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Residential green space linked to better cognitive function
Exposure to green space may boost cognitive function, new research suggests.
This association may be explained by a reduction in depression, researchers note. Scores for overall cognition and psychomotor speed/attention among women with high green-space exposure were equivalent to those of women an average of 1.2 years younger, they add.
“Despite the fact that the women in our study were relatively younger than those in previous studies, we were still able to detect protective associations between green space and cognition,” lead author Marcia Pescador Jimenez, PhD, assistant professor of epidemiology, Boston University School of Public Health, told this news organization.
“This may signal the public health importance of green space and the important clinical implications at the population level,” she said.
The findings were published online in JAMA Network Open.
Better psychomotor speed, attention
Recent studies on the benefits of green space have shown a link between higher exposure and reduced risks for schizophrenia and ischemic stroke. Other studies have explored the link between green space and dementia and Alzheimer’s disease.
Cognitive function in middle age is associated with subsequent dementia, so Dr. Jimenez said she and her colleagues wanted to analyze the effect of residential green space on cognitive function in middle-aged women.
The study included 13,594 women (median age, 61.2 years) who are participants in the ongoing Nurses’ Health Study II, one of the largest studies to examine risk factors for chronic illness in women.
To calculate the amount of green space, researchers used the Normalized Difference Vegetation Index (NDVI), a satellite-based indicator of green vegetation around a residential address. The data were based on each participant’s 2013 residence.
After adjusting for age at assessment, race, and childhood, adulthood, and neighborhood socioeconomic status, green space was associated with higher scores on the global CogState composite (mean difference per interquartile range in green space, 0.05; 95% confidence interval, .02-.07) and psychomotor speed and attention (mean difference in score, 0.05 standard units; 95% CI, .02-.08) scales.
There was no association between green-space exposure and learning and working memory. Investigators also found no differences based on urbanicity, suggesting the benefits were similar for urban versus rural settings.
Specific to cognitive domains
“We were surprised to see that while our study found that higher levels of residential green space were associated with higher scores on processing speed and attention and on overall cognition, we also found that higher levels of residential green space were not associated with learning/working memory battery scores,” Dr. Jimenez said.
“This is actually in-line with previous research suggesting differing associations between green space and cognition based on the cognitive domain examined,” she added.
About 98% of participants were White, limiting the generalizability of the findings, the researchers note. There was also no information on proximity to or size of green space, or how much time individuals spent in the green space and what kinds of activities they engaged in.
Dr. Jimenez said projects examining the amount of time of green-space exposure are underway.
In addition, the researchers found lower rates of depression might contribute to the cognitive benefits associated with green-space exposure, explaining 3.95% (95% CI, .35%-7.55%) of the association between green space and psychomotor speed/attention and 6.3% (95% CI, .77%-11.81%) of the association between green space and overall cognition.
Reduced air pollution and increased physical activity, which are other factors often thought to contribute to the cognitive benefits of green space, were not significant in this study.
‘Interesting and novel’
Commenting on the findings, Payam Dadvand, MD, PhD, associate research professor, Barcelona Institute for Global Health, called the finding that depression may mediate green-space benefits “quite interesting and novel.”
“The results of this study, given its large sample size and its geographical coverage, adds to an emerging body of evidence on the beneficial association of exposure to green space on aging, and in particular, cognitive aging in older adults,” said Dr. Dadvand, who was not involved with the research.
The study was funded by the National Institutes of Health. Dr. Jimenez and Dr. Dadvand have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Exposure to green space may boost cognitive function, new research suggests.
This association may be explained by a reduction in depression, researchers note. Scores for overall cognition and psychomotor speed/attention among women with high green-space exposure were equivalent to those of women an average of 1.2 years younger, they add.
“Despite the fact that the women in our study were relatively younger than those in previous studies, we were still able to detect protective associations between green space and cognition,” lead author Marcia Pescador Jimenez, PhD, assistant professor of epidemiology, Boston University School of Public Health, told this news organization.
“This may signal the public health importance of green space and the important clinical implications at the population level,” she said.
The findings were published online in JAMA Network Open.
Better psychomotor speed, attention
Recent studies on the benefits of green space have shown a link between higher exposure and reduced risks for schizophrenia and ischemic stroke. Other studies have explored the link between green space and dementia and Alzheimer’s disease.
Cognitive function in middle age is associated with subsequent dementia, so Dr. Jimenez said she and her colleagues wanted to analyze the effect of residential green space on cognitive function in middle-aged women.
The study included 13,594 women (median age, 61.2 years) who are participants in the ongoing Nurses’ Health Study II, one of the largest studies to examine risk factors for chronic illness in women.
To calculate the amount of green space, researchers used the Normalized Difference Vegetation Index (NDVI), a satellite-based indicator of green vegetation around a residential address. The data were based on each participant’s 2013 residence.
After adjusting for age at assessment, race, and childhood, adulthood, and neighborhood socioeconomic status, green space was associated with higher scores on the global CogState composite (mean difference per interquartile range in green space, 0.05; 95% confidence interval, .02-.07) and psychomotor speed and attention (mean difference in score, 0.05 standard units; 95% CI, .02-.08) scales.
There was no association between green-space exposure and learning and working memory. Investigators also found no differences based on urbanicity, suggesting the benefits were similar for urban versus rural settings.
Specific to cognitive domains
“We were surprised to see that while our study found that higher levels of residential green space were associated with higher scores on processing speed and attention and on overall cognition, we also found that higher levels of residential green space were not associated with learning/working memory battery scores,” Dr. Jimenez said.
“This is actually in-line with previous research suggesting differing associations between green space and cognition based on the cognitive domain examined,” she added.
About 98% of participants were White, limiting the generalizability of the findings, the researchers note. There was also no information on proximity to or size of green space, or how much time individuals spent in the green space and what kinds of activities they engaged in.
Dr. Jimenez said projects examining the amount of time of green-space exposure are underway.
In addition, the researchers found lower rates of depression might contribute to the cognitive benefits associated with green-space exposure, explaining 3.95% (95% CI, .35%-7.55%) of the association between green space and psychomotor speed/attention and 6.3% (95% CI, .77%-11.81%) of the association between green space and overall cognition.
Reduced air pollution and increased physical activity, which are other factors often thought to contribute to the cognitive benefits of green space, were not significant in this study.
‘Interesting and novel’
Commenting on the findings, Payam Dadvand, MD, PhD, associate research professor, Barcelona Institute for Global Health, called the finding that depression may mediate green-space benefits “quite interesting and novel.”
“The results of this study, given its large sample size and its geographical coverage, adds to an emerging body of evidence on the beneficial association of exposure to green space on aging, and in particular, cognitive aging in older adults,” said Dr. Dadvand, who was not involved with the research.
The study was funded by the National Institutes of Health. Dr. Jimenez and Dr. Dadvand have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Exposure to green space may boost cognitive function, new research suggests.
This association may be explained by a reduction in depression, researchers note. Scores for overall cognition and psychomotor speed/attention among women with high green-space exposure were equivalent to those of women an average of 1.2 years younger, they add.
“Despite the fact that the women in our study were relatively younger than those in previous studies, we were still able to detect protective associations between green space and cognition,” lead author Marcia Pescador Jimenez, PhD, assistant professor of epidemiology, Boston University School of Public Health, told this news organization.
“This may signal the public health importance of green space and the important clinical implications at the population level,” she said.
The findings were published online in JAMA Network Open.
Better psychomotor speed, attention
Recent studies on the benefits of green space have shown a link between higher exposure and reduced risks for schizophrenia and ischemic stroke. Other studies have explored the link between green space and dementia and Alzheimer’s disease.
Cognitive function in middle age is associated with subsequent dementia, so Dr. Jimenez said she and her colleagues wanted to analyze the effect of residential green space on cognitive function in middle-aged women.
The study included 13,594 women (median age, 61.2 years) who are participants in the ongoing Nurses’ Health Study II, one of the largest studies to examine risk factors for chronic illness in women.
To calculate the amount of green space, researchers used the Normalized Difference Vegetation Index (NDVI), a satellite-based indicator of green vegetation around a residential address. The data were based on each participant’s 2013 residence.
After adjusting for age at assessment, race, and childhood, adulthood, and neighborhood socioeconomic status, green space was associated with higher scores on the global CogState composite (mean difference per interquartile range in green space, 0.05; 95% confidence interval, .02-.07) and psychomotor speed and attention (mean difference in score, 0.05 standard units; 95% CI, .02-.08) scales.
There was no association between green-space exposure and learning and working memory. Investigators also found no differences based on urbanicity, suggesting the benefits were similar for urban versus rural settings.
Specific to cognitive domains
“We were surprised to see that while our study found that higher levels of residential green space were associated with higher scores on processing speed and attention and on overall cognition, we also found that higher levels of residential green space were not associated with learning/working memory battery scores,” Dr. Jimenez said.
“This is actually in-line with previous research suggesting differing associations between green space and cognition based on the cognitive domain examined,” she added.
About 98% of participants were White, limiting the generalizability of the findings, the researchers note. There was also no information on proximity to or size of green space, or how much time individuals spent in the green space and what kinds of activities they engaged in.
Dr. Jimenez said projects examining the amount of time of green-space exposure are underway.
In addition, the researchers found lower rates of depression might contribute to the cognitive benefits associated with green-space exposure, explaining 3.95% (95% CI, .35%-7.55%) of the association between green space and psychomotor speed/attention and 6.3% (95% CI, .77%-11.81%) of the association between green space and overall cognition.
Reduced air pollution and increased physical activity, which are other factors often thought to contribute to the cognitive benefits of green space, were not significant in this study.
‘Interesting and novel’
Commenting on the findings, Payam Dadvand, MD, PhD, associate research professor, Barcelona Institute for Global Health, called the finding that depression may mediate green-space benefits “quite interesting and novel.”
“The results of this study, given its large sample size and its geographical coverage, adds to an emerging body of evidence on the beneficial association of exposure to green space on aging, and in particular, cognitive aging in older adults,” said Dr. Dadvand, who was not involved with the research.
The study was funded by the National Institutes of Health. Dr. Jimenez and Dr. Dadvand have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Traumatic brain injury linked to ‘striking’ risk for CVD, diabetes, brain disorders
Mild traumatic brain injury (TBI) is linked to a significantly increased risk for a host of subsequent cardiovascular, endocrine, neurologic, and psychiatric disorders, new research shows.
Incidence of hypertension, coronary heart disease, diabetes, stroke, depression, and dementia all began to increase soon after the brain injury and persisted over a decade in both mild and moderate to severe TBI.
Researchers found the multisystem comorbidities in all age groups, including in patients as young as 18. They also found that patients who developed multiple postinjury problems had higher mortality during the decade-long follow-up.
The findings suggest patients with TBI may require longer follow-up and proactive screening for multisystem disease, regardless of age or injury severity.
“The fact that both patients with mild and moderate to severe injuries both had long-term ongoing associations with comorbidities that continued over time and that they are cardiovascular, endocrine, neurologic, and behavioral health oriented was pretty striking,” study author Ross Zafonte, DO, PhD, president of Spaulding Rehab Hospital and professor and chair of physical medicine and rehab at Harvard Medical School, both in Boston, told this news organization.
The study was published online in JAMA Network Open.
Injury severity not a factor
An estimated 2.8 million individuals in the United States experience TBI every year. Worldwide, the figure may be as high as 74 million.
Studies have long suggested a link between brain injury and subsequent neurologic disorders, but research suggesting a possible link to cardiovascular and endocrine problems has recently gained attention.
Building on a 2021 study that showed increased incidence of cardiovascular issues following a concussion, the researchers examined medical records of previously healthy patients treated for TBI between 2000 and 2015 who also had at least 1 follow-up visit between 6 months and 10 years after the initial injury.
Researchers analyzed data from 13,053 individuals – 4,351 with mild injury (mTBI), 4351 with moderate to severe injury (msTBI), and 4351 with no TBI. The most common cause of injury was a fall. Patients with sports-related injuries were excluded.
Incidence of hypertension was significantly higher among patients with mTBI (hazard ratio, 2.5; 95% confidence interval, 2.1-2.9) and msTBI (HR, 2.4; 95% CI, 2.0-2.9), compared with the unaffected group. Risk for other cardiovascular problems, including hyperlipidemia, obesity, and coronary artery disease, were also higher in the affected groups.
TBI patients also reported higher incidence of endocrine diseases, including diabetes (mTBI: HR, 1.9; 95% CI, 1.4-2.7; msTBI: HR, 1.9; 95% CI, 1.4-2.6). Elevated risk for ischemic stroke or transient ischemic attack was also increased (mTBI: HR, 2.2; 95% CI, 1.4-3.3; msTBI: HR, 3.6; 95% CI, 2.4-5.3).
Regardless of injury severity, patients with TBI had a higher risk for neurologic and psychiatric diseases, particularly depression, dementia, and psychotic disorders. “This tells us that mild TBI is not clean of events,” Dr. Zafonte said.
Surprising rate of comorbidity in youth
Investigators found increased risk for posttrauma comorbidities in all age groups, but researchers were struck by the high rates in younger patients, aged 18-40. Compared with age-matched individuals with no TBI history, hypertension risk was nearly six times higher in those with mTBI (HR, 5.9; 95% CI, 3.9-9.1) and nearly four times higher in patients with msTBI (HR, 3.9; 95% CI, 2.5-6.1).
Rates of hyperlipidemia and diabetes were also higher in younger patients in the mTBI group and posttraumatic seizures and psychiatric disorders were elevated regardless of TBI severity.
Overall, patients with msTBI, but not those with mTBI, were at higher risk for mortality, compared with the unexposed group (432 deaths [9.9%] vs. 250 deaths [5.7%]; P < .001).
“It’s clear that what we may be dealing with is that it holds up even for the younger people,” Dr. Zafonte said. “We used to think brain injury risk is worse in the severe cases, which it is, and it’s worse later on among those who are older, which it is. But our younger folks don’t get away either.”
While the study offers associations between TBI and multisystem health problems, Dr. Zafonte said it’s impossible to say at this point whether the brain injury caused the increased risk for cardiovascular or endocrine problems. Other organ injuries sustained in the trauma may be a contributing factor.
“Further data is needed to elucidate the mechanism and the causative relationships, which we do not have here,” he said.
Many of the postinjury comorbidities emerged a median of 3.5 years after TBI, regardless of severity. But some of the cardiovascular and psychiatric conditions emerged far sooner than that.
That’s important because research suggests less than half of patients with TBI receive follow-up care.
“It does make sense for folks who are interacting with people who’ve had a TBI to be suspicious of medical comorbidities relatively early on, within the first couple of years,” Dr. Zafonte said.
In an invited commentary, Vijay Krishnamoorthy, MD, MPH, PhD, Duke University, Durham, N.C., and Monica S. Vavilala, MD, University of Washington, Seattle, highlight some of the study’s limitations, including a lack of information on comorbidity severity and the lack of a matched group of patients who experienced non-head trauma.
Despite those limitations, the study offers important information on how TBI may affect organs beyond the brain, they noted.
“These observations, if replicated in future studies, raise intriguing implications in the future care of patients with TBI, including heightened chronic disease-screening measures and possibly enhanced guidelines for chronic extracranial organ system care for patients who experience TBI,” Dr. Krishnamoorthy and Dr. Vavilala wrote.
The study received no specific funding. Dr. Zafonte reported having received personal fees from Springer/Demos, serving on scientific advisory boards for Myomo and OnCare and has received funding from the Football Players Health Study at Harvard, funded in part by the National Football League Players Association. Dr. Krishnamoorthy and Dr. Vavilala disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Mild traumatic brain injury (TBI) is linked to a significantly increased risk for a host of subsequent cardiovascular, endocrine, neurologic, and psychiatric disorders, new research shows.
Incidence of hypertension, coronary heart disease, diabetes, stroke, depression, and dementia all began to increase soon after the brain injury and persisted over a decade in both mild and moderate to severe TBI.
Researchers found the multisystem comorbidities in all age groups, including in patients as young as 18. They also found that patients who developed multiple postinjury problems had higher mortality during the decade-long follow-up.
The findings suggest patients with TBI may require longer follow-up and proactive screening for multisystem disease, regardless of age or injury severity.
“The fact that both patients with mild and moderate to severe injuries both had long-term ongoing associations with comorbidities that continued over time and that they are cardiovascular, endocrine, neurologic, and behavioral health oriented was pretty striking,” study author Ross Zafonte, DO, PhD, president of Spaulding Rehab Hospital and professor and chair of physical medicine and rehab at Harvard Medical School, both in Boston, told this news organization.
The study was published online in JAMA Network Open.
Injury severity not a factor
An estimated 2.8 million individuals in the United States experience TBI every year. Worldwide, the figure may be as high as 74 million.
Studies have long suggested a link between brain injury and subsequent neurologic disorders, but research suggesting a possible link to cardiovascular and endocrine problems has recently gained attention.
Building on a 2021 study that showed increased incidence of cardiovascular issues following a concussion, the researchers examined medical records of previously healthy patients treated for TBI between 2000 and 2015 who also had at least 1 follow-up visit between 6 months and 10 years after the initial injury.
Researchers analyzed data from 13,053 individuals – 4,351 with mild injury (mTBI), 4351 with moderate to severe injury (msTBI), and 4351 with no TBI. The most common cause of injury was a fall. Patients with sports-related injuries were excluded.
Incidence of hypertension was significantly higher among patients with mTBI (hazard ratio, 2.5; 95% confidence interval, 2.1-2.9) and msTBI (HR, 2.4; 95% CI, 2.0-2.9), compared with the unaffected group. Risk for other cardiovascular problems, including hyperlipidemia, obesity, and coronary artery disease, were also higher in the affected groups.
TBI patients also reported higher incidence of endocrine diseases, including diabetes (mTBI: HR, 1.9; 95% CI, 1.4-2.7; msTBI: HR, 1.9; 95% CI, 1.4-2.6). Elevated risk for ischemic stroke or transient ischemic attack was also increased (mTBI: HR, 2.2; 95% CI, 1.4-3.3; msTBI: HR, 3.6; 95% CI, 2.4-5.3).
Regardless of injury severity, patients with TBI had a higher risk for neurologic and psychiatric diseases, particularly depression, dementia, and psychotic disorders. “This tells us that mild TBI is not clean of events,” Dr. Zafonte said.
Surprising rate of comorbidity in youth
Investigators found increased risk for posttrauma comorbidities in all age groups, but researchers were struck by the high rates in younger patients, aged 18-40. Compared with age-matched individuals with no TBI history, hypertension risk was nearly six times higher in those with mTBI (HR, 5.9; 95% CI, 3.9-9.1) and nearly four times higher in patients with msTBI (HR, 3.9; 95% CI, 2.5-6.1).
Rates of hyperlipidemia and diabetes were also higher in younger patients in the mTBI group and posttraumatic seizures and psychiatric disorders were elevated regardless of TBI severity.
Overall, patients with msTBI, but not those with mTBI, were at higher risk for mortality, compared with the unexposed group (432 deaths [9.9%] vs. 250 deaths [5.7%]; P < .001).
“It’s clear that what we may be dealing with is that it holds up even for the younger people,” Dr. Zafonte said. “We used to think brain injury risk is worse in the severe cases, which it is, and it’s worse later on among those who are older, which it is. But our younger folks don’t get away either.”
While the study offers associations between TBI and multisystem health problems, Dr. Zafonte said it’s impossible to say at this point whether the brain injury caused the increased risk for cardiovascular or endocrine problems. Other organ injuries sustained in the trauma may be a contributing factor.
“Further data is needed to elucidate the mechanism and the causative relationships, which we do not have here,” he said.
Many of the postinjury comorbidities emerged a median of 3.5 years after TBI, regardless of severity. But some of the cardiovascular and psychiatric conditions emerged far sooner than that.
That’s important because research suggests less than half of patients with TBI receive follow-up care.
“It does make sense for folks who are interacting with people who’ve had a TBI to be suspicious of medical comorbidities relatively early on, within the first couple of years,” Dr. Zafonte said.
In an invited commentary, Vijay Krishnamoorthy, MD, MPH, PhD, Duke University, Durham, N.C., and Monica S. Vavilala, MD, University of Washington, Seattle, highlight some of the study’s limitations, including a lack of information on comorbidity severity and the lack of a matched group of patients who experienced non-head trauma.
Despite those limitations, the study offers important information on how TBI may affect organs beyond the brain, they noted.
“These observations, if replicated in future studies, raise intriguing implications in the future care of patients with TBI, including heightened chronic disease-screening measures and possibly enhanced guidelines for chronic extracranial organ system care for patients who experience TBI,” Dr. Krishnamoorthy and Dr. Vavilala wrote.
The study received no specific funding. Dr. Zafonte reported having received personal fees from Springer/Demos, serving on scientific advisory boards for Myomo and OnCare and has received funding from the Football Players Health Study at Harvard, funded in part by the National Football League Players Association. Dr. Krishnamoorthy and Dr. Vavilala disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Mild traumatic brain injury (TBI) is linked to a significantly increased risk for a host of subsequent cardiovascular, endocrine, neurologic, and psychiatric disorders, new research shows.
Incidence of hypertension, coronary heart disease, diabetes, stroke, depression, and dementia all began to increase soon after the brain injury and persisted over a decade in both mild and moderate to severe TBI.
Researchers found the multisystem comorbidities in all age groups, including in patients as young as 18. They also found that patients who developed multiple postinjury problems had higher mortality during the decade-long follow-up.
The findings suggest patients with TBI may require longer follow-up and proactive screening for multisystem disease, regardless of age or injury severity.
“The fact that both patients with mild and moderate to severe injuries both had long-term ongoing associations with comorbidities that continued over time and that they are cardiovascular, endocrine, neurologic, and behavioral health oriented was pretty striking,” study author Ross Zafonte, DO, PhD, president of Spaulding Rehab Hospital and professor and chair of physical medicine and rehab at Harvard Medical School, both in Boston, told this news organization.
The study was published online in JAMA Network Open.
Injury severity not a factor
An estimated 2.8 million individuals in the United States experience TBI every year. Worldwide, the figure may be as high as 74 million.
Studies have long suggested a link between brain injury and subsequent neurologic disorders, but research suggesting a possible link to cardiovascular and endocrine problems has recently gained attention.
Building on a 2021 study that showed increased incidence of cardiovascular issues following a concussion, the researchers examined medical records of previously healthy patients treated for TBI between 2000 and 2015 who also had at least 1 follow-up visit between 6 months and 10 years after the initial injury.
Researchers analyzed data from 13,053 individuals – 4,351 with mild injury (mTBI), 4351 with moderate to severe injury (msTBI), and 4351 with no TBI. The most common cause of injury was a fall. Patients with sports-related injuries were excluded.
Incidence of hypertension was significantly higher among patients with mTBI (hazard ratio, 2.5; 95% confidence interval, 2.1-2.9) and msTBI (HR, 2.4; 95% CI, 2.0-2.9), compared with the unaffected group. Risk for other cardiovascular problems, including hyperlipidemia, obesity, and coronary artery disease, were also higher in the affected groups.
TBI patients also reported higher incidence of endocrine diseases, including diabetes (mTBI: HR, 1.9; 95% CI, 1.4-2.7; msTBI: HR, 1.9; 95% CI, 1.4-2.6). Elevated risk for ischemic stroke or transient ischemic attack was also increased (mTBI: HR, 2.2; 95% CI, 1.4-3.3; msTBI: HR, 3.6; 95% CI, 2.4-5.3).
Regardless of injury severity, patients with TBI had a higher risk for neurologic and psychiatric diseases, particularly depression, dementia, and psychotic disorders. “This tells us that mild TBI is not clean of events,” Dr. Zafonte said.
Surprising rate of comorbidity in youth
Investigators found increased risk for posttrauma comorbidities in all age groups, but researchers were struck by the high rates in younger patients, aged 18-40. Compared with age-matched individuals with no TBI history, hypertension risk was nearly six times higher in those with mTBI (HR, 5.9; 95% CI, 3.9-9.1) and nearly four times higher in patients with msTBI (HR, 3.9; 95% CI, 2.5-6.1).
Rates of hyperlipidemia and diabetes were also higher in younger patients in the mTBI group and posttraumatic seizures and psychiatric disorders were elevated regardless of TBI severity.
Overall, patients with msTBI, but not those with mTBI, were at higher risk for mortality, compared with the unexposed group (432 deaths [9.9%] vs. 250 deaths [5.7%]; P < .001).
“It’s clear that what we may be dealing with is that it holds up even for the younger people,” Dr. Zafonte said. “We used to think brain injury risk is worse in the severe cases, which it is, and it’s worse later on among those who are older, which it is. But our younger folks don’t get away either.”
While the study offers associations between TBI and multisystem health problems, Dr. Zafonte said it’s impossible to say at this point whether the brain injury caused the increased risk for cardiovascular or endocrine problems. Other organ injuries sustained in the trauma may be a contributing factor.
“Further data is needed to elucidate the mechanism and the causative relationships, which we do not have here,” he said.
Many of the postinjury comorbidities emerged a median of 3.5 years after TBI, regardless of severity. But some of the cardiovascular and psychiatric conditions emerged far sooner than that.
That’s important because research suggests less than half of patients with TBI receive follow-up care.
“It does make sense for folks who are interacting with people who’ve had a TBI to be suspicious of medical comorbidities relatively early on, within the first couple of years,” Dr. Zafonte said.
In an invited commentary, Vijay Krishnamoorthy, MD, MPH, PhD, Duke University, Durham, N.C., and Monica S. Vavilala, MD, University of Washington, Seattle, highlight some of the study’s limitations, including a lack of information on comorbidity severity and the lack of a matched group of patients who experienced non-head trauma.
Despite those limitations, the study offers important information on how TBI may affect organs beyond the brain, they noted.
“These observations, if replicated in future studies, raise intriguing implications in the future care of patients with TBI, including heightened chronic disease-screening measures and possibly enhanced guidelines for chronic extracranial organ system care for patients who experience TBI,” Dr. Krishnamoorthy and Dr. Vavilala wrote.
The study received no specific funding. Dr. Zafonte reported having received personal fees from Springer/Demos, serving on scientific advisory boards for Myomo and OnCare and has received funding from the Football Players Health Study at Harvard, funded in part by the National Football League Players Association. Dr. Krishnamoorthy and Dr. Vavilala disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM JAMA NETWORK OPEN
Two MS meds tied to higher COVID rates
Patients taking ocrelizumab (Ocrevus) or fingolimod (Gilenya) for treat multiple sclerosis (MS) have higher rates of COVID-19 infection and hospitalization before and after COVID vaccination, compared with those taking other treatments, a nationwide study in England found.
The study draws on a database that includes every patient with MS in England treated with a disease-modifying therapy (DMT) and national data on rates of COVID infection, hospitalization, mortality, and vaccination in those patients.
It’s the latest work to suggest varying levels of vaccine efficacy based on DMT use and is the first known study to offer this level of detail on the subject.
“What is obvious is that current vaccination protocols for these DMTs are not really working properly,” lead investigator Afagh Garjani, MD, clinical research fellow at the University of Nottingham (England), said in an interview.
Although the differences in infection rates and efficacy are significant in those two DMTs, the overall infection and hospitalization rates were low, Dr. Garjani noted, offering further evidence that vaccines are effective in most patients with MS.
The findings were presented at the 2022 annual meeting of the American Academy of Neurology.
Low mortality rate
The prospective, longitudinal study included National Health Service data on 44,170 people with MS. The data on hospitalization came from 29,353 patients with MS who had received at least two doses of a COVID-19 vaccine.
Patients taking dimethyl fumarate, the most commonly prescribed DMT in England, had similar rates of COVID infection in January 2021 – before they were fully vaccinated – and in December 2022, after they had received at least two vaccine doses.
However, among patients taking fingolimod and ocrelizumab there were significant increases in infection rates in that same time period. The incidence rate ratio in the fingolimod group was 0.50 (95% confidence interval, 0.37-0.66) in January 2021 and rose to 0.91 (95% CI, 0.80-1.03) in December 2022. In the ocrelizumab group, the IRR rose from 1.01 (95% CI, 0.79-1.26) to 1.57 (95% CI, 1.44-1.72) during that time frame.
Hospitalization rates were also higher in fully vaccinated patients with MS taking fingolimod and ocrelizumab. People taking dimethyl fumarate had a hospitalization rate of 32 (per 10,000 people), compared with a rate of 140 in patients on ocrelizumab and 94 in patients on fingolimod.
Mortality rates were low in all groups, but were slightly higher in the ocrelizumab group.
“However, the number of people who died due to COVID overall was small,” Dr. Garjani noted.
Following receipt of a third COVID-19 vaccine, the only hospitalizations were in patients taking ocrelizumab (4 out of 65 infections) and fingolimod (11 out of 78 infections), with no deaths.
Potential mechanism
Researchers suspect the reason for varying COVID-19 infection rates and vaccine efficacy among DMTs is related to their mode of action.
“With MS, the immune system attacks the central nervous system and the aim of these treatments is to modulate or suppress the immune system,” Dr. Garjani said. “Some of these medications are immune suppressants and therefore, in addition to preventing MS, might also put people at increased risk of infection from COVID or other diseases.”
Ocrelizumab and fingolimod have different modes of action, but both act as immunosuppressants.
Study data on beta-interferon offered an interesting twist. Patients taking that medication had far lower infection rates, compared with other DMTs and to the general population, and no COVID-related hospitalizations.
Interferons are known to have some antiviral effects, Dr. Garjani said. In fact, interferon is one of several existing drugs that scientists have considered as possible candidates to fight COVID infection.
Studies on COVID infection rates and vaccine efficacy have yielded conflicting results. Some suggest no differences based on DMT use, whereas others have shown immunological evidence pointing to lower or higher infections rates among the different therapies.
Based on some of those findings, up to 80% of specialists who treat MS in the United States said the pandemic may have changed their use of DMTs, one study found, which later studies suggested may not have been necessary.
While the findings shouldn’t necessarily prompt clinicians to consider changing their treatment approach, Dr. Garjani noted that her team tells patients who have not yet started treatment to get vaccinated before initiating MS treatment.
A balancing act
Commenting on the findings, Tyler Smith, MD, clinical assistant professor of neurology at New York University, said that, although the data suggest these MS therapies may affect COVID vaccine efficacy to varying degrees, there’s more to the story.
“This data builds upon a growing body of evidence that these treatments may attenuate vaccine responses to different degrees, and this should be balanced with their efficacy in controlling multiple sclerosis relapses, Dr. Smith said, adding that “real-life studies examining the effect of vaccines show benefit in limiting hospitalization and death.”
“Developing evidence continues to demonstrate the benefits of vaccination,” he said, “and I encourage all patients to follow the latest federal health guidelines regarding COVID-19 vaccinations.”
Dr. Garjani has received personal compensation for serving as a speaker with MS Academy and Biogen. Dr. Smith’s 2020-2021 fellowship was supported in part by Biogen and the National Multiple Sclerosis Society Clinical Care Physician Fellowship 2020-2021. Dr. Smith also received honoraria from the American Academy of Neurology in 2020.
A version of this article first appeared on Medscape.com.
Patients taking ocrelizumab (Ocrevus) or fingolimod (Gilenya) for treat multiple sclerosis (MS) have higher rates of COVID-19 infection and hospitalization before and after COVID vaccination, compared with those taking other treatments, a nationwide study in England found.
The study draws on a database that includes every patient with MS in England treated with a disease-modifying therapy (DMT) and national data on rates of COVID infection, hospitalization, mortality, and vaccination in those patients.
It’s the latest work to suggest varying levels of vaccine efficacy based on DMT use and is the first known study to offer this level of detail on the subject.
“What is obvious is that current vaccination protocols for these DMTs are not really working properly,” lead investigator Afagh Garjani, MD, clinical research fellow at the University of Nottingham (England), said in an interview.
Although the differences in infection rates and efficacy are significant in those two DMTs, the overall infection and hospitalization rates were low, Dr. Garjani noted, offering further evidence that vaccines are effective in most patients with MS.
The findings were presented at the 2022 annual meeting of the American Academy of Neurology.
Low mortality rate
The prospective, longitudinal study included National Health Service data on 44,170 people with MS. The data on hospitalization came from 29,353 patients with MS who had received at least two doses of a COVID-19 vaccine.
Patients taking dimethyl fumarate, the most commonly prescribed DMT in England, had similar rates of COVID infection in January 2021 – before they were fully vaccinated – and in December 2022, after they had received at least two vaccine doses.
However, among patients taking fingolimod and ocrelizumab there were significant increases in infection rates in that same time period. The incidence rate ratio in the fingolimod group was 0.50 (95% confidence interval, 0.37-0.66) in January 2021 and rose to 0.91 (95% CI, 0.80-1.03) in December 2022. In the ocrelizumab group, the IRR rose from 1.01 (95% CI, 0.79-1.26) to 1.57 (95% CI, 1.44-1.72) during that time frame.
Hospitalization rates were also higher in fully vaccinated patients with MS taking fingolimod and ocrelizumab. People taking dimethyl fumarate had a hospitalization rate of 32 (per 10,000 people), compared with a rate of 140 in patients on ocrelizumab and 94 in patients on fingolimod.
Mortality rates were low in all groups, but were slightly higher in the ocrelizumab group.
“However, the number of people who died due to COVID overall was small,” Dr. Garjani noted.
Following receipt of a third COVID-19 vaccine, the only hospitalizations were in patients taking ocrelizumab (4 out of 65 infections) and fingolimod (11 out of 78 infections), with no deaths.
Potential mechanism
Researchers suspect the reason for varying COVID-19 infection rates and vaccine efficacy among DMTs is related to their mode of action.
“With MS, the immune system attacks the central nervous system and the aim of these treatments is to modulate or suppress the immune system,” Dr. Garjani said. “Some of these medications are immune suppressants and therefore, in addition to preventing MS, might also put people at increased risk of infection from COVID or other diseases.”
Ocrelizumab and fingolimod have different modes of action, but both act as immunosuppressants.
Study data on beta-interferon offered an interesting twist. Patients taking that medication had far lower infection rates, compared with other DMTs and to the general population, and no COVID-related hospitalizations.
Interferons are known to have some antiviral effects, Dr. Garjani said. In fact, interferon is one of several existing drugs that scientists have considered as possible candidates to fight COVID infection.
Studies on COVID infection rates and vaccine efficacy have yielded conflicting results. Some suggest no differences based on DMT use, whereas others have shown immunological evidence pointing to lower or higher infections rates among the different therapies.
Based on some of those findings, up to 80% of specialists who treat MS in the United States said the pandemic may have changed their use of DMTs, one study found, which later studies suggested may not have been necessary.
While the findings shouldn’t necessarily prompt clinicians to consider changing their treatment approach, Dr. Garjani noted that her team tells patients who have not yet started treatment to get vaccinated before initiating MS treatment.
A balancing act
Commenting on the findings, Tyler Smith, MD, clinical assistant professor of neurology at New York University, said that, although the data suggest these MS therapies may affect COVID vaccine efficacy to varying degrees, there’s more to the story.
“This data builds upon a growing body of evidence that these treatments may attenuate vaccine responses to different degrees, and this should be balanced with their efficacy in controlling multiple sclerosis relapses, Dr. Smith said, adding that “real-life studies examining the effect of vaccines show benefit in limiting hospitalization and death.”
“Developing evidence continues to demonstrate the benefits of vaccination,” he said, “and I encourage all patients to follow the latest federal health guidelines regarding COVID-19 vaccinations.”
Dr. Garjani has received personal compensation for serving as a speaker with MS Academy and Biogen. Dr. Smith’s 2020-2021 fellowship was supported in part by Biogen and the National Multiple Sclerosis Society Clinical Care Physician Fellowship 2020-2021. Dr. Smith also received honoraria from the American Academy of Neurology in 2020.
A version of this article first appeared on Medscape.com.
Patients taking ocrelizumab (Ocrevus) or fingolimod (Gilenya) for treat multiple sclerosis (MS) have higher rates of COVID-19 infection and hospitalization before and after COVID vaccination, compared with those taking other treatments, a nationwide study in England found.
The study draws on a database that includes every patient with MS in England treated with a disease-modifying therapy (DMT) and national data on rates of COVID infection, hospitalization, mortality, and vaccination in those patients.
It’s the latest work to suggest varying levels of vaccine efficacy based on DMT use and is the first known study to offer this level of detail on the subject.
“What is obvious is that current vaccination protocols for these DMTs are not really working properly,” lead investigator Afagh Garjani, MD, clinical research fellow at the University of Nottingham (England), said in an interview.
Although the differences in infection rates and efficacy are significant in those two DMTs, the overall infection and hospitalization rates were low, Dr. Garjani noted, offering further evidence that vaccines are effective in most patients with MS.
The findings were presented at the 2022 annual meeting of the American Academy of Neurology.
Low mortality rate
The prospective, longitudinal study included National Health Service data on 44,170 people with MS. The data on hospitalization came from 29,353 patients with MS who had received at least two doses of a COVID-19 vaccine.
Patients taking dimethyl fumarate, the most commonly prescribed DMT in England, had similar rates of COVID infection in January 2021 – before they were fully vaccinated – and in December 2022, after they had received at least two vaccine doses.
However, among patients taking fingolimod and ocrelizumab there were significant increases in infection rates in that same time period. The incidence rate ratio in the fingolimod group was 0.50 (95% confidence interval, 0.37-0.66) in January 2021 and rose to 0.91 (95% CI, 0.80-1.03) in December 2022. In the ocrelizumab group, the IRR rose from 1.01 (95% CI, 0.79-1.26) to 1.57 (95% CI, 1.44-1.72) during that time frame.
Hospitalization rates were also higher in fully vaccinated patients with MS taking fingolimod and ocrelizumab. People taking dimethyl fumarate had a hospitalization rate of 32 (per 10,000 people), compared with a rate of 140 in patients on ocrelizumab and 94 in patients on fingolimod.
Mortality rates were low in all groups, but were slightly higher in the ocrelizumab group.
“However, the number of people who died due to COVID overall was small,” Dr. Garjani noted.
Following receipt of a third COVID-19 vaccine, the only hospitalizations were in patients taking ocrelizumab (4 out of 65 infections) and fingolimod (11 out of 78 infections), with no deaths.
Potential mechanism
Researchers suspect the reason for varying COVID-19 infection rates and vaccine efficacy among DMTs is related to their mode of action.
“With MS, the immune system attacks the central nervous system and the aim of these treatments is to modulate or suppress the immune system,” Dr. Garjani said. “Some of these medications are immune suppressants and therefore, in addition to preventing MS, might also put people at increased risk of infection from COVID or other diseases.”
Ocrelizumab and fingolimod have different modes of action, but both act as immunosuppressants.
Study data on beta-interferon offered an interesting twist. Patients taking that medication had far lower infection rates, compared with other DMTs and to the general population, and no COVID-related hospitalizations.
Interferons are known to have some antiviral effects, Dr. Garjani said. In fact, interferon is one of several existing drugs that scientists have considered as possible candidates to fight COVID infection.
Studies on COVID infection rates and vaccine efficacy have yielded conflicting results. Some suggest no differences based on DMT use, whereas others have shown immunological evidence pointing to lower or higher infections rates among the different therapies.
Based on some of those findings, up to 80% of specialists who treat MS in the United States said the pandemic may have changed their use of DMTs, one study found, which later studies suggested may not have been necessary.
While the findings shouldn’t necessarily prompt clinicians to consider changing their treatment approach, Dr. Garjani noted that her team tells patients who have not yet started treatment to get vaccinated before initiating MS treatment.
A balancing act
Commenting on the findings, Tyler Smith, MD, clinical assistant professor of neurology at New York University, said that, although the data suggest these MS therapies may affect COVID vaccine efficacy to varying degrees, there’s more to the story.
“This data builds upon a growing body of evidence that these treatments may attenuate vaccine responses to different degrees, and this should be balanced with their efficacy in controlling multiple sclerosis relapses, Dr. Smith said, adding that “real-life studies examining the effect of vaccines show benefit in limiting hospitalization and death.”
“Developing evidence continues to demonstrate the benefits of vaccination,” he said, “and I encourage all patients to follow the latest federal health guidelines regarding COVID-19 vaccinations.”
Dr. Garjani has received personal compensation for serving as a speaker with MS Academy and Biogen. Dr. Smith’s 2020-2021 fellowship was supported in part by Biogen and the National Multiple Sclerosis Society Clinical Care Physician Fellowship 2020-2021. Dr. Smith also received honoraria from the American Academy of Neurology in 2020.
A version of this article first appeared on Medscape.com.
FROM AAN 2022
Novel combo drug shows promise as first-line Parkinson’s disease treatment
, new research suggests. Results from a phase 3 trial of P2B001, a combination of pramipexole and rasagiline at currently unavailable low doses, showed the drug was more effective than its individual components and as effective as higher-dose pramipexole ER – with far less daytime sleepiness.
The combination drug is taken once per day and does not require titration, which investigators say make it a good option for first-line treatment of Parkinson’s disease.
“I don’t think people, including me, expected intuitively that if you used small doses and combined it with a little rasagiline it would be equal to full doses of pramipexole, but it appears that it is,” said lead investigator Warren Olanow, MD, professor and chair emeritus of neurology and professor emeritus of neuroscience at Icahn School of Medicine at Mount Sinai, New York.
The findings were presented at the 2022 annual meeting of the American Academy of Neurology.
‘Synergistic effects’
Levodopa is considered to be the most effective treatment for Parkinson’s disease, but long-term use is associated with increased risk for motor complications, such as dyskinesia. Dopamine agonists such as pramipexole have been linked in previous research to excessive daytime sleepiness and impulse control disorders. In addition, monoamine oxidase-B inhibitors such as rasagiline are not as effective at controlling Parkinson’s disease as other treatment options.
“There is no consistent agreement on how to initiate treatment because no one treatment is ideal,” Dr. Olanow said.
P2B001, developed by Pharma Two B, is a combination of 0.6 mg of pramipexole and 0.75 mg of rasagiline. The drugs work by dual mechanisms, which investigators suspected might have “synergistic effects.”
Following promising results from an earlier trial, researches launched a phase 3, 12-week, international, randomized, double-blind trial to study the efficacy, safety, and tolerability of P2B001, compared with its individual components and with a calibration arm of pramipexole ER in 519 patients with early Parkinson’s disease.
Participants received P2B001, 0.6 mg of pramipexole ER, 0.75 mg of rasagiline ER, or pramipexole ER titrated to an optimal dose for each patient (1.5-4.5 mg).
New first-line treatment?
Results showed that the adjusted mean change from baseline in total Unified Parkinson’s Disease Rating Scale (UPDRS) score was -2.66 points for P2B001 versus pramipexole (P = .0018) and -3.30 points for P2B001 versus rasagiline (P = .0001).
There was no significant difference in UPDRS scores between P2B001 and pramipexole ER, but patients who received P2B001 reported significantly less daytime sleepiness.
The adjusted mean change from baseline in Epworth Sleepiness Scale score for P2B001 versus pramipexole ER was -2.66 points (P < .0001).
In addition, fewer dopaminergic adverse events were reported with the combination drug versus pramipexole ER (44.7% vs. 66.2%), including somnolence (14.7% vs. 31.1%) and orthostatic hypotension (2.7% vs. 12.2%).
As a first-line treatment, P2B001 could offer an effective option instead of levodopa, Dr. Olanow said. “It could be really good for patients because it would delay the introduction of levodopa and allow levodopa to be used in lower doses when the time comes and hopefully reduce the risk of complications,” he added.
Questions, cost concerns
Commenting on the study, Alfonso Fasano, MD, PhD, professor of neurology and chair in neuromodulation, University of Toronto, agreed that better therapeutic options are needed for Parkinson’s disease.
Combining available treatments into one pill “might help patients’ adherence, although this can compromise our ability to dose each compound individually,” said Dr. Fasano, who was not involved with the research.
He added that there are also questions about dosage modification as a patient’s disease progresses and whether a higher dose might pose safety problems. There is also the issue of cost. “Conducting large clinical trials like this one is expensive, and I wonder about the cost of the drug when approved,” Dr. Fasano noted. “Do we really need to invest in combination pills containing two already well-known compounds?”
Dr. Olanow, who is not directly involved with Pharma Two B, the developer of P2B001, said he has no information on what the drug might cost or how it might be marketed if approved for use.
“The advantage of the combination is the component doses are not replicable, they are both in an extended-release formulation, it doesn’t require titration, and it has been tested and proven to work,” he said.
The study was funded by Pharma Two B. Dr. Olanow is employed by Clintrex Research Corporation and owns stock in Clintrex Research Corporation. Dr. Fasano reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, new research suggests. Results from a phase 3 trial of P2B001, a combination of pramipexole and rasagiline at currently unavailable low doses, showed the drug was more effective than its individual components and as effective as higher-dose pramipexole ER – with far less daytime sleepiness.
The combination drug is taken once per day and does not require titration, which investigators say make it a good option for first-line treatment of Parkinson’s disease.
“I don’t think people, including me, expected intuitively that if you used small doses and combined it with a little rasagiline it would be equal to full doses of pramipexole, but it appears that it is,” said lead investigator Warren Olanow, MD, professor and chair emeritus of neurology and professor emeritus of neuroscience at Icahn School of Medicine at Mount Sinai, New York.
The findings were presented at the 2022 annual meeting of the American Academy of Neurology.
‘Synergistic effects’
Levodopa is considered to be the most effective treatment for Parkinson’s disease, but long-term use is associated with increased risk for motor complications, such as dyskinesia. Dopamine agonists such as pramipexole have been linked in previous research to excessive daytime sleepiness and impulse control disorders. In addition, monoamine oxidase-B inhibitors such as rasagiline are not as effective at controlling Parkinson’s disease as other treatment options.
“There is no consistent agreement on how to initiate treatment because no one treatment is ideal,” Dr. Olanow said.
P2B001, developed by Pharma Two B, is a combination of 0.6 mg of pramipexole and 0.75 mg of rasagiline. The drugs work by dual mechanisms, which investigators suspected might have “synergistic effects.”
Following promising results from an earlier trial, researches launched a phase 3, 12-week, international, randomized, double-blind trial to study the efficacy, safety, and tolerability of P2B001, compared with its individual components and with a calibration arm of pramipexole ER in 519 patients with early Parkinson’s disease.
Participants received P2B001, 0.6 mg of pramipexole ER, 0.75 mg of rasagiline ER, or pramipexole ER titrated to an optimal dose for each patient (1.5-4.5 mg).
New first-line treatment?
Results showed that the adjusted mean change from baseline in total Unified Parkinson’s Disease Rating Scale (UPDRS) score was -2.66 points for P2B001 versus pramipexole (P = .0018) and -3.30 points for P2B001 versus rasagiline (P = .0001).
There was no significant difference in UPDRS scores between P2B001 and pramipexole ER, but patients who received P2B001 reported significantly less daytime sleepiness.
The adjusted mean change from baseline in Epworth Sleepiness Scale score for P2B001 versus pramipexole ER was -2.66 points (P < .0001).
In addition, fewer dopaminergic adverse events were reported with the combination drug versus pramipexole ER (44.7% vs. 66.2%), including somnolence (14.7% vs. 31.1%) and orthostatic hypotension (2.7% vs. 12.2%).
As a first-line treatment, P2B001 could offer an effective option instead of levodopa, Dr. Olanow said. “It could be really good for patients because it would delay the introduction of levodopa and allow levodopa to be used in lower doses when the time comes and hopefully reduce the risk of complications,” he added.
Questions, cost concerns
Commenting on the study, Alfonso Fasano, MD, PhD, professor of neurology and chair in neuromodulation, University of Toronto, agreed that better therapeutic options are needed for Parkinson’s disease.
Combining available treatments into one pill “might help patients’ adherence, although this can compromise our ability to dose each compound individually,” said Dr. Fasano, who was not involved with the research.
He added that there are also questions about dosage modification as a patient’s disease progresses and whether a higher dose might pose safety problems. There is also the issue of cost. “Conducting large clinical trials like this one is expensive, and I wonder about the cost of the drug when approved,” Dr. Fasano noted. “Do we really need to invest in combination pills containing two already well-known compounds?”
Dr. Olanow, who is not directly involved with Pharma Two B, the developer of P2B001, said he has no information on what the drug might cost or how it might be marketed if approved for use.
“The advantage of the combination is the component doses are not replicable, they are both in an extended-release formulation, it doesn’t require titration, and it has been tested and proven to work,” he said.
The study was funded by Pharma Two B. Dr. Olanow is employed by Clintrex Research Corporation and owns stock in Clintrex Research Corporation. Dr. Fasano reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, new research suggests. Results from a phase 3 trial of P2B001, a combination of pramipexole and rasagiline at currently unavailable low doses, showed the drug was more effective than its individual components and as effective as higher-dose pramipexole ER – with far less daytime sleepiness.
The combination drug is taken once per day and does not require titration, which investigators say make it a good option for first-line treatment of Parkinson’s disease.
“I don’t think people, including me, expected intuitively that if you used small doses and combined it with a little rasagiline it would be equal to full doses of pramipexole, but it appears that it is,” said lead investigator Warren Olanow, MD, professor and chair emeritus of neurology and professor emeritus of neuroscience at Icahn School of Medicine at Mount Sinai, New York.
The findings were presented at the 2022 annual meeting of the American Academy of Neurology.
‘Synergistic effects’
Levodopa is considered to be the most effective treatment for Parkinson’s disease, but long-term use is associated with increased risk for motor complications, such as dyskinesia. Dopamine agonists such as pramipexole have been linked in previous research to excessive daytime sleepiness and impulse control disorders. In addition, monoamine oxidase-B inhibitors such as rasagiline are not as effective at controlling Parkinson’s disease as other treatment options.
“There is no consistent agreement on how to initiate treatment because no one treatment is ideal,” Dr. Olanow said.
P2B001, developed by Pharma Two B, is a combination of 0.6 mg of pramipexole and 0.75 mg of rasagiline. The drugs work by dual mechanisms, which investigators suspected might have “synergistic effects.”
Following promising results from an earlier trial, researches launched a phase 3, 12-week, international, randomized, double-blind trial to study the efficacy, safety, and tolerability of P2B001, compared with its individual components and with a calibration arm of pramipexole ER in 519 patients with early Parkinson’s disease.
Participants received P2B001, 0.6 mg of pramipexole ER, 0.75 mg of rasagiline ER, or pramipexole ER titrated to an optimal dose for each patient (1.5-4.5 mg).
New first-line treatment?
Results showed that the adjusted mean change from baseline in total Unified Parkinson’s Disease Rating Scale (UPDRS) score was -2.66 points for P2B001 versus pramipexole (P = .0018) and -3.30 points for P2B001 versus rasagiline (P = .0001).
There was no significant difference in UPDRS scores between P2B001 and pramipexole ER, but patients who received P2B001 reported significantly less daytime sleepiness.
The adjusted mean change from baseline in Epworth Sleepiness Scale score for P2B001 versus pramipexole ER was -2.66 points (P < .0001).
In addition, fewer dopaminergic adverse events were reported with the combination drug versus pramipexole ER (44.7% vs. 66.2%), including somnolence (14.7% vs. 31.1%) and orthostatic hypotension (2.7% vs. 12.2%).
As a first-line treatment, P2B001 could offer an effective option instead of levodopa, Dr. Olanow said. “It could be really good for patients because it would delay the introduction of levodopa and allow levodopa to be used in lower doses when the time comes and hopefully reduce the risk of complications,” he added.
Questions, cost concerns
Commenting on the study, Alfonso Fasano, MD, PhD, professor of neurology and chair in neuromodulation, University of Toronto, agreed that better therapeutic options are needed for Parkinson’s disease.
Combining available treatments into one pill “might help patients’ adherence, although this can compromise our ability to dose each compound individually,” said Dr. Fasano, who was not involved with the research.
He added that there are also questions about dosage modification as a patient’s disease progresses and whether a higher dose might pose safety problems. There is also the issue of cost. “Conducting large clinical trials like this one is expensive, and I wonder about the cost of the drug when approved,” Dr. Fasano noted. “Do we really need to invest in combination pills containing two already well-known compounds?”
Dr. Olanow, who is not directly involved with Pharma Two B, the developer of P2B001, said he has no information on what the drug might cost or how it might be marketed if approved for use.
“The advantage of the combination is the component doses are not replicable, they are both in an extended-release formulation, it doesn’t require titration, and it has been tested and proven to work,” he said.
The study was funded by Pharma Two B. Dr. Olanow is employed by Clintrex Research Corporation and owns stock in Clintrex Research Corporation. Dr. Fasano reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM AAN 2022
Experimental drug may boost executive function in patients with Alzheimer’s disease
Patients performed better in cognitive testing after just 2 weeks, especially in areas of executive functioning. Clinicians involved in the study also reported improvements in patients’ ability to complete daily activities, especially in complex tasks such as using a computer, carrying out household chores, and managing their medications.
“It’s pretty incredible to see improvement over the course of a week to a week and a half,” said study investigator Aaron Koenig, MD, vice president of Early Clinical Development at Sage Therapeutics in Cambridge, Mass. “Not only are we seeing objective improvement, we’re also seeing a subjective benefit.”
The drug, SAGE-718, is also under study for MCI in patients with Huntington’s disease, the drug’s primary indication, and Parkinson’s disease.
The findings will be presented at the 2022 annual meeting of the American Academy of Neurology.
Improved executive function
SAGE-718 is in a new class of drugs called positive allosteric modulator of N-methyl-D-aspartate (NMDA) receptors, which are thought to improve neuroplasticity.
For the phase 2a open-label LUMINARY trial, researchers enrolled 26 patients ages 50-80 years with Alzheimer’s disease who had MCI. Patients completed a battery of cognitive tests at the study outset, again at the end of treatment, and again after 28 days.
Participants received SAGE-718 daily for 2 weeks and were followed for another 2 weeks.
The study’s primary outcome was safety. Seven patients (26.9%) reported mild or moderate treatment-emergent adverse events (AEs), and there were no serious AEs or deaths.
However, after 14 days, researchers also noted improvements from baseline on multiple tests of executive functioning, learning, and memory. And at 28 days, participants demonstrated significantly better Montreal Cognitive Assessment scores, compared with baseline (+2.3 points; P < .05), suggesting improvement in global cognition.
“We know that in Alzheimer’s and other neurodegenerative conditions there is a change in cognition, the ability to think, the ability to do things,” Dr. Koenig said. “What we’ve seen with SAGE-718 to date, all the way back to our phase 1 studies, is a cognitively beneficial effect, but more specifically an improvement in executive functioning.”
Intentional small study design
Commenting on the findings, Percy Griffin, PhD, MSc, director of scientific engagement for the Alzheimer’s Association, said that because of the small study size, short follow-up, and limited data available in the conference abstract, “we cannot speculate about the efficacy of this investigational therapy.”
“Bigger picture, the real-world clinical meaningfulness of research results that are generated in highly controlled circumstances is an important question that is being discussed right now throughout the Alzheimer’s field,” he added.
However, Dr. Koenig countered that the small study design was intentional. “Over the course of a year, we can get to the answer in different patient populations rather than running these rather large and arduous trials that may pan out to not be positive,” he said.
“The purpose here is to say, directionally, are we seeing improvement that warrants further investigation? If you don’t see an effect in a small number of patients, if you don’t see that effect rather quickly, and if you don’t see an effect that should translate into something meaningful, we at SAGE believe that you may not have a drug there,” he added.
Sage Therapeutics plans to launch a phase 2b placebo-controlled trial later this year to study SAGE-718 in more Alzheimer’s patients over a longer period of time.
The study was funded by SAGE Therapeutics. Dr. Koenig is an employee of SAGE and reports no other conflicts. Dr. Griffin has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Patients performed better in cognitive testing after just 2 weeks, especially in areas of executive functioning. Clinicians involved in the study also reported improvements in patients’ ability to complete daily activities, especially in complex tasks such as using a computer, carrying out household chores, and managing their medications.
“It’s pretty incredible to see improvement over the course of a week to a week and a half,” said study investigator Aaron Koenig, MD, vice president of Early Clinical Development at Sage Therapeutics in Cambridge, Mass. “Not only are we seeing objective improvement, we’re also seeing a subjective benefit.”
The drug, SAGE-718, is also under study for MCI in patients with Huntington’s disease, the drug’s primary indication, and Parkinson’s disease.
The findings will be presented at the 2022 annual meeting of the American Academy of Neurology.
Improved executive function
SAGE-718 is in a new class of drugs called positive allosteric modulator of N-methyl-D-aspartate (NMDA) receptors, which are thought to improve neuroplasticity.
For the phase 2a open-label LUMINARY trial, researchers enrolled 26 patients ages 50-80 years with Alzheimer’s disease who had MCI. Patients completed a battery of cognitive tests at the study outset, again at the end of treatment, and again after 28 days.
Participants received SAGE-718 daily for 2 weeks and were followed for another 2 weeks.
The study’s primary outcome was safety. Seven patients (26.9%) reported mild or moderate treatment-emergent adverse events (AEs), and there were no serious AEs or deaths.
However, after 14 days, researchers also noted improvements from baseline on multiple tests of executive functioning, learning, and memory. And at 28 days, participants demonstrated significantly better Montreal Cognitive Assessment scores, compared with baseline (+2.3 points; P < .05), suggesting improvement in global cognition.
“We know that in Alzheimer’s and other neurodegenerative conditions there is a change in cognition, the ability to think, the ability to do things,” Dr. Koenig said. “What we’ve seen with SAGE-718 to date, all the way back to our phase 1 studies, is a cognitively beneficial effect, but more specifically an improvement in executive functioning.”
Intentional small study design
Commenting on the findings, Percy Griffin, PhD, MSc, director of scientific engagement for the Alzheimer’s Association, said that because of the small study size, short follow-up, and limited data available in the conference abstract, “we cannot speculate about the efficacy of this investigational therapy.”
“Bigger picture, the real-world clinical meaningfulness of research results that are generated in highly controlled circumstances is an important question that is being discussed right now throughout the Alzheimer’s field,” he added.
However, Dr. Koenig countered that the small study design was intentional. “Over the course of a year, we can get to the answer in different patient populations rather than running these rather large and arduous trials that may pan out to not be positive,” he said.
“The purpose here is to say, directionally, are we seeing improvement that warrants further investigation? If you don’t see an effect in a small number of patients, if you don’t see that effect rather quickly, and if you don’t see an effect that should translate into something meaningful, we at SAGE believe that you may not have a drug there,” he added.
Sage Therapeutics plans to launch a phase 2b placebo-controlled trial later this year to study SAGE-718 in more Alzheimer’s patients over a longer period of time.
The study was funded by SAGE Therapeutics. Dr. Koenig is an employee of SAGE and reports no other conflicts. Dr. Griffin has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Patients performed better in cognitive testing after just 2 weeks, especially in areas of executive functioning. Clinicians involved in the study also reported improvements in patients’ ability to complete daily activities, especially in complex tasks such as using a computer, carrying out household chores, and managing their medications.
“It’s pretty incredible to see improvement over the course of a week to a week and a half,” said study investigator Aaron Koenig, MD, vice president of Early Clinical Development at Sage Therapeutics in Cambridge, Mass. “Not only are we seeing objective improvement, we’re also seeing a subjective benefit.”
The drug, SAGE-718, is also under study for MCI in patients with Huntington’s disease, the drug’s primary indication, and Parkinson’s disease.
The findings will be presented at the 2022 annual meeting of the American Academy of Neurology.
Improved executive function
SAGE-718 is in a new class of drugs called positive allosteric modulator of N-methyl-D-aspartate (NMDA) receptors, which are thought to improve neuroplasticity.
For the phase 2a open-label LUMINARY trial, researchers enrolled 26 patients ages 50-80 years with Alzheimer’s disease who had MCI. Patients completed a battery of cognitive tests at the study outset, again at the end of treatment, and again after 28 days.
Participants received SAGE-718 daily for 2 weeks and were followed for another 2 weeks.
The study’s primary outcome was safety. Seven patients (26.9%) reported mild or moderate treatment-emergent adverse events (AEs), and there were no serious AEs or deaths.
However, after 14 days, researchers also noted improvements from baseline on multiple tests of executive functioning, learning, and memory. And at 28 days, participants demonstrated significantly better Montreal Cognitive Assessment scores, compared with baseline (+2.3 points; P < .05), suggesting improvement in global cognition.
“We know that in Alzheimer’s and other neurodegenerative conditions there is a change in cognition, the ability to think, the ability to do things,” Dr. Koenig said. “What we’ve seen with SAGE-718 to date, all the way back to our phase 1 studies, is a cognitively beneficial effect, but more specifically an improvement in executive functioning.”
Intentional small study design
Commenting on the findings, Percy Griffin, PhD, MSc, director of scientific engagement for the Alzheimer’s Association, said that because of the small study size, short follow-up, and limited data available in the conference abstract, “we cannot speculate about the efficacy of this investigational therapy.”
“Bigger picture, the real-world clinical meaningfulness of research results that are generated in highly controlled circumstances is an important question that is being discussed right now throughout the Alzheimer’s field,” he added.
However, Dr. Koenig countered that the small study design was intentional. “Over the course of a year, we can get to the answer in different patient populations rather than running these rather large and arduous trials that may pan out to not be positive,” he said.
“The purpose here is to say, directionally, are we seeing improvement that warrants further investigation? If you don’t see an effect in a small number of patients, if you don’t see that effect rather quickly, and if you don’t see an effect that should translate into something meaningful, we at SAGE believe that you may not have a drug there,” he added.
Sage Therapeutics plans to launch a phase 2b placebo-controlled trial later this year to study SAGE-718 in more Alzheimer’s patients over a longer period of time.
The study was funded by SAGE Therapeutics. Dr. Koenig is an employee of SAGE and reports no other conflicts. Dr. Griffin has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM AAN 2022
More evidence that COVID ‘brain fog’ is biologically based
Researchers found elevated levels of CSF immune activation and immunovascular markers in individuals with cognitive postacute sequelae of SARS-CoV-2 infection (PASC). Patients whose cognitive symptoms developed during the acute phase of COVID-19 had the highest levels of brain inflammation.
The findings add to a growing body of evidence that suggests the condition often referred to as “brain fog” has a neurologic basis, said lead author Joanna Hellmuth, MD, MHS, assistant professor of neurology at the University of California, San Francisco Weill Institute of Neurosciences and the UCSF Memory and Aging Center.
The findings will be presented at the 2022 annual meeting of the American Academy of Neurology.
Inflammatory response
There are no effective diagnostic tests or treatments for cognitive PASC, which prompted the investigators to study inflammation in patients with the condition. Initial findings were reported earlier in 2022, which showed abnormalities in the CSF in 77% of patients with cognitive impairment. Patients without cognitive impairments had normal CSF.
Extending that work in this new study, researchers studied patients from the Long-term Impact of Infection With Novel Coronavirus (LIINC) study with confirmed SARS-CoV-2 infection who were not hospitalized. They conducted 2-hour neurocognitive interviews and identified 23 people with new, persistent cognitive symptoms (cognitive PASC) and 10 with no cognitive symptoms who served as controls.
All participants underwent additional neurologic examination and neuropsychological testing, and half agreed to a lumbar puncture to allow researchers to collect CSF samples. The CSF was collected a median of 10.2 months after initial COVID symptoms began.
Participants with cognitive PASC had higher median levels of CSF acute phase reactants C-reactive protein (0.007 mg/L vs. 0.000 mg/L; P =.004) and serum amyloid A (0.001 mg/L vs. 0.000 mg/L; P = .001), compared with COVID controls.
The PASC group also had elevated levels of CSF immune activation markers interferon gamma–inducible protein (IP-10), interleukin-8, and immunovascular markers vascular endothelial growth factor-C and VEGFR-1, although the differences with the control group were not statistically significant.
The timing of the onset of cognitive problems was also associated with higher levels of immune activation and immunovascular markers. Patients with brain fog that developed during the acute phase of COVID-19 had higher levels of CSF VEGF-C, compared with patients whose cognitive symptoms developed more than a month after initial COVID symptoms (173 pg/mL vs. 99 pg/mL; P = .048) and COVID controls (79 pg/mL; P = .048).
Acute onset cognitive PASC participants had higher CSF levels of IP-10 (P = .030), IL-8 (P = .048), placental growth factor (P = .030) and intercellular adhesion molecule-1 (P = .045), compared with COVID controls.
Researchers believe these new findings could mean that intrathecal immune activation and endothelial activation/dysfunction may contribute to cognitive PASC and that the mechanisms involved may be different in patients with acute cognitive PASC versus those with delayed onset.
“Our data suggests that perhaps in these people with more acute cognitive changes they don’t have the return to homeostasis,” Dr. Hellmuth said, while patients with delayed onset cognitive PASC had levels more in line with COVID patients who had no cognitive issues.
Moving the needle forward
Commenting on the findings, William Schaffner, MD, professor of infectious diseases, Vanderbilt University Medical Center, Nashville, Tenn., said that, while the study doesn’t rule out a possible psychological basis for cognitive PASC, it adds more weight to the biological argument.
“When you have nonspecific symptoms for which specific tests are unavailable,” Dr. Schaffner explained, “there is a natural question that always comes up: Is this principally a biologically induced phenomenon or psychological? This moves the needle substantially in the direction of a biological phenomenon.”
Another important element to the study, Dr. Schaffner said, is that the patients involved had mild COVID.
“Not every patient with long COVID symptoms had been hospitalized with severe disease,” he said. “There are inflammatory phenomenon in various organ systems such that even if the inflammatory response in the lung was not severe enough to get you into the hospital, there were inflammatory responses in other organ systems that could persist once the acute infection resolved.”
Although the small size of the study is a limitation, Dr. Schaffner said that shouldn’t minimize the importance of these findings.
“That it’s small doesn’t diminish its value,” he said. “The next step forward might be to try to associate the markers more specifically with COVID. The more precise we can be, the more convincing the story will become.”
The study was funded by the National Institutes of Health. Dr. Hellmuth received grant support from the National Institutes of Health/National Institute of Mental Health supporting this work and personal fees for medical-legal consultation outside of the submitted work. Dr. Schaffner disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Researchers found elevated levels of CSF immune activation and immunovascular markers in individuals with cognitive postacute sequelae of SARS-CoV-2 infection (PASC). Patients whose cognitive symptoms developed during the acute phase of COVID-19 had the highest levels of brain inflammation.
The findings add to a growing body of evidence that suggests the condition often referred to as “brain fog” has a neurologic basis, said lead author Joanna Hellmuth, MD, MHS, assistant professor of neurology at the University of California, San Francisco Weill Institute of Neurosciences and the UCSF Memory and Aging Center.
The findings will be presented at the 2022 annual meeting of the American Academy of Neurology.
Inflammatory response
There are no effective diagnostic tests or treatments for cognitive PASC, which prompted the investigators to study inflammation in patients with the condition. Initial findings were reported earlier in 2022, which showed abnormalities in the CSF in 77% of patients with cognitive impairment. Patients without cognitive impairments had normal CSF.
Extending that work in this new study, researchers studied patients from the Long-term Impact of Infection With Novel Coronavirus (LIINC) study with confirmed SARS-CoV-2 infection who were not hospitalized. They conducted 2-hour neurocognitive interviews and identified 23 people with new, persistent cognitive symptoms (cognitive PASC) and 10 with no cognitive symptoms who served as controls.
All participants underwent additional neurologic examination and neuropsychological testing, and half agreed to a lumbar puncture to allow researchers to collect CSF samples. The CSF was collected a median of 10.2 months after initial COVID symptoms began.
Participants with cognitive PASC had higher median levels of CSF acute phase reactants C-reactive protein (0.007 mg/L vs. 0.000 mg/L; P =.004) and serum amyloid A (0.001 mg/L vs. 0.000 mg/L; P = .001), compared with COVID controls.
The PASC group also had elevated levels of CSF immune activation markers interferon gamma–inducible protein (IP-10), interleukin-8, and immunovascular markers vascular endothelial growth factor-C and VEGFR-1, although the differences with the control group were not statistically significant.
The timing of the onset of cognitive problems was also associated with higher levels of immune activation and immunovascular markers. Patients with brain fog that developed during the acute phase of COVID-19 had higher levels of CSF VEGF-C, compared with patients whose cognitive symptoms developed more than a month after initial COVID symptoms (173 pg/mL vs. 99 pg/mL; P = .048) and COVID controls (79 pg/mL; P = .048).
Acute onset cognitive PASC participants had higher CSF levels of IP-10 (P = .030), IL-8 (P = .048), placental growth factor (P = .030) and intercellular adhesion molecule-1 (P = .045), compared with COVID controls.
Researchers believe these new findings could mean that intrathecal immune activation and endothelial activation/dysfunction may contribute to cognitive PASC and that the mechanisms involved may be different in patients with acute cognitive PASC versus those with delayed onset.
“Our data suggests that perhaps in these people with more acute cognitive changes they don’t have the return to homeostasis,” Dr. Hellmuth said, while patients with delayed onset cognitive PASC had levels more in line with COVID patients who had no cognitive issues.
Moving the needle forward
Commenting on the findings, William Schaffner, MD, professor of infectious diseases, Vanderbilt University Medical Center, Nashville, Tenn., said that, while the study doesn’t rule out a possible psychological basis for cognitive PASC, it adds more weight to the biological argument.
“When you have nonspecific symptoms for which specific tests are unavailable,” Dr. Schaffner explained, “there is a natural question that always comes up: Is this principally a biologically induced phenomenon or psychological? This moves the needle substantially in the direction of a biological phenomenon.”
Another important element to the study, Dr. Schaffner said, is that the patients involved had mild COVID.
“Not every patient with long COVID symptoms had been hospitalized with severe disease,” he said. “There are inflammatory phenomenon in various organ systems such that even if the inflammatory response in the lung was not severe enough to get you into the hospital, there were inflammatory responses in other organ systems that could persist once the acute infection resolved.”
Although the small size of the study is a limitation, Dr. Schaffner said that shouldn’t minimize the importance of these findings.
“That it’s small doesn’t diminish its value,” he said. “The next step forward might be to try to associate the markers more specifically with COVID. The more precise we can be, the more convincing the story will become.”
The study was funded by the National Institutes of Health. Dr. Hellmuth received grant support from the National Institutes of Health/National Institute of Mental Health supporting this work and personal fees for medical-legal consultation outside of the submitted work. Dr. Schaffner disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Researchers found elevated levels of CSF immune activation and immunovascular markers in individuals with cognitive postacute sequelae of SARS-CoV-2 infection (PASC). Patients whose cognitive symptoms developed during the acute phase of COVID-19 had the highest levels of brain inflammation.
The findings add to a growing body of evidence that suggests the condition often referred to as “brain fog” has a neurologic basis, said lead author Joanna Hellmuth, MD, MHS, assistant professor of neurology at the University of California, San Francisco Weill Institute of Neurosciences and the UCSF Memory and Aging Center.
The findings will be presented at the 2022 annual meeting of the American Academy of Neurology.
Inflammatory response
There are no effective diagnostic tests or treatments for cognitive PASC, which prompted the investigators to study inflammation in patients with the condition. Initial findings were reported earlier in 2022, which showed abnormalities in the CSF in 77% of patients with cognitive impairment. Patients without cognitive impairments had normal CSF.
Extending that work in this new study, researchers studied patients from the Long-term Impact of Infection With Novel Coronavirus (LIINC) study with confirmed SARS-CoV-2 infection who were not hospitalized. They conducted 2-hour neurocognitive interviews and identified 23 people with new, persistent cognitive symptoms (cognitive PASC) and 10 with no cognitive symptoms who served as controls.
All participants underwent additional neurologic examination and neuropsychological testing, and half agreed to a lumbar puncture to allow researchers to collect CSF samples. The CSF was collected a median of 10.2 months after initial COVID symptoms began.
Participants with cognitive PASC had higher median levels of CSF acute phase reactants C-reactive protein (0.007 mg/L vs. 0.000 mg/L; P =.004) and serum amyloid A (0.001 mg/L vs. 0.000 mg/L; P = .001), compared with COVID controls.
The PASC group also had elevated levels of CSF immune activation markers interferon gamma–inducible protein (IP-10), interleukin-8, and immunovascular markers vascular endothelial growth factor-C and VEGFR-1, although the differences with the control group were not statistically significant.
The timing of the onset of cognitive problems was also associated with higher levels of immune activation and immunovascular markers. Patients with brain fog that developed during the acute phase of COVID-19 had higher levels of CSF VEGF-C, compared with patients whose cognitive symptoms developed more than a month after initial COVID symptoms (173 pg/mL vs. 99 pg/mL; P = .048) and COVID controls (79 pg/mL; P = .048).
Acute onset cognitive PASC participants had higher CSF levels of IP-10 (P = .030), IL-8 (P = .048), placental growth factor (P = .030) and intercellular adhesion molecule-1 (P = .045), compared with COVID controls.
Researchers believe these new findings could mean that intrathecal immune activation and endothelial activation/dysfunction may contribute to cognitive PASC and that the mechanisms involved may be different in patients with acute cognitive PASC versus those with delayed onset.
“Our data suggests that perhaps in these people with more acute cognitive changes they don’t have the return to homeostasis,” Dr. Hellmuth said, while patients with delayed onset cognitive PASC had levels more in line with COVID patients who had no cognitive issues.
Moving the needle forward
Commenting on the findings, William Schaffner, MD, professor of infectious diseases, Vanderbilt University Medical Center, Nashville, Tenn., said that, while the study doesn’t rule out a possible psychological basis for cognitive PASC, it adds more weight to the biological argument.
“When you have nonspecific symptoms for which specific tests are unavailable,” Dr. Schaffner explained, “there is a natural question that always comes up: Is this principally a biologically induced phenomenon or psychological? This moves the needle substantially in the direction of a biological phenomenon.”
Another important element to the study, Dr. Schaffner said, is that the patients involved had mild COVID.
“Not every patient with long COVID symptoms had been hospitalized with severe disease,” he said. “There are inflammatory phenomenon in various organ systems such that even if the inflammatory response in the lung was not severe enough to get you into the hospital, there were inflammatory responses in other organ systems that could persist once the acute infection resolved.”
Although the small size of the study is a limitation, Dr. Schaffner said that shouldn’t minimize the importance of these findings.
“That it’s small doesn’t diminish its value,” he said. “The next step forward might be to try to associate the markers more specifically with COVID. The more precise we can be, the more convincing the story will become.”
The study was funded by the National Institutes of Health. Dr. Hellmuth received grant support from the National Institutes of Health/National Institute of Mental Health supporting this work and personal fees for medical-legal consultation outside of the submitted work. Dr. Schaffner disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM AAN 2022
Medications for opioid addiction vastly underutilized
Based on data from the National Survey on Drug Use and Health (NSDUH), investigators found only one in four individuals with OUD receive drug treatment.
In addition, receipt of medication for OUD (MOUD) was lowest among women, the uninsured, non-Hispanic Black or Hispanic people, people with low incomes, and those over age 50. Teens with OUD had the lowest rate of medication use among all demographic groups – zero.
The study is the first to estimate past-year MOUD use in a nationally representative community sample of individuals who may have needed OUD treatment.
“The overdose crisis in the U.S. is continuing unabated, unfortunately, and medication access is an important tool to target and reduce overdose deaths,” lead author Pia Mauro, PhD, assistant professor of epidemiology at Columbia University’s Mailman School of Public Health, New York, told this news organization. “Putting numbers to the distribution of people who are getting medication is important, because it shows that what we’re doing is not enough.”
The study was published online March 23 in JAMA Network Open.
Overdose deaths at an all-time high
U.S. drug overdose deaths are at a record high, with 100,306 American deaths between April 2020 and April 2021, a nearly 30% increase from the previous year. Nearly three-quarters of those deaths involved opioids.
There are currently three Food and Drug Administration–approved medications to treat OUD: methadone, buprenorphine, or naltrexone, all of which are highly effective. Buprenorphine is the only one approved for use in adolescents, and only in those 16 and older.
Before 2019, information about MOUD treatment use was not collected in the NSDUH, an annual survey conducted by the Substance Abuse and Mental Health Services Administration (SAMHSA).
Drawing on responses to the newly added MOUD-use question, Dr. Mauro and colleagues identified participants who may have needed MOUD in the previous year, including those who reported having a heroin or opioid use disorder, receiving medication for their disorder, or undergoing a non-medication OUD treatment, including cognitive behavioral therapy and self-help.
Only 27.8% of those eligible for OUD treatment received MOUD in the past year; 57.0% received no treatment; and 15.3% received non-MOUD services.
Individuals aged 18-25 were most likely to receive MOUD, with just 13.2% of those over age 50 and no one under age 18 receiving medication.
“This study points to extremely low medication use for people who may need it, and given the continued increase in drug-related overdose deaths, the majority of which involve opioids, the necessity to increase access to medication is more important than ever,” Dr. Mauro said.
MOUD use was significantly lower in non-Hispanic Black people, (adjusted relative risk ratio, 0.82; 95% confidence interval, 0.27-2.46), Hispanic people (aRRR, 0.57; 95% CI, 0.14-2.28), and in Asian, Native American or Alaska Native, Native Hawaiian, Pacific Islander, or multiracial people (aRRR, 0.28; 95% CI, 0.08-0.92) compared to White people.
Medication use was less likely in women than men (aRRR, 0.52; 95% CI, 0.29-0.95) and more likely in people who had both prescription opioid and heroin use disorder, compared with those who misused just one of the substances (aRRR, 5.07; 95% CI, 1.50-17.12).
MOUD was more common among people with public insurance than those with private or no insurance, but the overall use remained very low regardless of insurance status.
“Public insurance has consistently been positively associated with MOUD access, so our study builds on this showing the importance of public insurance to increase medication access,” Dr. Mauro said. “But even among those with public insurance, only 35% got medication. That’s only one in three.”
About 85% of participants who may have needed treatment for OUD had at least one contact with a health care provider in the past year, and more than half had contact with the criminal legal system. Only about one-third of these individuals received MOUD, which Dr. Mauro lamented as a lost opportunity for treatment.
Persistent barriers to treatment
The findings highlight persistent barriers to medication-based therapy for OUD, said Alan Leshner, PhD, chief executive officer emeritus of the American Association for the Advancement of Science and a former director of the National Institute on Drug Abuse.
“These kinds of data are critical to increase our understanding of the nature of the opioid epidemic and what to do about it,” Dr. Leshner said. “It’s particularly important to understand who does, and doesn’t, have access to lifesaving medications, but also where to focus efforts at working on the problem.”
In 2019, Dr. Leshner coauthored a report on the underutilization of medication to treat OUD. As previously reported by this news organization, that report argued that stigma, burdensome regulations, unfounded concerns about diversion of MOUDs, lack of insurance coverage, and inadequate professional training for health care providers, law enforcement, and criminal justice officials all acted as barriers that separate people with a medical disorder from desperately needed – and effective – treatment.
“The barriers are the same and have not been vigorously addressed,” Dr. Leshner said. However, recent moves by government leaders may signal a positive trend toward expanded treatment, he added.
Earlier this month, Dr. Leshner chaired a workshop on ways to improve access to methadone, one of the approved medications to treat OUD. Officials from SAMHSA, the Drug Enforcement Administration, and the FDA participated, as did Rahul Gupta, MD, director of the Office of National Drug Control Policy and the nation’s top drug policy official.
“I am optimistic that there may be a new commitment to working on this epidemic using a health-centered approach that takes into account the array of social issues that surround the problem, as well as the criminal justice issues,” Dr. Leshner said.
The study was funded by the National Institute on Drug Abuse grant. Dr. Mauro and Dr. Leshner reported no conflicts. Full disclosures are reported in the original article.
A version of this article first appeared on Medscape.com.
Based on data from the National Survey on Drug Use and Health (NSDUH), investigators found only one in four individuals with OUD receive drug treatment.
In addition, receipt of medication for OUD (MOUD) was lowest among women, the uninsured, non-Hispanic Black or Hispanic people, people with low incomes, and those over age 50. Teens with OUD had the lowest rate of medication use among all demographic groups – zero.
The study is the first to estimate past-year MOUD use in a nationally representative community sample of individuals who may have needed OUD treatment.
“The overdose crisis in the U.S. is continuing unabated, unfortunately, and medication access is an important tool to target and reduce overdose deaths,” lead author Pia Mauro, PhD, assistant professor of epidemiology at Columbia University’s Mailman School of Public Health, New York, told this news organization. “Putting numbers to the distribution of people who are getting medication is important, because it shows that what we’re doing is not enough.”
The study was published online March 23 in JAMA Network Open.
Overdose deaths at an all-time high
U.S. drug overdose deaths are at a record high, with 100,306 American deaths between April 2020 and April 2021, a nearly 30% increase from the previous year. Nearly three-quarters of those deaths involved opioids.
There are currently three Food and Drug Administration–approved medications to treat OUD: methadone, buprenorphine, or naltrexone, all of which are highly effective. Buprenorphine is the only one approved for use in adolescents, and only in those 16 and older.
Before 2019, information about MOUD treatment use was not collected in the NSDUH, an annual survey conducted by the Substance Abuse and Mental Health Services Administration (SAMHSA).
Drawing on responses to the newly added MOUD-use question, Dr. Mauro and colleagues identified participants who may have needed MOUD in the previous year, including those who reported having a heroin or opioid use disorder, receiving medication for their disorder, or undergoing a non-medication OUD treatment, including cognitive behavioral therapy and self-help.
Only 27.8% of those eligible for OUD treatment received MOUD in the past year; 57.0% received no treatment; and 15.3% received non-MOUD services.
Individuals aged 18-25 were most likely to receive MOUD, with just 13.2% of those over age 50 and no one under age 18 receiving medication.
“This study points to extremely low medication use for people who may need it, and given the continued increase in drug-related overdose deaths, the majority of which involve opioids, the necessity to increase access to medication is more important than ever,” Dr. Mauro said.
MOUD use was significantly lower in non-Hispanic Black people, (adjusted relative risk ratio, 0.82; 95% confidence interval, 0.27-2.46), Hispanic people (aRRR, 0.57; 95% CI, 0.14-2.28), and in Asian, Native American or Alaska Native, Native Hawaiian, Pacific Islander, or multiracial people (aRRR, 0.28; 95% CI, 0.08-0.92) compared to White people.
Medication use was less likely in women than men (aRRR, 0.52; 95% CI, 0.29-0.95) and more likely in people who had both prescription opioid and heroin use disorder, compared with those who misused just one of the substances (aRRR, 5.07; 95% CI, 1.50-17.12).
MOUD was more common among people with public insurance than those with private or no insurance, but the overall use remained very low regardless of insurance status.
“Public insurance has consistently been positively associated with MOUD access, so our study builds on this showing the importance of public insurance to increase medication access,” Dr. Mauro said. “But even among those with public insurance, only 35% got medication. That’s only one in three.”
About 85% of participants who may have needed treatment for OUD had at least one contact with a health care provider in the past year, and more than half had contact with the criminal legal system. Only about one-third of these individuals received MOUD, which Dr. Mauro lamented as a lost opportunity for treatment.
Persistent barriers to treatment
The findings highlight persistent barriers to medication-based therapy for OUD, said Alan Leshner, PhD, chief executive officer emeritus of the American Association for the Advancement of Science and a former director of the National Institute on Drug Abuse.
“These kinds of data are critical to increase our understanding of the nature of the opioid epidemic and what to do about it,” Dr. Leshner said. “It’s particularly important to understand who does, and doesn’t, have access to lifesaving medications, but also where to focus efforts at working on the problem.”
In 2019, Dr. Leshner coauthored a report on the underutilization of medication to treat OUD. As previously reported by this news organization, that report argued that stigma, burdensome regulations, unfounded concerns about diversion of MOUDs, lack of insurance coverage, and inadequate professional training for health care providers, law enforcement, and criminal justice officials all acted as barriers that separate people with a medical disorder from desperately needed – and effective – treatment.
“The barriers are the same and have not been vigorously addressed,” Dr. Leshner said. However, recent moves by government leaders may signal a positive trend toward expanded treatment, he added.
Earlier this month, Dr. Leshner chaired a workshop on ways to improve access to methadone, one of the approved medications to treat OUD. Officials from SAMHSA, the Drug Enforcement Administration, and the FDA participated, as did Rahul Gupta, MD, director of the Office of National Drug Control Policy and the nation’s top drug policy official.
“I am optimistic that there may be a new commitment to working on this epidemic using a health-centered approach that takes into account the array of social issues that surround the problem, as well as the criminal justice issues,” Dr. Leshner said.
The study was funded by the National Institute on Drug Abuse grant. Dr. Mauro and Dr. Leshner reported no conflicts. Full disclosures are reported in the original article.
A version of this article first appeared on Medscape.com.
Based on data from the National Survey on Drug Use and Health (NSDUH), investigators found only one in four individuals with OUD receive drug treatment.
In addition, receipt of medication for OUD (MOUD) was lowest among women, the uninsured, non-Hispanic Black or Hispanic people, people with low incomes, and those over age 50. Teens with OUD had the lowest rate of medication use among all demographic groups – zero.
The study is the first to estimate past-year MOUD use in a nationally representative community sample of individuals who may have needed OUD treatment.
“The overdose crisis in the U.S. is continuing unabated, unfortunately, and medication access is an important tool to target and reduce overdose deaths,” lead author Pia Mauro, PhD, assistant professor of epidemiology at Columbia University’s Mailman School of Public Health, New York, told this news organization. “Putting numbers to the distribution of people who are getting medication is important, because it shows that what we’re doing is not enough.”
The study was published online March 23 in JAMA Network Open.
Overdose deaths at an all-time high
U.S. drug overdose deaths are at a record high, with 100,306 American deaths between April 2020 and April 2021, a nearly 30% increase from the previous year. Nearly three-quarters of those deaths involved opioids.
There are currently three Food and Drug Administration–approved medications to treat OUD: methadone, buprenorphine, or naltrexone, all of which are highly effective. Buprenorphine is the only one approved for use in adolescents, and only in those 16 and older.
Before 2019, information about MOUD treatment use was not collected in the NSDUH, an annual survey conducted by the Substance Abuse and Mental Health Services Administration (SAMHSA).
Drawing on responses to the newly added MOUD-use question, Dr. Mauro and colleagues identified participants who may have needed MOUD in the previous year, including those who reported having a heroin or opioid use disorder, receiving medication for their disorder, or undergoing a non-medication OUD treatment, including cognitive behavioral therapy and self-help.
Only 27.8% of those eligible for OUD treatment received MOUD in the past year; 57.0% received no treatment; and 15.3% received non-MOUD services.
Individuals aged 18-25 were most likely to receive MOUD, with just 13.2% of those over age 50 and no one under age 18 receiving medication.
“This study points to extremely low medication use for people who may need it, and given the continued increase in drug-related overdose deaths, the majority of which involve opioids, the necessity to increase access to medication is more important than ever,” Dr. Mauro said.
MOUD use was significantly lower in non-Hispanic Black people, (adjusted relative risk ratio, 0.82; 95% confidence interval, 0.27-2.46), Hispanic people (aRRR, 0.57; 95% CI, 0.14-2.28), and in Asian, Native American or Alaska Native, Native Hawaiian, Pacific Islander, or multiracial people (aRRR, 0.28; 95% CI, 0.08-0.92) compared to White people.
Medication use was less likely in women than men (aRRR, 0.52; 95% CI, 0.29-0.95) and more likely in people who had both prescription opioid and heroin use disorder, compared with those who misused just one of the substances (aRRR, 5.07; 95% CI, 1.50-17.12).
MOUD was more common among people with public insurance than those with private or no insurance, but the overall use remained very low regardless of insurance status.
“Public insurance has consistently been positively associated with MOUD access, so our study builds on this showing the importance of public insurance to increase medication access,” Dr. Mauro said. “But even among those with public insurance, only 35% got medication. That’s only one in three.”
About 85% of participants who may have needed treatment for OUD had at least one contact with a health care provider in the past year, and more than half had contact with the criminal legal system. Only about one-third of these individuals received MOUD, which Dr. Mauro lamented as a lost opportunity for treatment.
Persistent barriers to treatment
The findings highlight persistent barriers to medication-based therapy for OUD, said Alan Leshner, PhD, chief executive officer emeritus of the American Association for the Advancement of Science and a former director of the National Institute on Drug Abuse.
“These kinds of data are critical to increase our understanding of the nature of the opioid epidemic and what to do about it,” Dr. Leshner said. “It’s particularly important to understand who does, and doesn’t, have access to lifesaving medications, but also where to focus efforts at working on the problem.”
In 2019, Dr. Leshner coauthored a report on the underutilization of medication to treat OUD. As previously reported by this news organization, that report argued that stigma, burdensome regulations, unfounded concerns about diversion of MOUDs, lack of insurance coverage, and inadequate professional training for health care providers, law enforcement, and criminal justice officials all acted as barriers that separate people with a medical disorder from desperately needed – and effective – treatment.
“The barriers are the same and have not been vigorously addressed,” Dr. Leshner said. However, recent moves by government leaders may signal a positive trend toward expanded treatment, he added.
Earlier this month, Dr. Leshner chaired a workshop on ways to improve access to methadone, one of the approved medications to treat OUD. Officials from SAMHSA, the Drug Enforcement Administration, and the FDA participated, as did Rahul Gupta, MD, director of the Office of National Drug Control Policy and the nation’s top drug policy official.
“I am optimistic that there may be a new commitment to working on this epidemic using a health-centered approach that takes into account the array of social issues that surround the problem, as well as the criminal justice issues,” Dr. Leshner said.
The study was funded by the National Institute on Drug Abuse grant. Dr. Mauro and Dr. Leshner reported no conflicts. Full disclosures are reported in the original article.
A version of this article first appeared on Medscape.com.
Brain implant allows fully paralyzed patient to communicate
Using a commercially available implant and newly designed software, the patient, who was in the advanced stages of Lou Gehrig’s disease and unable to move his eyes, was able to interact with researchers and caregivers, requesting goulash, beer, and music from the band Tool, thanking the researchers who developed the technology and inviting his 4-year-old son to watch a Disney film.
The investigators note the study shows for the first time that communication is possible in patients in a completely locked-in state (CLIS) and offers hope for a better quality of life in this population.
“It should encourage them to live after artificial respiration and to ask for brain-computer interfaces before they become CLIS,” study investigator Niels Birbaumer, PhD, a professor emeritus of the University of Tübingen, Germany, said in an interview. The study was published online March 22 in Nature Communications.
Although the findings appear promising, they build on previous research that was the subject of a 2019 investigation by the largest grant-funding agency in Germany. This controversy prompted the institute that led the current research to appoint an independent expert to audit and monitor the new study.
Mechanism a ‘mystery’
Use of brain-computer interface (BCI) technology to allow ALS patients to communicate has increased in recent years. BCIs capture brain signals, transmit them to a computer, and convert them into a command that the computer carries out.
Previous research shows patients with ALS who retain eye movement and control have been able to use BCIs to communicate. However, until now, the technology has not worked as well in CLIS patients, who have full-body paralysis.
In 2019, German and Swiss researchers implanted two 64-microde arrays in the brain of a 34-year-old patient who was diagnosed with ALS in 2015.
The electrodes measure neuronal activity while an amplifier located on the outside of the patient’s skull amplifies the signals to a computer. Software created by the research team decodes the signals and translates them into commands.
Using an auditory feedback system, the patient was able to use his mind to modulate the pitch of a tone to either high (meaning “yes”) or low (meaning “no.”) Just how the brain does this is a mystery, Dr. Birbaumer said.
A speller program reads letters aloud, first in groups and then individually. When a group contained letters the patient needed to spell a word, he used auditory feedback to select the high-pitch tone.
Initially, the patient was able to correctly spell his name. Ultimately, he was able to form complete sentences. The patient correctly spelled words on 44 of the 107 days in that phase of the experiment, spelling an average of just one character per minute.
Still, the researchers note he was able to interact with his caretakers, family, and researchers, even offering input on changes to make the device more effective.
Controversial history
In 2017, Dr. Birbaumer and Ujwal Chaudhary, PhD, who is the lead author on this current study, published a study in PLOS Biology. That research analyzed a brain-monitoring technique that the scientists claimed enabled patients with ALS who were completely locked in to answer yes or no questions correctly.
Allegations from a whistleblower at the University of Tübingen, where Dr. Birbaumer was a senior professor and Dr. Chaudhary was a postdoctoral researcher, prompted an investigation by the Deutsche Forschungsgemeinschaft, or German Research Foundation (DFG).
The whistleblower claimed that the 2017 paper and a second study published in 2019 contained incomplete data and misrepresented the findings. The DFG investigation found evidence of scientific misconduct and required that Dr. Birbaumer return the grant he had received for the research. The agency also banned Dr. Birbaumer from applying for grants or serving as a grant reviewer for 5 years. Dr. Chaudhary was banned for 3 years. PLOS Biology later retracted the papers.
Both researchers have refuted the allegations and have reportedly sued the German Research Foundation.
“We have no information about the status of our lawsuit against the DFG; it’s still pending,” Dr. Birbaumer told this news organization. “I hope they investigate our present study because the study of 2017 they did not investigate carefully enough.”
Results ‘not stunningly good’
The controversial history prompted the Wyss Center, Geneva, which led this new study, to seek out at an independent BCI expert to audit and monitor the study.
Nick Ramsey, PhD, a professor of cognitive neuroscience at the Brain Center of the University Medical Center Utrecht, the Netherlands, agreed to take on the assignment in March 2020.
Dr. Ramsey has also conducted research on BCI in patients with ALS, but his work has not included patients in CLIS.
“I judged the study to be compliant with universal standards of scientific integrity,” Dr. Ramsey told this news organization. “I am confident that the data and results presented in the paper are valid and will withstand academic and medical scrutiny.”
Commenting on the new findings, Dr. Ramsey noted that the results of the study are “not stunningly good, as the user could only communicate during a limited number of days, and even then with considerable slowness,” Dr. Ramsey said. However, he added that the study does provide proof of principle that communication is possible in CLIS patients.
“The question remains whether a BCI implant continues to work well in these patients, as there are some indications that people in such a state may lose their mental capabilities within months or a few years as a result of the disease and can thus no longer generate a wish to communicate,” Dr. Ramsey said.
Responding to a query from this news organization, a spokesperson for Nature Communications declined to comment on the new study but said that journal editors are “are alert to controversies within each field and take care when considering submissions during the peer-review process.”
“We have rigorous policies to safeguard the integrity of the research we publish,” the spokesperson continued, “including to ensure that research has been conducted to a high ethical standard and is reported transparently.”
The research was funded by Wyss Center for Bio and Neuroengineering, Geneva and Deutsche Forschungsgemeinschaft. The authors have disclosed no relevant financial relationships. Dr. Ramsey received payment from the Wyss Center for his advisory role in this project.
A version of this article first appeared on Medscape.com.
Using a commercially available implant and newly designed software, the patient, who was in the advanced stages of Lou Gehrig’s disease and unable to move his eyes, was able to interact with researchers and caregivers, requesting goulash, beer, and music from the band Tool, thanking the researchers who developed the technology and inviting his 4-year-old son to watch a Disney film.
The investigators note the study shows for the first time that communication is possible in patients in a completely locked-in state (CLIS) and offers hope for a better quality of life in this population.
“It should encourage them to live after artificial respiration and to ask for brain-computer interfaces before they become CLIS,” study investigator Niels Birbaumer, PhD, a professor emeritus of the University of Tübingen, Germany, said in an interview. The study was published online March 22 in Nature Communications.
Although the findings appear promising, they build on previous research that was the subject of a 2019 investigation by the largest grant-funding agency in Germany. This controversy prompted the institute that led the current research to appoint an independent expert to audit and monitor the new study.
Mechanism a ‘mystery’
Use of brain-computer interface (BCI) technology to allow ALS patients to communicate has increased in recent years. BCIs capture brain signals, transmit them to a computer, and convert them into a command that the computer carries out.
Previous research shows patients with ALS who retain eye movement and control have been able to use BCIs to communicate. However, until now, the technology has not worked as well in CLIS patients, who have full-body paralysis.
In 2019, German and Swiss researchers implanted two 64-microde arrays in the brain of a 34-year-old patient who was diagnosed with ALS in 2015.
The electrodes measure neuronal activity while an amplifier located on the outside of the patient’s skull amplifies the signals to a computer. Software created by the research team decodes the signals and translates them into commands.
Using an auditory feedback system, the patient was able to use his mind to modulate the pitch of a tone to either high (meaning “yes”) or low (meaning “no.”) Just how the brain does this is a mystery, Dr. Birbaumer said.
A speller program reads letters aloud, first in groups and then individually. When a group contained letters the patient needed to spell a word, he used auditory feedback to select the high-pitch tone.
Initially, the patient was able to correctly spell his name. Ultimately, he was able to form complete sentences. The patient correctly spelled words on 44 of the 107 days in that phase of the experiment, spelling an average of just one character per minute.
Still, the researchers note he was able to interact with his caretakers, family, and researchers, even offering input on changes to make the device more effective.
Controversial history
In 2017, Dr. Birbaumer and Ujwal Chaudhary, PhD, who is the lead author on this current study, published a study in PLOS Biology. That research analyzed a brain-monitoring technique that the scientists claimed enabled patients with ALS who were completely locked in to answer yes or no questions correctly.
Allegations from a whistleblower at the University of Tübingen, where Dr. Birbaumer was a senior professor and Dr. Chaudhary was a postdoctoral researcher, prompted an investigation by the Deutsche Forschungsgemeinschaft, or German Research Foundation (DFG).
The whistleblower claimed that the 2017 paper and a second study published in 2019 contained incomplete data and misrepresented the findings. The DFG investigation found evidence of scientific misconduct and required that Dr. Birbaumer return the grant he had received for the research. The agency also banned Dr. Birbaumer from applying for grants or serving as a grant reviewer for 5 years. Dr. Chaudhary was banned for 3 years. PLOS Biology later retracted the papers.
Both researchers have refuted the allegations and have reportedly sued the German Research Foundation.
“We have no information about the status of our lawsuit against the DFG; it’s still pending,” Dr. Birbaumer told this news organization. “I hope they investigate our present study because the study of 2017 they did not investigate carefully enough.”
Results ‘not stunningly good’
The controversial history prompted the Wyss Center, Geneva, which led this new study, to seek out at an independent BCI expert to audit and monitor the study.
Nick Ramsey, PhD, a professor of cognitive neuroscience at the Brain Center of the University Medical Center Utrecht, the Netherlands, agreed to take on the assignment in March 2020.
Dr. Ramsey has also conducted research on BCI in patients with ALS, but his work has not included patients in CLIS.
“I judged the study to be compliant with universal standards of scientific integrity,” Dr. Ramsey told this news organization. “I am confident that the data and results presented in the paper are valid and will withstand academic and medical scrutiny.”
Commenting on the new findings, Dr. Ramsey noted that the results of the study are “not stunningly good, as the user could only communicate during a limited number of days, and even then with considerable slowness,” Dr. Ramsey said. However, he added that the study does provide proof of principle that communication is possible in CLIS patients.
“The question remains whether a BCI implant continues to work well in these patients, as there are some indications that people in such a state may lose their mental capabilities within months or a few years as a result of the disease and can thus no longer generate a wish to communicate,” Dr. Ramsey said.
Responding to a query from this news organization, a spokesperson for Nature Communications declined to comment on the new study but said that journal editors are “are alert to controversies within each field and take care when considering submissions during the peer-review process.”
“We have rigorous policies to safeguard the integrity of the research we publish,” the spokesperson continued, “including to ensure that research has been conducted to a high ethical standard and is reported transparently.”
The research was funded by Wyss Center for Bio and Neuroengineering, Geneva and Deutsche Forschungsgemeinschaft. The authors have disclosed no relevant financial relationships. Dr. Ramsey received payment from the Wyss Center for his advisory role in this project.
A version of this article first appeared on Medscape.com.
Using a commercially available implant and newly designed software, the patient, who was in the advanced stages of Lou Gehrig’s disease and unable to move his eyes, was able to interact with researchers and caregivers, requesting goulash, beer, and music from the band Tool, thanking the researchers who developed the technology and inviting his 4-year-old son to watch a Disney film.
The investigators note the study shows for the first time that communication is possible in patients in a completely locked-in state (CLIS) and offers hope for a better quality of life in this population.
“It should encourage them to live after artificial respiration and to ask for brain-computer interfaces before they become CLIS,” study investigator Niels Birbaumer, PhD, a professor emeritus of the University of Tübingen, Germany, said in an interview. The study was published online March 22 in Nature Communications.
Although the findings appear promising, they build on previous research that was the subject of a 2019 investigation by the largest grant-funding agency in Germany. This controversy prompted the institute that led the current research to appoint an independent expert to audit and monitor the new study.
Mechanism a ‘mystery’
Use of brain-computer interface (BCI) technology to allow ALS patients to communicate has increased in recent years. BCIs capture brain signals, transmit them to a computer, and convert them into a command that the computer carries out.
Previous research shows patients with ALS who retain eye movement and control have been able to use BCIs to communicate. However, until now, the technology has not worked as well in CLIS patients, who have full-body paralysis.
In 2019, German and Swiss researchers implanted two 64-microde arrays in the brain of a 34-year-old patient who was diagnosed with ALS in 2015.
The electrodes measure neuronal activity while an amplifier located on the outside of the patient’s skull amplifies the signals to a computer. Software created by the research team decodes the signals and translates them into commands.
Using an auditory feedback system, the patient was able to use his mind to modulate the pitch of a tone to either high (meaning “yes”) or low (meaning “no.”) Just how the brain does this is a mystery, Dr. Birbaumer said.
A speller program reads letters aloud, first in groups and then individually. When a group contained letters the patient needed to spell a word, he used auditory feedback to select the high-pitch tone.
Initially, the patient was able to correctly spell his name. Ultimately, he was able to form complete sentences. The patient correctly spelled words on 44 of the 107 days in that phase of the experiment, spelling an average of just one character per minute.
Still, the researchers note he was able to interact with his caretakers, family, and researchers, even offering input on changes to make the device more effective.
Controversial history
In 2017, Dr. Birbaumer and Ujwal Chaudhary, PhD, who is the lead author on this current study, published a study in PLOS Biology. That research analyzed a brain-monitoring technique that the scientists claimed enabled patients with ALS who were completely locked in to answer yes or no questions correctly.
Allegations from a whistleblower at the University of Tübingen, where Dr. Birbaumer was a senior professor and Dr. Chaudhary was a postdoctoral researcher, prompted an investigation by the Deutsche Forschungsgemeinschaft, or German Research Foundation (DFG).
The whistleblower claimed that the 2017 paper and a second study published in 2019 contained incomplete data and misrepresented the findings. The DFG investigation found evidence of scientific misconduct and required that Dr. Birbaumer return the grant he had received for the research. The agency also banned Dr. Birbaumer from applying for grants or serving as a grant reviewer for 5 years. Dr. Chaudhary was banned for 3 years. PLOS Biology later retracted the papers.
Both researchers have refuted the allegations and have reportedly sued the German Research Foundation.
“We have no information about the status of our lawsuit against the DFG; it’s still pending,” Dr. Birbaumer told this news organization. “I hope they investigate our present study because the study of 2017 they did not investigate carefully enough.”
Results ‘not stunningly good’
The controversial history prompted the Wyss Center, Geneva, which led this new study, to seek out at an independent BCI expert to audit and monitor the study.
Nick Ramsey, PhD, a professor of cognitive neuroscience at the Brain Center of the University Medical Center Utrecht, the Netherlands, agreed to take on the assignment in March 2020.
Dr. Ramsey has also conducted research on BCI in patients with ALS, but his work has not included patients in CLIS.
“I judged the study to be compliant with universal standards of scientific integrity,” Dr. Ramsey told this news organization. “I am confident that the data and results presented in the paper are valid and will withstand academic and medical scrutiny.”
Commenting on the new findings, Dr. Ramsey noted that the results of the study are “not stunningly good, as the user could only communicate during a limited number of days, and even then with considerable slowness,” Dr. Ramsey said. However, he added that the study does provide proof of principle that communication is possible in CLIS patients.
“The question remains whether a BCI implant continues to work well in these patients, as there are some indications that people in such a state may lose their mental capabilities within months or a few years as a result of the disease and can thus no longer generate a wish to communicate,” Dr. Ramsey said.
Responding to a query from this news organization, a spokesperson for Nature Communications declined to comment on the new study but said that journal editors are “are alert to controversies within each field and take care when considering submissions during the peer-review process.”
“We have rigorous policies to safeguard the integrity of the research we publish,” the spokesperson continued, “including to ensure that research has been conducted to a high ethical standard and is reported transparently.”
The research was funded by Wyss Center for Bio and Neuroengineering, Geneva and Deutsche Forschungsgemeinschaft. The authors have disclosed no relevant financial relationships. Dr. Ramsey received payment from the Wyss Center for his advisory role in this project.
A version of this article first appeared on Medscape.com.
FROM NATURE COMMUNICATIONS
Schizophrenia risk lower for people with access to green space
The investigators, led by Martin Rotenberg, MD, of Centre for Addiction and Mental Health and the University of Toronto, found individuals living in areas with the lowest levels of green space were 24% more likely to develop schizophrenia.
This study contributes to a growing body of evidence showing the importance of exposure to green space to mental health.
“These findings contribute to a growing evidence base that environmental factors may play a role in the etiology of schizophrenia,” the researchers write.
The study was published online Feb. 4 in the Canadian Journal of Psychiatry.
Underlying mechanism unknown
For the study, researchers used a retrospective population-based cohort of 649,020 individuals between ages 14 and 40 years from different neighborhoods in Toronto.
Green space was calculated using geospatial data of all public parks and green spaces in the city; data were drawn from the Urban Health Equity Assessment and Response Tool.
Over a 10-year period, 4,841 participants were diagnosed with schizophrenia.
Those who lived in neighborhoods with the least amount of green space were significantly more likely to develop schizophrenia than those who lived in areas with the most green space, even after adjusting for age, sex, and neighborhood-level marginalization (adjusted incidence rate ratio, 1.24; 95% confidence interval, 1.06-1.45).
Overall, schizophrenia risk was also elevated in men vs. women (adjusted IRR, 1.59; 95% CI, 1.50-1.68). Those living in areas with moderate amounts of green space did not have an increased schizophrenia risk.
“We found that residing in an area with the lowest amount of green space was associated with an increased risk of developing schizophrenia, independent of other sociodemographic and socioenvironmental factors,” the researchers note. “The underlying mechanism at play is unknown and requires further study.”
One possibility, they added, is that exposure to green space may reduce the risk of air pollution, which other studies have suggested may be associated with increased schizophrenia risk.
The new study builds on a 2018 report from Denmark that showed a 52% increased risk of psychotic disorders in adulthood among people who spent their childhood in neighborhoods with little green space.
Important, longitudinal data
Commenting on the findings, John Torous, MD, director of digital psychiatry at Beth Israel Deaconess Medical Center, Boston, said the study provides important longitudinal data.
“The 10-year duration of the study and large sample size make the results very compelling and help confirm what has been thought about green space and risk of schizophrenia,” Dr. Torous said.
“Often, we think of green space at a very macro level,” he added. “This study is important because it shows us that green space matters on a block-by-block level just as much.”
The study was unfunded. The authors and Dr. Torous have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The investigators, led by Martin Rotenberg, MD, of Centre for Addiction and Mental Health and the University of Toronto, found individuals living in areas with the lowest levels of green space were 24% more likely to develop schizophrenia.
This study contributes to a growing body of evidence showing the importance of exposure to green space to mental health.
“These findings contribute to a growing evidence base that environmental factors may play a role in the etiology of schizophrenia,” the researchers write.
The study was published online Feb. 4 in the Canadian Journal of Psychiatry.
Underlying mechanism unknown
For the study, researchers used a retrospective population-based cohort of 649,020 individuals between ages 14 and 40 years from different neighborhoods in Toronto.
Green space was calculated using geospatial data of all public parks and green spaces in the city; data were drawn from the Urban Health Equity Assessment and Response Tool.
Over a 10-year period, 4,841 participants were diagnosed with schizophrenia.
Those who lived in neighborhoods with the least amount of green space were significantly more likely to develop schizophrenia than those who lived in areas with the most green space, even after adjusting for age, sex, and neighborhood-level marginalization (adjusted incidence rate ratio, 1.24; 95% confidence interval, 1.06-1.45).
Overall, schizophrenia risk was also elevated in men vs. women (adjusted IRR, 1.59; 95% CI, 1.50-1.68). Those living in areas with moderate amounts of green space did not have an increased schizophrenia risk.
“We found that residing in an area with the lowest amount of green space was associated with an increased risk of developing schizophrenia, independent of other sociodemographic and socioenvironmental factors,” the researchers note. “The underlying mechanism at play is unknown and requires further study.”
One possibility, they added, is that exposure to green space may reduce the risk of air pollution, which other studies have suggested may be associated with increased schizophrenia risk.
The new study builds on a 2018 report from Denmark that showed a 52% increased risk of psychotic disorders in adulthood among people who spent their childhood in neighborhoods with little green space.
Important, longitudinal data
Commenting on the findings, John Torous, MD, director of digital psychiatry at Beth Israel Deaconess Medical Center, Boston, said the study provides important longitudinal data.
“The 10-year duration of the study and large sample size make the results very compelling and help confirm what has been thought about green space and risk of schizophrenia,” Dr. Torous said.
“Often, we think of green space at a very macro level,” he added. “This study is important because it shows us that green space matters on a block-by-block level just as much.”
The study was unfunded. The authors and Dr. Torous have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The investigators, led by Martin Rotenberg, MD, of Centre for Addiction and Mental Health and the University of Toronto, found individuals living in areas with the lowest levels of green space were 24% more likely to develop schizophrenia.
This study contributes to a growing body of evidence showing the importance of exposure to green space to mental health.
“These findings contribute to a growing evidence base that environmental factors may play a role in the etiology of schizophrenia,” the researchers write.
The study was published online Feb. 4 in the Canadian Journal of Psychiatry.
Underlying mechanism unknown
For the study, researchers used a retrospective population-based cohort of 649,020 individuals between ages 14 and 40 years from different neighborhoods in Toronto.
Green space was calculated using geospatial data of all public parks and green spaces in the city; data were drawn from the Urban Health Equity Assessment and Response Tool.
Over a 10-year period, 4,841 participants were diagnosed with schizophrenia.
Those who lived in neighborhoods with the least amount of green space were significantly more likely to develop schizophrenia than those who lived in areas with the most green space, even after adjusting for age, sex, and neighborhood-level marginalization (adjusted incidence rate ratio, 1.24; 95% confidence interval, 1.06-1.45).
Overall, schizophrenia risk was also elevated in men vs. women (adjusted IRR, 1.59; 95% CI, 1.50-1.68). Those living in areas with moderate amounts of green space did not have an increased schizophrenia risk.
“We found that residing in an area with the lowest amount of green space was associated with an increased risk of developing schizophrenia, independent of other sociodemographic and socioenvironmental factors,” the researchers note. “The underlying mechanism at play is unknown and requires further study.”
One possibility, they added, is that exposure to green space may reduce the risk of air pollution, which other studies have suggested may be associated with increased schizophrenia risk.
The new study builds on a 2018 report from Denmark that showed a 52% increased risk of psychotic disorders in adulthood among people who spent their childhood in neighborhoods with little green space.
Important, longitudinal data
Commenting on the findings, John Torous, MD, director of digital psychiatry at Beth Israel Deaconess Medical Center, Boston, said the study provides important longitudinal data.
“The 10-year duration of the study and large sample size make the results very compelling and help confirm what has been thought about green space and risk of schizophrenia,” Dr. Torous said.
“Often, we think of green space at a very macro level,” he added. “This study is important because it shows us that green space matters on a block-by-block level just as much.”
The study was unfunded. The authors and Dr. Torous have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM CANADIAN JOURNAL OF PSYCHIATRY
‘Pandemic brain’ not limited to patients infected with COVID-19
The stress of living through a pandemic may cause brain inflammation even in those uninfected with SARS-CoV-2, a study suggests.
Healthy individuals who tested negative for the virus that causes COVID-19 had elevated levels of inflammatory markers known to be involved in depression, stress, and mental fatigue. The study indicates a possible link between pandemic-associated stressors and neuroimmune responses.
“The most important finding is the evidence of neuroinflammation in noninfected, otherwise healthy participants, which may explain the variety of sickness-behavior-like symptoms experienced by many during the pandemic,” lead author Ludovica Brusaferri, PhD, a postdoctoral research fellow at Massachusetts General Hospital and Harvard Medical School in Boston, told this news organization.
The study was published online Feb. 16 in Brain, Behavior, and Immunity.
Impact of pandemic stress?
Reports of psychological distress have increased considerably in the United States during the pandemic, including among those not infected with SARS-CoV-2.
To better understand the effects of the pandemic on brain and mental health, the investigators retrospectively analyzed data collected from 57 people who were enrolled as control subjects for unrelated studies before the pandemic began.
They also enrolled 15 people living in Massachusetts during that state’s 2-month lockdown/stay-at-home order from March to May 2020, all of whom had tested negative for COVID-19 antibodies.
The investigators used PET and MRI imaging and blood sample analyses to investigate whether there were any differences in the brains of healthy people before and during the pandemic following the lockdown.
Compared with the control group, the pandemic cohort had elevated levels of 18 kDa translocator protein (TSPO) and myoinositol, inflammatory markers in the brain. Increased TSPO has been associated with depression and suicidal thoughts and elevated myoinositol has been linked to schizophrenia.
Blood levels of two inflammatory markers, interleukin-16 and monocyte chemoattractant protein-1, were also elevated in the pandemic cohort, although to a lesser extent.
TSPO levels were especially high in participants in the pandemic cohort who reported moodiness and mental and physical fatigue, compared with those reporting few or no symptoms.
“These findings provide support to a role for neuroinflammation in stress, an observation that, if replicated, might help guide the development of novel treatments focused on the reduction of brain inflammation,” study author Marco Loggia, PhD, codirector of the Center for Integrative Pain NeuroImaging at Mass General and Harvard Medical School, told this news organization.
Although the data showing increased neuroinflammation were collected when participants were under a stay-at-home order, the researchers said it’s not clear that this was the cause.
“We’re not saying it is the lockdown that was causing it,” Dr. Loggia said. “It could have been social isolation, changes in diet, or changes in exercise patterns. We don’t know exactly what the cause was so, maybe.”
A significant contribution
Commenting on the study for this news organization, Ning Quan, PhD, professor of biomedical science at Florida Atlantic University, Boca Raton, said although questions remain, the findings offer valuable information.
“This study contributes significantly to our understanding of how pandemic stress might impact our brain and behavior,” Dr. Quan said. “The main advance that this paper provides is that fatigue or brain fog could be induced in individuals with COVID infection during the pandemic.”
However, Dr. Quan added, the study has a number of limitations, including a small sample size, which makes it difficult to generalize the results.
“Another issue is the subjects of the study all lived in Massachusetts,” Dr. Quan added. “Subjects from different states or different countries could yield different results.”
The study was funded by the National Institutes of Health and by the Landreth Family Foundation. The study authors and Dr. Quan have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The stress of living through a pandemic may cause brain inflammation even in those uninfected with SARS-CoV-2, a study suggests.
Healthy individuals who tested negative for the virus that causes COVID-19 had elevated levels of inflammatory markers known to be involved in depression, stress, and mental fatigue. The study indicates a possible link between pandemic-associated stressors and neuroimmune responses.
“The most important finding is the evidence of neuroinflammation in noninfected, otherwise healthy participants, which may explain the variety of sickness-behavior-like symptoms experienced by many during the pandemic,” lead author Ludovica Brusaferri, PhD, a postdoctoral research fellow at Massachusetts General Hospital and Harvard Medical School in Boston, told this news organization.
The study was published online Feb. 16 in Brain, Behavior, and Immunity.
Impact of pandemic stress?
Reports of psychological distress have increased considerably in the United States during the pandemic, including among those not infected with SARS-CoV-2.
To better understand the effects of the pandemic on brain and mental health, the investigators retrospectively analyzed data collected from 57 people who were enrolled as control subjects for unrelated studies before the pandemic began.
They also enrolled 15 people living in Massachusetts during that state’s 2-month lockdown/stay-at-home order from March to May 2020, all of whom had tested negative for COVID-19 antibodies.
The investigators used PET and MRI imaging and blood sample analyses to investigate whether there were any differences in the brains of healthy people before and during the pandemic following the lockdown.
Compared with the control group, the pandemic cohort had elevated levels of 18 kDa translocator protein (TSPO) and myoinositol, inflammatory markers in the brain. Increased TSPO has been associated with depression and suicidal thoughts and elevated myoinositol has been linked to schizophrenia.
Blood levels of two inflammatory markers, interleukin-16 and monocyte chemoattractant protein-1, were also elevated in the pandemic cohort, although to a lesser extent.
TSPO levels were especially high in participants in the pandemic cohort who reported moodiness and mental and physical fatigue, compared with those reporting few or no symptoms.
“These findings provide support to a role for neuroinflammation in stress, an observation that, if replicated, might help guide the development of novel treatments focused on the reduction of brain inflammation,” study author Marco Loggia, PhD, codirector of the Center for Integrative Pain NeuroImaging at Mass General and Harvard Medical School, told this news organization.
Although the data showing increased neuroinflammation were collected when participants were under a stay-at-home order, the researchers said it’s not clear that this was the cause.
“We’re not saying it is the lockdown that was causing it,” Dr. Loggia said. “It could have been social isolation, changes in diet, or changes in exercise patterns. We don’t know exactly what the cause was so, maybe.”
A significant contribution
Commenting on the study for this news organization, Ning Quan, PhD, professor of biomedical science at Florida Atlantic University, Boca Raton, said although questions remain, the findings offer valuable information.
“This study contributes significantly to our understanding of how pandemic stress might impact our brain and behavior,” Dr. Quan said. “The main advance that this paper provides is that fatigue or brain fog could be induced in individuals with COVID infection during the pandemic.”
However, Dr. Quan added, the study has a number of limitations, including a small sample size, which makes it difficult to generalize the results.
“Another issue is the subjects of the study all lived in Massachusetts,” Dr. Quan added. “Subjects from different states or different countries could yield different results.”
The study was funded by the National Institutes of Health and by the Landreth Family Foundation. The study authors and Dr. Quan have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The stress of living through a pandemic may cause brain inflammation even in those uninfected with SARS-CoV-2, a study suggests.
Healthy individuals who tested negative for the virus that causes COVID-19 had elevated levels of inflammatory markers known to be involved in depression, stress, and mental fatigue. The study indicates a possible link between pandemic-associated stressors and neuroimmune responses.
“The most important finding is the evidence of neuroinflammation in noninfected, otherwise healthy participants, which may explain the variety of sickness-behavior-like symptoms experienced by many during the pandemic,” lead author Ludovica Brusaferri, PhD, a postdoctoral research fellow at Massachusetts General Hospital and Harvard Medical School in Boston, told this news organization.
The study was published online Feb. 16 in Brain, Behavior, and Immunity.
Impact of pandemic stress?
Reports of psychological distress have increased considerably in the United States during the pandemic, including among those not infected with SARS-CoV-2.
To better understand the effects of the pandemic on brain and mental health, the investigators retrospectively analyzed data collected from 57 people who were enrolled as control subjects for unrelated studies before the pandemic began.
They also enrolled 15 people living in Massachusetts during that state’s 2-month lockdown/stay-at-home order from March to May 2020, all of whom had tested negative for COVID-19 antibodies.
The investigators used PET and MRI imaging and blood sample analyses to investigate whether there were any differences in the brains of healthy people before and during the pandemic following the lockdown.
Compared with the control group, the pandemic cohort had elevated levels of 18 kDa translocator protein (TSPO) and myoinositol, inflammatory markers in the brain. Increased TSPO has been associated with depression and suicidal thoughts and elevated myoinositol has been linked to schizophrenia.
Blood levels of two inflammatory markers, interleukin-16 and monocyte chemoattractant protein-1, were also elevated in the pandemic cohort, although to a lesser extent.
TSPO levels were especially high in participants in the pandemic cohort who reported moodiness and mental and physical fatigue, compared with those reporting few or no symptoms.
“These findings provide support to a role for neuroinflammation in stress, an observation that, if replicated, might help guide the development of novel treatments focused on the reduction of brain inflammation,” study author Marco Loggia, PhD, codirector of the Center for Integrative Pain NeuroImaging at Mass General and Harvard Medical School, told this news organization.
Although the data showing increased neuroinflammation were collected when participants were under a stay-at-home order, the researchers said it’s not clear that this was the cause.
“We’re not saying it is the lockdown that was causing it,” Dr. Loggia said. “It could have been social isolation, changes in diet, or changes in exercise patterns. We don’t know exactly what the cause was so, maybe.”
A significant contribution
Commenting on the study for this news organization, Ning Quan, PhD, professor of biomedical science at Florida Atlantic University, Boca Raton, said although questions remain, the findings offer valuable information.
“This study contributes significantly to our understanding of how pandemic stress might impact our brain and behavior,” Dr. Quan said. “The main advance that this paper provides is that fatigue or brain fog could be induced in individuals with COVID infection during the pandemic.”
However, Dr. Quan added, the study has a number of limitations, including a small sample size, which makes it difficult to generalize the results.
“Another issue is the subjects of the study all lived in Massachusetts,” Dr. Quan added. “Subjects from different states or different countries could yield different results.”
The study was funded by the National Institutes of Health and by the Landreth Family Foundation. The study authors and Dr. Quan have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM BRAIN, BEHAVIOR, AND IMMUNITY