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Virtual Reality Brings Relief to Hospitalized Patients With Cancer
suggests a new randomized controlled trial.
While both interventions brought some pain relief, VR therapy yielded greater, longer-lasting comfort, reported lead author Hunter Groninger, MD, of MedStar Health Research Institute, Hyattsville, Maryland, and colleagues.
“Investigators have explored immersive VR interventions in cancer populations for a variety of indications including anxiety, depression, fatigue, and procedure‐associated pain, particularly among patients with pediatric cancer and adult breast cancer,” the investigators wrote in Cancer. “Nevertheless, despite growing evidence supporting the efficacy of VR‐delivered interventions for analgesia, few data address its role to mitigate cancer‐related pain specifically.”
To address this knowledge gap, Dr. Groninger and colleagues enrolled 128 adult hospitalized patients with cancer of any kind, all of whom had moderate to severe pain (self-reported score at least 4 out of 10) within the past 24 hours.
Study Methods and Results
Patients were randomized to receive either 10 minutes of immersive VR distraction therapy or 10 minutes of two-dimensional guided imagery distraction therapy.
“[The VR therapy] provides noncompetitive experiences in which the user can move around and explore natural environments (e.g., beachscape, forest) from standing, seated, or fixed positions, including within a hospital bed or chair,” the investigators wrote. “We provided over‐the‐ear headphones to assure high sound quality for the experience in the virtual natural environment.”
The two-dimensional intervention, delivered via electronic tablet, featured a meditation with images of natural landscapes and instrumental background music.
“We chose this active control because it is readily available and reflects content similar to relaxation‐focused television channels that are increasingly common in hospital settings,” the investigators noted.
Compared with this more common approach, patients who received VR therapy had significantly greater immediate reduction in pain (mean change in pain score, –1.4 vs –0.7; P = .03). Twenty-four hours later, improvements in the VR group generally persisted, while pain level in the two-dimensional group returned almost to baseline (P = .004). In addition, patients in the VR group reported significantly greater improvements in general distress and pain bothersomeness.
“VR therapies may modulate the pain experience by reducing the level of attention paid to noxious stimuli, thereby suppressing transmission of painful sensations via pain processing pathways to the cerebral cortex, particularly with more active VR experiences compared to passive experiences,” the investigators wrote.
Downsides to Using VR
Although VR brought more benefit, participants in the VR group more often reported difficulty using the intervention compared with those who interacted with an electronic tablet.
Plus, one VR user described mild dizziness that resolved with pharmacologic intervention. Still, approximately 9 out of 10 participants in each group reported willingness to try the intervention again.
Future VR Research
“Virtual reality is a rapidly evolving technology with a wealth of potential patient‐facing applications,” the investigators wrote. “Future studies should explore repeated use, optimal dosing, and impact on VR therapy on opioid analgesic requirements as well as usability testing, VR content preferences and facilitators of analgesia, and barriers and facilitators to use in acute care settings.”
This study was supported by the American Cancer Society. The investigators disclosed no conflicts of interest.
suggests a new randomized controlled trial.
While both interventions brought some pain relief, VR therapy yielded greater, longer-lasting comfort, reported lead author Hunter Groninger, MD, of MedStar Health Research Institute, Hyattsville, Maryland, and colleagues.
“Investigators have explored immersive VR interventions in cancer populations for a variety of indications including anxiety, depression, fatigue, and procedure‐associated pain, particularly among patients with pediatric cancer and adult breast cancer,” the investigators wrote in Cancer. “Nevertheless, despite growing evidence supporting the efficacy of VR‐delivered interventions for analgesia, few data address its role to mitigate cancer‐related pain specifically.”
To address this knowledge gap, Dr. Groninger and colleagues enrolled 128 adult hospitalized patients with cancer of any kind, all of whom had moderate to severe pain (self-reported score at least 4 out of 10) within the past 24 hours.
Study Methods and Results
Patients were randomized to receive either 10 minutes of immersive VR distraction therapy or 10 minutes of two-dimensional guided imagery distraction therapy.
“[The VR therapy] provides noncompetitive experiences in which the user can move around and explore natural environments (e.g., beachscape, forest) from standing, seated, or fixed positions, including within a hospital bed or chair,” the investigators wrote. “We provided over‐the‐ear headphones to assure high sound quality for the experience in the virtual natural environment.”
The two-dimensional intervention, delivered via electronic tablet, featured a meditation with images of natural landscapes and instrumental background music.
“We chose this active control because it is readily available and reflects content similar to relaxation‐focused television channels that are increasingly common in hospital settings,” the investigators noted.
Compared with this more common approach, patients who received VR therapy had significantly greater immediate reduction in pain (mean change in pain score, –1.4 vs –0.7; P = .03). Twenty-four hours later, improvements in the VR group generally persisted, while pain level in the two-dimensional group returned almost to baseline (P = .004). In addition, patients in the VR group reported significantly greater improvements in general distress and pain bothersomeness.
“VR therapies may modulate the pain experience by reducing the level of attention paid to noxious stimuli, thereby suppressing transmission of painful sensations via pain processing pathways to the cerebral cortex, particularly with more active VR experiences compared to passive experiences,” the investigators wrote.
Downsides to Using VR
Although VR brought more benefit, participants in the VR group more often reported difficulty using the intervention compared with those who interacted with an electronic tablet.
Plus, one VR user described mild dizziness that resolved with pharmacologic intervention. Still, approximately 9 out of 10 participants in each group reported willingness to try the intervention again.
Future VR Research
“Virtual reality is a rapidly evolving technology with a wealth of potential patient‐facing applications,” the investigators wrote. “Future studies should explore repeated use, optimal dosing, and impact on VR therapy on opioid analgesic requirements as well as usability testing, VR content preferences and facilitators of analgesia, and barriers and facilitators to use in acute care settings.”
This study was supported by the American Cancer Society. The investigators disclosed no conflicts of interest.
suggests a new randomized controlled trial.
While both interventions brought some pain relief, VR therapy yielded greater, longer-lasting comfort, reported lead author Hunter Groninger, MD, of MedStar Health Research Institute, Hyattsville, Maryland, and colleagues.
“Investigators have explored immersive VR interventions in cancer populations for a variety of indications including anxiety, depression, fatigue, and procedure‐associated pain, particularly among patients with pediatric cancer and adult breast cancer,” the investigators wrote in Cancer. “Nevertheless, despite growing evidence supporting the efficacy of VR‐delivered interventions for analgesia, few data address its role to mitigate cancer‐related pain specifically.”
To address this knowledge gap, Dr. Groninger and colleagues enrolled 128 adult hospitalized patients with cancer of any kind, all of whom had moderate to severe pain (self-reported score at least 4 out of 10) within the past 24 hours.
Study Methods and Results
Patients were randomized to receive either 10 minutes of immersive VR distraction therapy or 10 minutes of two-dimensional guided imagery distraction therapy.
“[The VR therapy] provides noncompetitive experiences in which the user can move around and explore natural environments (e.g., beachscape, forest) from standing, seated, or fixed positions, including within a hospital bed or chair,” the investigators wrote. “We provided over‐the‐ear headphones to assure high sound quality for the experience in the virtual natural environment.”
The two-dimensional intervention, delivered via electronic tablet, featured a meditation with images of natural landscapes and instrumental background music.
“We chose this active control because it is readily available and reflects content similar to relaxation‐focused television channels that are increasingly common in hospital settings,” the investigators noted.
Compared with this more common approach, patients who received VR therapy had significantly greater immediate reduction in pain (mean change in pain score, –1.4 vs –0.7; P = .03). Twenty-four hours later, improvements in the VR group generally persisted, while pain level in the two-dimensional group returned almost to baseline (P = .004). In addition, patients in the VR group reported significantly greater improvements in general distress and pain bothersomeness.
“VR therapies may modulate the pain experience by reducing the level of attention paid to noxious stimuli, thereby suppressing transmission of painful sensations via pain processing pathways to the cerebral cortex, particularly with more active VR experiences compared to passive experiences,” the investigators wrote.
Downsides to Using VR
Although VR brought more benefit, participants in the VR group more often reported difficulty using the intervention compared with those who interacted with an electronic tablet.
Plus, one VR user described mild dizziness that resolved with pharmacologic intervention. Still, approximately 9 out of 10 participants in each group reported willingness to try the intervention again.
Future VR Research
“Virtual reality is a rapidly evolving technology with a wealth of potential patient‐facing applications,” the investigators wrote. “Future studies should explore repeated use, optimal dosing, and impact on VR therapy on opioid analgesic requirements as well as usability testing, VR content preferences and facilitators of analgesia, and barriers and facilitators to use in acute care settings.”
This study was supported by the American Cancer Society. The investigators disclosed no conflicts of interest.
FROM CANCER
Telestroke Outcomes Rival Traditional Care
These studies set the stage for larger studies comparing outcomes and efficiency of various telemedicine and transport models and gauging stakeholder satisfaction, authors said.
Surprising Results
In a single-site retrospective comparison of 252 patients with acute stroke assessed under an in-house telestroke protocol and 2437 assessed in person, telestroke provided statistically significant advantages in the following areas:
- Door-to-imaging times (median: 38 minutes vs 44)
- Rates of intravenous (18.2% vs 8.6%) and mechanical (10.4% vs 5.1%) treatment
- Length of stay (median: 6 days vs 8)
- Symptomatic hemorrhagic transformation rate (1.1% vs 5.1%)
- Mortality (6.7% vs 11.1%)
The better metrics observed in the telestroke group were especially surprising, said lead author Rodrigo Meirelles Massaud, MD, because the same team of neurologists conducted both types of evaluations. “This consistency ensures that the quality and expertise of medical care were maintained across both groups,” said Dr. Massaud, a neurologist at the Hospital Israelita Albert Einstein in São Paulo, Brazil. The study appeared online in Frontiers in Neurology.
The findings also counter the preconceived notion that distance medicine could be inferior because of the inability to conduct direct physical examinations and the potential for communication failures, he said. The telestroke group’s younger average age (63.5 years vs 69.5 years) and lower initial National Institutes of Health Stroke Scale (NIHSS) scores — 2 versus 3 — might explain the disparity, Dr. Massaud added, because both factors augur improved outcomes.
Conversely, the authors wrote that the in-person group’s lower median door-to-groin puncture time in ischemic stroke (103.5 minutes vs 151.5 for telemedicine) likely resulted from the need to transport patients from satellite facilities to a hub hospital with neurologists on continuous standby. After adjustment for initial NIHSS score and age, both groups achieved similar percentages of patients with modified Rankin Scale (mRS) scores of 0-2 at discharge: 58.5% for in-person evaluation versus 61.9% for telemedicine (P = .028).
Acute Ischemic Stroke
In another study, a systematic review that included 7396 thrombolysed patients with acute ischemic stroke, odds ratios (ORs) revealed no significant differences between telestroke and in-person care for the percentage of mRS scores 0-2 at discharge (1.06; P = .5), 90-day mortality (OR, 1.16; P = .17), and symptomatic intracranial hemorrhage (OR, 0.99; P = .93). The study appeared in the March International Journal of Stroke.
The lack of significant differences between telestroke and in-person care regarding mortality and mRS scores of 0-2 (which defines a good outcome) surprised researchers, said lead author Ahmed Mohamed, who is completing a master of health sciences degree in medical physiology at the University of Toronto Temerty Faculty of Medicine, Toronto, Ontario, Canada.
“When we were starting this project,” he said, “we thought that telemedicine would probably take longer than conventional treatment.” And waiting longer for treatment — especially for patients with acute ischemic stroke — leads to worse outcomes. “However,” Mr. Mohamed said, “that wasn’t the case.” Additional measures that showed no significant differences included rates of intravenous tissue plasminogen activator (ivtPA) use and endovascular mechanical thrombectomy.
Telestroke Expansion
Authors of a study that analyzed the impact of expanding telestroke coverage beyond community ERs credited many postexpansion improvements to the addition of advanced practice providers (APPs). ProMedica Stroke Network, Toledo, Ohio, added seven APPs in June 2020 to provide two-way audiovisual inpatient stroke and TIA consultations and follow-ups at 19 spoke facilities supported by vascular neurologists at the hub comprehensive stroke center (CSC).
Revamping the TS workflow resulted in a threefold increase in TS cart utilization, a 31% decrease in transfers to the CSC, and a higher home discharge rate from spoke hospitals than from the CSC (57.38% versus 52.8%, respectively). Diagnostic sensitivity also improved, with overall decreases in stroke and TIA diagnosis of 11.5% and 39.8%, respectively, and a 12.9% increase in identification of stroke mimics. The study was published in the March Annals of Neurology.
Future Directions
All three author groups called for larger, more granular follow-up studies. Mr. Mohamed said that the 7396-patient review of 33 studies does not show whether video consultations with neurologists produce better outcomes than phone calls, for example, or whether utilizing different telestroke modalities such as a third-party telemedicine service provides better outcomes than other methods. Additionally, authors wrote, future research should compare telestroke versus non-telestroke patient transport models to optimize treatment plans and outcomes and validate potential advantages and disadvantages of telemedicine for patients with acute ischemic stroke.
“There is also a need to understand the long-term outcomes of patients treated via telestroke versus in-person care,” said Dr. Massaud. Future studies could include randomized, controlled trials comparing telestroke to traditional care in various settings with larger sample sizes, he said. “Additionally, research into the cost-effectiveness of telestroke services, patient satisfaction, and the impact of telestroke on different subtypes of stroke could provide a more comprehensive understanding of its benefits and limitations.”
Dr. Massaud and Mr. Mohamed reported no relevant financial interests. Authors of all three studies reported no funding sources or potential conflicts of interest.
These studies set the stage for larger studies comparing outcomes and efficiency of various telemedicine and transport models and gauging stakeholder satisfaction, authors said.
Surprising Results
In a single-site retrospective comparison of 252 patients with acute stroke assessed under an in-house telestroke protocol and 2437 assessed in person, telestroke provided statistically significant advantages in the following areas:
- Door-to-imaging times (median: 38 minutes vs 44)
- Rates of intravenous (18.2% vs 8.6%) and mechanical (10.4% vs 5.1%) treatment
- Length of stay (median: 6 days vs 8)
- Symptomatic hemorrhagic transformation rate (1.1% vs 5.1%)
- Mortality (6.7% vs 11.1%)
The better metrics observed in the telestroke group were especially surprising, said lead author Rodrigo Meirelles Massaud, MD, because the same team of neurologists conducted both types of evaluations. “This consistency ensures that the quality and expertise of medical care were maintained across both groups,” said Dr. Massaud, a neurologist at the Hospital Israelita Albert Einstein in São Paulo, Brazil. The study appeared online in Frontiers in Neurology.
The findings also counter the preconceived notion that distance medicine could be inferior because of the inability to conduct direct physical examinations and the potential for communication failures, he said. The telestroke group’s younger average age (63.5 years vs 69.5 years) and lower initial National Institutes of Health Stroke Scale (NIHSS) scores — 2 versus 3 — might explain the disparity, Dr. Massaud added, because both factors augur improved outcomes.
Conversely, the authors wrote that the in-person group’s lower median door-to-groin puncture time in ischemic stroke (103.5 minutes vs 151.5 for telemedicine) likely resulted from the need to transport patients from satellite facilities to a hub hospital with neurologists on continuous standby. After adjustment for initial NIHSS score and age, both groups achieved similar percentages of patients with modified Rankin Scale (mRS) scores of 0-2 at discharge: 58.5% for in-person evaluation versus 61.9% for telemedicine (P = .028).
Acute Ischemic Stroke
In another study, a systematic review that included 7396 thrombolysed patients with acute ischemic stroke, odds ratios (ORs) revealed no significant differences between telestroke and in-person care for the percentage of mRS scores 0-2 at discharge (1.06; P = .5), 90-day mortality (OR, 1.16; P = .17), and symptomatic intracranial hemorrhage (OR, 0.99; P = .93). The study appeared in the March International Journal of Stroke.
The lack of significant differences between telestroke and in-person care regarding mortality and mRS scores of 0-2 (which defines a good outcome) surprised researchers, said lead author Ahmed Mohamed, who is completing a master of health sciences degree in medical physiology at the University of Toronto Temerty Faculty of Medicine, Toronto, Ontario, Canada.
“When we were starting this project,” he said, “we thought that telemedicine would probably take longer than conventional treatment.” And waiting longer for treatment — especially for patients with acute ischemic stroke — leads to worse outcomes. “However,” Mr. Mohamed said, “that wasn’t the case.” Additional measures that showed no significant differences included rates of intravenous tissue plasminogen activator (ivtPA) use and endovascular mechanical thrombectomy.
Telestroke Expansion
Authors of a study that analyzed the impact of expanding telestroke coverage beyond community ERs credited many postexpansion improvements to the addition of advanced practice providers (APPs). ProMedica Stroke Network, Toledo, Ohio, added seven APPs in June 2020 to provide two-way audiovisual inpatient stroke and TIA consultations and follow-ups at 19 spoke facilities supported by vascular neurologists at the hub comprehensive stroke center (CSC).
Revamping the TS workflow resulted in a threefold increase in TS cart utilization, a 31% decrease in transfers to the CSC, and a higher home discharge rate from spoke hospitals than from the CSC (57.38% versus 52.8%, respectively). Diagnostic sensitivity also improved, with overall decreases in stroke and TIA diagnosis of 11.5% and 39.8%, respectively, and a 12.9% increase in identification of stroke mimics. The study was published in the March Annals of Neurology.
Future Directions
All three author groups called for larger, more granular follow-up studies. Mr. Mohamed said that the 7396-patient review of 33 studies does not show whether video consultations with neurologists produce better outcomes than phone calls, for example, or whether utilizing different telestroke modalities such as a third-party telemedicine service provides better outcomes than other methods. Additionally, authors wrote, future research should compare telestroke versus non-telestroke patient transport models to optimize treatment plans and outcomes and validate potential advantages and disadvantages of telemedicine for patients with acute ischemic stroke.
“There is also a need to understand the long-term outcomes of patients treated via telestroke versus in-person care,” said Dr. Massaud. Future studies could include randomized, controlled trials comparing telestroke to traditional care in various settings with larger sample sizes, he said. “Additionally, research into the cost-effectiveness of telestroke services, patient satisfaction, and the impact of telestroke on different subtypes of stroke could provide a more comprehensive understanding of its benefits and limitations.”
Dr. Massaud and Mr. Mohamed reported no relevant financial interests. Authors of all three studies reported no funding sources or potential conflicts of interest.
These studies set the stage for larger studies comparing outcomes and efficiency of various telemedicine and transport models and gauging stakeholder satisfaction, authors said.
Surprising Results
In a single-site retrospective comparison of 252 patients with acute stroke assessed under an in-house telestroke protocol and 2437 assessed in person, telestroke provided statistically significant advantages in the following areas:
- Door-to-imaging times (median: 38 minutes vs 44)
- Rates of intravenous (18.2% vs 8.6%) and mechanical (10.4% vs 5.1%) treatment
- Length of stay (median: 6 days vs 8)
- Symptomatic hemorrhagic transformation rate (1.1% vs 5.1%)
- Mortality (6.7% vs 11.1%)
The better metrics observed in the telestroke group were especially surprising, said lead author Rodrigo Meirelles Massaud, MD, because the same team of neurologists conducted both types of evaluations. “This consistency ensures that the quality and expertise of medical care were maintained across both groups,” said Dr. Massaud, a neurologist at the Hospital Israelita Albert Einstein in São Paulo, Brazil. The study appeared online in Frontiers in Neurology.
The findings also counter the preconceived notion that distance medicine could be inferior because of the inability to conduct direct physical examinations and the potential for communication failures, he said. The telestroke group’s younger average age (63.5 years vs 69.5 years) and lower initial National Institutes of Health Stroke Scale (NIHSS) scores — 2 versus 3 — might explain the disparity, Dr. Massaud added, because both factors augur improved outcomes.
Conversely, the authors wrote that the in-person group’s lower median door-to-groin puncture time in ischemic stroke (103.5 minutes vs 151.5 for telemedicine) likely resulted from the need to transport patients from satellite facilities to a hub hospital with neurologists on continuous standby. After adjustment for initial NIHSS score and age, both groups achieved similar percentages of patients with modified Rankin Scale (mRS) scores of 0-2 at discharge: 58.5% for in-person evaluation versus 61.9% for telemedicine (P = .028).
Acute Ischemic Stroke
In another study, a systematic review that included 7396 thrombolysed patients with acute ischemic stroke, odds ratios (ORs) revealed no significant differences between telestroke and in-person care for the percentage of mRS scores 0-2 at discharge (1.06; P = .5), 90-day mortality (OR, 1.16; P = .17), and symptomatic intracranial hemorrhage (OR, 0.99; P = .93). The study appeared in the March International Journal of Stroke.
The lack of significant differences between telestroke and in-person care regarding mortality and mRS scores of 0-2 (which defines a good outcome) surprised researchers, said lead author Ahmed Mohamed, who is completing a master of health sciences degree in medical physiology at the University of Toronto Temerty Faculty of Medicine, Toronto, Ontario, Canada.
“When we were starting this project,” he said, “we thought that telemedicine would probably take longer than conventional treatment.” And waiting longer for treatment — especially for patients with acute ischemic stroke — leads to worse outcomes. “However,” Mr. Mohamed said, “that wasn’t the case.” Additional measures that showed no significant differences included rates of intravenous tissue plasminogen activator (ivtPA) use and endovascular mechanical thrombectomy.
Telestroke Expansion
Authors of a study that analyzed the impact of expanding telestroke coverage beyond community ERs credited many postexpansion improvements to the addition of advanced practice providers (APPs). ProMedica Stroke Network, Toledo, Ohio, added seven APPs in June 2020 to provide two-way audiovisual inpatient stroke and TIA consultations and follow-ups at 19 spoke facilities supported by vascular neurologists at the hub comprehensive stroke center (CSC).
Revamping the TS workflow resulted in a threefold increase in TS cart utilization, a 31% decrease in transfers to the CSC, and a higher home discharge rate from spoke hospitals than from the CSC (57.38% versus 52.8%, respectively). Diagnostic sensitivity also improved, with overall decreases in stroke and TIA diagnosis of 11.5% and 39.8%, respectively, and a 12.9% increase in identification of stroke mimics. The study was published in the March Annals of Neurology.
Future Directions
All three author groups called for larger, more granular follow-up studies. Mr. Mohamed said that the 7396-patient review of 33 studies does not show whether video consultations with neurologists produce better outcomes than phone calls, for example, or whether utilizing different telestroke modalities such as a third-party telemedicine service provides better outcomes than other methods. Additionally, authors wrote, future research should compare telestroke versus non-telestroke patient transport models to optimize treatment plans and outcomes and validate potential advantages and disadvantages of telemedicine for patients with acute ischemic stroke.
“There is also a need to understand the long-term outcomes of patients treated via telestroke versus in-person care,” said Dr. Massaud. Future studies could include randomized, controlled trials comparing telestroke to traditional care in various settings with larger sample sizes, he said. “Additionally, research into the cost-effectiveness of telestroke services, patient satisfaction, and the impact of telestroke on different subtypes of stroke could provide a more comprehensive understanding of its benefits and limitations.”
Dr. Massaud and Mr. Mohamed reported no relevant financial interests. Authors of all three studies reported no funding sources or potential conflicts of interest.
FROM FRONTIERS IN NEUROLOGY, INTERNATIONAL JOURNAL OF STROKE, AND ANNALS OF NEUROLOGY
Smartphone App Detects Early Signs of Frontotemporal Dementia
, new research showed.
Cognitive tests administered remotely on the phone “showed similar findings as our gold standard in-clinic cognitive tests and brain imaging,” said study investigator Adam M. Staffaroni, PhD, with the Memory and Aging Center, University of California San Francisco.
“We also provided evidence that these assessments may be useful for detecting early symptoms of the disease at a level that is on par, or perhaps slightly better, than our gold standard in-person tests,” Dr. Staffaroni said.
The study was published online in JAMA Network Open.
Tough to Diagnose
Although relatively rare, FTD is the top cause of dementia in patients younger than 60 years. Patients are usually diagnosed relatively late in the disease because they are young and because their symptoms may be mistaken for psychiatric disorders.
In addition, behavioral and motor symptoms of FTD can make it hard for families to get to an academic center for in-clinic assessments, making remote assessments a huge need.
Dr. Staffaroni and colleagues with the ALLFTD Consortium partnered with software company Datacubed Health to develop the ALLFTD-mApp, which includes cognitive, motor, and speech tasks.
They assessed the reliability and validity of the app, against standard in-clinic assessments, in 350 individuals (mean age, 54 years; 58% women; mean education level, 16.5 years).
Among the 329 individuals with data on disease stage, 195 (59%) were asymptomatic or had preclinical FTD, 66 (20%) had prodromal FTD, and 68 (21%) had symptomatic FTD with a range of clinical syndromes.
The smartphone app showed “moderate to excellent” reliability within a single administration (ie, internally consistent) and across repeated assessments (ie, test-retest reliability), the researchers reported.
Validity was supported by association of smartphones tests with disease severity, criterion-standard neuropsychological tests, and brain volume, they noted.
Of Great Interest
They also reported that a composite of brief smartphone tests accurately distinguished dementia from cognitively unimpaired participants, screening out participants without symptoms, and detected prodromal FTD with greater sensitivity than the Montreal Cognitive Assessment.
“This tool is currently being used in several research studies. The remote aspect of this technology is important because it could allow researchers to collect data more frequently, which may give them a more accurate picture of the disease. Furthermore, researchers can be more inclusive in their study designs and include participants who otherwise might have difficulty traveling to academic centers for standard in-person visits,” said Dr. Staffaroni.
“Because the app appears sensitive to early stages of the disease, it could be also used as a screening tool, possibly alongside other remote data collection, to help identify participants that might be appropriate for a clinical trial. At this point, these technologies are not ready for clinical use and require additional research studies to understand their clinical utility,” he cautioned.
Commenting on the study, Walter Kukull, PhD, director of the National Alzheimer’s Coordinating Center at the University of Washington in Seattle, noted that “remote direct and indirect testing/telemetry are of great interest to the field and are being examined carefully in comparison to in-person means both for validity and possibly earlier recognition.”
This research was supported by grants from the National Institutes of Health, the Association for Frontotemporal Degeneration, the Bluefield Project to Cure FTD, the Rainwater Charitable Foundation, and the Larry L. Hillblom Foundation. Dr. Staffaroni reported being a coinventor of four ALLFTD mobile application tasks (not analyzed in the current study); receiving licensing fees from Datacubed Health and research support from the National Institute on Aging of the NIH, Bluefield Project to Cure FTD, the Alzheimer’s Association, the Larry L. Hillblom Foundation, and the Rainwater Charitable Foundation; and consulting for Alector Inc., Eli Lilly and Company Prevail Therapeutics, Passage Bio Inc, and Takeda Pharmaceuticals. Dr. Kukull participated in the ALLFTD Consortium.
A version of this article appeared on Medscape.com.
, new research showed.
Cognitive tests administered remotely on the phone “showed similar findings as our gold standard in-clinic cognitive tests and brain imaging,” said study investigator Adam M. Staffaroni, PhD, with the Memory and Aging Center, University of California San Francisco.
“We also provided evidence that these assessments may be useful for detecting early symptoms of the disease at a level that is on par, or perhaps slightly better, than our gold standard in-person tests,” Dr. Staffaroni said.
The study was published online in JAMA Network Open.
Tough to Diagnose
Although relatively rare, FTD is the top cause of dementia in patients younger than 60 years. Patients are usually diagnosed relatively late in the disease because they are young and because their symptoms may be mistaken for psychiatric disorders.
In addition, behavioral and motor symptoms of FTD can make it hard for families to get to an academic center for in-clinic assessments, making remote assessments a huge need.
Dr. Staffaroni and colleagues with the ALLFTD Consortium partnered with software company Datacubed Health to develop the ALLFTD-mApp, which includes cognitive, motor, and speech tasks.
They assessed the reliability and validity of the app, against standard in-clinic assessments, in 350 individuals (mean age, 54 years; 58% women; mean education level, 16.5 years).
Among the 329 individuals with data on disease stage, 195 (59%) were asymptomatic or had preclinical FTD, 66 (20%) had prodromal FTD, and 68 (21%) had symptomatic FTD with a range of clinical syndromes.
The smartphone app showed “moderate to excellent” reliability within a single administration (ie, internally consistent) and across repeated assessments (ie, test-retest reliability), the researchers reported.
Validity was supported by association of smartphones tests with disease severity, criterion-standard neuropsychological tests, and brain volume, they noted.
Of Great Interest
They also reported that a composite of brief smartphone tests accurately distinguished dementia from cognitively unimpaired participants, screening out participants without symptoms, and detected prodromal FTD with greater sensitivity than the Montreal Cognitive Assessment.
“This tool is currently being used in several research studies. The remote aspect of this technology is important because it could allow researchers to collect data more frequently, which may give them a more accurate picture of the disease. Furthermore, researchers can be more inclusive in their study designs and include participants who otherwise might have difficulty traveling to academic centers for standard in-person visits,” said Dr. Staffaroni.
“Because the app appears sensitive to early stages of the disease, it could be also used as a screening tool, possibly alongside other remote data collection, to help identify participants that might be appropriate for a clinical trial. At this point, these technologies are not ready for clinical use and require additional research studies to understand their clinical utility,” he cautioned.
Commenting on the study, Walter Kukull, PhD, director of the National Alzheimer’s Coordinating Center at the University of Washington in Seattle, noted that “remote direct and indirect testing/telemetry are of great interest to the field and are being examined carefully in comparison to in-person means both for validity and possibly earlier recognition.”
This research was supported by grants from the National Institutes of Health, the Association for Frontotemporal Degeneration, the Bluefield Project to Cure FTD, the Rainwater Charitable Foundation, and the Larry L. Hillblom Foundation. Dr. Staffaroni reported being a coinventor of four ALLFTD mobile application tasks (not analyzed in the current study); receiving licensing fees from Datacubed Health and research support from the National Institute on Aging of the NIH, Bluefield Project to Cure FTD, the Alzheimer’s Association, the Larry L. Hillblom Foundation, and the Rainwater Charitable Foundation; and consulting for Alector Inc., Eli Lilly and Company Prevail Therapeutics, Passage Bio Inc, and Takeda Pharmaceuticals. Dr. Kukull participated in the ALLFTD Consortium.
A version of this article appeared on Medscape.com.
, new research showed.
Cognitive tests administered remotely on the phone “showed similar findings as our gold standard in-clinic cognitive tests and brain imaging,” said study investigator Adam M. Staffaroni, PhD, with the Memory and Aging Center, University of California San Francisco.
“We also provided evidence that these assessments may be useful for detecting early symptoms of the disease at a level that is on par, or perhaps slightly better, than our gold standard in-person tests,” Dr. Staffaroni said.
The study was published online in JAMA Network Open.
Tough to Diagnose
Although relatively rare, FTD is the top cause of dementia in patients younger than 60 years. Patients are usually diagnosed relatively late in the disease because they are young and because their symptoms may be mistaken for psychiatric disorders.
In addition, behavioral and motor symptoms of FTD can make it hard for families to get to an academic center for in-clinic assessments, making remote assessments a huge need.
Dr. Staffaroni and colleagues with the ALLFTD Consortium partnered with software company Datacubed Health to develop the ALLFTD-mApp, which includes cognitive, motor, and speech tasks.
They assessed the reliability and validity of the app, against standard in-clinic assessments, in 350 individuals (mean age, 54 years; 58% women; mean education level, 16.5 years).
Among the 329 individuals with data on disease stage, 195 (59%) were asymptomatic or had preclinical FTD, 66 (20%) had prodromal FTD, and 68 (21%) had symptomatic FTD with a range of clinical syndromes.
The smartphone app showed “moderate to excellent” reliability within a single administration (ie, internally consistent) and across repeated assessments (ie, test-retest reliability), the researchers reported.
Validity was supported by association of smartphones tests with disease severity, criterion-standard neuropsychological tests, and brain volume, they noted.
Of Great Interest
They also reported that a composite of brief smartphone tests accurately distinguished dementia from cognitively unimpaired participants, screening out participants without symptoms, and detected prodromal FTD with greater sensitivity than the Montreal Cognitive Assessment.
“This tool is currently being used in several research studies. The remote aspect of this technology is important because it could allow researchers to collect data more frequently, which may give them a more accurate picture of the disease. Furthermore, researchers can be more inclusive in their study designs and include participants who otherwise might have difficulty traveling to academic centers for standard in-person visits,” said Dr. Staffaroni.
“Because the app appears sensitive to early stages of the disease, it could be also used as a screening tool, possibly alongside other remote data collection, to help identify participants that might be appropriate for a clinical trial. At this point, these technologies are not ready for clinical use and require additional research studies to understand their clinical utility,” he cautioned.
Commenting on the study, Walter Kukull, PhD, director of the National Alzheimer’s Coordinating Center at the University of Washington in Seattle, noted that “remote direct and indirect testing/telemetry are of great interest to the field and are being examined carefully in comparison to in-person means both for validity and possibly earlier recognition.”
This research was supported by grants from the National Institutes of Health, the Association for Frontotemporal Degeneration, the Bluefield Project to Cure FTD, the Rainwater Charitable Foundation, and the Larry L. Hillblom Foundation. Dr. Staffaroni reported being a coinventor of four ALLFTD mobile application tasks (not analyzed in the current study); receiving licensing fees from Datacubed Health and research support from the National Institute on Aging of the NIH, Bluefield Project to Cure FTD, the Alzheimer’s Association, the Larry L. Hillblom Foundation, and the Rainwater Charitable Foundation; and consulting for Alector Inc., Eli Lilly and Company Prevail Therapeutics, Passage Bio Inc, and Takeda Pharmaceuticals. Dr. Kukull participated in the ALLFTD Consortium.
A version of this article appeared on Medscape.com.
FROM JAMA NETWORK OPEN
Nontraditional Risk Factors Play an Outsized Role in Young Adult Stroke Risk
, new research showed.
The findings may offer insight into the increased incidence of stroke in adults under age 45, which has more than doubled in the past 20 years in high-income countries, while incidence in those over 45 has decreased.
Investigators believe the findings are important because most conventional prevention efforts focus on traditional risk factors.
“The younger they are at the time of stroke, the more likely their stroke is due to a nontraditional risk factor,” lead author Michelle Leppert, MD, an assistant professor of neurology at the University of Colorado School of Medicine, Aurora, Colorado, said in a news release.
The findings were published online in Circulation: Cardiovascular Quality and Outcomes.
Traditional Versus Nontraditional
The researchers retrospectively analyzed 2618 stroke cases (52% female; 73% ischemic stroke) that resulted in an inpatient admission and 7827 controls, all aged 18-55 years. Data came from the Colorado All Payer Claims Database between January 2012 and April 2019. Controls were matched by age, sex, and insurance type.
Traditional risk factors were defined as being a well-established risk factor for stroke that is routinely noted during stroke prevention screenings in older adults, including hypertension, diabetes, hyperlipidemia, sleep apnea, cardiovascular disease, alcohol, substance use disorder, and obesity.
Nontraditional risk factors were defined as those that are rarely cited as a cause of stroke in older adults, including migraines, malignancy, HIV, hepatitis, thrombophilia, autoimmune disease, vasculitis, sickle cell disease, heart valve disease, renal failure, and hormonal risk factors in women, such as oral contraceptives, pregnancy, or puerperium.
Overall, traditional risk factors were more common in stroke cases, with nontraditional factors playing a smaller role. However, among adults aged 18-34 years, more strokes were associated with nontraditional than traditional risk factors in men (31% vs 25%, respectively) and in women (43% vs 33%, respectively).
Migraine, the most common nontraditional risk factor for stroke in this younger age group, was found in 20% of men (odds ratio [OR], 3.9) and 35% of women (OR, 3.3).
Other notable nontraditional risk factors included heart valve disease in both men and women (OR, 3.1 and OR, 4.2, respectively); renal failure in men (OR, 8.9); and autoimmune diseases in women (OR, 8.8).
An Underestimate?
The contribution of nontraditional risk factors declined with age. After the age of 44, they were no longer significant. Hypertension was the most important traditional risk factor and increased in contribution with age.
“There have been many studies demonstrating the association between migraines and strokes, but to our knowledge, this study may be the first to demonstrate just how much stroke risk may be attributable to migraines,” Dr. Leppert said.
Overall, women had significantly more risk factors for stroke than men. Among controls, 52% and 34% of women had at least one traditional and nontraditional risk factors, respectively, compared with 48% and 22% in men.
The total contribution of nontraditional risk factors was likely an underestimate because some such factors, including the autoimmune disorder antiphospholipid syndrome and patent foramen ovale, “lacked reliable administrative algorithms” and could not be assessed in this study, the researchers noted.
Further research on how nontraditional risk factors affect strokes could lead to better prevention.
“We need to better understand the underlying mechanisms of these nontraditional risk factors to develop targeted interventions,” Dr. Leppert said.
The study was funded by the National Institutes of Health/National Center for Advancing Translational Sciences Colorado Clinical and Translational Science Award. Dr. Leppert reports receiving an American Heart Association Career Development Grant. Other disclosures are included in the original article.
A version of this article appeared on Medscape.com.
, new research showed.
The findings may offer insight into the increased incidence of stroke in adults under age 45, which has more than doubled in the past 20 years in high-income countries, while incidence in those over 45 has decreased.
Investigators believe the findings are important because most conventional prevention efforts focus on traditional risk factors.
“The younger they are at the time of stroke, the more likely their stroke is due to a nontraditional risk factor,” lead author Michelle Leppert, MD, an assistant professor of neurology at the University of Colorado School of Medicine, Aurora, Colorado, said in a news release.
The findings were published online in Circulation: Cardiovascular Quality and Outcomes.
Traditional Versus Nontraditional
The researchers retrospectively analyzed 2618 stroke cases (52% female; 73% ischemic stroke) that resulted in an inpatient admission and 7827 controls, all aged 18-55 years. Data came from the Colorado All Payer Claims Database between January 2012 and April 2019. Controls were matched by age, sex, and insurance type.
Traditional risk factors were defined as being a well-established risk factor for stroke that is routinely noted during stroke prevention screenings in older adults, including hypertension, diabetes, hyperlipidemia, sleep apnea, cardiovascular disease, alcohol, substance use disorder, and obesity.
Nontraditional risk factors were defined as those that are rarely cited as a cause of stroke in older adults, including migraines, malignancy, HIV, hepatitis, thrombophilia, autoimmune disease, vasculitis, sickle cell disease, heart valve disease, renal failure, and hormonal risk factors in women, such as oral contraceptives, pregnancy, or puerperium.
Overall, traditional risk factors were more common in stroke cases, with nontraditional factors playing a smaller role. However, among adults aged 18-34 years, more strokes were associated with nontraditional than traditional risk factors in men (31% vs 25%, respectively) and in women (43% vs 33%, respectively).
Migraine, the most common nontraditional risk factor for stroke in this younger age group, was found in 20% of men (odds ratio [OR], 3.9) and 35% of women (OR, 3.3).
Other notable nontraditional risk factors included heart valve disease in both men and women (OR, 3.1 and OR, 4.2, respectively); renal failure in men (OR, 8.9); and autoimmune diseases in women (OR, 8.8).
An Underestimate?
The contribution of nontraditional risk factors declined with age. After the age of 44, they were no longer significant. Hypertension was the most important traditional risk factor and increased in contribution with age.
“There have been many studies demonstrating the association between migraines and strokes, but to our knowledge, this study may be the first to demonstrate just how much stroke risk may be attributable to migraines,” Dr. Leppert said.
Overall, women had significantly more risk factors for stroke than men. Among controls, 52% and 34% of women had at least one traditional and nontraditional risk factors, respectively, compared with 48% and 22% in men.
The total contribution of nontraditional risk factors was likely an underestimate because some such factors, including the autoimmune disorder antiphospholipid syndrome and patent foramen ovale, “lacked reliable administrative algorithms” and could not be assessed in this study, the researchers noted.
Further research on how nontraditional risk factors affect strokes could lead to better prevention.
“We need to better understand the underlying mechanisms of these nontraditional risk factors to develop targeted interventions,” Dr. Leppert said.
The study was funded by the National Institutes of Health/National Center for Advancing Translational Sciences Colorado Clinical and Translational Science Award. Dr. Leppert reports receiving an American Heart Association Career Development Grant. Other disclosures are included in the original article.
A version of this article appeared on Medscape.com.
, new research showed.
The findings may offer insight into the increased incidence of stroke in adults under age 45, which has more than doubled in the past 20 years in high-income countries, while incidence in those over 45 has decreased.
Investigators believe the findings are important because most conventional prevention efforts focus on traditional risk factors.
“The younger they are at the time of stroke, the more likely their stroke is due to a nontraditional risk factor,” lead author Michelle Leppert, MD, an assistant professor of neurology at the University of Colorado School of Medicine, Aurora, Colorado, said in a news release.
The findings were published online in Circulation: Cardiovascular Quality and Outcomes.
Traditional Versus Nontraditional
The researchers retrospectively analyzed 2618 stroke cases (52% female; 73% ischemic stroke) that resulted in an inpatient admission and 7827 controls, all aged 18-55 years. Data came from the Colorado All Payer Claims Database between January 2012 and April 2019. Controls were matched by age, sex, and insurance type.
Traditional risk factors were defined as being a well-established risk factor for stroke that is routinely noted during stroke prevention screenings in older adults, including hypertension, diabetes, hyperlipidemia, sleep apnea, cardiovascular disease, alcohol, substance use disorder, and obesity.
Nontraditional risk factors were defined as those that are rarely cited as a cause of stroke in older adults, including migraines, malignancy, HIV, hepatitis, thrombophilia, autoimmune disease, vasculitis, sickle cell disease, heart valve disease, renal failure, and hormonal risk factors in women, such as oral contraceptives, pregnancy, or puerperium.
Overall, traditional risk factors were more common in stroke cases, with nontraditional factors playing a smaller role. However, among adults aged 18-34 years, more strokes were associated with nontraditional than traditional risk factors in men (31% vs 25%, respectively) and in women (43% vs 33%, respectively).
Migraine, the most common nontraditional risk factor for stroke in this younger age group, was found in 20% of men (odds ratio [OR], 3.9) and 35% of women (OR, 3.3).
Other notable nontraditional risk factors included heart valve disease in both men and women (OR, 3.1 and OR, 4.2, respectively); renal failure in men (OR, 8.9); and autoimmune diseases in women (OR, 8.8).
An Underestimate?
The contribution of nontraditional risk factors declined with age. After the age of 44, they were no longer significant. Hypertension was the most important traditional risk factor and increased in contribution with age.
“There have been many studies demonstrating the association between migraines and strokes, but to our knowledge, this study may be the first to demonstrate just how much stroke risk may be attributable to migraines,” Dr. Leppert said.
Overall, women had significantly more risk factors for stroke than men. Among controls, 52% and 34% of women had at least one traditional and nontraditional risk factors, respectively, compared with 48% and 22% in men.
The total contribution of nontraditional risk factors was likely an underestimate because some such factors, including the autoimmune disorder antiphospholipid syndrome and patent foramen ovale, “lacked reliable administrative algorithms” and could not be assessed in this study, the researchers noted.
Further research on how nontraditional risk factors affect strokes could lead to better prevention.
“We need to better understand the underlying mechanisms of these nontraditional risk factors to develop targeted interventions,” Dr. Leppert said.
The study was funded by the National Institutes of Health/National Center for Advancing Translational Sciences Colorado Clinical and Translational Science Award. Dr. Leppert reports receiving an American Heart Association Career Development Grant. Other disclosures are included in the original article.
A version of this article appeared on Medscape.com.
FROM CIRCULATION: CARDIOVASCULAR QUALITY AND OUTCOMES
MS and Epstein-Barr Virus: What Do We Know and Where Do We Go From Here?
The Epstein-Barr virus (EBV) is our constant companion, infecting an estimated 90%-95% of adults. Many of us are first infected as children, when the germ may trigger cold and flu symptoms. EBV also causes mononucleosis, or kissing disease, a glandular fever that has afflicted generations of amorous young people.
Post infection, EBV settles in for the long haul and remains in the body until death. It’s thought to be largely innocuous, but EBV is now implicated as a cause of several types of cancer — including lymphoma and nasopharyngeal tumors – and multiple sclerosis (MS). In 2022, a landmark study in Science suggested that previous EBV infection is the primary cause of MS.
While there aren’t many implications for current treatment, greater insight into the origin story of MS may eventually help neurologists better diagnose and treat patients, experts said. The goal is to uncover clues that “can help us understand MS a little bit better and reveal insights that could lead to new disease-modifying therapy,” Bruce Bebo, PhD, executive vice president of research with the National MS Society, said in an interview.
EBV Boosts MS Risk 32-Fold
EBV was first linked to MS back in 1981. For the 2022 study, researchers at the Harvard T.H. Chan School of Public Health and Harvard Medical School, Boston, analyzed blood serum from 10 million active-duty members of the US military. They focused on 801 recruits with MS and matched them with more than 1500 controls. All but one of those with MS had been infected with EBV; infection appeared to boost the risk for MS 32-fold (95% CI, 4.3-245.3; P < .001).
Neurologist and associate professor Michael Levy, MD, PhD, of Harvard Medical School and Massachusetts General Hospital, said in an interview that the findings are “groundbreaking” and confirm that EBV is “likely the primary cause of MS.”
According to Dr. Levy, there are two main theories about why EBV causes MS. The first hypothesis, known as the “molecular mimicry” theory, suggests that “EBV is a trigger of MS, possibly when the immune system mistakes a viral protein for a myelin protein and then attacks myelin,” Dr. Levy said. In MS, the immune system attacks the protective myelin sheath and the axons it insulates.
“After that point, the virus is not necessary to maintain the disease state and eradicating the virus likely won’t have much effect since the immune response is already triggered,” he said.
The second theory is that “EBV is a driver of MS where there is an ongoing, lifelong immunological response to EBV that continuously causes damage in the central nervous system [CNS]. In theory, if we could eradicate the virus, the destructive immune response could also resolve. Thus, an EBV antiviral treatment could potentially treat and maybe cure MS,” Dr. Levy explained, noting that “removing the pathogenic antigen may be a more effective strategy than removing the immune response.”
However, “we don’t yet know which hypothesis is correct,” he said. But “there is preliminary evidence in favor of each one.”
‘Additional Fuses Must Be Ignited’
It’s also unclear why most people infected with EBV do not develop MS. It appears that “additional fuses must be ignited,” for MS to take hold, according to a commentary accompanying the landmark 2022 study.
“As far as clinical implications, knowing whether a patient has a medical or family history of mononucleosis may be a small clue, a small piece of evidence, to help with diagnosis,” Dr. Bebo said.
He agreed with Dr. Levy that an antiviral could be a promising approach “If the problem in MS is a dysfunctional immune response to EBV.”
Natalia Drosu, MD, PhD, a postdoctoral fellow at Harvard-MIT Biomedical Engineering Center, said that a clinical trial of a non-immunosuppressive antiviral targeting EBV in patients with MS would be a crucial step toward better understanding the MS-EBV connection. “If we learn that antivirals are effective in MS, we should develop non-immunosuppressive therapies for patients with MS as soon as possible,” she said.
Stanford University’s Lawrence Steinman, MD, professor of neurology and neurological sciences, pediatrics, and genetics, who coauthored the commentary on the original Science paper, agreed that it’s worth investigating whether antiviral therapies targeting EBV will benefit patients who already have MS. But he cautioned against clinicians experimenting on their own outside of a research study. “You’d want to use the right antiviral and a properly designed trial,” he said.
Antivirals May Place a Crucial Role in MS Control
While there are no approved therapies for EBV, several MS disease-modifying therapies have anti-EBV effects, Dr. Levy said, citing anti-CD20 therapy as a clear example. It depletes B cells from the circulation, and it depletes EBV because the virus lives in the B-cell compartment. “Some MS treatments may be inadvertent EBV antivirals,” he said.
Researchers are also thinking about how they might exploit the MS-EBV link to prevent MS from developing in the first place, but there are uncertainties on that front too.
Conceivably, there may be some way to intervene in patients to treat EBV and prevent MS, such as a unique treatment for infectious mononucleosis (IM), Dr. Levy said.
Researchers are especially intrigued by signs that the timing of infection may play a role, with people infected with EBV via IM after early childhood at especially a high risk of developing MS. A 2022 German study calculated that people who developed IM were almost twice as likely as those who didn’t to develop MS within 10 years, although the risks in both groups were very small. Subgroup analysis revealed the strongest association between IM and MS was in the group infected between age 14 and 20 years (hazard ratio, 3.52; 95% CI, 1.00-12.37). They also saw a stronger association in men than in women.
The authors of a 2023 review in Clinical & Translational Immunology wrote that “further understanding of IM may be critical in solving the mystery” of EBV’s role in MS.
Dr. Levy said this line of questioning is important.
However, “remember that while most of the world gets EBV infections, only 1 in 1000 will get MS. So, it might not be feasible to test everyone before neurological manifestations occur,” he said.
More Questions to Answer About EBV and MS
Researchers hope to answer several questions moving forward. For one, why is EBV uniquely connected to MS? “You would think that if there were cross-reactivity to myelin, there are many viruses that could cause MS. But the association seems to be very restricted to EBV,” Dr. Levy said. “It is probably due to the fact that EBV is one of the only human viruses that can infect B cells, which play important roles in controlling immune responses.”
The molecular mimicry theory also opens up a potential treatment pathway.
A 2022 study reported “high-affinity molecular mimicry between the EBV transcription factor EBV nuclear antigen 1 (EBNA1) and the central nervous system protein glial cell adhesion molecule (GlialCAM)”. Antibodies against EBNA1 and GlialCAM are prevalent in patients with MS. In a mouse model of MS, the researchers showed that EBNA1 immunization exacerbates disease. The authors wrote that “Our results provide a mechanistic link for the association between MS and EBV and could guide the development of new MS therapies.”
Could an EBV Vaccine Be the Answer?
On the prevention front, perhaps the most obvious question is whether an EBV vaccine could eliminate MS for good?
Dr. Bebo, from the National MS Society, said it will be important to determine which kind of vaccine is best. Is it one that neutralizes infection with EBV? Or is it enough to simply prevent clinical manifestations?
Both types of vaccines are in development, and at least two clinical trials are now in the works. The National Institute of Allergy and Infectious Diseases is sponsoring a phase 1 study of an adjuvanted EBV gp350-Ferritin nanoparticle vaccine. Forty subjects aged 18-29 years will take part: 20 with EBV and 20 who are not infected. The study is expected to end in 2025.
There is also a phase 1 placebo-controlled study in progress testing an EBV vaccine based on mRNA-1189 in 422 subjects aged 12-30 years. This trial is also due to end in 2025.
“This is very exciting, but it may take a decade or two to determine whether a vaccine is effective at preventing MS,” Dr. Levy said.
Dr. Levy, Dr. Steinman, Dr. Drosu, and Dr. Bebo had no disclosures.
A version of this article appeared on Medscape.com.
The Epstein-Barr virus (EBV) is our constant companion, infecting an estimated 90%-95% of adults. Many of us are first infected as children, when the germ may trigger cold and flu symptoms. EBV also causes mononucleosis, or kissing disease, a glandular fever that has afflicted generations of amorous young people.
Post infection, EBV settles in for the long haul and remains in the body until death. It’s thought to be largely innocuous, but EBV is now implicated as a cause of several types of cancer — including lymphoma and nasopharyngeal tumors – and multiple sclerosis (MS). In 2022, a landmark study in Science suggested that previous EBV infection is the primary cause of MS.
While there aren’t many implications for current treatment, greater insight into the origin story of MS may eventually help neurologists better diagnose and treat patients, experts said. The goal is to uncover clues that “can help us understand MS a little bit better and reveal insights that could lead to new disease-modifying therapy,” Bruce Bebo, PhD, executive vice president of research with the National MS Society, said in an interview.
EBV Boosts MS Risk 32-Fold
EBV was first linked to MS back in 1981. For the 2022 study, researchers at the Harvard T.H. Chan School of Public Health and Harvard Medical School, Boston, analyzed blood serum from 10 million active-duty members of the US military. They focused on 801 recruits with MS and matched them with more than 1500 controls. All but one of those with MS had been infected with EBV; infection appeared to boost the risk for MS 32-fold (95% CI, 4.3-245.3; P < .001).
Neurologist and associate professor Michael Levy, MD, PhD, of Harvard Medical School and Massachusetts General Hospital, said in an interview that the findings are “groundbreaking” and confirm that EBV is “likely the primary cause of MS.”
According to Dr. Levy, there are two main theories about why EBV causes MS. The first hypothesis, known as the “molecular mimicry” theory, suggests that “EBV is a trigger of MS, possibly when the immune system mistakes a viral protein for a myelin protein and then attacks myelin,” Dr. Levy said. In MS, the immune system attacks the protective myelin sheath and the axons it insulates.
“After that point, the virus is not necessary to maintain the disease state and eradicating the virus likely won’t have much effect since the immune response is already triggered,” he said.
The second theory is that “EBV is a driver of MS where there is an ongoing, lifelong immunological response to EBV that continuously causes damage in the central nervous system [CNS]. In theory, if we could eradicate the virus, the destructive immune response could also resolve. Thus, an EBV antiviral treatment could potentially treat and maybe cure MS,” Dr. Levy explained, noting that “removing the pathogenic antigen may be a more effective strategy than removing the immune response.”
However, “we don’t yet know which hypothesis is correct,” he said. But “there is preliminary evidence in favor of each one.”
‘Additional Fuses Must Be Ignited’
It’s also unclear why most people infected with EBV do not develop MS. It appears that “additional fuses must be ignited,” for MS to take hold, according to a commentary accompanying the landmark 2022 study.
“As far as clinical implications, knowing whether a patient has a medical or family history of mononucleosis may be a small clue, a small piece of evidence, to help with diagnosis,” Dr. Bebo said.
He agreed with Dr. Levy that an antiviral could be a promising approach “If the problem in MS is a dysfunctional immune response to EBV.”
Natalia Drosu, MD, PhD, a postdoctoral fellow at Harvard-MIT Biomedical Engineering Center, said that a clinical trial of a non-immunosuppressive antiviral targeting EBV in patients with MS would be a crucial step toward better understanding the MS-EBV connection. “If we learn that antivirals are effective in MS, we should develop non-immunosuppressive therapies for patients with MS as soon as possible,” she said.
Stanford University’s Lawrence Steinman, MD, professor of neurology and neurological sciences, pediatrics, and genetics, who coauthored the commentary on the original Science paper, agreed that it’s worth investigating whether antiviral therapies targeting EBV will benefit patients who already have MS. But he cautioned against clinicians experimenting on their own outside of a research study. “You’d want to use the right antiviral and a properly designed trial,” he said.
Antivirals May Place a Crucial Role in MS Control
While there are no approved therapies for EBV, several MS disease-modifying therapies have anti-EBV effects, Dr. Levy said, citing anti-CD20 therapy as a clear example. It depletes B cells from the circulation, and it depletes EBV because the virus lives in the B-cell compartment. “Some MS treatments may be inadvertent EBV antivirals,” he said.
Researchers are also thinking about how they might exploit the MS-EBV link to prevent MS from developing in the first place, but there are uncertainties on that front too.
Conceivably, there may be some way to intervene in patients to treat EBV and prevent MS, such as a unique treatment for infectious mononucleosis (IM), Dr. Levy said.
Researchers are especially intrigued by signs that the timing of infection may play a role, with people infected with EBV via IM after early childhood at especially a high risk of developing MS. A 2022 German study calculated that people who developed IM were almost twice as likely as those who didn’t to develop MS within 10 years, although the risks in both groups were very small. Subgroup analysis revealed the strongest association between IM and MS was in the group infected between age 14 and 20 years (hazard ratio, 3.52; 95% CI, 1.00-12.37). They also saw a stronger association in men than in women.
The authors of a 2023 review in Clinical & Translational Immunology wrote that “further understanding of IM may be critical in solving the mystery” of EBV’s role in MS.
Dr. Levy said this line of questioning is important.
However, “remember that while most of the world gets EBV infections, only 1 in 1000 will get MS. So, it might not be feasible to test everyone before neurological manifestations occur,” he said.
More Questions to Answer About EBV and MS
Researchers hope to answer several questions moving forward. For one, why is EBV uniquely connected to MS? “You would think that if there were cross-reactivity to myelin, there are many viruses that could cause MS. But the association seems to be very restricted to EBV,” Dr. Levy said. “It is probably due to the fact that EBV is one of the only human viruses that can infect B cells, which play important roles in controlling immune responses.”
The molecular mimicry theory also opens up a potential treatment pathway.
A 2022 study reported “high-affinity molecular mimicry between the EBV transcription factor EBV nuclear antigen 1 (EBNA1) and the central nervous system protein glial cell adhesion molecule (GlialCAM)”. Antibodies against EBNA1 and GlialCAM are prevalent in patients with MS. In a mouse model of MS, the researchers showed that EBNA1 immunization exacerbates disease. The authors wrote that “Our results provide a mechanistic link for the association between MS and EBV and could guide the development of new MS therapies.”
Could an EBV Vaccine Be the Answer?
On the prevention front, perhaps the most obvious question is whether an EBV vaccine could eliminate MS for good?
Dr. Bebo, from the National MS Society, said it will be important to determine which kind of vaccine is best. Is it one that neutralizes infection with EBV? Or is it enough to simply prevent clinical manifestations?
Both types of vaccines are in development, and at least two clinical trials are now in the works. The National Institute of Allergy and Infectious Diseases is sponsoring a phase 1 study of an adjuvanted EBV gp350-Ferritin nanoparticle vaccine. Forty subjects aged 18-29 years will take part: 20 with EBV and 20 who are not infected. The study is expected to end in 2025.
There is also a phase 1 placebo-controlled study in progress testing an EBV vaccine based on mRNA-1189 in 422 subjects aged 12-30 years. This trial is also due to end in 2025.
“This is very exciting, but it may take a decade or two to determine whether a vaccine is effective at preventing MS,” Dr. Levy said.
Dr. Levy, Dr. Steinman, Dr. Drosu, and Dr. Bebo had no disclosures.
A version of this article appeared on Medscape.com.
The Epstein-Barr virus (EBV) is our constant companion, infecting an estimated 90%-95% of adults. Many of us are first infected as children, when the germ may trigger cold and flu symptoms. EBV also causes mononucleosis, or kissing disease, a glandular fever that has afflicted generations of amorous young people.
Post infection, EBV settles in for the long haul and remains in the body until death. It’s thought to be largely innocuous, but EBV is now implicated as a cause of several types of cancer — including lymphoma and nasopharyngeal tumors – and multiple sclerosis (MS). In 2022, a landmark study in Science suggested that previous EBV infection is the primary cause of MS.
While there aren’t many implications for current treatment, greater insight into the origin story of MS may eventually help neurologists better diagnose and treat patients, experts said. The goal is to uncover clues that “can help us understand MS a little bit better and reveal insights that could lead to new disease-modifying therapy,” Bruce Bebo, PhD, executive vice president of research with the National MS Society, said in an interview.
EBV Boosts MS Risk 32-Fold
EBV was first linked to MS back in 1981. For the 2022 study, researchers at the Harvard T.H. Chan School of Public Health and Harvard Medical School, Boston, analyzed blood serum from 10 million active-duty members of the US military. They focused on 801 recruits with MS and matched them with more than 1500 controls. All but one of those with MS had been infected with EBV; infection appeared to boost the risk for MS 32-fold (95% CI, 4.3-245.3; P < .001).
Neurologist and associate professor Michael Levy, MD, PhD, of Harvard Medical School and Massachusetts General Hospital, said in an interview that the findings are “groundbreaking” and confirm that EBV is “likely the primary cause of MS.”
According to Dr. Levy, there are two main theories about why EBV causes MS. The first hypothesis, known as the “molecular mimicry” theory, suggests that “EBV is a trigger of MS, possibly when the immune system mistakes a viral protein for a myelin protein and then attacks myelin,” Dr. Levy said. In MS, the immune system attacks the protective myelin sheath and the axons it insulates.
“After that point, the virus is not necessary to maintain the disease state and eradicating the virus likely won’t have much effect since the immune response is already triggered,” he said.
The second theory is that “EBV is a driver of MS where there is an ongoing, lifelong immunological response to EBV that continuously causes damage in the central nervous system [CNS]. In theory, if we could eradicate the virus, the destructive immune response could also resolve. Thus, an EBV antiviral treatment could potentially treat and maybe cure MS,” Dr. Levy explained, noting that “removing the pathogenic antigen may be a more effective strategy than removing the immune response.”
However, “we don’t yet know which hypothesis is correct,” he said. But “there is preliminary evidence in favor of each one.”
‘Additional Fuses Must Be Ignited’
It’s also unclear why most people infected with EBV do not develop MS. It appears that “additional fuses must be ignited,” for MS to take hold, according to a commentary accompanying the landmark 2022 study.
“As far as clinical implications, knowing whether a patient has a medical or family history of mononucleosis may be a small clue, a small piece of evidence, to help with diagnosis,” Dr. Bebo said.
He agreed with Dr. Levy that an antiviral could be a promising approach “If the problem in MS is a dysfunctional immune response to EBV.”
Natalia Drosu, MD, PhD, a postdoctoral fellow at Harvard-MIT Biomedical Engineering Center, said that a clinical trial of a non-immunosuppressive antiviral targeting EBV in patients with MS would be a crucial step toward better understanding the MS-EBV connection. “If we learn that antivirals are effective in MS, we should develop non-immunosuppressive therapies for patients with MS as soon as possible,” she said.
Stanford University’s Lawrence Steinman, MD, professor of neurology and neurological sciences, pediatrics, and genetics, who coauthored the commentary on the original Science paper, agreed that it’s worth investigating whether antiviral therapies targeting EBV will benefit patients who already have MS. But he cautioned against clinicians experimenting on their own outside of a research study. “You’d want to use the right antiviral and a properly designed trial,” he said.
Antivirals May Place a Crucial Role in MS Control
While there are no approved therapies for EBV, several MS disease-modifying therapies have anti-EBV effects, Dr. Levy said, citing anti-CD20 therapy as a clear example. It depletes B cells from the circulation, and it depletes EBV because the virus lives in the B-cell compartment. “Some MS treatments may be inadvertent EBV antivirals,” he said.
Researchers are also thinking about how they might exploit the MS-EBV link to prevent MS from developing in the first place, but there are uncertainties on that front too.
Conceivably, there may be some way to intervene in patients to treat EBV and prevent MS, such as a unique treatment for infectious mononucleosis (IM), Dr. Levy said.
Researchers are especially intrigued by signs that the timing of infection may play a role, with people infected with EBV via IM after early childhood at especially a high risk of developing MS. A 2022 German study calculated that people who developed IM were almost twice as likely as those who didn’t to develop MS within 10 years, although the risks in both groups were very small. Subgroup analysis revealed the strongest association between IM and MS was in the group infected between age 14 and 20 years (hazard ratio, 3.52; 95% CI, 1.00-12.37). They also saw a stronger association in men than in women.
The authors of a 2023 review in Clinical & Translational Immunology wrote that “further understanding of IM may be critical in solving the mystery” of EBV’s role in MS.
Dr. Levy said this line of questioning is important.
However, “remember that while most of the world gets EBV infections, only 1 in 1000 will get MS. So, it might not be feasible to test everyone before neurological manifestations occur,” he said.
More Questions to Answer About EBV and MS
Researchers hope to answer several questions moving forward. For one, why is EBV uniquely connected to MS? “You would think that if there were cross-reactivity to myelin, there are many viruses that could cause MS. But the association seems to be very restricted to EBV,” Dr. Levy said. “It is probably due to the fact that EBV is one of the only human viruses that can infect B cells, which play important roles in controlling immune responses.”
The molecular mimicry theory also opens up a potential treatment pathway.
A 2022 study reported “high-affinity molecular mimicry between the EBV transcription factor EBV nuclear antigen 1 (EBNA1) and the central nervous system protein glial cell adhesion molecule (GlialCAM)”. Antibodies against EBNA1 and GlialCAM are prevalent in patients with MS. In a mouse model of MS, the researchers showed that EBNA1 immunization exacerbates disease. The authors wrote that “Our results provide a mechanistic link for the association between MS and EBV and could guide the development of new MS therapies.”
Could an EBV Vaccine Be the Answer?
On the prevention front, perhaps the most obvious question is whether an EBV vaccine could eliminate MS for good?
Dr. Bebo, from the National MS Society, said it will be important to determine which kind of vaccine is best. Is it one that neutralizes infection with EBV? Or is it enough to simply prevent clinical manifestations?
Both types of vaccines are in development, and at least two clinical trials are now in the works. The National Institute of Allergy and Infectious Diseases is sponsoring a phase 1 study of an adjuvanted EBV gp350-Ferritin nanoparticle vaccine. Forty subjects aged 18-29 years will take part: 20 with EBV and 20 who are not infected. The study is expected to end in 2025.
There is also a phase 1 placebo-controlled study in progress testing an EBV vaccine based on mRNA-1189 in 422 subjects aged 12-30 years. This trial is also due to end in 2025.
“This is very exciting, but it may take a decade or two to determine whether a vaccine is effective at preventing MS,” Dr. Levy said.
Dr. Levy, Dr. Steinman, Dr. Drosu, and Dr. Bebo had no disclosures.
A version of this article appeared on Medscape.com.
Human Brains Are Getting Bigger: Good News for Dementia Risk?
A secular trends analysis using brain imaging data from the long-running Framingham Heart Study revealed an increase in intracranial volume (ICV), cortical gray matter, white matter, and hippocampal volumes, as well as cortical surface area in people born in the 1970s versus those born in the 1930s.
“We hypothesize that the increased size of the brain will lead to increased ‘reserve’ against the diseases of aging, consequently reducing overall risk of dementia,” said Charles DeCarli, MD, director of the Alzheimer’s Disease Research Center and Imaging of Dementia and Aging Laboratory, Department of Neurology and Center for Neuroscience, University of California at Davis.
The study was published online in JAMA Neurology.
Dementia Protection?
An earlier report from the Framingham Heart Study suggested that dementia incidence is declining.
“This difference occurred among persons with at least a high school education and was not affected by differences in vascular risk. Our work was stimulated by this finding and the possibility that differences in brain size might be occurring over the three generations of the Framingham Heart Study which might explain an increased resilience to dementia,” said Dr. DeCarli.
The cross-sectional study used data from 3226 Framingham participants (53% women) born in the decades 1930–1970. None had dementia or a history of stroke. At a mean age of 57.7 years, they underwent brain MRI.
Compared with the 1930s birth decade, the 1970s birth decade had a 6.6% greater ICV (1321 mL vs 1234 mL), 7.7% greater white matter volume (476.3 mL vs 441.9 mL), 5.7% greater hippocampal volume (6.69 mL vs 6.51 mL), and 14.9% greater cortical surface area (2222 cm2 vs 1933 cm2).
Cortical thickness was thinner by 21% over the same period, coinciding with larger intracranial volume, cerebral white matter volume, and cortical surface area.
“We were surprised to find that the brain is getting larger, but the cortex is thinning very slightly. The apparent thinning of the cortex is related to the increased need for expansion of the cortical ribbon. This is based on hypotheses related to the effects of evolution and cortical development designed to make neuronal integration most efficient,” said Dr. DeCarli.
Repeat analysis applied to a subgroup of 1145 individuals of similar age range born in the 1940s (mean age, 60 years) and 1950s (mean age, 59 years) resulted in similar findings.
“These findings likely reflect both secular improvements in early life environmental influences through health, social-cultural, and educational factors, as well as secular improvements in modifiable dementia risk factors leading to better brain health and reserve,” the authors wrote.
While the effects observed are “likely to be small at the level of the individual, they are likely to be substantial at the population level, adding to growing literature that suggests optimized brain development and ideal health through modification of risk factors could substantially modify the effect of common neurodegenerative diseases such as stroke and Alzheiemer’s disease on dementia incidence,” they added.
Limitations included the predominately non-Hispanic White, healthy, and well-educated population that is the Framingham cohort, which is not representative of the broader US population. The cross-sectional nature of the study also limited causal inference.
Exciting Work
“If these results are confirmed by others and the observed differences by decade are as large as those reported, it has important implications for aging and dementia studies,” Prashanthi Lemuria, PhD, with Mayo Clinic, Rochester, Minnesota, wrote in an accompanying editorial.
“First, studies that use brain charts for the human life span to understand the mechanisms of aging, by stitching together data from individuals across the decades, are significantly overestimating the degree of brain health decline using volumes across the life span because the baseline brain health in individuals who are in their older decades is likely lower to begin with,” Dr. Lemuria noted.
“Second, cortical thickness measurements, often used in dementia studies as a cross-sectional marker for neurodegeneration, showed greatest decline due to secular trends and are not scaled for ICV. Therefore, these should be traded in favor of gray matter volumes after consideration of ICV to estimate the true degree of neurodegeneration,” Dr. Vemuri added.
The data also suggest that longitudinal imaging study designs should be preferred when testing hypotheses on brain health, Dr. Vemuri wrote.
Although this work is “exciting and will bring attention to secular trends in brain health, much work is yet to be done to validate and replicate these findings and, more importantly, understand the mechanistic basis of these trends,” she added.
“Do these secular trends in improvement of brain health underlie the decrease in dementia risk? The jury may be still out, but the authors are commended for investigating new avenues,” Dr. Vemuri concluded.
Support for this research was provided by the National Institute on Aging and the National Institute on Neurological Disorders and Stroke and the National Institutes of Health. Dr. DeCarli reported serving as a consultant to Novartis on a safety study of heart failure during the conduct of the study and receiving consultant fees from Eisai and Novo Nordisk outside the submitted work. Dr. Lemuria had no disclosures.
A version of this article appeared on Medscape.com.
A secular trends analysis using brain imaging data from the long-running Framingham Heart Study revealed an increase in intracranial volume (ICV), cortical gray matter, white matter, and hippocampal volumes, as well as cortical surface area in people born in the 1970s versus those born in the 1930s.
“We hypothesize that the increased size of the brain will lead to increased ‘reserve’ against the diseases of aging, consequently reducing overall risk of dementia,” said Charles DeCarli, MD, director of the Alzheimer’s Disease Research Center and Imaging of Dementia and Aging Laboratory, Department of Neurology and Center for Neuroscience, University of California at Davis.
The study was published online in JAMA Neurology.
Dementia Protection?
An earlier report from the Framingham Heart Study suggested that dementia incidence is declining.
“This difference occurred among persons with at least a high school education and was not affected by differences in vascular risk. Our work was stimulated by this finding and the possibility that differences in brain size might be occurring over the three generations of the Framingham Heart Study which might explain an increased resilience to dementia,” said Dr. DeCarli.
The cross-sectional study used data from 3226 Framingham participants (53% women) born in the decades 1930–1970. None had dementia or a history of stroke. At a mean age of 57.7 years, they underwent brain MRI.
Compared with the 1930s birth decade, the 1970s birth decade had a 6.6% greater ICV (1321 mL vs 1234 mL), 7.7% greater white matter volume (476.3 mL vs 441.9 mL), 5.7% greater hippocampal volume (6.69 mL vs 6.51 mL), and 14.9% greater cortical surface area (2222 cm2 vs 1933 cm2).
Cortical thickness was thinner by 21% over the same period, coinciding with larger intracranial volume, cerebral white matter volume, and cortical surface area.
“We were surprised to find that the brain is getting larger, but the cortex is thinning very slightly. The apparent thinning of the cortex is related to the increased need for expansion of the cortical ribbon. This is based on hypotheses related to the effects of evolution and cortical development designed to make neuronal integration most efficient,” said Dr. DeCarli.
Repeat analysis applied to a subgroup of 1145 individuals of similar age range born in the 1940s (mean age, 60 years) and 1950s (mean age, 59 years) resulted in similar findings.
“These findings likely reflect both secular improvements in early life environmental influences through health, social-cultural, and educational factors, as well as secular improvements in modifiable dementia risk factors leading to better brain health and reserve,” the authors wrote.
While the effects observed are “likely to be small at the level of the individual, they are likely to be substantial at the population level, adding to growing literature that suggests optimized brain development and ideal health through modification of risk factors could substantially modify the effect of common neurodegenerative diseases such as stroke and Alzheiemer’s disease on dementia incidence,” they added.
Limitations included the predominately non-Hispanic White, healthy, and well-educated population that is the Framingham cohort, which is not representative of the broader US population. The cross-sectional nature of the study also limited causal inference.
Exciting Work
“If these results are confirmed by others and the observed differences by decade are as large as those reported, it has important implications for aging and dementia studies,” Prashanthi Lemuria, PhD, with Mayo Clinic, Rochester, Minnesota, wrote in an accompanying editorial.
“First, studies that use brain charts for the human life span to understand the mechanisms of aging, by stitching together data from individuals across the decades, are significantly overestimating the degree of brain health decline using volumes across the life span because the baseline brain health in individuals who are in their older decades is likely lower to begin with,” Dr. Lemuria noted.
“Second, cortical thickness measurements, often used in dementia studies as a cross-sectional marker for neurodegeneration, showed greatest decline due to secular trends and are not scaled for ICV. Therefore, these should be traded in favor of gray matter volumes after consideration of ICV to estimate the true degree of neurodegeneration,” Dr. Vemuri added.
The data also suggest that longitudinal imaging study designs should be preferred when testing hypotheses on brain health, Dr. Vemuri wrote.
Although this work is “exciting and will bring attention to secular trends in brain health, much work is yet to be done to validate and replicate these findings and, more importantly, understand the mechanistic basis of these trends,” she added.
“Do these secular trends in improvement of brain health underlie the decrease in dementia risk? The jury may be still out, but the authors are commended for investigating new avenues,” Dr. Vemuri concluded.
Support for this research was provided by the National Institute on Aging and the National Institute on Neurological Disorders and Stroke and the National Institutes of Health. Dr. DeCarli reported serving as a consultant to Novartis on a safety study of heart failure during the conduct of the study and receiving consultant fees from Eisai and Novo Nordisk outside the submitted work. Dr. Lemuria had no disclosures.
A version of this article appeared on Medscape.com.
A secular trends analysis using brain imaging data from the long-running Framingham Heart Study revealed an increase in intracranial volume (ICV), cortical gray matter, white matter, and hippocampal volumes, as well as cortical surface area in people born in the 1970s versus those born in the 1930s.
“We hypothesize that the increased size of the brain will lead to increased ‘reserve’ against the diseases of aging, consequently reducing overall risk of dementia,” said Charles DeCarli, MD, director of the Alzheimer’s Disease Research Center and Imaging of Dementia and Aging Laboratory, Department of Neurology and Center for Neuroscience, University of California at Davis.
The study was published online in JAMA Neurology.
Dementia Protection?
An earlier report from the Framingham Heart Study suggested that dementia incidence is declining.
“This difference occurred among persons with at least a high school education and was not affected by differences in vascular risk. Our work was stimulated by this finding and the possibility that differences in brain size might be occurring over the three generations of the Framingham Heart Study which might explain an increased resilience to dementia,” said Dr. DeCarli.
The cross-sectional study used data from 3226 Framingham participants (53% women) born in the decades 1930–1970. None had dementia or a history of stroke. At a mean age of 57.7 years, they underwent brain MRI.
Compared with the 1930s birth decade, the 1970s birth decade had a 6.6% greater ICV (1321 mL vs 1234 mL), 7.7% greater white matter volume (476.3 mL vs 441.9 mL), 5.7% greater hippocampal volume (6.69 mL vs 6.51 mL), and 14.9% greater cortical surface area (2222 cm2 vs 1933 cm2).
Cortical thickness was thinner by 21% over the same period, coinciding with larger intracranial volume, cerebral white matter volume, and cortical surface area.
“We were surprised to find that the brain is getting larger, but the cortex is thinning very slightly. The apparent thinning of the cortex is related to the increased need for expansion of the cortical ribbon. This is based on hypotheses related to the effects of evolution and cortical development designed to make neuronal integration most efficient,” said Dr. DeCarli.
Repeat analysis applied to a subgroup of 1145 individuals of similar age range born in the 1940s (mean age, 60 years) and 1950s (mean age, 59 years) resulted in similar findings.
“These findings likely reflect both secular improvements in early life environmental influences through health, social-cultural, and educational factors, as well as secular improvements in modifiable dementia risk factors leading to better brain health and reserve,” the authors wrote.
While the effects observed are “likely to be small at the level of the individual, they are likely to be substantial at the population level, adding to growing literature that suggests optimized brain development and ideal health through modification of risk factors could substantially modify the effect of common neurodegenerative diseases such as stroke and Alzheiemer’s disease on dementia incidence,” they added.
Limitations included the predominately non-Hispanic White, healthy, and well-educated population that is the Framingham cohort, which is not representative of the broader US population. The cross-sectional nature of the study also limited causal inference.
Exciting Work
“If these results are confirmed by others and the observed differences by decade are as large as those reported, it has important implications for aging and dementia studies,” Prashanthi Lemuria, PhD, with Mayo Clinic, Rochester, Minnesota, wrote in an accompanying editorial.
“First, studies that use brain charts for the human life span to understand the mechanisms of aging, by stitching together data from individuals across the decades, are significantly overestimating the degree of brain health decline using volumes across the life span because the baseline brain health in individuals who are in their older decades is likely lower to begin with,” Dr. Lemuria noted.
“Second, cortical thickness measurements, often used in dementia studies as a cross-sectional marker for neurodegeneration, showed greatest decline due to secular trends and are not scaled for ICV. Therefore, these should be traded in favor of gray matter volumes after consideration of ICV to estimate the true degree of neurodegeneration,” Dr. Vemuri added.
The data also suggest that longitudinal imaging study designs should be preferred when testing hypotheses on brain health, Dr. Vemuri wrote.
Although this work is “exciting and will bring attention to secular trends in brain health, much work is yet to be done to validate and replicate these findings and, more importantly, understand the mechanistic basis of these trends,” she added.
“Do these secular trends in improvement of brain health underlie the decrease in dementia risk? The jury may be still out, but the authors are commended for investigating new avenues,” Dr. Vemuri concluded.
Support for this research was provided by the National Institute on Aging and the National Institute on Neurological Disorders and Stroke and the National Institutes of Health. Dr. DeCarli reported serving as a consultant to Novartis on a safety study of heart failure during the conduct of the study and receiving consultant fees from Eisai and Novo Nordisk outside the submitted work. Dr. Lemuria had no disclosures.
A version of this article appeared on Medscape.com.
FROM JAMA NEUROLOGY
Severe Flu Confers Higher Risk for Neurologic Disorders Versus COVID
TOPLINE:
, results of a large study show.
METHODOLOGY:
- Researchers used healthcare claims data to compare 77,300 people hospitalized with COVID-19 with 77,300 hospitalized with influenza. The study did not include individuals with long COVID.
- In the final sample of 154,500 participants, the mean age was 51 years, and more than half (58%) were female.
- Investigators followed participants from both cohorts for a year to find out how many of them had medical care for six of the most common neurologic disorders: migraine, epilepsy, stroke, neuropathy, movement disorders, and dementia.
- If participants had one of these neurologic disorders prior to the original hospitalization, the primary outcome involved subsequent healthcare encounters for the neurologic diagnosis.
TAKEAWAY:
- Participants hospitalized with COVID-19 versus influenza were significantly less likely to require care in the following year for migraine (2% vs 3.2%), epilepsy (1.6% vs 2.1%), neuropathy (1.9% vs 3.6%), movement disorders (1.5% vs 2.5%), stroke (2% vs 2.4%), and dementia (2% vs 2.3%) (all P < .001).
- After adjusting for age, sex, and other health conditions, researchers found that people hospitalized with COVID-19 had a 35% lower risk of receiving care for migraine, a 22% lower risk of receiving care for epilepsy, and a 44% lower risk of receiving care for neuropathy than those with influenza. They also had a 36% lower risk of receiving care for movement disorders, a 10% lower risk for stroke (all P < .001), as well as a 7% lower risk for dementia (P = .0007).
- In participants who did not have a preexisting neurologic condition at the time of hospitalization for either COVID-19 or influenza, 2.8% hospitalized with COVID-19 developed one in the next year compared with 5% of those hospitalized with influenza.
IN PRACTICE:
“While the results were not what we expected to find, they are reassuring in that we found being hospitalized with COVID did not lead to more care for common neurologic conditions when compared to being hospitalized with influenza,” study investigator Brian C. Callaghan, MD, of University of Michigan, Ann Arbor, said in a press release.
SOURCE:
Adam de Havenon, MD, of Yale University in New Haven, Connecticut, led the study, which was published online on March 20 in Neurology.
LIMITATIONS:
The study relied on ICD codes in health claims databases, which could introduce misclassification bias. Also, by selecting only individuals who had associated hospital-based care, there may have been a selection bias based on disease severity.
DISCLOSURES:
The study was funded by the American Academy of Neurology. Dr. De Havenon reported receiving consultant fees from Integra and Novo Nordisk and royalty fees from UpToDate and has equity in Titin KM and Certus. Dr. Callaghan has consulted for DynaMed and the Vaccine Injury Compensation Program. Other disclosures were noted in the original article.
A version of this article appeared on Medscape.com.
TOPLINE:
, results of a large study show.
METHODOLOGY:
- Researchers used healthcare claims data to compare 77,300 people hospitalized with COVID-19 with 77,300 hospitalized with influenza. The study did not include individuals with long COVID.
- In the final sample of 154,500 participants, the mean age was 51 years, and more than half (58%) were female.
- Investigators followed participants from both cohorts for a year to find out how many of them had medical care for six of the most common neurologic disorders: migraine, epilepsy, stroke, neuropathy, movement disorders, and dementia.
- If participants had one of these neurologic disorders prior to the original hospitalization, the primary outcome involved subsequent healthcare encounters for the neurologic diagnosis.
TAKEAWAY:
- Participants hospitalized with COVID-19 versus influenza were significantly less likely to require care in the following year for migraine (2% vs 3.2%), epilepsy (1.6% vs 2.1%), neuropathy (1.9% vs 3.6%), movement disorders (1.5% vs 2.5%), stroke (2% vs 2.4%), and dementia (2% vs 2.3%) (all P < .001).
- After adjusting for age, sex, and other health conditions, researchers found that people hospitalized with COVID-19 had a 35% lower risk of receiving care for migraine, a 22% lower risk of receiving care for epilepsy, and a 44% lower risk of receiving care for neuropathy than those with influenza. They also had a 36% lower risk of receiving care for movement disorders, a 10% lower risk for stroke (all P < .001), as well as a 7% lower risk for dementia (P = .0007).
- In participants who did not have a preexisting neurologic condition at the time of hospitalization for either COVID-19 or influenza, 2.8% hospitalized with COVID-19 developed one in the next year compared with 5% of those hospitalized with influenza.
IN PRACTICE:
“While the results were not what we expected to find, they are reassuring in that we found being hospitalized with COVID did not lead to more care for common neurologic conditions when compared to being hospitalized with influenza,” study investigator Brian C. Callaghan, MD, of University of Michigan, Ann Arbor, said in a press release.
SOURCE:
Adam de Havenon, MD, of Yale University in New Haven, Connecticut, led the study, which was published online on March 20 in Neurology.
LIMITATIONS:
The study relied on ICD codes in health claims databases, which could introduce misclassification bias. Also, by selecting only individuals who had associated hospital-based care, there may have been a selection bias based on disease severity.
DISCLOSURES:
The study was funded by the American Academy of Neurology. Dr. De Havenon reported receiving consultant fees from Integra and Novo Nordisk and royalty fees from UpToDate and has equity in Titin KM and Certus. Dr. Callaghan has consulted for DynaMed and the Vaccine Injury Compensation Program. Other disclosures were noted in the original article.
A version of this article appeared on Medscape.com.
TOPLINE:
, results of a large study show.
METHODOLOGY:
- Researchers used healthcare claims data to compare 77,300 people hospitalized with COVID-19 with 77,300 hospitalized with influenza. The study did not include individuals with long COVID.
- In the final sample of 154,500 participants, the mean age was 51 years, and more than half (58%) were female.
- Investigators followed participants from both cohorts for a year to find out how many of them had medical care for six of the most common neurologic disorders: migraine, epilepsy, stroke, neuropathy, movement disorders, and dementia.
- If participants had one of these neurologic disorders prior to the original hospitalization, the primary outcome involved subsequent healthcare encounters for the neurologic diagnosis.
TAKEAWAY:
- Participants hospitalized with COVID-19 versus influenza were significantly less likely to require care in the following year for migraine (2% vs 3.2%), epilepsy (1.6% vs 2.1%), neuropathy (1.9% vs 3.6%), movement disorders (1.5% vs 2.5%), stroke (2% vs 2.4%), and dementia (2% vs 2.3%) (all P < .001).
- After adjusting for age, sex, and other health conditions, researchers found that people hospitalized with COVID-19 had a 35% lower risk of receiving care for migraine, a 22% lower risk of receiving care for epilepsy, and a 44% lower risk of receiving care for neuropathy than those with influenza. They also had a 36% lower risk of receiving care for movement disorders, a 10% lower risk for stroke (all P < .001), as well as a 7% lower risk for dementia (P = .0007).
- In participants who did not have a preexisting neurologic condition at the time of hospitalization for either COVID-19 or influenza, 2.8% hospitalized with COVID-19 developed one in the next year compared with 5% of those hospitalized with influenza.
IN PRACTICE:
“While the results were not what we expected to find, they are reassuring in that we found being hospitalized with COVID did not lead to more care for common neurologic conditions when compared to being hospitalized with influenza,” study investigator Brian C. Callaghan, MD, of University of Michigan, Ann Arbor, said in a press release.
SOURCE:
Adam de Havenon, MD, of Yale University in New Haven, Connecticut, led the study, which was published online on March 20 in Neurology.
LIMITATIONS:
The study relied on ICD codes in health claims databases, which could introduce misclassification bias. Also, by selecting only individuals who had associated hospital-based care, there may have been a selection bias based on disease severity.
DISCLOSURES:
The study was funded by the American Academy of Neurology. Dr. De Havenon reported receiving consultant fees from Integra and Novo Nordisk and royalty fees from UpToDate and has equity in Titin KM and Certus. Dr. Callaghan has consulted for DynaMed and the Vaccine Injury Compensation Program. Other disclosures were noted in the original article.
A version of this article appeared on Medscape.com.
Does Abdominal Fat Location Matter for Brain Health?
TOPLINE:
METHODOLOGY:
- Obesity is a well-known risk factor for poorer cognition and dementia, but the distribution of body fat may influence the risk and underlying mechanisms in the fat-brain-cognition pathway.
- The study examined associations of several abdominal fat depots with cognitive functioning and AD-related brain volumes.
- The study sample included 204 men and women from the Israel Registry for Alzheimer’s Prevention (mean age, 59 years; 60% women) who had a high AD risk due to parental family history.
- Abdominal MRI scans assessed fat stored as subcutaneous adipose tissue (SAT) beneath the skin, visceral adipose tissue (VAT) around abdominal organs, and ectopic, a harmful condition in which lipids accumulate in lean tissues such as the liver and pancreas.
- A structural volumetric brain MRI scan was undertaken by 142 participants to assess specific regions implicated in chosen previous research.
TAKEAWAY:
- High body mass index was associated with high pancreatic fat percentage in both men and women (P < .001) and with high SAT percentage in women (P = .01) but not with VAT percentage in either sex.
- After adjustment for cardiovascular risk factors, a higher pancreatic fat percentage was linked to lower global cognition (beta, −0.33; P = .02) and executive function (beta, −0.32; P = .02) in men, and with lower hippocampal volume in women (beta, −0.25; P = .03).
- In men only, a higher SAT percentage was associated with a lower middle frontal gyrus volume (beta, −0.27; P = .03), while a higher VAT percentage was linked to higher middle frontal gyrus (beta, 0.29; P = .03) and superior frontal gyrus volumes (beta, 0.31; P = .02).
- Hepatic fat was not associated with brain volumes or cognition in either men or women.
IN PRACTICE:
“These results suggest that already in midlife, abdominal fat accumulation may have deleterious effects on brain health, especially in men,” the authors wrote.
SOURCE:
This study was led by Sapir G. Shekhtman, Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel, and published online in Obesity (Silver Spring).
LIMITATIONS:
No causal inferences could be drawn from this study due to its cross-sectional nature. It did not represent the population of middle-aged adults as a whole, but rather those at high risk of developing AD. Factors contributing to fat accumulation, such as menopausal status or treatment, inflammation, insulin resistance, daily exercise, and dietary factors, were not included in this study.
DISCLOSURES:
This work was supported by grants from the National Institutes of Health. The authors declared no conflicts of interest.
A version of this article appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Obesity is a well-known risk factor for poorer cognition and dementia, but the distribution of body fat may influence the risk and underlying mechanisms in the fat-brain-cognition pathway.
- The study examined associations of several abdominal fat depots with cognitive functioning and AD-related brain volumes.
- The study sample included 204 men and women from the Israel Registry for Alzheimer’s Prevention (mean age, 59 years; 60% women) who had a high AD risk due to parental family history.
- Abdominal MRI scans assessed fat stored as subcutaneous adipose tissue (SAT) beneath the skin, visceral adipose tissue (VAT) around abdominal organs, and ectopic, a harmful condition in which lipids accumulate in lean tissues such as the liver and pancreas.
- A structural volumetric brain MRI scan was undertaken by 142 participants to assess specific regions implicated in chosen previous research.
TAKEAWAY:
- High body mass index was associated with high pancreatic fat percentage in both men and women (P < .001) and with high SAT percentage in women (P = .01) but not with VAT percentage in either sex.
- After adjustment for cardiovascular risk factors, a higher pancreatic fat percentage was linked to lower global cognition (beta, −0.33; P = .02) and executive function (beta, −0.32; P = .02) in men, and with lower hippocampal volume in women (beta, −0.25; P = .03).
- In men only, a higher SAT percentage was associated with a lower middle frontal gyrus volume (beta, −0.27; P = .03), while a higher VAT percentage was linked to higher middle frontal gyrus (beta, 0.29; P = .03) and superior frontal gyrus volumes (beta, 0.31; P = .02).
- Hepatic fat was not associated with brain volumes or cognition in either men or women.
IN PRACTICE:
“These results suggest that already in midlife, abdominal fat accumulation may have deleterious effects on brain health, especially in men,” the authors wrote.
SOURCE:
This study was led by Sapir G. Shekhtman, Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel, and published online in Obesity (Silver Spring).
LIMITATIONS:
No causal inferences could be drawn from this study due to its cross-sectional nature. It did not represent the population of middle-aged adults as a whole, but rather those at high risk of developing AD. Factors contributing to fat accumulation, such as menopausal status or treatment, inflammation, insulin resistance, daily exercise, and dietary factors, were not included in this study.
DISCLOSURES:
This work was supported by grants from the National Institutes of Health. The authors declared no conflicts of interest.
A version of this article appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Obesity is a well-known risk factor for poorer cognition and dementia, but the distribution of body fat may influence the risk and underlying mechanisms in the fat-brain-cognition pathway.
- The study examined associations of several abdominal fat depots with cognitive functioning and AD-related brain volumes.
- The study sample included 204 men and women from the Israel Registry for Alzheimer’s Prevention (mean age, 59 years; 60% women) who had a high AD risk due to parental family history.
- Abdominal MRI scans assessed fat stored as subcutaneous adipose tissue (SAT) beneath the skin, visceral adipose tissue (VAT) around abdominal organs, and ectopic, a harmful condition in which lipids accumulate in lean tissues such as the liver and pancreas.
- A structural volumetric brain MRI scan was undertaken by 142 participants to assess specific regions implicated in chosen previous research.
TAKEAWAY:
- High body mass index was associated with high pancreatic fat percentage in both men and women (P < .001) and with high SAT percentage in women (P = .01) but not with VAT percentage in either sex.
- After adjustment for cardiovascular risk factors, a higher pancreatic fat percentage was linked to lower global cognition (beta, −0.33; P = .02) and executive function (beta, −0.32; P = .02) in men, and with lower hippocampal volume in women (beta, −0.25; P = .03).
- In men only, a higher SAT percentage was associated with a lower middle frontal gyrus volume (beta, −0.27; P = .03), while a higher VAT percentage was linked to higher middle frontal gyrus (beta, 0.29; P = .03) and superior frontal gyrus volumes (beta, 0.31; P = .02).
- Hepatic fat was not associated with brain volumes or cognition in either men or women.
IN PRACTICE:
“These results suggest that already in midlife, abdominal fat accumulation may have deleterious effects on brain health, especially in men,” the authors wrote.
SOURCE:
This study was led by Sapir G. Shekhtman, Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel, and published online in Obesity (Silver Spring).
LIMITATIONS:
No causal inferences could be drawn from this study due to its cross-sectional nature. It did not represent the population of middle-aged adults as a whole, but rather those at high risk of developing AD. Factors contributing to fat accumulation, such as menopausal status or treatment, inflammation, insulin resistance, daily exercise, and dietary factors, were not included in this study.
DISCLOSURES:
This work was supported by grants from the National Institutes of Health. The authors declared no conflicts of interest.
A version of this article appeared on Medscape.com.
Risk Factors for Headache in Youth Identified
, new data from a population-based study showed.
Children and teens with anxiety or mood disorders had twice the risk for frequent headaches, defined as occurring once or more per week, and those who regularly ate breakfast and dinners with their family had an 8% lower risk for frequent headaches than those who did not eat regular meals.
“It is not uncommon for children and teens to have headaches, and while medications are used to stop and sometimes prevent headaches, lifestyle changes also may offer an effective route to relief by preventing headaches from happening and improving quality of life,” study investigator Serena L. Orr, MD, MSc, University of Calgary in Alberta, Canada, said in a press release.
The findings were published online in Neurology.
Negative Consequences
Previous research shows frequent recurrent headaches occur in up to 30% of children and adolescents and can lead to lower academic achievement and lower quality of life.
Treatment recommendations often focus on adjusting lifestyle behaviors, such as sleep and meal timing or smoking.
To further investigate these links, researchers used data from the 2019 Canadian Health Survey on Children and Youth and included about 5 million children and teens aged 5-17 years. In most cases, a parent or guardian answered the survey questions.
In addition to assessing participants for headache frequency in the past week, the survey included questions about how often they had breakfast, were physically active, or spent playing video games or with a mobile device, for instance. Parents/guardians were also asked whether the youth had ever been diagnosed with a mood or anxiety disorder.
For participants aged between 12 and 17 years, there were also questions about smoking, alcohol consumption, and substance use.
The mean age of participants was 11 years, and 48% were female. About 6% of the participants had frequent recurrent headaches.
Investigators found that meal regularity was inversely associated with frequent headaches (P < .001). In an adjusted model, youth who often ate breakfast and dinner with their families had an 8% lower risk for frequent headaches than those who didn’t dine with their families regularly.
“It is possible regular family meals may lead to greater connectedness and communication within the family and better mental health outcomes, which in turn may impact headache frequency,” Dr. Orr noted.
Youth who spent more than 21 hours per week in front of computer screens or with video games had higher odds for frequent headaches (P < .001), but this association did not survive statistical adjustment for demographics or lifestyle factors.
Both mood and anxiety disorders were associated with twice the risk for frequent headaches, and this risk survived adjustment for age, sex, household income, and other lifestyle factors.
In adolescents aged 12-17 years, there was an association between drinking alcohol and frequent headache, with higher alcohol consumption increasing the likelihood of frequent headache. For instance, those who drank once or more per week had three times the risk for frequent headache (P < .001), and those who indulged in binge drinking at least five times per month had five times the risk for frequent headache (P < .001).
Smoking cannabis was also associated with frequent headache in a dose-dependent manner. Daily users had a threefold increased risk for frequent headache vs those who didn’t use cannabis (P < .001).
Similarly, those who smoked or used e-cigarettes daily also had a threefold increased risk for frequent headaches versus nonusers.
One of the study’s limitations was that it didn’t include participants living in foster homes, institutions or on First Nation reserves. Investigators also were not able to determine headache type and did not assess hydration, which can be an important lifestyle factor in headache etiology.
Prioritize Questions About Lifestyle?
In an accompanying editorial, Irene Patniyot, MD, of Baylor College of Medicine in Houston, Texas, noted that lifestyle advice is an important part of managing headache disorders in children and youth and questioned whether neurologists should prioritize discussions about lifestyle habits in this patient population. However, she noted, given the heavy demands on neurologists’ time, this may be “idealistic.”
One potential solution may lie in automating electronic questionnaires for inclusion in patients’ medical records. “Data extraction from electronic questionnaires has already led to new data on symptoms associated with headache in youth and can potentially lead to earlier identification and treatment of mental health disorders and lifestyle habits that negatively affect headache burden and overall well-being,” Dr. Patniyot wrote.
The study was funded by the Social Sciences and Humanities Research Council of Canada, the Canadian Institutes of Health Research, the Canada Foundation for Innovation, and Statistics Canada. Dr. Orr reported receiving royalties from Cambridge University Press; serving on the editorial boards of Headache, Neurology, and the American Migraine Foundation; and receiving research funding from the Canadian Institutes of Health Research and the Alberta Children’s Hospital Research Institute. Other disclosures were noted in the original article.
A version of this article appeared on Medscape.com.
, new data from a population-based study showed.
Children and teens with anxiety or mood disorders had twice the risk for frequent headaches, defined as occurring once or more per week, and those who regularly ate breakfast and dinners with their family had an 8% lower risk for frequent headaches than those who did not eat regular meals.
“It is not uncommon for children and teens to have headaches, and while medications are used to stop and sometimes prevent headaches, lifestyle changes also may offer an effective route to relief by preventing headaches from happening and improving quality of life,” study investigator Serena L. Orr, MD, MSc, University of Calgary in Alberta, Canada, said in a press release.
The findings were published online in Neurology.
Negative Consequences
Previous research shows frequent recurrent headaches occur in up to 30% of children and adolescents and can lead to lower academic achievement and lower quality of life.
Treatment recommendations often focus on adjusting lifestyle behaviors, such as sleep and meal timing or smoking.
To further investigate these links, researchers used data from the 2019 Canadian Health Survey on Children and Youth and included about 5 million children and teens aged 5-17 years. In most cases, a parent or guardian answered the survey questions.
In addition to assessing participants for headache frequency in the past week, the survey included questions about how often they had breakfast, were physically active, or spent playing video games or with a mobile device, for instance. Parents/guardians were also asked whether the youth had ever been diagnosed with a mood or anxiety disorder.
For participants aged between 12 and 17 years, there were also questions about smoking, alcohol consumption, and substance use.
The mean age of participants was 11 years, and 48% were female. About 6% of the participants had frequent recurrent headaches.
Investigators found that meal regularity was inversely associated with frequent headaches (P < .001). In an adjusted model, youth who often ate breakfast and dinner with their families had an 8% lower risk for frequent headaches than those who didn’t dine with their families regularly.
“It is possible regular family meals may lead to greater connectedness and communication within the family and better mental health outcomes, which in turn may impact headache frequency,” Dr. Orr noted.
Youth who spent more than 21 hours per week in front of computer screens or with video games had higher odds for frequent headaches (P < .001), but this association did not survive statistical adjustment for demographics or lifestyle factors.
Both mood and anxiety disorders were associated with twice the risk for frequent headaches, and this risk survived adjustment for age, sex, household income, and other lifestyle factors.
In adolescents aged 12-17 years, there was an association between drinking alcohol and frequent headache, with higher alcohol consumption increasing the likelihood of frequent headache. For instance, those who drank once or more per week had three times the risk for frequent headache (P < .001), and those who indulged in binge drinking at least five times per month had five times the risk for frequent headache (P < .001).
Smoking cannabis was also associated with frequent headache in a dose-dependent manner. Daily users had a threefold increased risk for frequent headache vs those who didn’t use cannabis (P < .001).
Similarly, those who smoked or used e-cigarettes daily also had a threefold increased risk for frequent headaches versus nonusers.
One of the study’s limitations was that it didn’t include participants living in foster homes, institutions or on First Nation reserves. Investigators also were not able to determine headache type and did not assess hydration, which can be an important lifestyle factor in headache etiology.
Prioritize Questions About Lifestyle?
In an accompanying editorial, Irene Patniyot, MD, of Baylor College of Medicine in Houston, Texas, noted that lifestyle advice is an important part of managing headache disorders in children and youth and questioned whether neurologists should prioritize discussions about lifestyle habits in this patient population. However, she noted, given the heavy demands on neurologists’ time, this may be “idealistic.”
One potential solution may lie in automating electronic questionnaires for inclusion in patients’ medical records. “Data extraction from electronic questionnaires has already led to new data on symptoms associated with headache in youth and can potentially lead to earlier identification and treatment of mental health disorders and lifestyle habits that negatively affect headache burden and overall well-being,” Dr. Patniyot wrote.
The study was funded by the Social Sciences and Humanities Research Council of Canada, the Canadian Institutes of Health Research, the Canada Foundation for Innovation, and Statistics Canada. Dr. Orr reported receiving royalties from Cambridge University Press; serving on the editorial boards of Headache, Neurology, and the American Migraine Foundation; and receiving research funding from the Canadian Institutes of Health Research and the Alberta Children’s Hospital Research Institute. Other disclosures were noted in the original article.
A version of this article appeared on Medscape.com.
, new data from a population-based study showed.
Children and teens with anxiety or mood disorders had twice the risk for frequent headaches, defined as occurring once or more per week, and those who regularly ate breakfast and dinners with their family had an 8% lower risk for frequent headaches than those who did not eat regular meals.
“It is not uncommon for children and teens to have headaches, and while medications are used to stop and sometimes prevent headaches, lifestyle changes also may offer an effective route to relief by preventing headaches from happening and improving quality of life,” study investigator Serena L. Orr, MD, MSc, University of Calgary in Alberta, Canada, said in a press release.
The findings were published online in Neurology.
Negative Consequences
Previous research shows frequent recurrent headaches occur in up to 30% of children and adolescents and can lead to lower academic achievement and lower quality of life.
Treatment recommendations often focus on adjusting lifestyle behaviors, such as sleep and meal timing or smoking.
To further investigate these links, researchers used data from the 2019 Canadian Health Survey on Children and Youth and included about 5 million children and teens aged 5-17 years. In most cases, a parent or guardian answered the survey questions.
In addition to assessing participants for headache frequency in the past week, the survey included questions about how often they had breakfast, were physically active, or spent playing video games or with a mobile device, for instance. Parents/guardians were also asked whether the youth had ever been diagnosed with a mood or anxiety disorder.
For participants aged between 12 and 17 years, there were also questions about smoking, alcohol consumption, and substance use.
The mean age of participants was 11 years, and 48% were female. About 6% of the participants had frequent recurrent headaches.
Investigators found that meal regularity was inversely associated with frequent headaches (P < .001). In an adjusted model, youth who often ate breakfast and dinner with their families had an 8% lower risk for frequent headaches than those who didn’t dine with their families regularly.
“It is possible regular family meals may lead to greater connectedness and communication within the family and better mental health outcomes, which in turn may impact headache frequency,” Dr. Orr noted.
Youth who spent more than 21 hours per week in front of computer screens or with video games had higher odds for frequent headaches (P < .001), but this association did not survive statistical adjustment for demographics or lifestyle factors.
Both mood and anxiety disorders were associated with twice the risk for frequent headaches, and this risk survived adjustment for age, sex, household income, and other lifestyle factors.
In adolescents aged 12-17 years, there was an association between drinking alcohol and frequent headache, with higher alcohol consumption increasing the likelihood of frequent headache. For instance, those who drank once or more per week had three times the risk for frequent headache (P < .001), and those who indulged in binge drinking at least five times per month had five times the risk for frequent headache (P < .001).
Smoking cannabis was also associated with frequent headache in a dose-dependent manner. Daily users had a threefold increased risk for frequent headache vs those who didn’t use cannabis (P < .001).
Similarly, those who smoked or used e-cigarettes daily also had a threefold increased risk for frequent headaches versus nonusers.
One of the study’s limitations was that it didn’t include participants living in foster homes, institutions or on First Nation reserves. Investigators also were not able to determine headache type and did not assess hydration, which can be an important lifestyle factor in headache etiology.
Prioritize Questions About Lifestyle?
In an accompanying editorial, Irene Patniyot, MD, of Baylor College of Medicine in Houston, Texas, noted that lifestyle advice is an important part of managing headache disorders in children and youth and questioned whether neurologists should prioritize discussions about lifestyle habits in this patient population. However, she noted, given the heavy demands on neurologists’ time, this may be “idealistic.”
One potential solution may lie in automating electronic questionnaires for inclusion in patients’ medical records. “Data extraction from electronic questionnaires has already led to new data on symptoms associated with headache in youth and can potentially lead to earlier identification and treatment of mental health disorders and lifestyle habits that negatively affect headache burden and overall well-being,” Dr. Patniyot wrote.
The study was funded by the Social Sciences and Humanities Research Council of Canada, the Canadian Institutes of Health Research, the Canada Foundation for Innovation, and Statistics Canada. Dr. Orr reported receiving royalties from Cambridge University Press; serving on the editorial boards of Headache, Neurology, and the American Migraine Foundation; and receiving research funding from the Canadian Institutes of Health Research and the Alberta Children’s Hospital Research Institute. Other disclosures were noted in the original article.
A version of this article appeared on Medscape.com.
FROM NEUROLOGY
Epilepsy Linked to Higher COVID Hospitalization, Death Rates
, data from two linked studies showed.
Results showed that individuals with epilepsy had a 60% higher risk for hospitalization and a 33% higher risk of dying from COVID-19 than those without the disorder. However, during the pandemic, the number of hospitalizations and ER visits by people with epilepsy dropped by as much as 30%.
“The neurotropic effects of Sars-CoV-2 might explain some of this increased risk for people with epilepsy, or epilepsy might be associated with alterations in the immune system, predisposing to more severe COVID-19,” wrote the investigators, led by Owen Pickrell, MBBChirm, PhD, Swansea University, United Kingdom.
The findings were published online March 5 in Epilepsia.
Skill Shifting
Epilepsy is one of the most common neurological conditions and affects approximately 50 million people worldwide, with significant comorbidity and an increased risk for early death.
During the pandemic, clinicians treating people with epilepsy and other conditions shifted their skills to treat an ever-increasing number of patients with COVID-19, which may have hindered epilepsy-specific services for a time.
To further explore how the COVID-19 pandemic may have affected the health of this patient population, researchers analyzed health records from a large database with information about hospital admissions, primary care visits, COVID-19 vaccination status, and demographics of 90% of Welsh residents.
Those living with epilepsy before or during the study period (March 1, 2020, to June 31, 2021) were identified and compared with controls without epilepsy.
The analysis included approximately 27,280 people with epilepsy and 136,400 matched controls. Among those with epilepsy, there were 158 deaths (0.58%) and 933 hospitalizations (3.4%). In comparison, there were 370 deaths (0.27%) and 1871 hospitalizations (1.4%) in the control group.
Unadjusted analyses showed the risk of dying from COVID-19 for those with epilepsy vs controls was more than twofold higher (hazard ratio [HR], 2.15; 95% CI; 1.78-2.59) and the increase in the risk for hospitalization was similar (HR, 2.15; 95% CI; 1.94-2.37).
After adjusting for 40 comorbidities, including serious mental illness, asthma, and diabetes, those with epilepsy had a 60% increased risk for hospitalization (adjusted HR [aHR], 1.60) and a 33% increased risk for death (aHR, 1.33) than those without epilepsy (all P < .0001).
The findings “may have implications for prioritizing future COVID-19 treatments and vaccinations for people with epilepsy,” the investigators wrote.
Study limitations included the inability to account for the effect of vaccinations or prior infections with SARS-CoV-2. Moreover, the study did not account for geographical or temporal variations in prevalence and COVID-19 variants.
Consultations Canceled
In the related study, researchers analyzed healthcare utilization by people with epilepsy before and after the pandemic using the same database. Results showed hospital admissions, ER visits, and outpatient visits significantly decreased during the pandemic.
In the year before the pandemic, people with epilepsy had double the rate of ER visits (rate ratio [RR], 2.36), hospital admissions (RR, 2.08), and outpatient appointments (RR, 1.92) compared with matched controls.
However, during the pandemic there was a greater reduction in hospital admissions (RR, 0.70; 95% CI, 0.69-0.72) and ER visits (RR, 0.78; 95% CI, 0.77-0.70) in those with epilepsy versus matched controls (RR, 0.82; 95% CI, 0.81-0.83) as well as hospital visits and ER visits (RR, 0.87; 95% CI, 0.86-0.88; all P < .0001). New epilepsy diagnoses also decreased during the pandemic (RR, 0.73; P < .0001)
The redeployment of epileptologists during the pandemic also meant that epilepsy consultations and investigations were canceled, making it harder for people with epilepsy to access specialty care, the researchers noted.
“Our research also showed that there were fewer new diagnoses of epilepsy and fewer contacts with health services by people with epilepsy, during the period we examined,” Huw Strafford, lead data analyst for the studies, said in a release.
Both studies were funded by Health and Care Research Wales. Dr. Pickrell reported receiving speaker fees from UCB Pharma and Angelini Pharma, travel grants from Angelini Pharma, and an unrestricted grant from UCB Pharma.
A version of this article appeared on Medscape.com .
, data from two linked studies showed.
Results showed that individuals with epilepsy had a 60% higher risk for hospitalization and a 33% higher risk of dying from COVID-19 than those without the disorder. However, during the pandemic, the number of hospitalizations and ER visits by people with epilepsy dropped by as much as 30%.
“The neurotropic effects of Sars-CoV-2 might explain some of this increased risk for people with epilepsy, or epilepsy might be associated with alterations in the immune system, predisposing to more severe COVID-19,” wrote the investigators, led by Owen Pickrell, MBBChirm, PhD, Swansea University, United Kingdom.
The findings were published online March 5 in Epilepsia.
Skill Shifting
Epilepsy is one of the most common neurological conditions and affects approximately 50 million people worldwide, with significant comorbidity and an increased risk for early death.
During the pandemic, clinicians treating people with epilepsy and other conditions shifted their skills to treat an ever-increasing number of patients with COVID-19, which may have hindered epilepsy-specific services for a time.
To further explore how the COVID-19 pandemic may have affected the health of this patient population, researchers analyzed health records from a large database with information about hospital admissions, primary care visits, COVID-19 vaccination status, and demographics of 90% of Welsh residents.
Those living with epilepsy before or during the study period (March 1, 2020, to June 31, 2021) were identified and compared with controls without epilepsy.
The analysis included approximately 27,280 people with epilepsy and 136,400 matched controls. Among those with epilepsy, there were 158 deaths (0.58%) and 933 hospitalizations (3.4%). In comparison, there were 370 deaths (0.27%) and 1871 hospitalizations (1.4%) in the control group.
Unadjusted analyses showed the risk of dying from COVID-19 for those with epilepsy vs controls was more than twofold higher (hazard ratio [HR], 2.15; 95% CI; 1.78-2.59) and the increase in the risk for hospitalization was similar (HR, 2.15; 95% CI; 1.94-2.37).
After adjusting for 40 comorbidities, including serious mental illness, asthma, and diabetes, those with epilepsy had a 60% increased risk for hospitalization (adjusted HR [aHR], 1.60) and a 33% increased risk for death (aHR, 1.33) than those without epilepsy (all P < .0001).
The findings “may have implications for prioritizing future COVID-19 treatments and vaccinations for people with epilepsy,” the investigators wrote.
Study limitations included the inability to account for the effect of vaccinations or prior infections with SARS-CoV-2. Moreover, the study did not account for geographical or temporal variations in prevalence and COVID-19 variants.
Consultations Canceled
In the related study, researchers analyzed healthcare utilization by people with epilepsy before and after the pandemic using the same database. Results showed hospital admissions, ER visits, and outpatient visits significantly decreased during the pandemic.
In the year before the pandemic, people with epilepsy had double the rate of ER visits (rate ratio [RR], 2.36), hospital admissions (RR, 2.08), and outpatient appointments (RR, 1.92) compared with matched controls.
However, during the pandemic there was a greater reduction in hospital admissions (RR, 0.70; 95% CI, 0.69-0.72) and ER visits (RR, 0.78; 95% CI, 0.77-0.70) in those with epilepsy versus matched controls (RR, 0.82; 95% CI, 0.81-0.83) as well as hospital visits and ER visits (RR, 0.87; 95% CI, 0.86-0.88; all P < .0001). New epilepsy diagnoses also decreased during the pandemic (RR, 0.73; P < .0001)
The redeployment of epileptologists during the pandemic also meant that epilepsy consultations and investigations were canceled, making it harder for people with epilepsy to access specialty care, the researchers noted.
“Our research also showed that there were fewer new diagnoses of epilepsy and fewer contacts with health services by people with epilepsy, during the period we examined,” Huw Strafford, lead data analyst for the studies, said in a release.
Both studies were funded by Health and Care Research Wales. Dr. Pickrell reported receiving speaker fees from UCB Pharma and Angelini Pharma, travel grants from Angelini Pharma, and an unrestricted grant from UCB Pharma.
A version of this article appeared on Medscape.com .
, data from two linked studies showed.
Results showed that individuals with epilepsy had a 60% higher risk for hospitalization and a 33% higher risk of dying from COVID-19 than those without the disorder. However, during the pandemic, the number of hospitalizations and ER visits by people with epilepsy dropped by as much as 30%.
“The neurotropic effects of Sars-CoV-2 might explain some of this increased risk for people with epilepsy, or epilepsy might be associated with alterations in the immune system, predisposing to more severe COVID-19,” wrote the investigators, led by Owen Pickrell, MBBChirm, PhD, Swansea University, United Kingdom.
The findings were published online March 5 in Epilepsia.
Skill Shifting
Epilepsy is one of the most common neurological conditions and affects approximately 50 million people worldwide, with significant comorbidity and an increased risk for early death.
During the pandemic, clinicians treating people with epilepsy and other conditions shifted their skills to treat an ever-increasing number of patients with COVID-19, which may have hindered epilepsy-specific services for a time.
To further explore how the COVID-19 pandemic may have affected the health of this patient population, researchers analyzed health records from a large database with information about hospital admissions, primary care visits, COVID-19 vaccination status, and demographics of 90% of Welsh residents.
Those living with epilepsy before or during the study period (March 1, 2020, to June 31, 2021) were identified and compared with controls without epilepsy.
The analysis included approximately 27,280 people with epilepsy and 136,400 matched controls. Among those with epilepsy, there were 158 deaths (0.58%) and 933 hospitalizations (3.4%). In comparison, there were 370 deaths (0.27%) and 1871 hospitalizations (1.4%) in the control group.
Unadjusted analyses showed the risk of dying from COVID-19 for those with epilepsy vs controls was more than twofold higher (hazard ratio [HR], 2.15; 95% CI; 1.78-2.59) and the increase in the risk for hospitalization was similar (HR, 2.15; 95% CI; 1.94-2.37).
After adjusting for 40 comorbidities, including serious mental illness, asthma, and diabetes, those with epilepsy had a 60% increased risk for hospitalization (adjusted HR [aHR], 1.60) and a 33% increased risk for death (aHR, 1.33) than those without epilepsy (all P < .0001).
The findings “may have implications for prioritizing future COVID-19 treatments and vaccinations for people with epilepsy,” the investigators wrote.
Study limitations included the inability to account for the effect of vaccinations or prior infections with SARS-CoV-2. Moreover, the study did not account for geographical or temporal variations in prevalence and COVID-19 variants.
Consultations Canceled
In the related study, researchers analyzed healthcare utilization by people with epilepsy before and after the pandemic using the same database. Results showed hospital admissions, ER visits, and outpatient visits significantly decreased during the pandemic.
In the year before the pandemic, people with epilepsy had double the rate of ER visits (rate ratio [RR], 2.36), hospital admissions (RR, 2.08), and outpatient appointments (RR, 1.92) compared with matched controls.
However, during the pandemic there was a greater reduction in hospital admissions (RR, 0.70; 95% CI, 0.69-0.72) and ER visits (RR, 0.78; 95% CI, 0.77-0.70) in those with epilepsy versus matched controls (RR, 0.82; 95% CI, 0.81-0.83) as well as hospital visits and ER visits (RR, 0.87; 95% CI, 0.86-0.88; all P < .0001). New epilepsy diagnoses also decreased during the pandemic (RR, 0.73; P < .0001)
The redeployment of epileptologists during the pandemic also meant that epilepsy consultations and investigations were canceled, making it harder for people with epilepsy to access specialty care, the researchers noted.
“Our research also showed that there were fewer new diagnoses of epilepsy and fewer contacts with health services by people with epilepsy, during the period we examined,” Huw Strafford, lead data analyst for the studies, said in a release.
Both studies were funded by Health and Care Research Wales. Dr. Pickrell reported receiving speaker fees from UCB Pharma and Angelini Pharma, travel grants from Angelini Pharma, and an unrestricted grant from UCB Pharma.
A version of this article appeared on Medscape.com .
FROM EPILEPSIA