the investigators were unable to determine the appropriateness of the particular combinations used or to examine the specific harms associated with CNS-active polypharmacy.
A major clinical challenge
Weighing in on the results, Howard Fillit, MD, founding executive director and chief science officer of the Alzheimer’s Drug Discovery Foundation, said the study is important because polypharmacy is one of the “geriatric giants, and the question is, what do you do about it?”
Dr. Fillit said it is important to conduct a careful medication review for all older patients, “making sure that the use of each drug is appropriate. The most important thing is to define what is the appropriate utilization of these kinds of drugs. That goes for both overutilization or misuse of these drugs and underutilization, where people are undertreated for symptoms that can’t be managed by behavioral management, for example,” Dr. Fillit said.
Dr. Fillit also said the finding that about 14% of dementia patients were receiving three or more of these drugs “may not be an outrageous number, because these patients, especially as they get into moderate and severe stages of disease, can be incredibly difficult to manage.
“Very often, dementia patients have depression, and up to 90% will have agitation and even psychosis during the course of dementia. And many of these patients need these types of drugs,” said Dr. Fillit.
Echoing the authors, Dr. Fillit said a key limitation of the study is not knowing whether the prescribing was appropriate or not.
The study was supported by a grant from the National Institute on Aging. Dr. Maust and Dr. Fillit have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM JAMA
Novel Alzheimer’s drug slows cognitive decline in phase 2 trial
Results from the TRAILBLAZER-ALZ trial were presented at the 2021 International Conference on Alzheimer’s and Parkinson’s Diseases (AD/PD) and were simultaneously published online March 13 in the New England Journal of Medicine.
As previously reported by Medscape Medical News, topline results showed that donanemab slowed cognitive decline by 32% on the Integrated AD Rating Scale (iADRS) from baseline to 76 weeks relative to placebo.
The newly released detailed findings showed that “the use of donanemab resulted in a better composite score for cognition and for the ability to perform activities of daily living than placebo at 76 weeks, although results for secondary outcomes were mixed,” the investigators, with first author Mark A. Mintun, MD, an employee of Eli Lilly, reported.
Results revealed improvement in scores on the Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB) and the 13-item cognitive subscale of the AD Assessment Scale (ADAS-Cog13), but the differences between the two treatment groups were not significant. In addition, score changes on the AD Cooperative Study–Instrumental Activities of Daily Inventory (ADCS-iADL) and the Mini-Mental State Examination (MMSE) were not “substantial.”
However, the donanemab group did show an 85-centiloid greater reduction in amyloid plaque level at 76 weeks, as shown on PET, compared with the placebo group.
Proof of concept?
The humanized antibody donanemab, which was previously known as LY3002813, targets a modified form of deposited amyloid-beta (A-beta) peptide called N3pG.
The randomized, placebo-controlled, double-blind TRAILBLAZER-ALZ trial, which was described as a “phase 2 proof of concept trial” in the AD/PD program, was conducted at 56 sites in the United States and Canada and included 257 patients between the ages of 60 and 85 years (52% were women). PET confirmed tau and amyloid deposition in all participants.
The active treatment group (n = 131) was randomly assigned to receive donanemab 700 mg for three doses; after that, treatment was bumped up to 1,400 mg. Both the donanemab and placebo groups (n = 126) received treatment intravenously every 4 weeks for up to 72 weeks.
Participants also underwent F-florbetapir and F-flortaucipir PET scans at various timepoints and completed a slew of cognitive tests.
The study’s primary outcome measure was change between baseline and 76 weeks post treatment on composite score for cognition, as measured by the iADRS. The iADRS combines the ADAS-Cog13 and the ADCS-iADL.
This measure ranges from 0 to 144, with lower scores associated with greater cognitive impairment. Both treatment groups had an iADRS score of 106 at baseline.
More research needed
Results showed that the score change from baseline on the iADRS was –6.86 for the active treatment group vs –10.06 for the placebo group (group difference, 3.2; 95% confidence interval [CI], 0.12-6.27; P = .04). Although significant, “the trial was powered to show a 6-point difference,” which was not met, the investigators note.
Differences in score changes from baseline to 76 weeks for the treatment vs. placebo groups on the following secondary outcome measures were:
- CDR-SB: –0.36 (95% CI, –0.83 to –0.12).
- ADAS-Cog13: –1.86 (95% CI, –3.63 to –0.09).
- ADCS-iADL: 1.21 (95% CI, –0.77 to 3.2).
- MMSE: 0.64 (95% CI, –0.4 to 1.67).
The CDR-SB was designated as the first secondary outcome, and because it did not show a significant between-group difference, “the hierarchy failed and no definite conclusions can be drawn from data regarding the differences between groups in the change in the ADAS-Cog13,” the investigators wrote.
In addition, the differences in scores on the latter two secondary outcomes were not “substantial,” they reported.
However, at 76 weeks, the donanemab group showed a reduction of 84.13 centiloids in amyloid plaque level vs. an increase of 0.93 centiloids in the placebo group (between-group difference, 85.06 centiloids). At 24 weeks, the active-treatment group had a 67.83-centiloids greater reduction vs. the placebo group.
In addition, 40%, 59.8%, and 67.8% of the donanemab group achieved “amyloid-negative status” at 24, 52, and 76 weeks, respectively. Amyloid-negative status was defined as an amyloid plaque level of less than 24.1 centiloids.
Total incidence of death or serious adverse events did not differ significantly between the groups. However, the donanemab group had significantly more reports of ARIA-E compared with the placebo group (26.7% vs. 0.8%).
Overall, the researchers noted that more trials of longer duration with larger patient numbers are warranted “to further determine the efficacy and safety of donanemab” in AD.
Positive signal?
In a statement, Maria Carrillo, PhD, chief science officer for the Alzheimer’s Association, said the organization “is encouraged by this promising data.
“It is the first phase 2 Alzheimer’s trial to show positive results on a primary outcome measure related to memory and thinking,” Dr. Carrillo said. However, “more work needs to be done on this experimental drug therapy.”
Dr. Carrillo noted that because the trial was moderately sized and only 180 participants completed the study, “we look forward to the results of a second, larger phase 2 trial of this drug.”
Still, she added, there were several “novel and innovative aspects” in the way the study was conducted noting that it showcases the evolution of AD research.
“I’m hopeful for the future,” Dr. Carrillo said.
Also commenting on the results, Howard Fillit, MD, neuroscientist and founding executive director and chief science officer of the Alzheimer’s Drug Discovery Foundation, said the study showed “the pharmacology works” and that the drug did what it was supposed to do in terms of removing A-beta plaque.
“It also gave us a signal in a relatively small phase 2 study that there might be a modest cognitive benefit,” said Dr. Fillit, who was not involved with the research.
He noted that although the rate of decline slowing was statistically significant it remains to be seen whether this is clinically meaningful, particularly in light of the fact that the secondary outcome results were mixed.
“Basically, it was a positive study that probably needs to be followed by another, much larger study to get us to really see the benefit,” Dr. Fillit said.
Dr. Mintun is an employee of Eli Lilly, which funded the study. Dr. Carrillo and Dr. Fillit have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Results from the TRAILBLAZER-ALZ trial were presented at the 2021 International Conference on Alzheimer’s and Parkinson’s Diseases (AD/PD) and were simultaneously published online March 13 in the New England Journal of Medicine.
As previously reported by Medscape Medical News, topline results showed that donanemab slowed cognitive decline by 32% on the Integrated AD Rating Scale (iADRS) from baseline to 76 weeks relative to placebo.
The newly released detailed findings showed that “the use of donanemab resulted in a better composite score for cognition and for the ability to perform activities of daily living than placebo at 76 weeks, although results for secondary outcomes were mixed,” the investigators, with first author Mark A. Mintun, MD, an employee of Eli Lilly, reported.
Results revealed improvement in scores on the Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB) and the 13-item cognitive subscale of the AD Assessment Scale (ADAS-Cog13), but the differences between the two treatment groups were not significant. In addition, score changes on the AD Cooperative Study–Instrumental Activities of Daily Inventory (ADCS-iADL) and the Mini-Mental State Examination (MMSE) were not “substantial.”
However, the donanemab group did show an 85-centiloid greater reduction in amyloid plaque level at 76 weeks, as shown on PET, compared with the placebo group.
Proof of concept?
The humanized antibody donanemab, which was previously known as LY3002813, targets a modified form of deposited amyloid-beta (A-beta) peptide called N3pG.
The randomized, placebo-controlled, double-blind TRAILBLAZER-ALZ trial, which was described as a “phase 2 proof of concept trial” in the AD/PD program, was conducted at 56 sites in the United States and Canada and included 257 patients between the ages of 60 and 85 years (52% were women). PET confirmed tau and amyloid deposition in all participants.
The active treatment group (n = 131) was randomly assigned to receive donanemab 700 mg for three doses; after that, treatment was bumped up to 1,400 mg. Both the donanemab and placebo groups (n = 126) received treatment intravenously every 4 weeks for up to 72 weeks.
Participants also underwent F-florbetapir and F-flortaucipir PET scans at various timepoints and completed a slew of cognitive tests.
The study’s primary outcome measure was change between baseline and 76 weeks post treatment on composite score for cognition, as measured by the iADRS. The iADRS combines the ADAS-Cog13 and the ADCS-iADL.
This measure ranges from 0 to 144, with lower scores associated with greater cognitive impairment. Both treatment groups had an iADRS score of 106 at baseline.
More research needed
Results showed that the score change from baseline on the iADRS was –6.86 for the active treatment group vs –10.06 for the placebo group (group difference, 3.2; 95% confidence interval [CI], 0.12-6.27; P = .04). Although significant, “the trial was powered to show a 6-point difference,” which was not met, the investigators note.
Differences in score changes from baseline to 76 weeks for the treatment vs. placebo groups on the following secondary outcome measures were:
- CDR-SB: –0.36 (95% CI, –0.83 to –0.12).
- ADAS-Cog13: –1.86 (95% CI, –3.63 to –0.09).
- ADCS-iADL: 1.21 (95% CI, –0.77 to 3.2).
- MMSE: 0.64 (95% CI, –0.4 to 1.67).
The CDR-SB was designated as the first secondary outcome, and because it did not show a significant between-group difference, “the hierarchy failed and no definite conclusions can be drawn from data regarding the differences between groups in the change in the ADAS-Cog13,” the investigators wrote.
In addition, the differences in scores on the latter two secondary outcomes were not “substantial,” they reported.
However, at 76 weeks, the donanemab group showed a reduction of 84.13 centiloids in amyloid plaque level vs. an increase of 0.93 centiloids in the placebo group (between-group difference, 85.06 centiloids). At 24 weeks, the active-treatment group had a 67.83-centiloids greater reduction vs. the placebo group.
In addition, 40%, 59.8%, and 67.8% of the donanemab group achieved “amyloid-negative status” at 24, 52, and 76 weeks, respectively. Amyloid-negative status was defined as an amyloid plaque level of less than 24.1 centiloids.
Total incidence of death or serious adverse events did not differ significantly between the groups. However, the donanemab group had significantly more reports of ARIA-E compared with the placebo group (26.7% vs. 0.8%).
Overall, the researchers noted that more trials of longer duration with larger patient numbers are warranted “to further determine the efficacy and safety of donanemab” in AD.
Positive signal?
In a statement, Maria Carrillo, PhD, chief science officer for the Alzheimer’s Association, said the organization “is encouraged by this promising data.
“It is the first phase 2 Alzheimer’s trial to show positive results on a primary outcome measure related to memory and thinking,” Dr. Carrillo said. However, “more work needs to be done on this experimental drug therapy.”
Dr. Carrillo noted that because the trial was moderately sized and only 180 participants completed the study, “we look forward to the results of a second, larger phase 2 trial of this drug.”
Still, she added, there were several “novel and innovative aspects” in the way the study was conducted noting that it showcases the evolution of AD research.
“I’m hopeful for the future,” Dr. Carrillo said.
Also commenting on the results, Howard Fillit, MD, neuroscientist and founding executive director and chief science officer of the Alzheimer’s Drug Discovery Foundation, said the study showed “the pharmacology works” and that the drug did what it was supposed to do in terms of removing A-beta plaque.
“It also gave us a signal in a relatively small phase 2 study that there might be a modest cognitive benefit,” said Dr. Fillit, who was not involved with the research.
He noted that although the rate of decline slowing was statistically significant it remains to be seen whether this is clinically meaningful, particularly in light of the fact that the secondary outcome results were mixed.
“Basically, it was a positive study that probably needs to be followed by another, much larger study to get us to really see the benefit,” Dr. Fillit said.
Dr. Mintun is an employee of Eli Lilly, which funded the study. Dr. Carrillo and Dr. Fillit have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Results from the TRAILBLAZER-ALZ trial were presented at the 2021 International Conference on Alzheimer’s and Parkinson’s Diseases (AD/PD) and were simultaneously published online March 13 in the New England Journal of Medicine.
As previously reported by Medscape Medical News, topline results showed that donanemab slowed cognitive decline by 32% on the Integrated AD Rating Scale (iADRS) from baseline to 76 weeks relative to placebo.
The newly released detailed findings showed that “the use of donanemab resulted in a better composite score for cognition and for the ability to perform activities of daily living than placebo at 76 weeks, although results for secondary outcomes were mixed,” the investigators, with first author Mark A. Mintun, MD, an employee of Eli Lilly, reported.
Results revealed improvement in scores on the Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB) and the 13-item cognitive subscale of the AD Assessment Scale (ADAS-Cog13), but the differences between the two treatment groups were not significant. In addition, score changes on the AD Cooperative Study–Instrumental Activities of Daily Inventory (ADCS-iADL) and the Mini-Mental State Examination (MMSE) were not “substantial.”
However, the donanemab group did show an 85-centiloid greater reduction in amyloid plaque level at 76 weeks, as shown on PET, compared with the placebo group.
Proof of concept?
The humanized antibody donanemab, which was previously known as LY3002813, targets a modified form of deposited amyloid-beta (A-beta) peptide called N3pG.
The randomized, placebo-controlled, double-blind TRAILBLAZER-ALZ trial, which was described as a “phase 2 proof of concept trial” in the AD/PD program, was conducted at 56 sites in the United States and Canada and included 257 patients between the ages of 60 and 85 years (52% were women). PET confirmed tau and amyloid deposition in all participants.
The active treatment group (n = 131) was randomly assigned to receive donanemab 700 mg for three doses; after that, treatment was bumped up to 1,400 mg. Both the donanemab and placebo groups (n = 126) received treatment intravenously every 4 weeks for up to 72 weeks.
Participants also underwent F-florbetapir and F-flortaucipir PET scans at various timepoints and completed a slew of cognitive tests.
The study’s primary outcome measure was change between baseline and 76 weeks post treatment on composite score for cognition, as measured by the iADRS. The iADRS combines the ADAS-Cog13 and the ADCS-iADL.
This measure ranges from 0 to 144, with lower scores associated with greater cognitive impairment. Both treatment groups had an iADRS score of 106 at baseline.
More research needed
Results showed that the score change from baseline on the iADRS was –6.86 for the active treatment group vs –10.06 for the placebo group (group difference, 3.2; 95% confidence interval [CI], 0.12-6.27; P = .04). Although significant, “the trial was powered to show a 6-point difference,” which was not met, the investigators note.
Differences in score changes from baseline to 76 weeks for the treatment vs. placebo groups on the following secondary outcome measures were:
- CDR-SB: –0.36 (95% CI, –0.83 to –0.12).
- ADAS-Cog13: –1.86 (95% CI, –3.63 to –0.09).
- ADCS-iADL: 1.21 (95% CI, –0.77 to 3.2).
- MMSE: 0.64 (95% CI, –0.4 to 1.67).
The CDR-SB was designated as the first secondary outcome, and because it did not show a significant between-group difference, “the hierarchy failed and no definite conclusions can be drawn from data regarding the differences between groups in the change in the ADAS-Cog13,” the investigators wrote.
In addition, the differences in scores on the latter two secondary outcomes were not “substantial,” they reported.
However, at 76 weeks, the donanemab group showed a reduction of 84.13 centiloids in amyloid plaque level vs. an increase of 0.93 centiloids in the placebo group (between-group difference, 85.06 centiloids). At 24 weeks, the active-treatment group had a 67.83-centiloids greater reduction vs. the placebo group.
In addition, 40%, 59.8%, and 67.8% of the donanemab group achieved “amyloid-negative status” at 24, 52, and 76 weeks, respectively. Amyloid-negative status was defined as an amyloid plaque level of less than 24.1 centiloids.
Total incidence of death or serious adverse events did not differ significantly between the groups. However, the donanemab group had significantly more reports of ARIA-E compared with the placebo group (26.7% vs. 0.8%).
Overall, the researchers noted that more trials of longer duration with larger patient numbers are warranted “to further determine the efficacy and safety of donanemab” in AD.
Positive signal?
In a statement, Maria Carrillo, PhD, chief science officer for the Alzheimer’s Association, said the organization “is encouraged by this promising data.
“It is the first phase 2 Alzheimer’s trial to show positive results on a primary outcome measure related to memory and thinking,” Dr. Carrillo said. However, “more work needs to be done on this experimental drug therapy.”
Dr. Carrillo noted that because the trial was moderately sized and only 180 participants completed the study, “we look forward to the results of a second, larger phase 2 trial of this drug.”
Still, she added, there were several “novel and innovative aspects” in the way the study was conducted noting that it showcases the evolution of AD research.
“I’m hopeful for the future,” Dr. Carrillo said.
Also commenting on the results, Howard Fillit, MD, neuroscientist and founding executive director and chief science officer of the Alzheimer’s Drug Discovery Foundation, said the study showed “the pharmacology works” and that the drug did what it was supposed to do in terms of removing A-beta plaque.
“It also gave us a signal in a relatively small phase 2 study that there might be a modest cognitive benefit,” said Dr. Fillit, who was not involved with the research.
He noted that although the rate of decline slowing was statistically significant it remains to be seen whether this is clinically meaningful, particularly in light of the fact that the secondary outcome results were mixed.
“Basically, it was a positive study that probably needs to be followed by another, much larger study to get us to really see the benefit,” Dr. Fillit said.
Dr. Mintun is an employee of Eli Lilly, which funded the study. Dr. Carrillo and Dr. Fillit have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Sun exposure linked to reduced pediatric MS risk
, research shows. The use of sunscreen does not appear to affect the risk.
“This is the first study, as far as we are aware, to investigate the effect of sun exposure in pediatric MS,” first author Prince Sebastian, of the ANU Medical School, Australian National University, Canberra, said during a presentation at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
“In order to reduce the incidence of MS, parents should be encouraged to allow their children to spend at least 30 minutes outdoors in the sun every day, while using adequate sun protection,” Mr. Sebastian said.
“This is especially important for children with a family history of MS,” he said. As the findings show, “you can use adequate sun protection and still get the benefit of sun exposure in terms of MS risk reduction.”
Low sun exposure, exposure to ultraviolet light, and vitamin D have been well established as modifiable risk factors for MS in adults. However, research is lacking on the effect of these factors upon patients younger than 18 years who have pediatric MS, a less common form of the disease. Pediatric MS constitutes about 5% of all MS cases.
To investigate the issue, Mr. Sebastian and colleagues evaluated data on 332 patients with pediatric MS who were between the ages of 4 and 22 years. The patients were enrolled at 16 MS centers around the United States. They were compared by sex and age with 534 control persons aged 3-22 years who did not have MS.
For the patients with MS, the median disease duration was 7.3 months, and 63% were female. The median age of the patients was 15.9 years.
Compared with those who did not have MS, patients with MS were significantly less likely to have been exposed to cigarette smoke (17.8% vs. 14.2%). They were significantly more likely to be overweight (23.8% vs. 14.2%), and the median anti-VCA level was higher (3.7 vs. 2.2).
Those who were exposed to the sun during the most recent summer for a duration of 30 minutes to 1 hour daily, as determined on the basis of self-report or parent report, had a 2.6-fold reduced risk of having MS, compared with those who spent less than 30 minutes outdoors daily (odds ratio, 0.39; P < .05), after adjusting for age, sex, birth season, the child’s skin color, the mother’s education, smoke exposure, being overweight, and Epstein-Barr virus infection.
Sun exposure for 1-2 hours daily was associated with a 7.4-fold reduced risk for MS, compared with exposure of 30 minutes or less (OR, 0.13; P < .001).
The odds were similar for those with 2-3 hours of sun exposure (OR, 0.21; P < .001) and for those with more than 3 hours of daily exposure (OR, 0.14; P < .001), versus less than 30 minutes.
Mr. Sebastian and his team also assessed the role of summer ambient levels of UV light and whether such exposure conferred a similar degree of protection. The risk for MS was lower among those who were exposed to higher summer ambient UV levels than among those exposed to lower levels (OR, 0.80; P = .046).
He noted, “Based on the results, individuals residing in Florida (28° N) would have 20% lower odds of MS, compared with an individual residing in New York (40° N).”
Interestingly, median rates of the use of sun protection were similar for the participants with MS and those without MS (OR, 0.95), suggesting that the use of sunscreen did not reduce the protective effect of sun exposure.
“We predicted that greater use of protection would limit effective sun exposure and would therefore increase MS risk,” Mr. Sebastian said, “but we don’t see that, and it’s probably because someone who uses sun protection likely gets more sun exposure anyway.”
“Our results suggest that you can use adequate sun protection and still get most of the benefit in terms of MS prevention, which is quite encouraging,” he added.
For those with MS, median serum 25(OH)D levels were higher (27.7 ng/mL vs. 23.7 ng/mL; P < .001), but Mr. Sebastian noted that this difference was likely attributable to the use of vitamin D supplementation after an MS diagnosis. An important limitation of the study was a lack of data on supplementation.
Stronger effect of frequent sun protection
Previous studies have shown a link between sun exposure and MS. A study published in 2018 compared 2,251 patients with MS with 4,028 control persons who did not have MS. The participants were in Canada, Italy, and Norway.
In that study, for most of the patients with MS, the age of onset was older than 18 years. In that study, there was a nearly 50% increased risk among those with the lowest degree of summer sun exposure in comparison with those who had the highest level of exposure (risk ratio, 1.47).
Contrary to the current study, that study did show an effect of the use of sun protection – those with the lowest degree of sun exposure during summer and winter and the highest use of sun protection had the highest risk for MS. They had a 76% increased risk, compared with those who had the highest degree of sun exposure and the least use of sun protection (RR, 1.76).
Sandra Magalhaes, PhD, of the University of New Brunswick, Fredericton, Canada, who was first author on that study, noted that the new study of pediatric MS adds valuable evidence on the issue.
“This study is important, as it adds to the etiological literature on MS implicating relevance of sun exposure,” Dr. Magalhaes said.
“We have a number of studies that have demonstrated an important effect of reduced levels of sun exposure and increased risk of MS. However, these studies focus on adult-onset MS populations; rather, the new study adds to the existing literature, as it also implicates sun exposure in etiology of pediatric-onset MS,” she said.
Notably, their previous work, unlike the current study, showed that, among those who experienced low levels of sun exposure, the risk for MS was higher for those who used sunscreen frequently.
“Overall, in their limited time outdoors, use of sunscreen may further increase risk of MS, which makes sense, since limited time outdoors in less sun, adding sun protection means [exposure to] even less sun.”
The findings of both studies support the bulk of research indicating that sun exposure is beneficial with regard to MS.
“There is a need for promoting balanced safe sun practices to reduce disease burden, especially in countries and cultures where children spend a lot of time indoors,” Dr. Magalhaes said. “Sun exposure has a number of important physiological roles, including vitamin D synthesis but also immune system functioning.”
Mr. Sebastian and Dr. Magalhaes have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, research shows. The use of sunscreen does not appear to affect the risk.
“This is the first study, as far as we are aware, to investigate the effect of sun exposure in pediatric MS,” first author Prince Sebastian, of the ANU Medical School, Australian National University, Canberra, said during a presentation at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
“In order to reduce the incidence of MS, parents should be encouraged to allow their children to spend at least 30 minutes outdoors in the sun every day, while using adequate sun protection,” Mr. Sebastian said.
“This is especially important for children with a family history of MS,” he said. As the findings show, “you can use adequate sun protection and still get the benefit of sun exposure in terms of MS risk reduction.”
Low sun exposure, exposure to ultraviolet light, and vitamin D have been well established as modifiable risk factors for MS in adults. However, research is lacking on the effect of these factors upon patients younger than 18 years who have pediatric MS, a less common form of the disease. Pediatric MS constitutes about 5% of all MS cases.
To investigate the issue, Mr. Sebastian and colleagues evaluated data on 332 patients with pediatric MS who were between the ages of 4 and 22 years. The patients were enrolled at 16 MS centers around the United States. They were compared by sex and age with 534 control persons aged 3-22 years who did not have MS.
For the patients with MS, the median disease duration was 7.3 months, and 63% were female. The median age of the patients was 15.9 years.
Compared with those who did not have MS, patients with MS were significantly less likely to have been exposed to cigarette smoke (17.8% vs. 14.2%). They were significantly more likely to be overweight (23.8% vs. 14.2%), and the median anti-VCA level was higher (3.7 vs. 2.2).
Those who were exposed to the sun during the most recent summer for a duration of 30 minutes to 1 hour daily, as determined on the basis of self-report or parent report, had a 2.6-fold reduced risk of having MS, compared with those who spent less than 30 minutes outdoors daily (odds ratio, 0.39; P < .05), after adjusting for age, sex, birth season, the child’s skin color, the mother’s education, smoke exposure, being overweight, and Epstein-Barr virus infection.
Sun exposure for 1-2 hours daily was associated with a 7.4-fold reduced risk for MS, compared with exposure of 30 minutes or less (OR, 0.13; P < .001).
The odds were similar for those with 2-3 hours of sun exposure (OR, 0.21; P < .001) and for those with more than 3 hours of daily exposure (OR, 0.14; P < .001), versus less than 30 minutes.
Mr. Sebastian and his team also assessed the role of summer ambient levels of UV light and whether such exposure conferred a similar degree of protection. The risk for MS was lower among those who were exposed to higher summer ambient UV levels than among those exposed to lower levels (OR, 0.80; P = .046).
He noted, “Based on the results, individuals residing in Florida (28° N) would have 20% lower odds of MS, compared with an individual residing in New York (40° N).”
Interestingly, median rates of the use of sun protection were similar for the participants with MS and those without MS (OR, 0.95), suggesting that the use of sunscreen did not reduce the protective effect of sun exposure.
“We predicted that greater use of protection would limit effective sun exposure and would therefore increase MS risk,” Mr. Sebastian said, “but we don’t see that, and it’s probably because someone who uses sun protection likely gets more sun exposure anyway.”
“Our results suggest that you can use adequate sun protection and still get most of the benefit in terms of MS prevention, which is quite encouraging,” he added.
For those with MS, median serum 25(OH)D levels were higher (27.7 ng/mL vs. 23.7 ng/mL; P < .001), but Mr. Sebastian noted that this difference was likely attributable to the use of vitamin D supplementation after an MS diagnosis. An important limitation of the study was a lack of data on supplementation.
Stronger effect of frequent sun protection
Previous studies have shown a link between sun exposure and MS. A study published in 2018 compared 2,251 patients with MS with 4,028 control persons who did not have MS. The participants were in Canada, Italy, and Norway.
In that study, for most of the patients with MS, the age of onset was older than 18 years. In that study, there was a nearly 50% increased risk among those with the lowest degree of summer sun exposure in comparison with those who had the highest level of exposure (risk ratio, 1.47).
Contrary to the current study, that study did show an effect of the use of sun protection – those with the lowest degree of sun exposure during summer and winter and the highest use of sun protection had the highest risk for MS. They had a 76% increased risk, compared with those who had the highest degree of sun exposure and the least use of sun protection (RR, 1.76).
Sandra Magalhaes, PhD, of the University of New Brunswick, Fredericton, Canada, who was first author on that study, noted that the new study of pediatric MS adds valuable evidence on the issue.
“This study is important, as it adds to the etiological literature on MS implicating relevance of sun exposure,” Dr. Magalhaes said.
“We have a number of studies that have demonstrated an important effect of reduced levels of sun exposure and increased risk of MS. However, these studies focus on adult-onset MS populations; rather, the new study adds to the existing literature, as it also implicates sun exposure in etiology of pediatric-onset MS,” she said.
Notably, their previous work, unlike the current study, showed that, among those who experienced low levels of sun exposure, the risk for MS was higher for those who used sunscreen frequently.
“Overall, in their limited time outdoors, use of sunscreen may further increase risk of MS, which makes sense, since limited time outdoors in less sun, adding sun protection means [exposure to] even less sun.”
The findings of both studies support the bulk of research indicating that sun exposure is beneficial with regard to MS.
“There is a need for promoting balanced safe sun practices to reduce disease burden, especially in countries and cultures where children spend a lot of time indoors,” Dr. Magalhaes said. “Sun exposure has a number of important physiological roles, including vitamin D synthesis but also immune system functioning.”
Mr. Sebastian and Dr. Magalhaes have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, research shows. The use of sunscreen does not appear to affect the risk.
“This is the first study, as far as we are aware, to investigate the effect of sun exposure in pediatric MS,” first author Prince Sebastian, of the ANU Medical School, Australian National University, Canberra, said during a presentation at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
“In order to reduce the incidence of MS, parents should be encouraged to allow their children to spend at least 30 minutes outdoors in the sun every day, while using adequate sun protection,” Mr. Sebastian said.
“This is especially important for children with a family history of MS,” he said. As the findings show, “you can use adequate sun protection and still get the benefit of sun exposure in terms of MS risk reduction.”
Low sun exposure, exposure to ultraviolet light, and vitamin D have been well established as modifiable risk factors for MS in adults. However, research is lacking on the effect of these factors upon patients younger than 18 years who have pediatric MS, a less common form of the disease. Pediatric MS constitutes about 5% of all MS cases.
To investigate the issue, Mr. Sebastian and colleagues evaluated data on 332 patients with pediatric MS who were between the ages of 4 and 22 years. The patients were enrolled at 16 MS centers around the United States. They were compared by sex and age with 534 control persons aged 3-22 years who did not have MS.
For the patients with MS, the median disease duration was 7.3 months, and 63% were female. The median age of the patients was 15.9 years.
Compared with those who did not have MS, patients with MS were significantly less likely to have been exposed to cigarette smoke (17.8% vs. 14.2%). They were significantly more likely to be overweight (23.8% vs. 14.2%), and the median anti-VCA level was higher (3.7 vs. 2.2).
Those who were exposed to the sun during the most recent summer for a duration of 30 minutes to 1 hour daily, as determined on the basis of self-report or parent report, had a 2.6-fold reduced risk of having MS, compared with those who spent less than 30 minutes outdoors daily (odds ratio, 0.39; P < .05), after adjusting for age, sex, birth season, the child’s skin color, the mother’s education, smoke exposure, being overweight, and Epstein-Barr virus infection.
Sun exposure for 1-2 hours daily was associated with a 7.4-fold reduced risk for MS, compared with exposure of 30 minutes or less (OR, 0.13; P < .001).
The odds were similar for those with 2-3 hours of sun exposure (OR, 0.21; P < .001) and for those with more than 3 hours of daily exposure (OR, 0.14; P < .001), versus less than 30 minutes.
Mr. Sebastian and his team also assessed the role of summer ambient levels of UV light and whether such exposure conferred a similar degree of protection. The risk for MS was lower among those who were exposed to higher summer ambient UV levels than among those exposed to lower levels (OR, 0.80; P = .046).
He noted, “Based on the results, individuals residing in Florida (28° N) would have 20% lower odds of MS, compared with an individual residing in New York (40° N).”
Interestingly, median rates of the use of sun protection were similar for the participants with MS and those without MS (OR, 0.95), suggesting that the use of sunscreen did not reduce the protective effect of sun exposure.
“We predicted that greater use of protection would limit effective sun exposure and would therefore increase MS risk,” Mr. Sebastian said, “but we don’t see that, and it’s probably because someone who uses sun protection likely gets more sun exposure anyway.”
“Our results suggest that you can use adequate sun protection and still get most of the benefit in terms of MS prevention, which is quite encouraging,” he added.
For those with MS, median serum 25(OH)D levels were higher (27.7 ng/mL vs. 23.7 ng/mL; P < .001), but Mr. Sebastian noted that this difference was likely attributable to the use of vitamin D supplementation after an MS diagnosis. An important limitation of the study was a lack of data on supplementation.
Stronger effect of frequent sun protection
Previous studies have shown a link between sun exposure and MS. A study published in 2018 compared 2,251 patients with MS with 4,028 control persons who did not have MS. The participants were in Canada, Italy, and Norway.
In that study, for most of the patients with MS, the age of onset was older than 18 years. In that study, there was a nearly 50% increased risk among those with the lowest degree of summer sun exposure in comparison with those who had the highest level of exposure (risk ratio, 1.47).
Contrary to the current study, that study did show an effect of the use of sun protection – those with the lowest degree of sun exposure during summer and winter and the highest use of sun protection had the highest risk for MS. They had a 76% increased risk, compared with those who had the highest degree of sun exposure and the least use of sun protection (RR, 1.76).
Sandra Magalhaes, PhD, of the University of New Brunswick, Fredericton, Canada, who was first author on that study, noted that the new study of pediatric MS adds valuable evidence on the issue.
“This study is important, as it adds to the etiological literature on MS implicating relevance of sun exposure,” Dr. Magalhaes said.
“We have a number of studies that have demonstrated an important effect of reduced levels of sun exposure and increased risk of MS. However, these studies focus on adult-onset MS populations; rather, the new study adds to the existing literature, as it also implicates sun exposure in etiology of pediatric-onset MS,” she said.
Notably, their previous work, unlike the current study, showed that, among those who experienced low levels of sun exposure, the risk for MS was higher for those who used sunscreen frequently.
“Overall, in their limited time outdoors, use of sunscreen may further increase risk of MS, which makes sense, since limited time outdoors in less sun, adding sun protection means [exposure to] even less sun.”
The findings of both studies support the bulk of research indicating that sun exposure is beneficial with regard to MS.
“There is a need for promoting balanced safe sun practices to reduce disease burden, especially in countries and cultures where children spend a lot of time indoors,” Dr. Magalhaes said. “Sun exposure has a number of important physiological roles, including vitamin D synthesis but also immune system functioning.”
Mr. Sebastian and Dr. Magalhaes have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM ACTRIMS FORUM 2021
ERRATUM
In the January 2019 article “Migraine: Expanding our Tx arsenal” (J Fam Pract. 2019;68:10-14,16-24), Table 2: Establishing the differential diagnosis of headache provided information that was incorrectly categorized. The table should not have included “Temporal arteritis” as a trigger for a headache caused by infection. Rather, the table should have listed “Temporal arteritis” among the triggers for a headache caused by an autoimmune disorder. In addition, “Acute and chronic sinusitis” and “Meningitis” should not have been listed as triggers for a headache with an iatrogenic or intoxication cause. Rather, they should have been the only triggers attributed to headaches with an infectious origin. The revised table can be found here.
In the January 2019 article “Migraine: Expanding our Tx arsenal” (J Fam Pract. 2019;68:10-14,16-24), Table 2: Establishing the differential diagnosis of headache provided information that was incorrectly categorized. The table should not have included “Temporal arteritis” as a trigger for a headache caused by infection. Rather, the table should have listed “Temporal arteritis” among the triggers for a headache caused by an autoimmune disorder. In addition, “Acute and chronic sinusitis” and “Meningitis” should not have been listed as triggers for a headache with an iatrogenic or intoxication cause. Rather, they should have been the only triggers attributed to headaches with an infectious origin. The revised table can be found here.
In the January 2019 article “Migraine: Expanding our Tx arsenal” (J Fam Pract. 2019;68:10-14,16-24), Table 2: Establishing the differential diagnosis of headache provided information that was incorrectly categorized. The table should not have included “Temporal arteritis” as a trigger for a headache caused by infection. Rather, the table should have listed “Temporal arteritis” among the triggers for a headache caused by an autoimmune disorder. In addition, “Acute and chronic sinusitis” and “Meningitis” should not have been listed as triggers for a headache with an iatrogenic or intoxication cause. Rather, they should have been the only triggers attributed to headaches with an infectious origin. The revised table can be found here.