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Progressive disability in MS explained?
Results from a retrospective study show that complete resolution of brain lesions on MRI was more common among patients with myelin-oligodendrocyte-glycoprotein-IgG-associated disorder (MOGAD). Complete resolution occurred in 72% of the group with MOGAD, versus 17% of those with MS and 14% of those with aquaporin-4-positive neuromyelitis optica spectrum disorder (AQP4+ NMOSD).
“What we found was, with MOGAD in particular, many of the lesions resolved completely,” said co-investigator Eoin Flanagan, MBBCh, neurologist, Mayo Clinic, Rochester, Minn. “That fits with MOGAD having a fairly good prognosis and patients not developing much long-term disability with that disease,” he said.
The researchers also studied whether scarring may account for the absence of slowly progressive disability among patients with AQP4+ NMOSD and MOGAD compared with patients with MS. “The differences in scarring that we found will help physicians distinguish these three diseases more easily to aid in diagnosis. More importantly, our findings improve our understanding of the mechanisms of nerve damage in these three diseases and may suggest an important role of such scars in the development of long-term disability in MS,” Dr. Flanagan said in a statement.
The findings were published online July 14 in Neurology.
Lesion evolution
MOGAD, AQP4+ NMOSD, and MS are inflammatory demyelinating disorders that share certain manifestations. However, these disorders differ in important ways, including the severity of attacks and their clinical course.
Although patients with MOGAD and AQP4+ NMOSD generally have severe attacks that bring major disability, the clinical course of these disorders is better than initial attacks would suggest. In contrast, patients with MS have comparatively mild attacks that are associated with a high risk for progressive disability.
Previous studies of these demyelinating disorders have examined the shape and location of lesions but not change over time. Observing these lesions’ development and resolution could provide information about disease course and influence treatment and the monitoring of disease activity, the current researchers noted.
They retrospectively identified consecutive patients with MOGAD, AQP4+ NMOSD, or MS who presented to the Mayo Clinic between January 2000 and August 2019. Data from a cohort of patients with MS in Olmsted County, Minn., were also included.
Eligible participants had experienced a first brain or myelitis attack, had undergone MRI of the brain or spinal cord within 6 weeks of the attack nadir, and had undergone a follow-up MRI 6 months after the attack.
Patients who experienced a relapse during follow-up in the same region as the initial attack were excluded. Concomitant brain and myelitis attacks were analyzed separately.
An index lesion was identified for each patient. The index lesion was defined as an acute lesion that provided an anatomic explanation for the clinical symptoms. If multiple lesions were present, the largest of them was chosen as the index lesion. MRIs were examined by neuroradiologists who were blinded to patients’ diagnoses and serology results.
Among the 156 participants, 67 had MS (76% women), 51 had AQP4+ NMOSD (80% women), and 38 had MOGAD (45% women). The median age at first attack for the groups was 37, 53, and 25 years, respectively.
In addition, 63 patients had relapsing-remitting MS, two had a single attack of progressive MS, and two had clinically isolated syndrome. No patients with NMOSD or MOGAD had developed progressive disease at final follow-up.
Participants experienced a total of 81 brain attacks and 91 myelitis attacks. Sixteen patients had experienced both a brain attack and a myelitis attack.
Symptoms corresponding to the index brain lesions were brainstem or cerebellar syndrome (56), encephalopathy or focal symptoms (12), or combinations of these (13). Among patients with an index myelitis attack, 31 had cervical involvement, 21 had thoracic involvement, and 39 had involvement of both regions.
Complete resolution
Results showed that 72% of patients with MOGAD experienced complete resolution of the brain index lesion, compared with 17% of patients with MS and 14% of patients with NMOSD (P < .001).
Similarly, 79% of the MOGAD group experienced complete resolution of the myelitis index lesion, compared with no members of the MS or NMOSD groups (P < .001 for both comparisons).
Complete resolution of all T2-abnormalities at MRI follow-up was more common in the MOGAD group than in the other two groups.
For brain attacks, complete resolution occurred in 39% of patients with MOGAD, 10% of patients with NMOSD, and 5% of patients with MS. For spinal cord attacks, complete resolution occurred in 79% of patients with MOGAD, versus none of the patients with NMOSD or MS.
Median reduction in T2 lesion area on follow-up axial brain MRI was larger in patients with MOGAD (213 mm2) than in those with NMOSD (104 mm2; P = .02) or MS (36 mm2; P < .001).
Reductions in lesion size on sagittal spine MRI follow-up were similar between the MOGAD (262 mm2) and NMOSD (309 mm2) groups; both experienced greater reductions than the MS group (23 mm2; P < .001).
Lesion prevention
Dr. Flanagan noted that the diagnosis of MOGAD is based on a test for MOG antibody, but sometimes false positive results occur. “A single follow-up MRI can be useful, showing that if all the lesions went away, you would be more confident that it would be MOGAD,” he said.
Study participants with MS experienced less lesion healing than the patients with MOGAD or NMOSD.
“We now have very effective medications in MS to prevent new lesions from occurring,” Dr. Flanagan said. The study highlights the importance of lesion prevention, “because when you do get a lesion, it does tend to stay and not recover completely,” he added.
He noted that the resolution of lesions in the study population may reflect remyelination. Future research examining whether remyelination is more efficient in MOGAD than in the other disorders could possibly lead to new approaches for MS treatment, said Dr. Flanagan.
“Maybe some of the MOGAD lesions are from edema. When we use steroids, that tends to resolve and not leave a scar. So, that’s another possibility. We’d like to better understand that,” he said.
Differences in pathology
Commenting on the findings, Bruce Cree, MD, PhD, professor of neurology, Weill Institute for Neurosciences, University of California, San Francisco, noted that the study is one of the first to systematically examine and compare MRI lesion evolution across three disease states.
“What they put their finger on are differences in the fundamental pathology of these three different diseases,” said Dr. Cree, who was not involved with the research.
The study’s cross-sectional comparison was its main strength, he noted.
“The main weakness, from my point of view, is that in these three disorders, optic nerve involvement is very common,” Dr. Cree said. “In this paper, no analysis of optic nerve lesions by MRI was performed.”
The researchers acknowledge this limitation and explain that they did not have consistent, dedicated orbital imaging for such an analysis.
Dr. Cree noted that the findings also provide a reminder that the pathogenesis of MOGAD is not yet clear.
“We know that these anti-MOG antibodies are associated with this demyelinating disorder, but whether these antibodies have a pathogenic role has yet to be clearly demonstrated,” said Dr. Cree. “What is actually going on within these lesions [is also] not fully understood.”
The finding that MOGAD lesions can resolve completely suggests that repair mechanisms are at work within the brain and spinal cord, he noted.
Being able to understand and comprehend what those mechanisms at work are and why they occur in MOGAD but not in NMOSD or MS “would be of enormous clinical advantage,” he said.
The current study also highlights the importance of incorporating imaging into clinical trials that study these rare disorders, especially serial imaging for MOGAD, Dr. Cree added.
This imaging is vital not only for developing new treatments but also for understanding the clinical impact of a given medication. “We really need rigorous imaging to be applied to these rare disorders, just as was done with MS,” Dr. Cree concluded.
The study was funded by the National Institute of Neurological Disorders and Stroke. Dr. Flanagan has received research support from MedImmune/Viela Bio. Dr. Cree is working with two of the researchers on the steering committee for the N-MOmentum trial of inebilizumab in patients with NMOSD. He has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Results from a retrospective study show that complete resolution of brain lesions on MRI was more common among patients with myelin-oligodendrocyte-glycoprotein-IgG-associated disorder (MOGAD). Complete resolution occurred in 72% of the group with MOGAD, versus 17% of those with MS and 14% of those with aquaporin-4-positive neuromyelitis optica spectrum disorder (AQP4+ NMOSD).
“What we found was, with MOGAD in particular, many of the lesions resolved completely,” said co-investigator Eoin Flanagan, MBBCh, neurologist, Mayo Clinic, Rochester, Minn. “That fits with MOGAD having a fairly good prognosis and patients not developing much long-term disability with that disease,” he said.
The researchers also studied whether scarring may account for the absence of slowly progressive disability among patients with AQP4+ NMOSD and MOGAD compared with patients with MS. “The differences in scarring that we found will help physicians distinguish these three diseases more easily to aid in diagnosis. More importantly, our findings improve our understanding of the mechanisms of nerve damage in these three diseases and may suggest an important role of such scars in the development of long-term disability in MS,” Dr. Flanagan said in a statement.
The findings were published online July 14 in Neurology.
Lesion evolution
MOGAD, AQP4+ NMOSD, and MS are inflammatory demyelinating disorders that share certain manifestations. However, these disorders differ in important ways, including the severity of attacks and their clinical course.
Although patients with MOGAD and AQP4+ NMOSD generally have severe attacks that bring major disability, the clinical course of these disorders is better than initial attacks would suggest. In contrast, patients with MS have comparatively mild attacks that are associated with a high risk for progressive disability.
Previous studies of these demyelinating disorders have examined the shape and location of lesions but not change over time. Observing these lesions’ development and resolution could provide information about disease course and influence treatment and the monitoring of disease activity, the current researchers noted.
They retrospectively identified consecutive patients with MOGAD, AQP4+ NMOSD, or MS who presented to the Mayo Clinic between January 2000 and August 2019. Data from a cohort of patients with MS in Olmsted County, Minn., were also included.
Eligible participants had experienced a first brain or myelitis attack, had undergone MRI of the brain or spinal cord within 6 weeks of the attack nadir, and had undergone a follow-up MRI 6 months after the attack.
Patients who experienced a relapse during follow-up in the same region as the initial attack were excluded. Concomitant brain and myelitis attacks were analyzed separately.
An index lesion was identified for each patient. The index lesion was defined as an acute lesion that provided an anatomic explanation for the clinical symptoms. If multiple lesions were present, the largest of them was chosen as the index lesion. MRIs were examined by neuroradiologists who were blinded to patients’ diagnoses and serology results.
Among the 156 participants, 67 had MS (76% women), 51 had AQP4+ NMOSD (80% women), and 38 had MOGAD (45% women). The median age at first attack for the groups was 37, 53, and 25 years, respectively.
In addition, 63 patients had relapsing-remitting MS, two had a single attack of progressive MS, and two had clinically isolated syndrome. No patients with NMOSD or MOGAD had developed progressive disease at final follow-up.
Participants experienced a total of 81 brain attacks and 91 myelitis attacks. Sixteen patients had experienced both a brain attack and a myelitis attack.
Symptoms corresponding to the index brain lesions were brainstem or cerebellar syndrome (56), encephalopathy or focal symptoms (12), or combinations of these (13). Among patients with an index myelitis attack, 31 had cervical involvement, 21 had thoracic involvement, and 39 had involvement of both regions.
Complete resolution
Results showed that 72% of patients with MOGAD experienced complete resolution of the brain index lesion, compared with 17% of patients with MS and 14% of patients with NMOSD (P < .001).
Similarly, 79% of the MOGAD group experienced complete resolution of the myelitis index lesion, compared with no members of the MS or NMOSD groups (P < .001 for both comparisons).
Complete resolution of all T2-abnormalities at MRI follow-up was more common in the MOGAD group than in the other two groups.
For brain attacks, complete resolution occurred in 39% of patients with MOGAD, 10% of patients with NMOSD, and 5% of patients with MS. For spinal cord attacks, complete resolution occurred in 79% of patients with MOGAD, versus none of the patients with NMOSD or MS.
Median reduction in T2 lesion area on follow-up axial brain MRI was larger in patients with MOGAD (213 mm2) than in those with NMOSD (104 mm2; P = .02) or MS (36 mm2; P < .001).
Reductions in lesion size on sagittal spine MRI follow-up were similar between the MOGAD (262 mm2) and NMOSD (309 mm2) groups; both experienced greater reductions than the MS group (23 mm2; P < .001).
Lesion prevention
Dr. Flanagan noted that the diagnosis of MOGAD is based on a test for MOG antibody, but sometimes false positive results occur. “A single follow-up MRI can be useful, showing that if all the lesions went away, you would be more confident that it would be MOGAD,” he said.
Study participants with MS experienced less lesion healing than the patients with MOGAD or NMOSD.
“We now have very effective medications in MS to prevent new lesions from occurring,” Dr. Flanagan said. The study highlights the importance of lesion prevention, “because when you do get a lesion, it does tend to stay and not recover completely,” he added.
He noted that the resolution of lesions in the study population may reflect remyelination. Future research examining whether remyelination is more efficient in MOGAD than in the other disorders could possibly lead to new approaches for MS treatment, said Dr. Flanagan.
“Maybe some of the MOGAD lesions are from edema. When we use steroids, that tends to resolve and not leave a scar. So, that’s another possibility. We’d like to better understand that,” he said.
Differences in pathology
Commenting on the findings, Bruce Cree, MD, PhD, professor of neurology, Weill Institute for Neurosciences, University of California, San Francisco, noted that the study is one of the first to systematically examine and compare MRI lesion evolution across three disease states.
“What they put their finger on are differences in the fundamental pathology of these three different diseases,” said Dr. Cree, who was not involved with the research.
The study’s cross-sectional comparison was its main strength, he noted.
“The main weakness, from my point of view, is that in these three disorders, optic nerve involvement is very common,” Dr. Cree said. “In this paper, no analysis of optic nerve lesions by MRI was performed.”
The researchers acknowledge this limitation and explain that they did not have consistent, dedicated orbital imaging for such an analysis.
Dr. Cree noted that the findings also provide a reminder that the pathogenesis of MOGAD is not yet clear.
“We know that these anti-MOG antibodies are associated with this demyelinating disorder, but whether these antibodies have a pathogenic role has yet to be clearly demonstrated,” said Dr. Cree. “What is actually going on within these lesions [is also] not fully understood.”
The finding that MOGAD lesions can resolve completely suggests that repair mechanisms are at work within the brain and spinal cord, he noted.
Being able to understand and comprehend what those mechanisms at work are and why they occur in MOGAD but not in NMOSD or MS “would be of enormous clinical advantage,” he said.
The current study also highlights the importance of incorporating imaging into clinical trials that study these rare disorders, especially serial imaging for MOGAD, Dr. Cree added.
This imaging is vital not only for developing new treatments but also for understanding the clinical impact of a given medication. “We really need rigorous imaging to be applied to these rare disorders, just as was done with MS,” Dr. Cree concluded.
The study was funded by the National Institute of Neurological Disorders and Stroke. Dr. Flanagan has received research support from MedImmune/Viela Bio. Dr. Cree is working with two of the researchers on the steering committee for the N-MOmentum trial of inebilizumab in patients with NMOSD. He has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Results from a retrospective study show that complete resolution of brain lesions on MRI was more common among patients with myelin-oligodendrocyte-glycoprotein-IgG-associated disorder (MOGAD). Complete resolution occurred in 72% of the group with MOGAD, versus 17% of those with MS and 14% of those with aquaporin-4-positive neuromyelitis optica spectrum disorder (AQP4+ NMOSD).
“What we found was, with MOGAD in particular, many of the lesions resolved completely,” said co-investigator Eoin Flanagan, MBBCh, neurologist, Mayo Clinic, Rochester, Minn. “That fits with MOGAD having a fairly good prognosis and patients not developing much long-term disability with that disease,” he said.
The researchers also studied whether scarring may account for the absence of slowly progressive disability among patients with AQP4+ NMOSD and MOGAD compared with patients with MS. “The differences in scarring that we found will help physicians distinguish these three diseases more easily to aid in diagnosis. More importantly, our findings improve our understanding of the mechanisms of nerve damage in these three diseases and may suggest an important role of such scars in the development of long-term disability in MS,” Dr. Flanagan said in a statement.
The findings were published online July 14 in Neurology.
Lesion evolution
MOGAD, AQP4+ NMOSD, and MS are inflammatory demyelinating disorders that share certain manifestations. However, these disorders differ in important ways, including the severity of attacks and their clinical course.
Although patients with MOGAD and AQP4+ NMOSD generally have severe attacks that bring major disability, the clinical course of these disorders is better than initial attacks would suggest. In contrast, patients with MS have comparatively mild attacks that are associated with a high risk for progressive disability.
Previous studies of these demyelinating disorders have examined the shape and location of lesions but not change over time. Observing these lesions’ development and resolution could provide information about disease course and influence treatment and the monitoring of disease activity, the current researchers noted.
They retrospectively identified consecutive patients with MOGAD, AQP4+ NMOSD, or MS who presented to the Mayo Clinic between January 2000 and August 2019. Data from a cohort of patients with MS in Olmsted County, Minn., were also included.
Eligible participants had experienced a first brain or myelitis attack, had undergone MRI of the brain or spinal cord within 6 weeks of the attack nadir, and had undergone a follow-up MRI 6 months after the attack.
Patients who experienced a relapse during follow-up in the same region as the initial attack were excluded. Concomitant brain and myelitis attacks were analyzed separately.
An index lesion was identified for each patient. The index lesion was defined as an acute lesion that provided an anatomic explanation for the clinical symptoms. If multiple lesions were present, the largest of them was chosen as the index lesion. MRIs were examined by neuroradiologists who were blinded to patients’ diagnoses and serology results.
Among the 156 participants, 67 had MS (76% women), 51 had AQP4+ NMOSD (80% women), and 38 had MOGAD (45% women). The median age at first attack for the groups was 37, 53, and 25 years, respectively.
In addition, 63 patients had relapsing-remitting MS, two had a single attack of progressive MS, and two had clinically isolated syndrome. No patients with NMOSD or MOGAD had developed progressive disease at final follow-up.
Participants experienced a total of 81 brain attacks and 91 myelitis attacks. Sixteen patients had experienced both a brain attack and a myelitis attack.
Symptoms corresponding to the index brain lesions were brainstem or cerebellar syndrome (56), encephalopathy or focal symptoms (12), or combinations of these (13). Among patients with an index myelitis attack, 31 had cervical involvement, 21 had thoracic involvement, and 39 had involvement of both regions.
Complete resolution
Results showed that 72% of patients with MOGAD experienced complete resolution of the brain index lesion, compared with 17% of patients with MS and 14% of patients with NMOSD (P < .001).
Similarly, 79% of the MOGAD group experienced complete resolution of the myelitis index lesion, compared with no members of the MS or NMOSD groups (P < .001 for both comparisons).
Complete resolution of all T2-abnormalities at MRI follow-up was more common in the MOGAD group than in the other two groups.
For brain attacks, complete resolution occurred in 39% of patients with MOGAD, 10% of patients with NMOSD, and 5% of patients with MS. For spinal cord attacks, complete resolution occurred in 79% of patients with MOGAD, versus none of the patients with NMOSD or MS.
Median reduction in T2 lesion area on follow-up axial brain MRI was larger in patients with MOGAD (213 mm2) than in those with NMOSD (104 mm2; P = .02) or MS (36 mm2; P < .001).
Reductions in lesion size on sagittal spine MRI follow-up were similar between the MOGAD (262 mm2) and NMOSD (309 mm2) groups; both experienced greater reductions than the MS group (23 mm2; P < .001).
Lesion prevention
Dr. Flanagan noted that the diagnosis of MOGAD is based on a test for MOG antibody, but sometimes false positive results occur. “A single follow-up MRI can be useful, showing that if all the lesions went away, you would be more confident that it would be MOGAD,” he said.
Study participants with MS experienced less lesion healing than the patients with MOGAD or NMOSD.
“We now have very effective medications in MS to prevent new lesions from occurring,” Dr. Flanagan said. The study highlights the importance of lesion prevention, “because when you do get a lesion, it does tend to stay and not recover completely,” he added.
He noted that the resolution of lesions in the study population may reflect remyelination. Future research examining whether remyelination is more efficient in MOGAD than in the other disorders could possibly lead to new approaches for MS treatment, said Dr. Flanagan.
“Maybe some of the MOGAD lesions are from edema. When we use steroids, that tends to resolve and not leave a scar. So, that’s another possibility. We’d like to better understand that,” he said.
Differences in pathology
Commenting on the findings, Bruce Cree, MD, PhD, professor of neurology, Weill Institute for Neurosciences, University of California, San Francisco, noted that the study is one of the first to systematically examine and compare MRI lesion evolution across three disease states.
“What they put their finger on are differences in the fundamental pathology of these three different diseases,” said Dr. Cree, who was not involved with the research.
The study’s cross-sectional comparison was its main strength, he noted.
“The main weakness, from my point of view, is that in these three disorders, optic nerve involvement is very common,” Dr. Cree said. “In this paper, no analysis of optic nerve lesions by MRI was performed.”
The researchers acknowledge this limitation and explain that they did not have consistent, dedicated orbital imaging for such an analysis.
Dr. Cree noted that the findings also provide a reminder that the pathogenesis of MOGAD is not yet clear.
“We know that these anti-MOG antibodies are associated with this demyelinating disorder, but whether these antibodies have a pathogenic role has yet to be clearly demonstrated,” said Dr. Cree. “What is actually going on within these lesions [is also] not fully understood.”
The finding that MOGAD lesions can resolve completely suggests that repair mechanisms are at work within the brain and spinal cord, he noted.
Being able to understand and comprehend what those mechanisms at work are and why they occur in MOGAD but not in NMOSD or MS “would be of enormous clinical advantage,” he said.
The current study also highlights the importance of incorporating imaging into clinical trials that study these rare disorders, especially serial imaging for MOGAD, Dr. Cree added.
This imaging is vital not only for developing new treatments but also for understanding the clinical impact of a given medication. “We really need rigorous imaging to be applied to these rare disorders, just as was done with MS,” Dr. Cree concluded.
The study was funded by the National Institute of Neurological Disorders and Stroke. Dr. Flanagan has received research support from MedImmune/Viela Bio. Dr. Cree is working with two of the researchers on the steering committee for the N-MOmentum trial of inebilizumab in patients with NMOSD. He has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
From Neurology
Young Black and White athletes differ in how they recover from concussions
, according to a new study on racial differences in concussion recovery.
“The findings from this study provide novel evidence that the recovery experience following sport-related concussion likely differs between Black and White athletes, and understanding these differences may serve to provide better and more personalized intervention and management strategies,” wrote lead author Aaron M. Yengo-Kahn, MD, of Vanderbilt University Medical Center in Nashville, Tenn. The study was published in the Journal of Neurosurgery: Pediatrics.
To assess how postconcussion experiences and recovery time differ among young White and Black athletes, the researchers launched a retrospective cohort study of youths between the ages of 12 and 23 from the middle Tennessee, northern Alabama, and southern Kentucky regions who had been treated for sport-related concussion. Using data from the Vanderbilt Sports Concussion Center’s outcome registry, they examined the records of 247 student-athletes, 211 of whom were White and 36 of whom were Black.
The majority of the athletes were male – 58% of the White group and 78% of the Black group – and their average age across groups was roughly 16 years. Thirty-three percent of the Black athletes were on public insurance, compared with just 6% of the White athletes, and 41% of the Black athletes lived in low–median income areas while 55% of the White athletes lived in areas with a high median income. Approximately 90% of each group played contact sports.
The median time to symptom resolution was 21 days (interquartile range, 10.5-61.0) for White athletes but just 12.3 days (IQR, 6.8-28.0) for Black athletes. Multivariable regression confirmed that Black athletes reached asymptomatic status sooner than White athletes (hazard ratio, 1.497; 95% confidence interval, 1.014-2.209; P = .042). “The observed shorter symptom resolution among the Black athletes may be explained by a complex interplay among race, concussion knowledge, attitudes toward sport-related concussion, reporting behavior, and sociodemographic disparities,” the authors noted.
The median time until returning to school post injury was 2 school days (IQR, 0-5) for White athletes and 0 school days (IQR, 0-2) for Black athletes. After multivariable analysis, being Black was indeed associated with returning to school sooner, compared with being White (HR, 1.522; 95% CI, 1.02-2,27; P = .040). Being Black was also associated with being less likely to a report a change in daily activity post concussion (odds ratio, 0.368; 95% CI, 0.136-0.996; P = .049).
Adding race to research
To make headway toward understanding race’s impact on concussion research, the authors proposed three immediate steps: Work directly with schools instead of clinics or emergency departments, match the diversity of study cohorts with the racial makeup of the surrounding community, and consider race as a covariate during study design.
“In our work with concussions, there is very little reported on race or racism or how racism affects how patients are navigating these spaces,” said coauthor Jessica Wallace, PhD, of the department of health science at the University of Alabama in Tuscaloosa, Ala., in an interview. “But we have so many athletes at the youth level, adolescent level, even the collegiate level; it’s such a diverse array of patients. We need to have data representative of all of our groups so that we know where we need to be intentional about reducing disparities and closing gaps.”
Dr. Wallace, who recently authored a study on the underreporting of concussions among Black and White high school athletes, emphasized the need for concussion research to be a true collaboration across disciplines.
“I approach this work from this public health and athletic training lens, whereas a lot of my collaborators are in neurosurgery and neurology,” she said. “Moving forward, we as a scientific clinical community have to do interdisciplinary work and be very intentional about how we go about closing these gaps. We have to recognize that there are differences in knowledge and in care, and they’re unacceptable, and we have to work collaboratively in providing resources to communities equitably to decrease them.”
The authors acknowledged their study’s limitations, including the retrospective nature of the study, using zip codes to determine median household income, and an unbalanced number of White and Black athletes. They did add, however, that the ratio of participants “generally aligns with census data in the surrounding metropolitan and county areas.” That said, they also surmised that the scarcity of Black athletes could indicate a deeper disparity in health care system usage and asked future researchers to “consider enrolling athletes directly from schools rather than from within the concussion clinic only.”
Dr. Yengo-Kahn disclosed holding a compensated position on the scientific advisory board of BlinkTBI, but the authors noted that the company had no role in the study and its products were not used. No other conflicts of interest were reported.
, according to a new study on racial differences in concussion recovery.
“The findings from this study provide novel evidence that the recovery experience following sport-related concussion likely differs between Black and White athletes, and understanding these differences may serve to provide better and more personalized intervention and management strategies,” wrote lead author Aaron M. Yengo-Kahn, MD, of Vanderbilt University Medical Center in Nashville, Tenn. The study was published in the Journal of Neurosurgery: Pediatrics.
To assess how postconcussion experiences and recovery time differ among young White and Black athletes, the researchers launched a retrospective cohort study of youths between the ages of 12 and 23 from the middle Tennessee, northern Alabama, and southern Kentucky regions who had been treated for sport-related concussion. Using data from the Vanderbilt Sports Concussion Center’s outcome registry, they examined the records of 247 student-athletes, 211 of whom were White and 36 of whom were Black.
The majority of the athletes were male – 58% of the White group and 78% of the Black group – and their average age across groups was roughly 16 years. Thirty-three percent of the Black athletes were on public insurance, compared with just 6% of the White athletes, and 41% of the Black athletes lived in low–median income areas while 55% of the White athletes lived in areas with a high median income. Approximately 90% of each group played contact sports.
The median time to symptom resolution was 21 days (interquartile range, 10.5-61.0) for White athletes but just 12.3 days (IQR, 6.8-28.0) for Black athletes. Multivariable regression confirmed that Black athletes reached asymptomatic status sooner than White athletes (hazard ratio, 1.497; 95% confidence interval, 1.014-2.209; P = .042). “The observed shorter symptom resolution among the Black athletes may be explained by a complex interplay among race, concussion knowledge, attitudes toward sport-related concussion, reporting behavior, and sociodemographic disparities,” the authors noted.
The median time until returning to school post injury was 2 school days (IQR, 0-5) for White athletes and 0 school days (IQR, 0-2) for Black athletes. After multivariable analysis, being Black was indeed associated with returning to school sooner, compared with being White (HR, 1.522; 95% CI, 1.02-2,27; P = .040). Being Black was also associated with being less likely to a report a change in daily activity post concussion (odds ratio, 0.368; 95% CI, 0.136-0.996; P = .049).
Adding race to research
To make headway toward understanding race’s impact on concussion research, the authors proposed three immediate steps: Work directly with schools instead of clinics or emergency departments, match the diversity of study cohorts with the racial makeup of the surrounding community, and consider race as a covariate during study design.
“In our work with concussions, there is very little reported on race or racism or how racism affects how patients are navigating these spaces,” said coauthor Jessica Wallace, PhD, of the department of health science at the University of Alabama in Tuscaloosa, Ala., in an interview. “But we have so many athletes at the youth level, adolescent level, even the collegiate level; it’s such a diverse array of patients. We need to have data representative of all of our groups so that we know where we need to be intentional about reducing disparities and closing gaps.”
Dr. Wallace, who recently authored a study on the underreporting of concussions among Black and White high school athletes, emphasized the need for concussion research to be a true collaboration across disciplines.
“I approach this work from this public health and athletic training lens, whereas a lot of my collaborators are in neurosurgery and neurology,” she said. “Moving forward, we as a scientific clinical community have to do interdisciplinary work and be very intentional about how we go about closing these gaps. We have to recognize that there are differences in knowledge and in care, and they’re unacceptable, and we have to work collaboratively in providing resources to communities equitably to decrease them.”
The authors acknowledged their study’s limitations, including the retrospective nature of the study, using zip codes to determine median household income, and an unbalanced number of White and Black athletes. They did add, however, that the ratio of participants “generally aligns with census data in the surrounding metropolitan and county areas.” That said, they also surmised that the scarcity of Black athletes could indicate a deeper disparity in health care system usage and asked future researchers to “consider enrolling athletes directly from schools rather than from within the concussion clinic only.”
Dr. Yengo-Kahn disclosed holding a compensated position on the scientific advisory board of BlinkTBI, but the authors noted that the company had no role in the study and its products were not used. No other conflicts of interest were reported.
, according to a new study on racial differences in concussion recovery.
“The findings from this study provide novel evidence that the recovery experience following sport-related concussion likely differs between Black and White athletes, and understanding these differences may serve to provide better and more personalized intervention and management strategies,” wrote lead author Aaron M. Yengo-Kahn, MD, of Vanderbilt University Medical Center in Nashville, Tenn. The study was published in the Journal of Neurosurgery: Pediatrics.
To assess how postconcussion experiences and recovery time differ among young White and Black athletes, the researchers launched a retrospective cohort study of youths between the ages of 12 and 23 from the middle Tennessee, northern Alabama, and southern Kentucky regions who had been treated for sport-related concussion. Using data from the Vanderbilt Sports Concussion Center’s outcome registry, they examined the records of 247 student-athletes, 211 of whom were White and 36 of whom were Black.
The majority of the athletes were male – 58% of the White group and 78% of the Black group – and their average age across groups was roughly 16 years. Thirty-three percent of the Black athletes were on public insurance, compared with just 6% of the White athletes, and 41% of the Black athletes lived in low–median income areas while 55% of the White athletes lived in areas with a high median income. Approximately 90% of each group played contact sports.
The median time to symptom resolution was 21 days (interquartile range, 10.5-61.0) for White athletes but just 12.3 days (IQR, 6.8-28.0) for Black athletes. Multivariable regression confirmed that Black athletes reached asymptomatic status sooner than White athletes (hazard ratio, 1.497; 95% confidence interval, 1.014-2.209; P = .042). “The observed shorter symptom resolution among the Black athletes may be explained by a complex interplay among race, concussion knowledge, attitudes toward sport-related concussion, reporting behavior, and sociodemographic disparities,” the authors noted.
The median time until returning to school post injury was 2 school days (IQR, 0-5) for White athletes and 0 school days (IQR, 0-2) for Black athletes. After multivariable analysis, being Black was indeed associated with returning to school sooner, compared with being White (HR, 1.522; 95% CI, 1.02-2,27; P = .040). Being Black was also associated with being less likely to a report a change in daily activity post concussion (odds ratio, 0.368; 95% CI, 0.136-0.996; P = .049).
Adding race to research
To make headway toward understanding race’s impact on concussion research, the authors proposed three immediate steps: Work directly with schools instead of clinics or emergency departments, match the diversity of study cohorts with the racial makeup of the surrounding community, and consider race as a covariate during study design.
“In our work with concussions, there is very little reported on race or racism or how racism affects how patients are navigating these spaces,” said coauthor Jessica Wallace, PhD, of the department of health science at the University of Alabama in Tuscaloosa, Ala., in an interview. “But we have so many athletes at the youth level, adolescent level, even the collegiate level; it’s such a diverse array of patients. We need to have data representative of all of our groups so that we know where we need to be intentional about reducing disparities and closing gaps.”
Dr. Wallace, who recently authored a study on the underreporting of concussions among Black and White high school athletes, emphasized the need for concussion research to be a true collaboration across disciplines.
“I approach this work from this public health and athletic training lens, whereas a lot of my collaborators are in neurosurgery and neurology,” she said. “Moving forward, we as a scientific clinical community have to do interdisciplinary work and be very intentional about how we go about closing these gaps. We have to recognize that there are differences in knowledge and in care, and they’re unacceptable, and we have to work collaboratively in providing resources to communities equitably to decrease them.”
The authors acknowledged their study’s limitations, including the retrospective nature of the study, using zip codes to determine median household income, and an unbalanced number of White and Black athletes. They did add, however, that the ratio of participants “generally aligns with census data in the surrounding metropolitan and county areas.” That said, they also surmised that the scarcity of Black athletes could indicate a deeper disparity in health care system usage and asked future researchers to “consider enrolling athletes directly from schools rather than from within the concussion clinic only.”
Dr. Yengo-Kahn disclosed holding a compensated position on the scientific advisory board of BlinkTBI, but the authors noted that the company had no role in the study and its products were not used. No other conflicts of interest were reported.
FROM THE JOURNAL OF NEUROSURGERY: PEDIATRICS
Atogepant reduces migraine days: ADVANCE trial results published
full results from a phase 3 trial suggest.
AbbVie, the company developing the oral therapy, announced topline results of the ADVANCE trial of atogepant last year. Safety results were presented in April at the 2021 annual meeting of the American Academy of Neurology.
The full results were published online Aug. 19 in the New England Journal of Medicine ahead of the upcoming target action date of the U.S. Food and Drug Administration.
The multicenter study included nearly 900 patients who were randomly assigned to receive either placebo or one of three doses of atogepant for 12 weeks. The mean number of monthly migraine days decreased by about 4 for all three doses of the active treatment, compared with a reduction of 2.5 days with placebo.
“Overall, this study showed us that atogepant was safe and surprisingly seems to be pretty effective regardless of the dose,” said lead author Jessica Ailani, MD, director of MedStar Georgetown Headache Center and associate professor of neurology at Georgetown University, Washington.
All doses effective
The study included 873 patients with episodic migraine with or without aura. Patients who were not assigned to the placebo control group received either 10 mg, 30 mg, or 60 mg of atogepant once daily.
After a 4-week screening period, all patients received treatment for 12 weeks and then entered a 4-week safety follow-up period. In total, the participants completed eight scheduled clinical visits.
The mean reduction from baseline in the mean number of migraine days per month was 3.7 with the 10-mg dose of atogepant, 3.9 with the 30-mg dose, 4.2 with the 60-mg dose, and 2.5 with placebo. The differences between each active dose and placebo was statistically significant (P < .001).
Treatment with the CGRP inhibitor was also associated with a reduction in the mean number of headache days per month. The mean reduction from baseline was 3.9 days for the 10-mg dose, 4.0 days for the 30-mg dose, 4.2 days for the 60-mg dose, and 2.5 days for placebo (P < .001 for all comparisons with placebo).
In addition, for 55.6% of the 10-mg group, 58.7% of the 30-mg group, 60.8% of the 60-mg group, and 29.0% of the control group, there was a reduction of at least 50% in the 3-month average number of migraine days per month (P < .001 for each vs. placebo).
The most commonly reported adverse events (AEs) among patients who received atogepant were constipation (6.9%-7.7% across doses), nausea (4.4%-6.1%), and upper respiratory tract infection (1.4%-3.9%). Frequency of AEs did not differ between the active-treatment groups and the control group, and no relationships between AEs and atogepant dose were observed.
Multidose flexibility
“Side effects were pretty even across the board,” said Dr. Ailani. She noted that the reported AEs were expected because of atogepant’s mechanism of action. In addition, the rate of discontinuation in the study was low.
The proportion of participants who experienced a reduction in monthly migraine days of at least 50% grew as time passed. “By the end of this study, your chance of having a greater than 50% response is about 75%,” Dr. Ailani said.
“Imagine telling your patient, ‘You stick on this drug for 3 months, and I can almost guarantee you that you’re going to get better,’” she added.
Although the treatment has no drug-drug contraindications, drug-drug interactions may occur. “The availability of various doses would allow clinicians to adjust treatment to avoid potential drug-drug interactions,” said Dr. Ailani. “That multidose flexibility is very important.”
An FDA decision on atogepant could be made in the coming months. “I’m hopeful, as a clinician, that it is positive news, because we really have waited a long time for something like this,” Dr. Ailani said.
“You can easily identify patients who would do well on this medication,” she added.
In a different study of atogepant among patients with chronic migraine, there were recruitment delays because of the pandemic. That study is now almost complete, Dr. Ailani reported.
“Well-conducted study”
Commenting on the findings, Kathleen B. Digre, MD, chief of the division of headache and neuro-ophthalmology at the University of Utah Health, Salt Lake City, expressed enthusiasm for the experimental drug. “I’m excited to see another treatment modality for migraine,” said Dr. Digre, who was not involved with the research. “It was a very well-conducted study,” she added.
The treatment arms were almost identical in regard to disease severity, and all the doses showed an effect. Although the difference in reduction of monthly migraine days in comparison with placebo was numerically small, “for people who have frequent migraine, it’s important,” Dr. Digre said.
The results for atogepant should be viewed in a larger context, however. “Even though it’s a treatment that works better than placebo for well-matched controls, it may not be a medication that everybody’s going to respond to,” she noted. “And we can’t generalize it for some of the most disabled people, which is for chronic migraine,” she said.
It is significant that the study was published in the New England Journal of Medicine, Dr. Digre noted. “Sometimes migraine is dismissed as not important and not affecting people’s lives,” she said. “That makes me very happy to see migraine being taken seriously by our major journals.”
In addition, she noted that the prospects for FDA approval of atogepant seem favorable. “I’m hopeful that they will approve it, because it’s got a low side-effect profile, plus it’s effective.”
Migraine-specific preventive therapy has emerged only in the past few years. “I’m so excited to see this surge of preventive medicine for migraine,” Dr. Digre said. “It’s so important, because we see so many people who are disabled by migraine,” she added.
The study was funded by Allergan before atogepant was acquired by AbbVie. Dr. Ailani has received honoraria from AbbVie for consulting, has received compensation from Allergan and AbbVie for participating in a speakers’ bureau, and has received clinical trial grants from Allergan. Dr. Digre has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
full results from a phase 3 trial suggest.
AbbVie, the company developing the oral therapy, announced topline results of the ADVANCE trial of atogepant last year. Safety results were presented in April at the 2021 annual meeting of the American Academy of Neurology.
The full results were published online Aug. 19 in the New England Journal of Medicine ahead of the upcoming target action date of the U.S. Food and Drug Administration.
The multicenter study included nearly 900 patients who were randomly assigned to receive either placebo or one of three doses of atogepant for 12 weeks. The mean number of monthly migraine days decreased by about 4 for all three doses of the active treatment, compared with a reduction of 2.5 days with placebo.
“Overall, this study showed us that atogepant was safe and surprisingly seems to be pretty effective regardless of the dose,” said lead author Jessica Ailani, MD, director of MedStar Georgetown Headache Center and associate professor of neurology at Georgetown University, Washington.
All doses effective
The study included 873 patients with episodic migraine with or without aura. Patients who were not assigned to the placebo control group received either 10 mg, 30 mg, or 60 mg of atogepant once daily.
After a 4-week screening period, all patients received treatment for 12 weeks and then entered a 4-week safety follow-up period. In total, the participants completed eight scheduled clinical visits.
The mean reduction from baseline in the mean number of migraine days per month was 3.7 with the 10-mg dose of atogepant, 3.9 with the 30-mg dose, 4.2 with the 60-mg dose, and 2.5 with placebo. The differences between each active dose and placebo was statistically significant (P < .001).
Treatment with the CGRP inhibitor was also associated with a reduction in the mean number of headache days per month. The mean reduction from baseline was 3.9 days for the 10-mg dose, 4.0 days for the 30-mg dose, 4.2 days for the 60-mg dose, and 2.5 days for placebo (P < .001 for all comparisons with placebo).
In addition, for 55.6% of the 10-mg group, 58.7% of the 30-mg group, 60.8% of the 60-mg group, and 29.0% of the control group, there was a reduction of at least 50% in the 3-month average number of migraine days per month (P < .001 for each vs. placebo).
The most commonly reported adverse events (AEs) among patients who received atogepant were constipation (6.9%-7.7% across doses), nausea (4.4%-6.1%), and upper respiratory tract infection (1.4%-3.9%). Frequency of AEs did not differ between the active-treatment groups and the control group, and no relationships between AEs and atogepant dose were observed.
Multidose flexibility
“Side effects were pretty even across the board,” said Dr. Ailani. She noted that the reported AEs were expected because of atogepant’s mechanism of action. In addition, the rate of discontinuation in the study was low.
The proportion of participants who experienced a reduction in monthly migraine days of at least 50% grew as time passed. “By the end of this study, your chance of having a greater than 50% response is about 75%,” Dr. Ailani said.
“Imagine telling your patient, ‘You stick on this drug for 3 months, and I can almost guarantee you that you’re going to get better,’” she added.
Although the treatment has no drug-drug contraindications, drug-drug interactions may occur. “The availability of various doses would allow clinicians to adjust treatment to avoid potential drug-drug interactions,” said Dr. Ailani. “That multidose flexibility is very important.”
An FDA decision on atogepant could be made in the coming months. “I’m hopeful, as a clinician, that it is positive news, because we really have waited a long time for something like this,” Dr. Ailani said.
“You can easily identify patients who would do well on this medication,” she added.
In a different study of atogepant among patients with chronic migraine, there were recruitment delays because of the pandemic. That study is now almost complete, Dr. Ailani reported.
“Well-conducted study”
Commenting on the findings, Kathleen B. Digre, MD, chief of the division of headache and neuro-ophthalmology at the University of Utah Health, Salt Lake City, expressed enthusiasm for the experimental drug. “I’m excited to see another treatment modality for migraine,” said Dr. Digre, who was not involved with the research. “It was a very well-conducted study,” she added.
The treatment arms were almost identical in regard to disease severity, and all the doses showed an effect. Although the difference in reduction of monthly migraine days in comparison with placebo was numerically small, “for people who have frequent migraine, it’s important,” Dr. Digre said.
The results for atogepant should be viewed in a larger context, however. “Even though it’s a treatment that works better than placebo for well-matched controls, it may not be a medication that everybody’s going to respond to,” she noted. “And we can’t generalize it for some of the most disabled people, which is for chronic migraine,” she said.
It is significant that the study was published in the New England Journal of Medicine, Dr. Digre noted. “Sometimes migraine is dismissed as not important and not affecting people’s lives,” she said. “That makes me very happy to see migraine being taken seriously by our major journals.”
In addition, she noted that the prospects for FDA approval of atogepant seem favorable. “I’m hopeful that they will approve it, because it’s got a low side-effect profile, plus it’s effective.”
Migraine-specific preventive therapy has emerged only in the past few years. “I’m so excited to see this surge of preventive medicine for migraine,” Dr. Digre said. “It’s so important, because we see so many people who are disabled by migraine,” she added.
The study was funded by Allergan before atogepant was acquired by AbbVie. Dr. Ailani has received honoraria from AbbVie for consulting, has received compensation from Allergan and AbbVie for participating in a speakers’ bureau, and has received clinical trial grants from Allergan. Dr. Digre has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
full results from a phase 3 trial suggest.
AbbVie, the company developing the oral therapy, announced topline results of the ADVANCE trial of atogepant last year. Safety results were presented in April at the 2021 annual meeting of the American Academy of Neurology.
The full results were published online Aug. 19 in the New England Journal of Medicine ahead of the upcoming target action date of the U.S. Food and Drug Administration.
The multicenter study included nearly 900 patients who were randomly assigned to receive either placebo or one of three doses of atogepant for 12 weeks. The mean number of monthly migraine days decreased by about 4 for all three doses of the active treatment, compared with a reduction of 2.5 days with placebo.
“Overall, this study showed us that atogepant was safe and surprisingly seems to be pretty effective regardless of the dose,” said lead author Jessica Ailani, MD, director of MedStar Georgetown Headache Center and associate professor of neurology at Georgetown University, Washington.
All doses effective
The study included 873 patients with episodic migraine with or without aura. Patients who were not assigned to the placebo control group received either 10 mg, 30 mg, or 60 mg of atogepant once daily.
After a 4-week screening period, all patients received treatment for 12 weeks and then entered a 4-week safety follow-up period. In total, the participants completed eight scheduled clinical visits.
The mean reduction from baseline in the mean number of migraine days per month was 3.7 with the 10-mg dose of atogepant, 3.9 with the 30-mg dose, 4.2 with the 60-mg dose, and 2.5 with placebo. The differences between each active dose and placebo was statistically significant (P < .001).
Treatment with the CGRP inhibitor was also associated with a reduction in the mean number of headache days per month. The mean reduction from baseline was 3.9 days for the 10-mg dose, 4.0 days for the 30-mg dose, 4.2 days for the 60-mg dose, and 2.5 days for placebo (P < .001 for all comparisons with placebo).
In addition, for 55.6% of the 10-mg group, 58.7% of the 30-mg group, 60.8% of the 60-mg group, and 29.0% of the control group, there was a reduction of at least 50% in the 3-month average number of migraine days per month (P < .001 for each vs. placebo).
The most commonly reported adverse events (AEs) among patients who received atogepant were constipation (6.9%-7.7% across doses), nausea (4.4%-6.1%), and upper respiratory tract infection (1.4%-3.9%). Frequency of AEs did not differ between the active-treatment groups and the control group, and no relationships between AEs and atogepant dose were observed.
Multidose flexibility
“Side effects were pretty even across the board,” said Dr. Ailani. She noted that the reported AEs were expected because of atogepant’s mechanism of action. In addition, the rate of discontinuation in the study was low.
The proportion of participants who experienced a reduction in monthly migraine days of at least 50% grew as time passed. “By the end of this study, your chance of having a greater than 50% response is about 75%,” Dr. Ailani said.
“Imagine telling your patient, ‘You stick on this drug for 3 months, and I can almost guarantee you that you’re going to get better,’” she added.
Although the treatment has no drug-drug contraindications, drug-drug interactions may occur. “The availability of various doses would allow clinicians to adjust treatment to avoid potential drug-drug interactions,” said Dr. Ailani. “That multidose flexibility is very important.”
An FDA decision on atogepant could be made in the coming months. “I’m hopeful, as a clinician, that it is positive news, because we really have waited a long time for something like this,” Dr. Ailani said.
“You can easily identify patients who would do well on this medication,” she added.
In a different study of atogepant among patients with chronic migraine, there were recruitment delays because of the pandemic. That study is now almost complete, Dr. Ailani reported.
“Well-conducted study”
Commenting on the findings, Kathleen B. Digre, MD, chief of the division of headache and neuro-ophthalmology at the University of Utah Health, Salt Lake City, expressed enthusiasm for the experimental drug. “I’m excited to see another treatment modality for migraine,” said Dr. Digre, who was not involved with the research. “It was a very well-conducted study,” she added.
The treatment arms were almost identical in regard to disease severity, and all the doses showed an effect. Although the difference in reduction of monthly migraine days in comparison with placebo was numerically small, “for people who have frequent migraine, it’s important,” Dr. Digre said.
The results for atogepant should be viewed in a larger context, however. “Even though it’s a treatment that works better than placebo for well-matched controls, it may not be a medication that everybody’s going to respond to,” she noted. “And we can’t generalize it for some of the most disabled people, which is for chronic migraine,” she said.
It is significant that the study was published in the New England Journal of Medicine, Dr. Digre noted. “Sometimes migraine is dismissed as not important and not affecting people’s lives,” she said. “That makes me very happy to see migraine being taken seriously by our major journals.”
In addition, she noted that the prospects for FDA approval of atogepant seem favorable. “I’m hopeful that they will approve it, because it’s got a low side-effect profile, plus it’s effective.”
Migraine-specific preventive therapy has emerged only in the past few years. “I’m so excited to see this surge of preventive medicine for migraine,” Dr. Digre said. “It’s so important, because we see so many people who are disabled by migraine,” she added.
The study was funded by Allergan before atogepant was acquired by AbbVie. Dr. Ailani has received honoraria from AbbVie for consulting, has received compensation from Allergan and AbbVie for participating in a speakers’ bureau, and has received clinical trial grants from Allergan. Dr. Digre has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Anxiety, inactivity linked to cognitive impairment in Parkinson’s
Parkinson’s disease patients who develop anxiety early in their disease are at risk for reduced physical activity, which promotes further anxiety and cognitive decline, data from nearly 500 individuals show.
Anxiety occurs in 20%-60% of Parkinson’s disease (PD) patients but often goes undiagnosed, wrote Jacob D. Jones, PhD, of California State University, San Bernardino, and colleagues.
“Anxiety can attenuate motivation to engage in physical activity leading to more anxiety and other negative cognitive outcomes,” although physical activity has been shown to improve cognitive function in PD patients, they said. However, physical activity as a mediator between anxiety and cognitive function in PD has not been well studied, they noted.
In a study published in Mental Health and Physical Activity Participants were followed for up to 5 years and completed neuropsychological tests, tests of motor severity, and self-reports on anxiety and physical activity. Anxiety was assessed using the State-Trait Anxiety Inventory-Trait (STAI-T) subscale. Physical activity was assessed using the Physical Activity Scale for the Elderly (PASE). Motor severity was assessed using the Unified Parkinson’s Disease Rating Scale-Part III (UPDRS). The average age of the participants was 61 years, 65% were men, and 96% were White.
Using a direct-effect model, the researchers found that individuals whose anxiety increased during the study period also showed signs of cognitive decline. A significant between-person effect showed that individuals who were generally more anxious also scored lower on cognitive tests over the 5-year study period.
In a mediation model computed with structural equation modeling, physical activity mediated the link between anxiety and cognition, most notably household activity.
“There was a significant within-person association between anxiety and household activities, meaning that individuals who became more anxious over the 5-year study also became less active in the home,” reported Dr. Jones and colleagues.
However, no significant indirect effect was noted regarding the between-person findings of the impact of physical activity on anxiety and cognitive decline. Although more severe anxiety was associated with less activity, cognitive performance was not associated with either type of physical activity.
The presence of a within-person effect “suggests that reductions in physical activity, specifically within the first 5 years of disease onset, may be detrimental to mental health,” the researchers emphasized. Given that the study population was newly diagnosed with PD “it is likely the within-person terms are more sensitive to changes in anxiety, physical activity, and cognition that are more directly the result of the PD process, as opposed to lifestyle/preexisting traits,” they said.
The study findings were limited by several factors, including the use of self-reports to measure physical activity, and the lack of granular information about the details of physical activity, the researchers noted. Another limitation was the inclusion of only newly diagnosed PD patients, which might limit generalizability.
“Future research is warranted to understand if other modes, intensities, or complexities of physical activity impact individuals with PD in a different manner in relation to cognition,” they said.
Dr. Jones and colleagues had no disclosures. The PPMI is supported by the Michael J. Fox Foundation for Parkinson’s Research and funding partners, including numerous pharmaceutical companies.
Parkinson’s disease patients who develop anxiety early in their disease are at risk for reduced physical activity, which promotes further anxiety and cognitive decline, data from nearly 500 individuals show.
Anxiety occurs in 20%-60% of Parkinson’s disease (PD) patients but often goes undiagnosed, wrote Jacob D. Jones, PhD, of California State University, San Bernardino, and colleagues.
“Anxiety can attenuate motivation to engage in physical activity leading to more anxiety and other negative cognitive outcomes,” although physical activity has been shown to improve cognitive function in PD patients, they said. However, physical activity as a mediator between anxiety and cognitive function in PD has not been well studied, they noted.
In a study published in Mental Health and Physical Activity Participants were followed for up to 5 years and completed neuropsychological tests, tests of motor severity, and self-reports on anxiety and physical activity. Anxiety was assessed using the State-Trait Anxiety Inventory-Trait (STAI-T) subscale. Physical activity was assessed using the Physical Activity Scale for the Elderly (PASE). Motor severity was assessed using the Unified Parkinson’s Disease Rating Scale-Part III (UPDRS). The average age of the participants was 61 years, 65% were men, and 96% were White.
Using a direct-effect model, the researchers found that individuals whose anxiety increased during the study period also showed signs of cognitive decline. A significant between-person effect showed that individuals who were generally more anxious also scored lower on cognitive tests over the 5-year study period.
In a mediation model computed with structural equation modeling, physical activity mediated the link between anxiety and cognition, most notably household activity.
“There was a significant within-person association between anxiety and household activities, meaning that individuals who became more anxious over the 5-year study also became less active in the home,” reported Dr. Jones and colleagues.
However, no significant indirect effect was noted regarding the between-person findings of the impact of physical activity on anxiety and cognitive decline. Although more severe anxiety was associated with less activity, cognitive performance was not associated with either type of physical activity.
The presence of a within-person effect “suggests that reductions in physical activity, specifically within the first 5 years of disease onset, may be detrimental to mental health,” the researchers emphasized. Given that the study population was newly diagnosed with PD “it is likely the within-person terms are more sensitive to changes in anxiety, physical activity, and cognition that are more directly the result of the PD process, as opposed to lifestyle/preexisting traits,” they said.
The study findings were limited by several factors, including the use of self-reports to measure physical activity, and the lack of granular information about the details of physical activity, the researchers noted. Another limitation was the inclusion of only newly diagnosed PD patients, which might limit generalizability.
“Future research is warranted to understand if other modes, intensities, or complexities of physical activity impact individuals with PD in a different manner in relation to cognition,” they said.
Dr. Jones and colleagues had no disclosures. The PPMI is supported by the Michael J. Fox Foundation for Parkinson’s Research and funding partners, including numerous pharmaceutical companies.
Parkinson’s disease patients who develop anxiety early in their disease are at risk for reduced physical activity, which promotes further anxiety and cognitive decline, data from nearly 500 individuals show.
Anxiety occurs in 20%-60% of Parkinson’s disease (PD) patients but often goes undiagnosed, wrote Jacob D. Jones, PhD, of California State University, San Bernardino, and colleagues.
“Anxiety can attenuate motivation to engage in physical activity leading to more anxiety and other negative cognitive outcomes,” although physical activity has been shown to improve cognitive function in PD patients, they said. However, physical activity as a mediator between anxiety and cognitive function in PD has not been well studied, they noted.
In a study published in Mental Health and Physical Activity Participants were followed for up to 5 years and completed neuropsychological tests, tests of motor severity, and self-reports on anxiety and physical activity. Anxiety was assessed using the State-Trait Anxiety Inventory-Trait (STAI-T) subscale. Physical activity was assessed using the Physical Activity Scale for the Elderly (PASE). Motor severity was assessed using the Unified Parkinson’s Disease Rating Scale-Part III (UPDRS). The average age of the participants was 61 years, 65% were men, and 96% were White.
Using a direct-effect model, the researchers found that individuals whose anxiety increased during the study period also showed signs of cognitive decline. A significant between-person effect showed that individuals who were generally more anxious also scored lower on cognitive tests over the 5-year study period.
In a mediation model computed with structural equation modeling, physical activity mediated the link between anxiety and cognition, most notably household activity.
“There was a significant within-person association between anxiety and household activities, meaning that individuals who became more anxious over the 5-year study also became less active in the home,” reported Dr. Jones and colleagues.
However, no significant indirect effect was noted regarding the between-person findings of the impact of physical activity on anxiety and cognitive decline. Although more severe anxiety was associated with less activity, cognitive performance was not associated with either type of physical activity.
The presence of a within-person effect “suggests that reductions in physical activity, specifically within the first 5 years of disease onset, may be detrimental to mental health,” the researchers emphasized. Given that the study population was newly diagnosed with PD “it is likely the within-person terms are more sensitive to changes in anxiety, physical activity, and cognition that are more directly the result of the PD process, as opposed to lifestyle/preexisting traits,” they said.
The study findings were limited by several factors, including the use of self-reports to measure physical activity, and the lack of granular information about the details of physical activity, the researchers noted. Another limitation was the inclusion of only newly diagnosed PD patients, which might limit generalizability.
“Future research is warranted to understand if other modes, intensities, or complexities of physical activity impact individuals with PD in a different manner in relation to cognition,” they said.
Dr. Jones and colleagues had no disclosures. The PPMI is supported by the Michael J. Fox Foundation for Parkinson’s Research and funding partners, including numerous pharmaceutical companies.
FROM MENTAL HEALTH AND PHYSICAL ACTIVITY
Headache seen affecting some pregnancy outcomes
, according to results from an observational study.
Migraine during pregnancy has been associated in previous studies with hypertensive pregnancy complications including preeclampsia; however, little is known about other headache types and their effects on pregnancy and birth outcomes.
For their research, published online July 20 in Cephalalgia, Isabella Neri, MD, PhD, and colleagues at Hospital Policlinico of Modena, Italy, looked at headache status for 515 consecutive pregnant women evaluated during their first trimester and followed through childbirth.
Altogether 224 women, or 43.5% of the cohort, were diagnosed with migraine without aura (n = 72), migraine with aura (n = 27), or tension-type headache (n = 125). The authors did not report on the severity or frequency of headaches.
Women with migraine with aura and tension-type headache saw higher rates of small-for-gestational-age infants (25.9% and 10.4% of births, respectively) compared with 5.5% for women without headache. Women presenting with tension-type headache saw elevated risk for small-for-gestational-age infants (odds ratio [OR] 4.19, P = .004) as did women with migraine with aura (OR 5.37, P = .02).
Admission to neonatal intensive care was significantly higher in all the headache groups. However, the authors found no statistically significant associations between headaches and any other perinatal outcome investigated in the study, including gestational diabetes, placental abruption, gestational hypertension, and preterm delivery.
A previous study conducted by the same research group had reported a relationship between migraine and gestational hypertension. The authors cited the small sample size of the migraine groups in the current study, “the diverse features of the population,” and the popularity of low-dose aspirin administration as potentially affecting that outcome.
Interpret findings with caution
Asked by this news organization to comment on the research, two headache neurologists praised Dr. Neri and colleagues’ research for focusing on an understudied topic – but also said that the results would not change their practice unless replicated in larger studies.
Elizabeth W. Loder, MD, MPH, chief emeritus of the division of headache at Brigham and Women’s Faulkner Hospital in Boston, urged caution in interpreting the findings, particularly with regard to tension-type headache. “This study adds to information suggesting that pregnancy complications probably are higher in women who have migraine with aura, and there’s biological plausibility for that,” Dr. Loder said. “Having aura means you may have some vascular abnormalities and things that logically might be associated with an increased risk of small-for-gestational age infants.” But the small size of the migraine-with-aura group in this study – 27 women – and the fact that other perinatal outcomes measured in the study did not reach significance, allows for the possibility that the small-for-gestational-age findings were due to chance, Dr. Loder noted.
With tension-type headache, a biological rationale for small-for-gestational-age risk is more elusive, Dr. Loder said. “I would want to see that association replicated in another study before I thought that I needed to warn women with tension-type headache about this potential outcome. There’s lot of uncertainty here about the magnitude of the risk.”
While Dr. Neri and colleagues described the instruments used in their study to diagnose migraine and migraine with aura, they did not explain how tension-type headache was diagnosed.
Tension-type headache, while common, is still not well characterized, Dr. Loder noted, and may represent a heterogeneous condition or the milder end of a biological continuum that includes migraine with aura. Also, the group in the study had a higher prevalence of smoking, and though the authors made statistical adjustments for smoking status, “smokers are systematically different than people who aren’t in other ways that could be associated with these outcomes,” Dr. Loder said.
While the authors of the study suggested that interventions might be indicated for women with tension-type headache in pregnancy, “showing an association doesn’t necessarily mean that intervening would make a difference” on pregnancy outcomes, Dr. Loder said.
Amaal J. Starling, MD, of the Mayo Clinic in Phoenix, Ariz., said in an interview that she, too, appreciated that this study looked at pregnancy outcomes in the setting of headache disorders. “Unfortunately even though headache disorders and especially migraine affect women so much, we still know very little about migraine in pregnancy,” she said.
Dr. Starling noted that many women with migraine are discouraged by their health care providers from becoming pregnant, because of the false belief that migraine cannot be managed in pregnancy. In her own practice, she said, she treats many patients with severe headache who become pregnant and who require pharmacological intervention during pregnancy.
This does not mean she regards headache in pregnancy as innocent. “I want patients to be on high alert for changes in headache symptoms in pregnancy. If someone has worsening of headache or migraine or aura in the setting of pregnancy, we consider that a red flag,” potentially indicating complications such as high blood pressure, gestational hypertension, or a blood clot.
Like Dr. Loder, Dr. Starling said she was not surprised by Dr. Neri and colleagues’ finding that migraine with aura might impact pregnancy outcomes. “We know that migraine with aura has a lot of vascular abnormalities that underlie the pathogenesis,” she said.
Dr. Starling found the findings related to tension-type headache less convincing, not least because the diagnostic criteria for tension-type headache was not made clear in the study. “I view this as an exploratory study that says maybe there’s a signal here. A larger epidemiological study would need to be done to confirm or refute this data,” Dr. Starling said. Until the findings can be replicated, “this study would not affect my clinical practice in any way.”
Dr. Neri and colleagues described no outside funding for their research or financial conflicts of interest. Dr. Starling has received consulting fees from pharmaceutical manufacturers but reported no disclosures relevant to the study discussed. Dr. Loder reported no financial conflicts of interest.
, according to results from an observational study.
Migraine during pregnancy has been associated in previous studies with hypertensive pregnancy complications including preeclampsia; however, little is known about other headache types and their effects on pregnancy and birth outcomes.
For their research, published online July 20 in Cephalalgia, Isabella Neri, MD, PhD, and colleagues at Hospital Policlinico of Modena, Italy, looked at headache status for 515 consecutive pregnant women evaluated during their first trimester and followed through childbirth.
Altogether 224 women, or 43.5% of the cohort, were diagnosed with migraine without aura (n = 72), migraine with aura (n = 27), or tension-type headache (n = 125). The authors did not report on the severity or frequency of headaches.
Women with migraine with aura and tension-type headache saw higher rates of small-for-gestational-age infants (25.9% and 10.4% of births, respectively) compared with 5.5% for women without headache. Women presenting with tension-type headache saw elevated risk for small-for-gestational-age infants (odds ratio [OR] 4.19, P = .004) as did women with migraine with aura (OR 5.37, P = .02).
Admission to neonatal intensive care was significantly higher in all the headache groups. However, the authors found no statistically significant associations between headaches and any other perinatal outcome investigated in the study, including gestational diabetes, placental abruption, gestational hypertension, and preterm delivery.
A previous study conducted by the same research group had reported a relationship between migraine and gestational hypertension. The authors cited the small sample size of the migraine groups in the current study, “the diverse features of the population,” and the popularity of low-dose aspirin administration as potentially affecting that outcome.
Interpret findings with caution
Asked by this news organization to comment on the research, two headache neurologists praised Dr. Neri and colleagues’ research for focusing on an understudied topic – but also said that the results would not change their practice unless replicated in larger studies.
Elizabeth W. Loder, MD, MPH, chief emeritus of the division of headache at Brigham and Women’s Faulkner Hospital in Boston, urged caution in interpreting the findings, particularly with regard to tension-type headache. “This study adds to information suggesting that pregnancy complications probably are higher in women who have migraine with aura, and there’s biological plausibility for that,” Dr. Loder said. “Having aura means you may have some vascular abnormalities and things that logically might be associated with an increased risk of small-for-gestational age infants.” But the small size of the migraine-with-aura group in this study – 27 women – and the fact that other perinatal outcomes measured in the study did not reach significance, allows for the possibility that the small-for-gestational-age findings were due to chance, Dr. Loder noted.
With tension-type headache, a biological rationale for small-for-gestational-age risk is more elusive, Dr. Loder said. “I would want to see that association replicated in another study before I thought that I needed to warn women with tension-type headache about this potential outcome. There’s lot of uncertainty here about the magnitude of the risk.”
While Dr. Neri and colleagues described the instruments used in their study to diagnose migraine and migraine with aura, they did not explain how tension-type headache was diagnosed.
Tension-type headache, while common, is still not well characterized, Dr. Loder noted, and may represent a heterogeneous condition or the milder end of a biological continuum that includes migraine with aura. Also, the group in the study had a higher prevalence of smoking, and though the authors made statistical adjustments for smoking status, “smokers are systematically different than people who aren’t in other ways that could be associated with these outcomes,” Dr. Loder said.
While the authors of the study suggested that interventions might be indicated for women with tension-type headache in pregnancy, “showing an association doesn’t necessarily mean that intervening would make a difference” on pregnancy outcomes, Dr. Loder said.
Amaal J. Starling, MD, of the Mayo Clinic in Phoenix, Ariz., said in an interview that she, too, appreciated that this study looked at pregnancy outcomes in the setting of headache disorders. “Unfortunately even though headache disorders and especially migraine affect women so much, we still know very little about migraine in pregnancy,” she said.
Dr. Starling noted that many women with migraine are discouraged by their health care providers from becoming pregnant, because of the false belief that migraine cannot be managed in pregnancy. In her own practice, she said, she treats many patients with severe headache who become pregnant and who require pharmacological intervention during pregnancy.
This does not mean she regards headache in pregnancy as innocent. “I want patients to be on high alert for changes in headache symptoms in pregnancy. If someone has worsening of headache or migraine or aura in the setting of pregnancy, we consider that a red flag,” potentially indicating complications such as high blood pressure, gestational hypertension, or a blood clot.
Like Dr. Loder, Dr. Starling said she was not surprised by Dr. Neri and colleagues’ finding that migraine with aura might impact pregnancy outcomes. “We know that migraine with aura has a lot of vascular abnormalities that underlie the pathogenesis,” she said.
Dr. Starling found the findings related to tension-type headache less convincing, not least because the diagnostic criteria for tension-type headache was not made clear in the study. “I view this as an exploratory study that says maybe there’s a signal here. A larger epidemiological study would need to be done to confirm or refute this data,” Dr. Starling said. Until the findings can be replicated, “this study would not affect my clinical practice in any way.”
Dr. Neri and colleagues described no outside funding for their research or financial conflicts of interest. Dr. Starling has received consulting fees from pharmaceutical manufacturers but reported no disclosures relevant to the study discussed. Dr. Loder reported no financial conflicts of interest.
, according to results from an observational study.
Migraine during pregnancy has been associated in previous studies with hypertensive pregnancy complications including preeclampsia; however, little is known about other headache types and their effects on pregnancy and birth outcomes.
For their research, published online July 20 in Cephalalgia, Isabella Neri, MD, PhD, and colleagues at Hospital Policlinico of Modena, Italy, looked at headache status for 515 consecutive pregnant women evaluated during their first trimester and followed through childbirth.
Altogether 224 women, or 43.5% of the cohort, were diagnosed with migraine without aura (n = 72), migraine with aura (n = 27), or tension-type headache (n = 125). The authors did not report on the severity or frequency of headaches.
Women with migraine with aura and tension-type headache saw higher rates of small-for-gestational-age infants (25.9% and 10.4% of births, respectively) compared with 5.5% for women without headache. Women presenting with tension-type headache saw elevated risk for small-for-gestational-age infants (odds ratio [OR] 4.19, P = .004) as did women with migraine with aura (OR 5.37, P = .02).
Admission to neonatal intensive care was significantly higher in all the headache groups. However, the authors found no statistically significant associations between headaches and any other perinatal outcome investigated in the study, including gestational diabetes, placental abruption, gestational hypertension, and preterm delivery.
A previous study conducted by the same research group had reported a relationship between migraine and gestational hypertension. The authors cited the small sample size of the migraine groups in the current study, “the diverse features of the population,” and the popularity of low-dose aspirin administration as potentially affecting that outcome.
Interpret findings with caution
Asked by this news organization to comment on the research, two headache neurologists praised Dr. Neri and colleagues’ research for focusing on an understudied topic – but also said that the results would not change their practice unless replicated in larger studies.
Elizabeth W. Loder, MD, MPH, chief emeritus of the division of headache at Brigham and Women’s Faulkner Hospital in Boston, urged caution in interpreting the findings, particularly with regard to tension-type headache. “This study adds to information suggesting that pregnancy complications probably are higher in women who have migraine with aura, and there’s biological plausibility for that,” Dr. Loder said. “Having aura means you may have some vascular abnormalities and things that logically might be associated with an increased risk of small-for-gestational age infants.” But the small size of the migraine-with-aura group in this study – 27 women – and the fact that other perinatal outcomes measured in the study did not reach significance, allows for the possibility that the small-for-gestational-age findings were due to chance, Dr. Loder noted.
With tension-type headache, a biological rationale for small-for-gestational-age risk is more elusive, Dr. Loder said. “I would want to see that association replicated in another study before I thought that I needed to warn women with tension-type headache about this potential outcome. There’s lot of uncertainty here about the magnitude of the risk.”
While Dr. Neri and colleagues described the instruments used in their study to diagnose migraine and migraine with aura, they did not explain how tension-type headache was diagnosed.
Tension-type headache, while common, is still not well characterized, Dr. Loder noted, and may represent a heterogeneous condition or the milder end of a biological continuum that includes migraine with aura. Also, the group in the study had a higher prevalence of smoking, and though the authors made statistical adjustments for smoking status, “smokers are systematically different than people who aren’t in other ways that could be associated with these outcomes,” Dr. Loder said.
While the authors of the study suggested that interventions might be indicated for women with tension-type headache in pregnancy, “showing an association doesn’t necessarily mean that intervening would make a difference” on pregnancy outcomes, Dr. Loder said.
Amaal J. Starling, MD, of the Mayo Clinic in Phoenix, Ariz., said in an interview that she, too, appreciated that this study looked at pregnancy outcomes in the setting of headache disorders. “Unfortunately even though headache disorders and especially migraine affect women so much, we still know very little about migraine in pregnancy,” she said.
Dr. Starling noted that many women with migraine are discouraged by their health care providers from becoming pregnant, because of the false belief that migraine cannot be managed in pregnancy. In her own practice, she said, she treats many patients with severe headache who become pregnant and who require pharmacological intervention during pregnancy.
This does not mean she regards headache in pregnancy as innocent. “I want patients to be on high alert for changes in headache symptoms in pregnancy. If someone has worsening of headache or migraine or aura in the setting of pregnancy, we consider that a red flag,” potentially indicating complications such as high blood pressure, gestational hypertension, or a blood clot.
Like Dr. Loder, Dr. Starling said she was not surprised by Dr. Neri and colleagues’ finding that migraine with aura might impact pregnancy outcomes. “We know that migraine with aura has a lot of vascular abnormalities that underlie the pathogenesis,” she said.
Dr. Starling found the findings related to tension-type headache less convincing, not least because the diagnostic criteria for tension-type headache was not made clear in the study. “I view this as an exploratory study that says maybe there’s a signal here. A larger epidemiological study would need to be done to confirm or refute this data,” Dr. Starling said. Until the findings can be replicated, “this study would not affect my clinical practice in any way.”
Dr. Neri and colleagues described no outside funding for their research or financial conflicts of interest. Dr. Starling has received consulting fees from pharmaceutical manufacturers but reported no disclosures relevant to the study discussed. Dr. Loder reported no financial conflicts of interest.
FROM CEPHALALGIA
Increased risk of hospitalization and death with Parkinson’s drug
, according to a new study.
A retrospective cohort study of elderly patients with Parkinson’s disease who were in long-term care facilities found that the use of pimavanserin (Nuplazid) was associated with an increased risk of 30-day hospitalization and mortality for up to a year.
“Given that a previous study showed typical and atypical antipsychotics more than doubled mortality risk in patients with Parkinson’s disease, we aimed to assess the risk of hospitalization and death associated with pimavanserin,” wrote lead author Y. Joseph Hwang, MD, Johns Hopkins University, Baltimore, and colleagues in the paper. “These findings, in a large real-world cohort within long-term care facilities, may help to inform decisions regarding its risk-benefit balance among patients with Parkinson’s disease.”
The findings were published online Aug. 13 in Neurology.
The researchers enrolled 2,186 patients with Parkinson’s disease aged 65 years and older in Medicare-certified long-term care facilities who also had a pimavanserin prescription and 18,212 nonusers of pimavanserin between Nov. 1, 2015, and December 31, 2018. Patients in the pimavanserin group used the drug over the course of the entire study period. Hospitalization and mortality were calculated from the date of pimavanserin prescription. Propensity score–based inverse probability of treatment weighting (IPTW) was used to balance the two groups on 24 baseline characteristics such as age, sex, and comorbidities.
Pimavanserin use was associated with a 24% higher risk of 30-day hospitalization (adjusted hazard ratio, 1.24; 95% confidence interval, 1.06-1.43). However, “the association did not reach statistical significance in a smaller subcohort of propensity score-matched users and nonusers,” Dr. Hwang and colleagues wrote.
Pimavanserin use was also linked to higher mortality at:
- 90 days (aHR, 1.20; 95% CI, 1.02-1.41).
- 180 days (aHR, 1.28; 95% CI, 1.13-1.45).
- 365 days (aHR, 1.56; 95% CI, 1.42-1.72).
No associations were found between pimavanserin use and 90-day hospitalization (aHR, 1.10; 95% CI, 0.99-1.24) nor with 30-day mortality (aHR, 0.76; 95% CI, 0.56-1.03).
Important considerations
“This study raises three important points to consider for any practicing neurology provider: 1) how to address and interpret risks associated with pimavanserin use in this patient population 2) utility of pimavanserin 3) interpretation of data showing increased mortality in patients being treated for Parkinson’s disease psychosis,” wrote Farwa Ali, MBBS, of the Mayo Clinic, Rochester, Minn., in an accompanying editorial published in Neurology.
Hallucinations and delusions are highly prevalent in Parkinson’s disease; as many as 60% of patients will develop psychosis over the course of their illness. Pimavanserin is a selective serotonin inverse agonist which targets 5-HT2A serotonin receptors in the brain, decreasing their activity in order to attenuate hallucinations and delusions.
“Pimavanserin has been approved by the FDA [Food and Drug Administration] for Parkinson’s disease psychosis, but its safety has been called into question based on previous reports of increased mortality risk, compared with a rather modest benefit seen in a 6-week clinical trial, the duration of which limits determination of long-term safety,” wrote Dr. Ali.
Pimavanserin carries a boxed warning that elderly patients with dementia may be at an increased risk of death. After its approval in 2016, the U.S. FDA later reviewed 893 deaths in association with pimavanserin during the postmarketing surveillance period – “an unexpected number in a new drug,” Dr. Hwang and colleagues noted. “It [the FDA] noted that most reports occurred in a population with high underlying death rates and did not signal any additional risk beyond the current warning for all antipsychotics, which could have resulted in annual mortality rates of up to 60%.”
As the first cohort study to examine hospitalization and death between pimavanserin users and nonusers, “the study confirms previous concerns regarding safety of pimavanserin and more importantly brings to attention the importance of carefully considering risks and benefits of pharmacotherapy in Parkinson’s disease psychosis, clear communication with patients and families, and close observation to ensure safety,” wrote Dr. Ali.
The study limitations include its observational design, which subjected the findings to residual confounding.
“While we developed models to maximize the strength of causal inference, our comparison group was pimavanserin nonusers and the very reason for prescription of pimavanserin could have predisposed its users to the outcomes of hospitalization and death, introducing confounding by indication,” Dr. Hwang and colleagues wrote in the paper.
Additionally, “while robust analyses were conducted to ensure pimavanserin users and nonusers were comparable, Dr. Hwang et al. did find that pimavanserin users were more likely to concomitantly use other antipsychotic drugs which has been demonstrated as increasing the mortality risk,” Dr. Ali pointed out.
Since patients living in long-term care facilities may have a higher risk of mortality because of more severe or later-stage Parkinson’s disease, the study results “may not be generalizable to community-dwelling PD patients,” Dr. Ali wrote. “These factors are important to consider while making individual management decisions.”
Dr. Hwang and Dr. Ali disclosed no relevant financial relationships. The study authors reported no targeted funding.
, according to a new study.
A retrospective cohort study of elderly patients with Parkinson’s disease who were in long-term care facilities found that the use of pimavanserin (Nuplazid) was associated with an increased risk of 30-day hospitalization and mortality for up to a year.
“Given that a previous study showed typical and atypical antipsychotics more than doubled mortality risk in patients with Parkinson’s disease, we aimed to assess the risk of hospitalization and death associated with pimavanserin,” wrote lead author Y. Joseph Hwang, MD, Johns Hopkins University, Baltimore, and colleagues in the paper. “These findings, in a large real-world cohort within long-term care facilities, may help to inform decisions regarding its risk-benefit balance among patients with Parkinson’s disease.”
The findings were published online Aug. 13 in Neurology.
The researchers enrolled 2,186 patients with Parkinson’s disease aged 65 years and older in Medicare-certified long-term care facilities who also had a pimavanserin prescription and 18,212 nonusers of pimavanserin between Nov. 1, 2015, and December 31, 2018. Patients in the pimavanserin group used the drug over the course of the entire study period. Hospitalization and mortality were calculated from the date of pimavanserin prescription. Propensity score–based inverse probability of treatment weighting (IPTW) was used to balance the two groups on 24 baseline characteristics such as age, sex, and comorbidities.
Pimavanserin use was associated with a 24% higher risk of 30-day hospitalization (adjusted hazard ratio, 1.24; 95% confidence interval, 1.06-1.43). However, “the association did not reach statistical significance in a smaller subcohort of propensity score-matched users and nonusers,” Dr. Hwang and colleagues wrote.
Pimavanserin use was also linked to higher mortality at:
- 90 days (aHR, 1.20; 95% CI, 1.02-1.41).
- 180 days (aHR, 1.28; 95% CI, 1.13-1.45).
- 365 days (aHR, 1.56; 95% CI, 1.42-1.72).
No associations were found between pimavanserin use and 90-day hospitalization (aHR, 1.10; 95% CI, 0.99-1.24) nor with 30-day mortality (aHR, 0.76; 95% CI, 0.56-1.03).
Important considerations
“This study raises three important points to consider for any practicing neurology provider: 1) how to address and interpret risks associated with pimavanserin use in this patient population 2) utility of pimavanserin 3) interpretation of data showing increased mortality in patients being treated for Parkinson’s disease psychosis,” wrote Farwa Ali, MBBS, of the Mayo Clinic, Rochester, Minn., in an accompanying editorial published in Neurology.
Hallucinations and delusions are highly prevalent in Parkinson’s disease; as many as 60% of patients will develop psychosis over the course of their illness. Pimavanserin is a selective serotonin inverse agonist which targets 5-HT2A serotonin receptors in the brain, decreasing their activity in order to attenuate hallucinations and delusions.
“Pimavanserin has been approved by the FDA [Food and Drug Administration] for Parkinson’s disease psychosis, but its safety has been called into question based on previous reports of increased mortality risk, compared with a rather modest benefit seen in a 6-week clinical trial, the duration of which limits determination of long-term safety,” wrote Dr. Ali.
Pimavanserin carries a boxed warning that elderly patients with dementia may be at an increased risk of death. After its approval in 2016, the U.S. FDA later reviewed 893 deaths in association with pimavanserin during the postmarketing surveillance period – “an unexpected number in a new drug,” Dr. Hwang and colleagues noted. “It [the FDA] noted that most reports occurred in a population with high underlying death rates and did not signal any additional risk beyond the current warning for all antipsychotics, which could have resulted in annual mortality rates of up to 60%.”
As the first cohort study to examine hospitalization and death between pimavanserin users and nonusers, “the study confirms previous concerns regarding safety of pimavanserin and more importantly brings to attention the importance of carefully considering risks and benefits of pharmacotherapy in Parkinson’s disease psychosis, clear communication with patients and families, and close observation to ensure safety,” wrote Dr. Ali.
The study limitations include its observational design, which subjected the findings to residual confounding.
“While we developed models to maximize the strength of causal inference, our comparison group was pimavanserin nonusers and the very reason for prescription of pimavanserin could have predisposed its users to the outcomes of hospitalization and death, introducing confounding by indication,” Dr. Hwang and colleagues wrote in the paper.
Additionally, “while robust analyses were conducted to ensure pimavanserin users and nonusers were comparable, Dr. Hwang et al. did find that pimavanserin users were more likely to concomitantly use other antipsychotic drugs which has been demonstrated as increasing the mortality risk,” Dr. Ali pointed out.
Since patients living in long-term care facilities may have a higher risk of mortality because of more severe or later-stage Parkinson’s disease, the study results “may not be generalizable to community-dwelling PD patients,” Dr. Ali wrote. “These factors are important to consider while making individual management decisions.”
Dr. Hwang and Dr. Ali disclosed no relevant financial relationships. The study authors reported no targeted funding.
, according to a new study.
A retrospective cohort study of elderly patients with Parkinson’s disease who were in long-term care facilities found that the use of pimavanserin (Nuplazid) was associated with an increased risk of 30-day hospitalization and mortality for up to a year.
“Given that a previous study showed typical and atypical antipsychotics more than doubled mortality risk in patients with Parkinson’s disease, we aimed to assess the risk of hospitalization and death associated with pimavanserin,” wrote lead author Y. Joseph Hwang, MD, Johns Hopkins University, Baltimore, and colleagues in the paper. “These findings, in a large real-world cohort within long-term care facilities, may help to inform decisions regarding its risk-benefit balance among patients with Parkinson’s disease.”
The findings were published online Aug. 13 in Neurology.
The researchers enrolled 2,186 patients with Parkinson’s disease aged 65 years and older in Medicare-certified long-term care facilities who also had a pimavanserin prescription and 18,212 nonusers of pimavanserin between Nov. 1, 2015, and December 31, 2018. Patients in the pimavanserin group used the drug over the course of the entire study period. Hospitalization and mortality were calculated from the date of pimavanserin prescription. Propensity score–based inverse probability of treatment weighting (IPTW) was used to balance the two groups on 24 baseline characteristics such as age, sex, and comorbidities.
Pimavanserin use was associated with a 24% higher risk of 30-day hospitalization (adjusted hazard ratio, 1.24; 95% confidence interval, 1.06-1.43). However, “the association did not reach statistical significance in a smaller subcohort of propensity score-matched users and nonusers,” Dr. Hwang and colleagues wrote.
Pimavanserin use was also linked to higher mortality at:
- 90 days (aHR, 1.20; 95% CI, 1.02-1.41).
- 180 days (aHR, 1.28; 95% CI, 1.13-1.45).
- 365 days (aHR, 1.56; 95% CI, 1.42-1.72).
No associations were found between pimavanserin use and 90-day hospitalization (aHR, 1.10; 95% CI, 0.99-1.24) nor with 30-day mortality (aHR, 0.76; 95% CI, 0.56-1.03).
Important considerations
“This study raises three important points to consider for any practicing neurology provider: 1) how to address and interpret risks associated with pimavanserin use in this patient population 2) utility of pimavanserin 3) interpretation of data showing increased mortality in patients being treated for Parkinson’s disease psychosis,” wrote Farwa Ali, MBBS, of the Mayo Clinic, Rochester, Minn., in an accompanying editorial published in Neurology.
Hallucinations and delusions are highly prevalent in Parkinson’s disease; as many as 60% of patients will develop psychosis over the course of their illness. Pimavanserin is a selective serotonin inverse agonist which targets 5-HT2A serotonin receptors in the brain, decreasing their activity in order to attenuate hallucinations and delusions.
“Pimavanserin has been approved by the FDA [Food and Drug Administration] for Parkinson’s disease psychosis, but its safety has been called into question based on previous reports of increased mortality risk, compared with a rather modest benefit seen in a 6-week clinical trial, the duration of which limits determination of long-term safety,” wrote Dr. Ali.
Pimavanserin carries a boxed warning that elderly patients with dementia may be at an increased risk of death. After its approval in 2016, the U.S. FDA later reviewed 893 deaths in association with pimavanserin during the postmarketing surveillance period – “an unexpected number in a new drug,” Dr. Hwang and colleagues noted. “It [the FDA] noted that most reports occurred in a population with high underlying death rates and did not signal any additional risk beyond the current warning for all antipsychotics, which could have resulted in annual mortality rates of up to 60%.”
As the first cohort study to examine hospitalization and death between pimavanserin users and nonusers, “the study confirms previous concerns regarding safety of pimavanserin and more importantly brings to attention the importance of carefully considering risks and benefits of pharmacotherapy in Parkinson’s disease psychosis, clear communication with patients and families, and close observation to ensure safety,” wrote Dr. Ali.
The study limitations include its observational design, which subjected the findings to residual confounding.
“While we developed models to maximize the strength of causal inference, our comparison group was pimavanserin nonusers and the very reason for prescription of pimavanserin could have predisposed its users to the outcomes of hospitalization and death, introducing confounding by indication,” Dr. Hwang and colleagues wrote in the paper.
Additionally, “while robust analyses were conducted to ensure pimavanserin users and nonusers were comparable, Dr. Hwang et al. did find that pimavanserin users were more likely to concomitantly use other antipsychotic drugs which has been demonstrated as increasing the mortality risk,” Dr. Ali pointed out.
Since patients living in long-term care facilities may have a higher risk of mortality because of more severe or later-stage Parkinson’s disease, the study results “may not be generalizable to community-dwelling PD patients,” Dr. Ali wrote. “These factors are important to consider while making individual management decisions.”
Dr. Hwang and Dr. Ali disclosed no relevant financial relationships. The study authors reported no targeted funding.
FROM NEUROLOGY
Trial finds that intranasal DHE is well tolerated and may reduce migraine symptoms
, a new study suggests.
A phase 3, open-label trial of INP104, or Trudhesa – Impel NeuroPharma’s proprietary Precision Olfactory Delivery of DHE – found that most patients experienced symptom relief within 2 hours and reported that the medication was easy to use and preferable to their current therapy.
Another treatment option?
Of about 18 million diagnosed migraine patients in the United States, 4 million receive prescription treatment. Nearly 80% of migraine therapies involve triptans, but 30%-40% of patients don’t find adequate relief with triptans. Moreover, the majority of patients who do respond to triptans report that they’d like to try a different therapy.
“INP104 has the potential to deliver rapid symptom relief, without injection, that is well tolerated and suitable for outpatient us,” lead author Timothy Smith, MD, of StudyMetrix Research, St. Louis, and colleagues wrote in the paper.
The results were published online Aug. 7 in Headache.
A total of 360 patients aged 18-65 years with a diagnosis of migraine with or without aura with at least two attacks per month over the course of the previous 6 months were enrolled in the 24-week safety study, which had a 28-week extension period. Participants used their “best usual care” to treat their migraines during the initial 28-day screening period. Afterward, they were given 1.45-mg doses of INP04 to self-administer into the upper nasal space to treat self-recognized attacks. No more than two doses per 24 hours and three doses per 7 days were allowed. The Full Safety Set analysis comprised 354 patients who dosed at least once. The Primary Safety Set involved 185 patients who administered an average of two or more doses per 28-day period during the 24-week treatment period. A total of 4,515 self-recognized migraines were treated during the 24-week period; 6,332 doses of INP04 were analyzed.
Nearly 37% (130/354) of patients reported treatment-emergent adverse events (TEAEs); 6.8% (24/354) discontinued treatment because of the TEAEs over the 24 weeks. The most common TEAE was nasal congestion (15%, 53/354), followed by nausea (6.8%, 24/354).
Within an hour of INP104 administration, 47.6% of patients reported pain relief. After 2 hours of INP104 administration, 38% reported pain freedom and 66.3% reported pain relief. Headache recurrence was observed in 7.1% and 14.3% of patients at 24 and 48 hours, respectively.
In a questionnaire, 84% of patients agreed or strongly agreed that INP04 was easy to use. Most reported that INP104 slowed the recurrence of their migraines and was more rapidly and consistently effective than their previous best usual care treatment.
Intranasal delivery of DHE was developed in response to the challenges of traditional IV administration.
“While intravenous (IV) dihydroergotamine (DHE) mesylate has a long, established history as an effective migraine therapy, its use as an acute treatment can be limited by the high rate of nausea and vomiting reported by patients, which often requires pretreatment with antiemetics,” Dr. Smith and colleagues wrote. “Furthermore, IV DHE mesylate needs to be administered in emergency room settings or by headache specialists, limiting convenience.”
A novel delivery system
“There’s already a nasal spray on the market right now which doesn’t seem to work that well in a large number of people. This device [INP04] was designed to get the same substances to a part of the nose that’s higher and farther back, where there may be better absorption,” said Alan Rapoport, MD, clinical professor of neurology at the University of California, Los Angeles, said in an interview. Dr. Rapoport was not involved with the study.
The proprietary Precision Olfactory Delivery (POD) is meant to improve on current nasal delivery methods such as sprays, droppers, and pumps, which may deliver “less than 5% of the active drug to the upper nasal space,” according to a press release from Impel NeuroPharma.
Nasal delivery also may have advantages over oral medications. People with migraines may be more likely to have gastroparesis – delayed stomach emptying – which may affect their ability to absorb oral medications and delay symptom relief. However, patients may hesitate to agree to a medication that involves nasal delivery, Dr. Rapoport said.
“I will say it’s a little more difficult getting your patients to take a nasal spray,” Dr. Rapoport said. “Patients are used to taking tablets for their headaches,” he said. “But if the doctor spends a little more time with the patient and says, ‘Look, this could work faster for your migraine as a nasal spray. Why don’t you try it a couple of times and see if you like it or not?’ patients are usually willing to give it a try.”
The study’s limitations include the lack of a control group given that it was an open-label trial. It was carried out at 38 sites in one geographical area, which may affect the generalizability of the results. The study did not assess patients with new-onset migraine or chronic migraine.
The Food and Drug Administration approved Trudhesa on Sept. 2, 2021.
The study was funded by Impel NeuroPharma. Dr. Smith has received funding from a number of pharmaceutical companies. Dr. Rapoport disclosed no relevant financial relationships.
, a new study suggests.
A phase 3, open-label trial of INP104, or Trudhesa – Impel NeuroPharma’s proprietary Precision Olfactory Delivery of DHE – found that most patients experienced symptom relief within 2 hours and reported that the medication was easy to use and preferable to their current therapy.
Another treatment option?
Of about 18 million diagnosed migraine patients in the United States, 4 million receive prescription treatment. Nearly 80% of migraine therapies involve triptans, but 30%-40% of patients don’t find adequate relief with triptans. Moreover, the majority of patients who do respond to triptans report that they’d like to try a different therapy.
“INP104 has the potential to deliver rapid symptom relief, without injection, that is well tolerated and suitable for outpatient us,” lead author Timothy Smith, MD, of StudyMetrix Research, St. Louis, and colleagues wrote in the paper.
The results were published online Aug. 7 in Headache.
A total of 360 patients aged 18-65 years with a diagnosis of migraine with or without aura with at least two attacks per month over the course of the previous 6 months were enrolled in the 24-week safety study, which had a 28-week extension period. Participants used their “best usual care” to treat their migraines during the initial 28-day screening period. Afterward, they were given 1.45-mg doses of INP04 to self-administer into the upper nasal space to treat self-recognized attacks. No more than two doses per 24 hours and three doses per 7 days were allowed. The Full Safety Set analysis comprised 354 patients who dosed at least once. The Primary Safety Set involved 185 patients who administered an average of two or more doses per 28-day period during the 24-week treatment period. A total of 4,515 self-recognized migraines were treated during the 24-week period; 6,332 doses of INP04 were analyzed.
Nearly 37% (130/354) of patients reported treatment-emergent adverse events (TEAEs); 6.8% (24/354) discontinued treatment because of the TEAEs over the 24 weeks. The most common TEAE was nasal congestion (15%, 53/354), followed by nausea (6.8%, 24/354).
Within an hour of INP104 administration, 47.6% of patients reported pain relief. After 2 hours of INP104 administration, 38% reported pain freedom and 66.3% reported pain relief. Headache recurrence was observed in 7.1% and 14.3% of patients at 24 and 48 hours, respectively.
In a questionnaire, 84% of patients agreed or strongly agreed that INP04 was easy to use. Most reported that INP104 slowed the recurrence of their migraines and was more rapidly and consistently effective than their previous best usual care treatment.
Intranasal delivery of DHE was developed in response to the challenges of traditional IV administration.
“While intravenous (IV) dihydroergotamine (DHE) mesylate has a long, established history as an effective migraine therapy, its use as an acute treatment can be limited by the high rate of nausea and vomiting reported by patients, which often requires pretreatment with antiemetics,” Dr. Smith and colleagues wrote. “Furthermore, IV DHE mesylate needs to be administered in emergency room settings or by headache specialists, limiting convenience.”
A novel delivery system
“There’s already a nasal spray on the market right now which doesn’t seem to work that well in a large number of people. This device [INP04] was designed to get the same substances to a part of the nose that’s higher and farther back, where there may be better absorption,” said Alan Rapoport, MD, clinical professor of neurology at the University of California, Los Angeles, said in an interview. Dr. Rapoport was not involved with the study.
The proprietary Precision Olfactory Delivery (POD) is meant to improve on current nasal delivery methods such as sprays, droppers, and pumps, which may deliver “less than 5% of the active drug to the upper nasal space,” according to a press release from Impel NeuroPharma.
Nasal delivery also may have advantages over oral medications. People with migraines may be more likely to have gastroparesis – delayed stomach emptying – which may affect their ability to absorb oral medications and delay symptom relief. However, patients may hesitate to agree to a medication that involves nasal delivery, Dr. Rapoport said.
“I will say it’s a little more difficult getting your patients to take a nasal spray,” Dr. Rapoport said. “Patients are used to taking tablets for their headaches,” he said. “But if the doctor spends a little more time with the patient and says, ‘Look, this could work faster for your migraine as a nasal spray. Why don’t you try it a couple of times and see if you like it or not?’ patients are usually willing to give it a try.”
The study’s limitations include the lack of a control group given that it was an open-label trial. It was carried out at 38 sites in one geographical area, which may affect the generalizability of the results. The study did not assess patients with new-onset migraine or chronic migraine.
The Food and Drug Administration approved Trudhesa on Sept. 2, 2021.
The study was funded by Impel NeuroPharma. Dr. Smith has received funding from a number of pharmaceutical companies. Dr. Rapoport disclosed no relevant financial relationships.
, a new study suggests.
A phase 3, open-label trial of INP104, or Trudhesa – Impel NeuroPharma’s proprietary Precision Olfactory Delivery of DHE – found that most patients experienced symptom relief within 2 hours and reported that the medication was easy to use and preferable to their current therapy.
Another treatment option?
Of about 18 million diagnosed migraine patients in the United States, 4 million receive prescription treatment. Nearly 80% of migraine therapies involve triptans, but 30%-40% of patients don’t find adequate relief with triptans. Moreover, the majority of patients who do respond to triptans report that they’d like to try a different therapy.
“INP104 has the potential to deliver rapid symptom relief, without injection, that is well tolerated and suitable for outpatient us,” lead author Timothy Smith, MD, of StudyMetrix Research, St. Louis, and colleagues wrote in the paper.
The results were published online Aug. 7 in Headache.
A total of 360 patients aged 18-65 years with a diagnosis of migraine with or without aura with at least two attacks per month over the course of the previous 6 months were enrolled in the 24-week safety study, which had a 28-week extension period. Participants used their “best usual care” to treat their migraines during the initial 28-day screening period. Afterward, they were given 1.45-mg doses of INP04 to self-administer into the upper nasal space to treat self-recognized attacks. No more than two doses per 24 hours and three doses per 7 days were allowed. The Full Safety Set analysis comprised 354 patients who dosed at least once. The Primary Safety Set involved 185 patients who administered an average of two or more doses per 28-day period during the 24-week treatment period. A total of 4,515 self-recognized migraines were treated during the 24-week period; 6,332 doses of INP04 were analyzed.
Nearly 37% (130/354) of patients reported treatment-emergent adverse events (TEAEs); 6.8% (24/354) discontinued treatment because of the TEAEs over the 24 weeks. The most common TEAE was nasal congestion (15%, 53/354), followed by nausea (6.8%, 24/354).
Within an hour of INP104 administration, 47.6% of patients reported pain relief. After 2 hours of INP104 administration, 38% reported pain freedom and 66.3% reported pain relief. Headache recurrence was observed in 7.1% and 14.3% of patients at 24 and 48 hours, respectively.
In a questionnaire, 84% of patients agreed or strongly agreed that INP04 was easy to use. Most reported that INP104 slowed the recurrence of their migraines and was more rapidly and consistently effective than their previous best usual care treatment.
Intranasal delivery of DHE was developed in response to the challenges of traditional IV administration.
“While intravenous (IV) dihydroergotamine (DHE) mesylate has a long, established history as an effective migraine therapy, its use as an acute treatment can be limited by the high rate of nausea and vomiting reported by patients, which often requires pretreatment with antiemetics,” Dr. Smith and colleagues wrote. “Furthermore, IV DHE mesylate needs to be administered in emergency room settings or by headache specialists, limiting convenience.”
A novel delivery system
“There’s already a nasal spray on the market right now which doesn’t seem to work that well in a large number of people. This device [INP04] was designed to get the same substances to a part of the nose that’s higher and farther back, where there may be better absorption,” said Alan Rapoport, MD, clinical professor of neurology at the University of California, Los Angeles, said in an interview. Dr. Rapoport was not involved with the study.
The proprietary Precision Olfactory Delivery (POD) is meant to improve on current nasal delivery methods such as sprays, droppers, and pumps, which may deliver “less than 5% of the active drug to the upper nasal space,” according to a press release from Impel NeuroPharma.
Nasal delivery also may have advantages over oral medications. People with migraines may be more likely to have gastroparesis – delayed stomach emptying – which may affect their ability to absorb oral medications and delay symptom relief. However, patients may hesitate to agree to a medication that involves nasal delivery, Dr. Rapoport said.
“I will say it’s a little more difficult getting your patients to take a nasal spray,” Dr. Rapoport said. “Patients are used to taking tablets for their headaches,” he said. “But if the doctor spends a little more time with the patient and says, ‘Look, this could work faster for your migraine as a nasal spray. Why don’t you try it a couple of times and see if you like it or not?’ patients are usually willing to give it a try.”
The study’s limitations include the lack of a control group given that it was an open-label trial. It was carried out at 38 sites in one geographical area, which may affect the generalizability of the results. The study did not assess patients with new-onset migraine or chronic migraine.
The Food and Drug Administration approved Trudhesa on Sept. 2, 2021.
The study was funded by Impel NeuroPharma. Dr. Smith has received funding from a number of pharmaceutical companies. Dr. Rapoport disclosed no relevant financial relationships.
From Headache
‘No justification’ for suicide warning on all antiseizure meds
, new research shows. “There appears to be no justification for the FDA to label every new antiseizure medication with a warning that it may increase risk of suicidality,” said study investigator Michael R. Sperling, MD, professor of neurology, Thomas Jefferson University, Philadelphia.
“How many patients are afraid of their medication and do not take it because of the warning – and are consequently at risk because of that? We do not know, but have anecdotal experience that this is certainly an issue,” Dr. Sperling, who is director of the Jefferson Comprehensive Epilepsy Center, added.
The study was published online August 2 in JAMA Neurology.
Blanket warning
In 2008, the FDA issued an alert stating that antiseizure medications increase suicidality. The alert was based on pooled data from placebo-controlled clinical trials that included 11 antiseizure medications – carbamazepine, felbamate, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, pregabalin, tiagabine, topiramate, valproate, and zonisamide.
The meta-analytic review showed that, compared with placebo, antiseizure medications nearly doubled suicide risk among patients treated for epilepsy, psychiatric disorders, and other diseases. As a result of the FDA study, all antiseizure medications that have been approved since 2008 carry a warning for suicidality.
However, subsequent analyses did not show the same results, Dr. Sperling and colleagues noted.
“Pivotal” antiseizure medication epilepsy trials since 2008 have evaluated suicidality prospectively. Since 2011, trials have included the validated Columbia Suicidality Severity Rating Scale, they noted.
Meta analysis showed no increased risk
Dr. Sperling and colleagues conducted a meta-analysis of 17 randomized placebo-controlled epilepsy trials of five antiseizure medications approved since 2008. These antiseizure medications were eslicarbazepine, perampanel, brivaracetam, cannabidiol, and cenobamate. The trials involved 5,996 patients, including 4,000 who were treated with antiseizure medications and 1,996 who were treated with placebo.
Confining the analysis to epilepsy trials avoids potential confounders, such as possible differences in suicidality risks between different diseases, the researchers noted.
They found no evidence of increased risk for suicidal ideation (overall risk ratio, antiseizure medications vs. placebo: 0.75; 95% confidence interval: 0.35-1.60) or suicide attempt (risk ratio, 0.75; 95% CI: 0.30-1.87) overall or for any individual antiseizure medication.
Suicidal ideation occurred in 12 of 4,000 patients treated with antiseizure medications (0.30%), versus 7 of 1,996 patients treated with placebo (0.35%) (P = .74). Three patients who were treated with antiseizure medications attempted suicide; no patients who were treated with placebo attempted suicide (P = .22). There were no completed suicides.
“There is no current evidence that the five antiseizure medications evaluated in this study increase suicidality in epilepsy and merit a suicidality class warning,” the investigators wrote. When prescribed for epilepsy, “evidence does not support the FDA’s labeling practice of a blanket assumption of increased suicidality,” said Dr. Sperling.
“Our findings indicate the nonspecific suicide warning for all epilepsy drugs is simply not justifiable,” he said. “The results are not surprising. Different drugs affect cells in different ways. So there’s no reason to expect that every drug would increase suicide risk for every patient,” Dr. Sperling said in a statement.
“It’s important to recognize that epilepsy has many causes – perinatal injury, stroke, tumor, head trauma, developmental malformations, genetic causes, and others – and these underlying etiologies may well contribute to the presence of depression and suicidality in this population,” he said in an interview. “Psychodynamic influences also may occur as a consequence of having seizures. This is a complicated area, and drugs are simply one piece of the puzzle,” he added.
Dr. Sperling said the FDA has accomplished “one useful thing with its warning – it highlighted that physicians and other health care providers must pay attention to their patients’ psychological state, ask questions, and treat accordingly.”
The study had no specific funding. Dr. Sperling has received grants from Eisai, Medtronic, Neurelis, SK Life Science, Sunovion, Takeda, Xenon, Cerevel Therapeutics, UCB Pharma, and Engage Pharma; personal fees from Neurelis, Medscape, Neurology Live, International Medical Press, UCB Pharma, Eisai, Oxford University Press, and Projects in Knowledge. He has also consulted for Medtronic outside the submitted work; payments went to Thomas Jefferson University. A complete list of authors’ disclosures is available with the original article.
A version of this article first appeared on Medscape.com.
, new research shows. “There appears to be no justification for the FDA to label every new antiseizure medication with a warning that it may increase risk of suicidality,” said study investigator Michael R. Sperling, MD, professor of neurology, Thomas Jefferson University, Philadelphia.
“How many patients are afraid of their medication and do not take it because of the warning – and are consequently at risk because of that? We do not know, but have anecdotal experience that this is certainly an issue,” Dr. Sperling, who is director of the Jefferson Comprehensive Epilepsy Center, added.
The study was published online August 2 in JAMA Neurology.
Blanket warning
In 2008, the FDA issued an alert stating that antiseizure medications increase suicidality. The alert was based on pooled data from placebo-controlled clinical trials that included 11 antiseizure medications – carbamazepine, felbamate, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, pregabalin, tiagabine, topiramate, valproate, and zonisamide.
The meta-analytic review showed that, compared with placebo, antiseizure medications nearly doubled suicide risk among patients treated for epilepsy, psychiatric disorders, and other diseases. As a result of the FDA study, all antiseizure medications that have been approved since 2008 carry a warning for suicidality.
However, subsequent analyses did not show the same results, Dr. Sperling and colleagues noted.
“Pivotal” antiseizure medication epilepsy trials since 2008 have evaluated suicidality prospectively. Since 2011, trials have included the validated Columbia Suicidality Severity Rating Scale, they noted.
Meta analysis showed no increased risk
Dr. Sperling and colleagues conducted a meta-analysis of 17 randomized placebo-controlled epilepsy trials of five antiseizure medications approved since 2008. These antiseizure medications were eslicarbazepine, perampanel, brivaracetam, cannabidiol, and cenobamate. The trials involved 5,996 patients, including 4,000 who were treated with antiseizure medications and 1,996 who were treated with placebo.
Confining the analysis to epilepsy trials avoids potential confounders, such as possible differences in suicidality risks between different diseases, the researchers noted.
They found no evidence of increased risk for suicidal ideation (overall risk ratio, antiseizure medications vs. placebo: 0.75; 95% confidence interval: 0.35-1.60) or suicide attempt (risk ratio, 0.75; 95% CI: 0.30-1.87) overall or for any individual antiseizure medication.
Suicidal ideation occurred in 12 of 4,000 patients treated with antiseizure medications (0.30%), versus 7 of 1,996 patients treated with placebo (0.35%) (P = .74). Three patients who were treated with antiseizure medications attempted suicide; no patients who were treated with placebo attempted suicide (P = .22). There were no completed suicides.
“There is no current evidence that the five antiseizure medications evaluated in this study increase suicidality in epilepsy and merit a suicidality class warning,” the investigators wrote. When prescribed for epilepsy, “evidence does not support the FDA’s labeling practice of a blanket assumption of increased suicidality,” said Dr. Sperling.
“Our findings indicate the nonspecific suicide warning for all epilepsy drugs is simply not justifiable,” he said. “The results are not surprising. Different drugs affect cells in different ways. So there’s no reason to expect that every drug would increase suicide risk for every patient,” Dr. Sperling said in a statement.
“It’s important to recognize that epilepsy has many causes – perinatal injury, stroke, tumor, head trauma, developmental malformations, genetic causes, and others – and these underlying etiologies may well contribute to the presence of depression and suicidality in this population,” he said in an interview. “Psychodynamic influences also may occur as a consequence of having seizures. This is a complicated area, and drugs are simply one piece of the puzzle,” he added.
Dr. Sperling said the FDA has accomplished “one useful thing with its warning – it highlighted that physicians and other health care providers must pay attention to their patients’ psychological state, ask questions, and treat accordingly.”
The study had no specific funding. Dr. Sperling has received grants from Eisai, Medtronic, Neurelis, SK Life Science, Sunovion, Takeda, Xenon, Cerevel Therapeutics, UCB Pharma, and Engage Pharma; personal fees from Neurelis, Medscape, Neurology Live, International Medical Press, UCB Pharma, Eisai, Oxford University Press, and Projects in Knowledge. He has also consulted for Medtronic outside the submitted work; payments went to Thomas Jefferson University. A complete list of authors’ disclosures is available with the original article.
A version of this article first appeared on Medscape.com.
, new research shows. “There appears to be no justification for the FDA to label every new antiseizure medication with a warning that it may increase risk of suicidality,” said study investigator Michael R. Sperling, MD, professor of neurology, Thomas Jefferson University, Philadelphia.
“How many patients are afraid of their medication and do not take it because of the warning – and are consequently at risk because of that? We do not know, but have anecdotal experience that this is certainly an issue,” Dr. Sperling, who is director of the Jefferson Comprehensive Epilepsy Center, added.
The study was published online August 2 in JAMA Neurology.
Blanket warning
In 2008, the FDA issued an alert stating that antiseizure medications increase suicidality. The alert was based on pooled data from placebo-controlled clinical trials that included 11 antiseizure medications – carbamazepine, felbamate, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, pregabalin, tiagabine, topiramate, valproate, and zonisamide.
The meta-analytic review showed that, compared with placebo, antiseizure medications nearly doubled suicide risk among patients treated for epilepsy, psychiatric disorders, and other diseases. As a result of the FDA study, all antiseizure medications that have been approved since 2008 carry a warning for suicidality.
However, subsequent analyses did not show the same results, Dr. Sperling and colleagues noted.
“Pivotal” antiseizure medication epilepsy trials since 2008 have evaluated suicidality prospectively. Since 2011, trials have included the validated Columbia Suicidality Severity Rating Scale, they noted.
Meta analysis showed no increased risk
Dr. Sperling and colleagues conducted a meta-analysis of 17 randomized placebo-controlled epilepsy trials of five antiseizure medications approved since 2008. These antiseizure medications were eslicarbazepine, perampanel, brivaracetam, cannabidiol, and cenobamate. The trials involved 5,996 patients, including 4,000 who were treated with antiseizure medications and 1,996 who were treated with placebo.
Confining the analysis to epilepsy trials avoids potential confounders, such as possible differences in suicidality risks between different diseases, the researchers noted.
They found no evidence of increased risk for suicidal ideation (overall risk ratio, antiseizure medications vs. placebo: 0.75; 95% confidence interval: 0.35-1.60) or suicide attempt (risk ratio, 0.75; 95% CI: 0.30-1.87) overall or for any individual antiseizure medication.
Suicidal ideation occurred in 12 of 4,000 patients treated with antiseizure medications (0.30%), versus 7 of 1,996 patients treated with placebo (0.35%) (P = .74). Three patients who were treated with antiseizure medications attempted suicide; no patients who were treated with placebo attempted suicide (P = .22). There were no completed suicides.
“There is no current evidence that the five antiseizure medications evaluated in this study increase suicidality in epilepsy and merit a suicidality class warning,” the investigators wrote. When prescribed for epilepsy, “evidence does not support the FDA’s labeling practice of a blanket assumption of increased suicidality,” said Dr. Sperling.
“Our findings indicate the nonspecific suicide warning for all epilepsy drugs is simply not justifiable,” he said. “The results are not surprising. Different drugs affect cells in different ways. So there’s no reason to expect that every drug would increase suicide risk for every patient,” Dr. Sperling said in a statement.
“It’s important to recognize that epilepsy has many causes – perinatal injury, stroke, tumor, head trauma, developmental malformations, genetic causes, and others – and these underlying etiologies may well contribute to the presence of depression and suicidality in this population,” he said in an interview. “Psychodynamic influences also may occur as a consequence of having seizures. This is a complicated area, and drugs are simply one piece of the puzzle,” he added.
Dr. Sperling said the FDA has accomplished “one useful thing with its warning – it highlighted that physicians and other health care providers must pay attention to their patients’ psychological state, ask questions, and treat accordingly.”
The study had no specific funding. Dr. Sperling has received grants from Eisai, Medtronic, Neurelis, SK Life Science, Sunovion, Takeda, Xenon, Cerevel Therapeutics, UCB Pharma, and Engage Pharma; personal fees from Neurelis, Medscape, Neurology Live, International Medical Press, UCB Pharma, Eisai, Oxford University Press, and Projects in Knowledge. He has also consulted for Medtronic outside the submitted work; payments went to Thomas Jefferson University. A complete list of authors’ disclosures is available with the original article.
A version of this article first appeared on Medscape.com.
FROM JAMA NEUROLOGY
Exercise tied to 50% reduction in mortality after stroke
, with a greater than 50% reduction in risk.
Lead study author Raed A. Joundi, MD, DPhil, of the University of Calgary (Alta.), said he expected results to show exercise was beneficial, but was surprised by the magnitude of the association between physical activity and lower mortality risk.
The impact of physical activity also differed significantly by age; those younger than 75 had a 79% reduction in mortality risk, compared with 32% in those age 75 and older.
“This is even after adjusting for factors such heart disease, respiratory conditions, smoking, and other functional limitations,” said Dr. Joundi.
The study was published online Aug. 11 in the journal Neurology.
For this analysis, the researchers used data on a cohort of people across Canada (excluding the province of Quebec) over 3-9 years. The 895 patients with prior stroke averaged 72 years of age, while the 97,805 in the control group had an average age of 63.
Weekly physical activity averages were evaluated using the self-reporting Canadian Community Health Survey, which was linked with administrative databases to evaluate the association of physical activity with long-term risk for mortality among stroke survivors, compared with controls.
Physical activity was measured in metabolic equivalents (METs); meeting minimum physical activity guidelines was defined as 10 MET-hours/week.
During the study period, more stroke patients than controls died (24.7% vs. 5.7%). However, those who met the physical activity guideline recommendations of 10 MET-hours/week had a lower mortality, both in the stroke survivor group (14.6% vs. 33.2%; adjusted hazard ratio, 0.46; 95% confidence interval, 0.29-0.73) and among control participants (3.6% vs. 7.9%; aHR 0.69; 95% CI, 0.62-0.76).
The largest absolute and relative reduction in mortality was among stroke respondents younger than 75 (10.5% vs. 29%; aHR, 0.21; 95% CI, 0.10-0.43), the researchers note.
There was a significant interaction with age for the stroke patients but not the control group.
“The greatest reduction in mortality was seen between 0 and 10 METs per week … so the main point is that something is better than nothing,” said Dr. Joundi.
Exercise guidelines for the future
Although current guidelines recommend physical activity in stroke survivors, investigators noted that these are largely based on studies in the general population. Therefore, the aim of this research was to get a better understanding of the role of physical activity in the health of stroke survivors in the community, which could ultimately be used to design improved public health campaigns and physical activity interventions.
Given that this is a large study of stroke survivors in the community, Dr. Joundi hopes the results will influence future activity guidelines for those who have suffered a stroke.
“We found a log-linear relationship between physical activity and mortality such that 10 MET-hours/week was associated with large reductions in mortality with most benefit achieved by 20 MET-hours/week,” the authors concluded. “These thresholds could be considered for use in future guidelines for stroke.”
Clinical trials are underway to provide evidence for the implementation of exercise programs after stroke, they add, and offering physical activity programs to stroke survivors in the community “is an increasing priority in the U.S., Canada, and Europe.”
“People are at higher risk of death early on after a stroke but also months and years later, so if we can identify a relatively low-cost and easy intervention like physical activity to improve health and reduce the risk of death for stroke survivors it would be important,” Dr. Joundi said.
Key barriers
Paul George, MD, PhD, a stroke and vascular neurologist at Stanford (Calif.) University, said findings such as these further strengthen the argument that physical exercise is important after stroke.
“Because the study looked specifically at stroke patients, it can provide further guidance on physical activity recommendations that we provide to our patients following stroke,” said Dr. George, who was not associated with the study.
Going forward, he said, more research is needed to identify specifically what is preventing stroke patients from exercising more. What is required, he said, is “future research to determine the key barriers to physical activity following stroke and methods to reduce these will also be important to increasing physical activity in stroke survivors.”
Dr. Joundi said determining how to tailor exercise recommendations to meet the wide range of capabilities of stroke survivors will be another key factor.
“Stroke survivors may have some disabilities, so we need to be able to engage them at an [exercise] level that’s possible for them,” he said.
The study did not include stroke survivors living in long-term care homes.
The study had no targeted funding. Coauthor Eric E. Smith, MD, MPH, reports royalties from UpToDate, and consulting fees from Alnylam, Biogen, and Javelin. Dr. Joundi and the other coauthors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, with a greater than 50% reduction in risk.
Lead study author Raed A. Joundi, MD, DPhil, of the University of Calgary (Alta.), said he expected results to show exercise was beneficial, but was surprised by the magnitude of the association between physical activity and lower mortality risk.
The impact of physical activity also differed significantly by age; those younger than 75 had a 79% reduction in mortality risk, compared with 32% in those age 75 and older.
“This is even after adjusting for factors such heart disease, respiratory conditions, smoking, and other functional limitations,” said Dr. Joundi.
The study was published online Aug. 11 in the journal Neurology.
For this analysis, the researchers used data on a cohort of people across Canada (excluding the province of Quebec) over 3-9 years. The 895 patients with prior stroke averaged 72 years of age, while the 97,805 in the control group had an average age of 63.
Weekly physical activity averages were evaluated using the self-reporting Canadian Community Health Survey, which was linked with administrative databases to evaluate the association of physical activity with long-term risk for mortality among stroke survivors, compared with controls.
Physical activity was measured in metabolic equivalents (METs); meeting minimum physical activity guidelines was defined as 10 MET-hours/week.
During the study period, more stroke patients than controls died (24.7% vs. 5.7%). However, those who met the physical activity guideline recommendations of 10 MET-hours/week had a lower mortality, both in the stroke survivor group (14.6% vs. 33.2%; adjusted hazard ratio, 0.46; 95% confidence interval, 0.29-0.73) and among control participants (3.6% vs. 7.9%; aHR 0.69; 95% CI, 0.62-0.76).
The largest absolute and relative reduction in mortality was among stroke respondents younger than 75 (10.5% vs. 29%; aHR, 0.21; 95% CI, 0.10-0.43), the researchers note.
There was a significant interaction with age for the stroke patients but not the control group.
“The greatest reduction in mortality was seen between 0 and 10 METs per week … so the main point is that something is better than nothing,” said Dr. Joundi.
Exercise guidelines for the future
Although current guidelines recommend physical activity in stroke survivors, investigators noted that these are largely based on studies in the general population. Therefore, the aim of this research was to get a better understanding of the role of physical activity in the health of stroke survivors in the community, which could ultimately be used to design improved public health campaigns and physical activity interventions.
Given that this is a large study of stroke survivors in the community, Dr. Joundi hopes the results will influence future activity guidelines for those who have suffered a stroke.
“We found a log-linear relationship between physical activity and mortality such that 10 MET-hours/week was associated with large reductions in mortality with most benefit achieved by 20 MET-hours/week,” the authors concluded. “These thresholds could be considered for use in future guidelines for stroke.”
Clinical trials are underway to provide evidence for the implementation of exercise programs after stroke, they add, and offering physical activity programs to stroke survivors in the community “is an increasing priority in the U.S., Canada, and Europe.”
“People are at higher risk of death early on after a stroke but also months and years later, so if we can identify a relatively low-cost and easy intervention like physical activity to improve health and reduce the risk of death for stroke survivors it would be important,” Dr. Joundi said.
Key barriers
Paul George, MD, PhD, a stroke and vascular neurologist at Stanford (Calif.) University, said findings such as these further strengthen the argument that physical exercise is important after stroke.
“Because the study looked specifically at stroke patients, it can provide further guidance on physical activity recommendations that we provide to our patients following stroke,” said Dr. George, who was not associated with the study.
Going forward, he said, more research is needed to identify specifically what is preventing stroke patients from exercising more. What is required, he said, is “future research to determine the key barriers to physical activity following stroke and methods to reduce these will also be important to increasing physical activity in stroke survivors.”
Dr. Joundi said determining how to tailor exercise recommendations to meet the wide range of capabilities of stroke survivors will be another key factor.
“Stroke survivors may have some disabilities, so we need to be able to engage them at an [exercise] level that’s possible for them,” he said.
The study did not include stroke survivors living in long-term care homes.
The study had no targeted funding. Coauthor Eric E. Smith, MD, MPH, reports royalties from UpToDate, and consulting fees from Alnylam, Biogen, and Javelin. Dr. Joundi and the other coauthors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, with a greater than 50% reduction in risk.
Lead study author Raed A. Joundi, MD, DPhil, of the University of Calgary (Alta.), said he expected results to show exercise was beneficial, but was surprised by the magnitude of the association between physical activity and lower mortality risk.
The impact of physical activity also differed significantly by age; those younger than 75 had a 79% reduction in mortality risk, compared with 32% in those age 75 and older.
“This is even after adjusting for factors such heart disease, respiratory conditions, smoking, and other functional limitations,” said Dr. Joundi.
The study was published online Aug. 11 in the journal Neurology.
For this analysis, the researchers used data on a cohort of people across Canada (excluding the province of Quebec) over 3-9 years. The 895 patients with prior stroke averaged 72 years of age, while the 97,805 in the control group had an average age of 63.
Weekly physical activity averages were evaluated using the self-reporting Canadian Community Health Survey, which was linked with administrative databases to evaluate the association of physical activity with long-term risk for mortality among stroke survivors, compared with controls.
Physical activity was measured in metabolic equivalents (METs); meeting minimum physical activity guidelines was defined as 10 MET-hours/week.
During the study period, more stroke patients than controls died (24.7% vs. 5.7%). However, those who met the physical activity guideline recommendations of 10 MET-hours/week had a lower mortality, both in the stroke survivor group (14.6% vs. 33.2%; adjusted hazard ratio, 0.46; 95% confidence interval, 0.29-0.73) and among control participants (3.6% vs. 7.9%; aHR 0.69; 95% CI, 0.62-0.76).
The largest absolute and relative reduction in mortality was among stroke respondents younger than 75 (10.5% vs. 29%; aHR, 0.21; 95% CI, 0.10-0.43), the researchers note.
There was a significant interaction with age for the stroke patients but not the control group.
“The greatest reduction in mortality was seen between 0 and 10 METs per week … so the main point is that something is better than nothing,” said Dr. Joundi.
Exercise guidelines for the future
Although current guidelines recommend physical activity in stroke survivors, investigators noted that these are largely based on studies in the general population. Therefore, the aim of this research was to get a better understanding of the role of physical activity in the health of stroke survivors in the community, which could ultimately be used to design improved public health campaigns and physical activity interventions.
Given that this is a large study of stroke survivors in the community, Dr. Joundi hopes the results will influence future activity guidelines for those who have suffered a stroke.
“We found a log-linear relationship between physical activity and mortality such that 10 MET-hours/week was associated with large reductions in mortality with most benefit achieved by 20 MET-hours/week,” the authors concluded. “These thresholds could be considered for use in future guidelines for stroke.”
Clinical trials are underway to provide evidence for the implementation of exercise programs after stroke, they add, and offering physical activity programs to stroke survivors in the community “is an increasing priority in the U.S., Canada, and Europe.”
“People are at higher risk of death early on after a stroke but also months and years later, so if we can identify a relatively low-cost and easy intervention like physical activity to improve health and reduce the risk of death for stroke survivors it would be important,” Dr. Joundi said.
Key barriers
Paul George, MD, PhD, a stroke and vascular neurologist at Stanford (Calif.) University, said findings such as these further strengthen the argument that physical exercise is important after stroke.
“Because the study looked specifically at stroke patients, it can provide further guidance on physical activity recommendations that we provide to our patients following stroke,” said Dr. George, who was not associated with the study.
Going forward, he said, more research is needed to identify specifically what is preventing stroke patients from exercising more. What is required, he said, is “future research to determine the key barriers to physical activity following stroke and methods to reduce these will also be important to increasing physical activity in stroke survivors.”
Dr. Joundi said determining how to tailor exercise recommendations to meet the wide range of capabilities of stroke survivors will be another key factor.
“Stroke survivors may have some disabilities, so we need to be able to engage them at an [exercise] level that’s possible for them,” he said.
The study did not include stroke survivors living in long-term care homes.
The study had no targeted funding. Coauthor Eric E. Smith, MD, MPH, reports royalties from UpToDate, and consulting fees from Alnylam, Biogen, and Javelin. Dr. Joundi and the other coauthors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Flavonoids dietary ‘powerhouses’ for cognitive decline prevention
, new research shows.
Among the different types of flavonoids, flavones (found in some spices and yellow or orange fruits and vegetables) and anthocyanins (found in blueberries, blackberries, and cherries) seem to have most protective effect, the researchers report.
“There is mounting evidence suggesting flavonoids are powerhouses when it comes to preventing your thinking skills from declining as you get older,” study investigator Walter Willett, MD, DrPH, Harvard University, Boston, said in a statement.
“Our results are exciting because they show that making simple changes to your diet could help prevent cognitive decline,” said Dr. Willett.
The study was published online July 28 in the journal Neurology.
Antioxidant punch
Flavonoids, naturally occurring phytochemicals found in plants, are strong antioxidants. Considering the likely role of oxidative stress in age-related cognitive decline, flavonoids have been proposed as a potentially important preventive.
For the study, Dr. Willett and colleagues prospectively examined associations between long-term dietary flavonoids (flavonols, flavones, flavanones, flavan-3-ols, anthocyanins, polymeric flavonoids, and proanthocyanidins) and subjective cognitive decline in 49,493 women from the Nurses’ Health Study (1984-2006) and 27,842 men from the Health Professionals Follow-up Study (1986-2002).
Those in the highest quintile of flavonoid consumption consumed about 600 mg daily on average while those in the lowest quintile got only about 150 mg daily.
After adjusting for age, total energy intake, major nondietary factors, and specific dietary factors, a higher intake of total flavonoids was associated with lower likelihood of self-reported subjective cognitive decline during follow up.
Individuals in the highest quintile of daily consumption had about a 20% lower risk of subjective cognitive decline relative to peers in the lowest quintile (pooled multivariable-adjusted odds ratio: 0.81; 95% confidence interval, 0.76-0.89).
The strongest protective associations were found for flavones (OR, 0.62; 95% confidence interval, 0.57-0.68), flavanones (OR, 0.64; 95% CI, 0.58-0.68), and anthocyanins (OR, 0.76; 95% CI, 0.72-0.84) (P trend < .0001 for all groups).
“The people in our study who did the best over time ate an average of at least half a serving per day of foods like orange juice, oranges, peppers, celery, grapefruits, grapefruit juice, apples, and pears,” Dr. Willett said.
“While it is possible other phytochemicals are at work here, a colorful diet rich in flavonoids – and specifically flavones and anthocyanins – seems to be a good bet for promoting long-term brain health,” he added.
A limitation of the study is that participants reported on their diets and may not recall perfectly what they ate or how much.
Healthy diet best bet for brain health
Reached for comment, Christopher Weber, PhD, director of global science initiatives for the Alzheimer’s Association, said this study “adds to our understanding of which elements of a healthy diet may be important in reducing dementia risk; flavonols may be one of those elements.”
“However, at this point, people should not put too much stock in specific nutrients – including subsets of flavonols – for reducing dementia risk until more research is done. Rather, they should focus on eating an overall healthy diet,” he said.
“It would be wonderful if a particular food or supplement could delay or prevent Alzheimer’s disease, but we do not have scientific evidence to support such claims. Randomized controlled clinical trials are necessary to evaluate whether any food or supplement has a scientifically proven beneficial effect,” Dr. Weber added.
For now, the Alzheimer’s Association “encourages everyone to eat a healthy and balanced diet as a way to help reduce the risk of cognitive decline,” Dr. Weber said.
“With more than 6 million Americans living with Alzheimer’s disease and other dementia today, there is a pressing need to test the effectiveness of a healthy lifestyle regimen to reduce risk of cognitive decline in a large and diverse population,” he added.
The Alzheimer’s Association has launched a 2-year clinical trial, called the U.S. Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk (U.S. POINTER), to do just that.
“While we research that definitive lifestyle ‘recipe,’ there are things we can do today that may decrease our risk of cognitive decline as we age. Eating a heart-healthy diet, exercising regularly, and staying cognitively engaged are just a few,” Dr. Weber added.
Also weighing in, Taylor Wallace, PhD, adjunct professor, department of nutrition and food studies, George Mason University, Fairfax, Va., said the study results are not surprising.
“Scientific data on the ability of flavonoids to prevent age-related chronic diseases, including cognitive decline, has accumulated immensely over the last decade. This epidemiological study reinforces findings from smaller shorter-duration clinical trials and mechanistic studies,” said Dr. Wallace, who was not involved in the study.
“Flavonoids show great potential in reducing inflammation and oxidative stress in the body. They are also vasodilators that help improve blood flow, which is important for the cardiovascular and cerebrovascular systems,” he noted.
“Typically, foods rich in flavonoids are also nutrient-dense in vitamins, minerals, and dietary fiber (eg, fruits and vegetables). Anthocyanins in blueberries have long been known to prevent cognitive decline with age,” Dr. Wallace said.
Dr. Wallace was part of a 14-member panel of nutrition scientists who recently reviewed available evidence around fruit and vegetable intake and health.
“Our findings are consistent with this study in regard to cognitive decline and other disease states. Cruciferous vegetables, dark-green leafy vegetables, citrus fruits, and dark-colored berries seem to have superior effects on health promotion and disease prevention in general,” said Dr. Wallace.
This work was supported by grants from the National Institutes of Health. The authors have disclosed no relevant financial relationships. Dr. Weber has no relevant disclosures. Dr. Wallace is principal and chief executive officer of the Think Healthy Group; editor of the Journal of Dietary Supplements; and deputy editor-in-chief of the Journal of the American College of Nutrition.
A version of this article first appeared on Medscape.com.
, new research shows.
Among the different types of flavonoids, flavones (found in some spices and yellow or orange fruits and vegetables) and anthocyanins (found in blueberries, blackberries, and cherries) seem to have most protective effect, the researchers report.
“There is mounting evidence suggesting flavonoids are powerhouses when it comes to preventing your thinking skills from declining as you get older,” study investigator Walter Willett, MD, DrPH, Harvard University, Boston, said in a statement.
“Our results are exciting because they show that making simple changes to your diet could help prevent cognitive decline,” said Dr. Willett.
The study was published online July 28 in the journal Neurology.
Antioxidant punch
Flavonoids, naturally occurring phytochemicals found in plants, are strong antioxidants. Considering the likely role of oxidative stress in age-related cognitive decline, flavonoids have been proposed as a potentially important preventive.
For the study, Dr. Willett and colleagues prospectively examined associations between long-term dietary flavonoids (flavonols, flavones, flavanones, flavan-3-ols, anthocyanins, polymeric flavonoids, and proanthocyanidins) and subjective cognitive decline in 49,493 women from the Nurses’ Health Study (1984-2006) and 27,842 men from the Health Professionals Follow-up Study (1986-2002).
Those in the highest quintile of flavonoid consumption consumed about 600 mg daily on average while those in the lowest quintile got only about 150 mg daily.
After adjusting for age, total energy intake, major nondietary factors, and specific dietary factors, a higher intake of total flavonoids was associated with lower likelihood of self-reported subjective cognitive decline during follow up.
Individuals in the highest quintile of daily consumption had about a 20% lower risk of subjective cognitive decline relative to peers in the lowest quintile (pooled multivariable-adjusted odds ratio: 0.81; 95% confidence interval, 0.76-0.89).
The strongest protective associations were found for flavones (OR, 0.62; 95% confidence interval, 0.57-0.68), flavanones (OR, 0.64; 95% CI, 0.58-0.68), and anthocyanins (OR, 0.76; 95% CI, 0.72-0.84) (P trend < .0001 for all groups).
“The people in our study who did the best over time ate an average of at least half a serving per day of foods like orange juice, oranges, peppers, celery, grapefruits, grapefruit juice, apples, and pears,” Dr. Willett said.
“While it is possible other phytochemicals are at work here, a colorful diet rich in flavonoids – and specifically flavones and anthocyanins – seems to be a good bet for promoting long-term brain health,” he added.
A limitation of the study is that participants reported on their diets and may not recall perfectly what they ate or how much.
Healthy diet best bet for brain health
Reached for comment, Christopher Weber, PhD, director of global science initiatives for the Alzheimer’s Association, said this study “adds to our understanding of which elements of a healthy diet may be important in reducing dementia risk; flavonols may be one of those elements.”
“However, at this point, people should not put too much stock in specific nutrients – including subsets of flavonols – for reducing dementia risk until more research is done. Rather, they should focus on eating an overall healthy diet,” he said.
“It would be wonderful if a particular food or supplement could delay or prevent Alzheimer’s disease, but we do not have scientific evidence to support such claims. Randomized controlled clinical trials are necessary to evaluate whether any food or supplement has a scientifically proven beneficial effect,” Dr. Weber added.
For now, the Alzheimer’s Association “encourages everyone to eat a healthy and balanced diet as a way to help reduce the risk of cognitive decline,” Dr. Weber said.
“With more than 6 million Americans living with Alzheimer’s disease and other dementia today, there is a pressing need to test the effectiveness of a healthy lifestyle regimen to reduce risk of cognitive decline in a large and diverse population,” he added.
The Alzheimer’s Association has launched a 2-year clinical trial, called the U.S. Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk (U.S. POINTER), to do just that.
“While we research that definitive lifestyle ‘recipe,’ there are things we can do today that may decrease our risk of cognitive decline as we age. Eating a heart-healthy diet, exercising regularly, and staying cognitively engaged are just a few,” Dr. Weber added.
Also weighing in, Taylor Wallace, PhD, adjunct professor, department of nutrition and food studies, George Mason University, Fairfax, Va., said the study results are not surprising.
“Scientific data on the ability of flavonoids to prevent age-related chronic diseases, including cognitive decline, has accumulated immensely over the last decade. This epidemiological study reinforces findings from smaller shorter-duration clinical trials and mechanistic studies,” said Dr. Wallace, who was not involved in the study.
“Flavonoids show great potential in reducing inflammation and oxidative stress in the body. They are also vasodilators that help improve blood flow, which is important for the cardiovascular and cerebrovascular systems,” he noted.
“Typically, foods rich in flavonoids are also nutrient-dense in vitamins, minerals, and dietary fiber (eg, fruits and vegetables). Anthocyanins in blueberries have long been known to prevent cognitive decline with age,” Dr. Wallace said.
Dr. Wallace was part of a 14-member panel of nutrition scientists who recently reviewed available evidence around fruit and vegetable intake and health.
“Our findings are consistent with this study in regard to cognitive decline and other disease states. Cruciferous vegetables, dark-green leafy vegetables, citrus fruits, and dark-colored berries seem to have superior effects on health promotion and disease prevention in general,” said Dr. Wallace.
This work was supported by grants from the National Institutes of Health. The authors have disclosed no relevant financial relationships. Dr. Weber has no relevant disclosures. Dr. Wallace is principal and chief executive officer of the Think Healthy Group; editor of the Journal of Dietary Supplements; and deputy editor-in-chief of the Journal of the American College of Nutrition.
A version of this article first appeared on Medscape.com.
, new research shows.
Among the different types of flavonoids, flavones (found in some spices and yellow or orange fruits and vegetables) and anthocyanins (found in blueberries, blackberries, and cherries) seem to have most protective effect, the researchers report.
“There is mounting evidence suggesting flavonoids are powerhouses when it comes to preventing your thinking skills from declining as you get older,” study investigator Walter Willett, MD, DrPH, Harvard University, Boston, said in a statement.
“Our results are exciting because they show that making simple changes to your diet could help prevent cognitive decline,” said Dr. Willett.
The study was published online July 28 in the journal Neurology.
Antioxidant punch
Flavonoids, naturally occurring phytochemicals found in plants, are strong antioxidants. Considering the likely role of oxidative stress in age-related cognitive decline, flavonoids have been proposed as a potentially important preventive.
For the study, Dr. Willett and colleagues prospectively examined associations between long-term dietary flavonoids (flavonols, flavones, flavanones, flavan-3-ols, anthocyanins, polymeric flavonoids, and proanthocyanidins) and subjective cognitive decline in 49,493 women from the Nurses’ Health Study (1984-2006) and 27,842 men from the Health Professionals Follow-up Study (1986-2002).
Those in the highest quintile of flavonoid consumption consumed about 600 mg daily on average while those in the lowest quintile got only about 150 mg daily.
After adjusting for age, total energy intake, major nondietary factors, and specific dietary factors, a higher intake of total flavonoids was associated with lower likelihood of self-reported subjective cognitive decline during follow up.
Individuals in the highest quintile of daily consumption had about a 20% lower risk of subjective cognitive decline relative to peers in the lowest quintile (pooled multivariable-adjusted odds ratio: 0.81; 95% confidence interval, 0.76-0.89).
The strongest protective associations were found for flavones (OR, 0.62; 95% confidence interval, 0.57-0.68), flavanones (OR, 0.64; 95% CI, 0.58-0.68), and anthocyanins (OR, 0.76; 95% CI, 0.72-0.84) (P trend < .0001 for all groups).
“The people in our study who did the best over time ate an average of at least half a serving per day of foods like orange juice, oranges, peppers, celery, grapefruits, grapefruit juice, apples, and pears,” Dr. Willett said.
“While it is possible other phytochemicals are at work here, a colorful diet rich in flavonoids – and specifically flavones and anthocyanins – seems to be a good bet for promoting long-term brain health,” he added.
A limitation of the study is that participants reported on their diets and may not recall perfectly what they ate or how much.
Healthy diet best bet for brain health
Reached for comment, Christopher Weber, PhD, director of global science initiatives for the Alzheimer’s Association, said this study “adds to our understanding of which elements of a healthy diet may be important in reducing dementia risk; flavonols may be one of those elements.”
“However, at this point, people should not put too much stock in specific nutrients – including subsets of flavonols – for reducing dementia risk until more research is done. Rather, they should focus on eating an overall healthy diet,” he said.
“It would be wonderful if a particular food or supplement could delay or prevent Alzheimer’s disease, but we do not have scientific evidence to support such claims. Randomized controlled clinical trials are necessary to evaluate whether any food or supplement has a scientifically proven beneficial effect,” Dr. Weber added.
For now, the Alzheimer’s Association “encourages everyone to eat a healthy and balanced diet as a way to help reduce the risk of cognitive decline,” Dr. Weber said.
“With more than 6 million Americans living with Alzheimer’s disease and other dementia today, there is a pressing need to test the effectiveness of a healthy lifestyle regimen to reduce risk of cognitive decline in a large and diverse population,” he added.
The Alzheimer’s Association has launched a 2-year clinical trial, called the U.S. Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk (U.S. POINTER), to do just that.
“While we research that definitive lifestyle ‘recipe,’ there are things we can do today that may decrease our risk of cognitive decline as we age. Eating a heart-healthy diet, exercising regularly, and staying cognitively engaged are just a few,” Dr. Weber added.
Also weighing in, Taylor Wallace, PhD, adjunct professor, department of nutrition and food studies, George Mason University, Fairfax, Va., said the study results are not surprising.
“Scientific data on the ability of flavonoids to prevent age-related chronic diseases, including cognitive decline, has accumulated immensely over the last decade. This epidemiological study reinforces findings from smaller shorter-duration clinical trials and mechanistic studies,” said Dr. Wallace, who was not involved in the study.
“Flavonoids show great potential in reducing inflammation and oxidative stress in the body. They are also vasodilators that help improve blood flow, which is important for the cardiovascular and cerebrovascular systems,” he noted.
“Typically, foods rich in flavonoids are also nutrient-dense in vitamins, minerals, and dietary fiber (eg, fruits and vegetables). Anthocyanins in blueberries have long been known to prevent cognitive decline with age,” Dr. Wallace said.
Dr. Wallace was part of a 14-member panel of nutrition scientists who recently reviewed available evidence around fruit and vegetable intake and health.
“Our findings are consistent with this study in regard to cognitive decline and other disease states. Cruciferous vegetables, dark-green leafy vegetables, citrus fruits, and dark-colored berries seem to have superior effects on health promotion and disease prevention in general,” said Dr. Wallace.
This work was supported by grants from the National Institutes of Health. The authors have disclosed no relevant financial relationships. Dr. Weber has no relevant disclosures. Dr. Wallace is principal and chief executive officer of the Think Healthy Group; editor of the Journal of Dietary Supplements; and deputy editor-in-chief of the Journal of the American College of Nutrition.
A version of this article first appeared on Medscape.com.
FROM NEUROLOGY