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CTE common among young athletes in largest brain donor study
Analysis of brain tissue from athletes who were exposed to RHIs and died before the age of 30 revealed neuropathological evidence of shrinkage of the brain and microscopic changes that indicate a breach of the blood-brain barrier. The case series also identified the first known American female athlete with CTE.
Nearly all of those with CTE had a mild form of the disease and 71% played only at the amateur level in youth, high school, or college sports.
“A lot of people think CTE is a result of high-level, professional play such as football, ice hockey, and boxing, but it can affect amateur athletes and can affect people at a young age,” lead author Ann McKee, MD, professor of neurology and pathology and director of the Chronic Traumatic Encephalopathy Center at Boston University, said in an interview.
The findings were published online in JAMA Neurology.
A rare look
Brain donation at younger ages is rare, so most of what is known about CTE comes from studies in older athletes.
“We’ve always known that young people could develop this disease early after just amateur high school, youth, and college exposure, but this is the largest study of donor brains at this age,” Dr. McKee said.
The case series included 152 brains of athletes who played contact sports, experienced RHIs, and died before age 30. The tissues are part of the Understanding Neurologic Injury and Traumatic Encephalopathy (UNITE) Brain Bank and were donated between February 2008 and September 2022.
Researchers reviewed the donors’ medical records and conducted retrospective interviews with the donors’ next of kin to assess cognitive symptoms, mood disturbances, and neurobehavioral issues.
Donors died between the ages of 13 and 29 years, 92.8% were male and 73% were White. In 57.2% of the cases, suicide was the cause of death, with no difference between those with or without CTE.
CTE was neuropathologically diagnosed in 41.4% of athletes, using diagnostic criteria developed by the National Institute of Neurological Disorders and Stroke.
More than 95% had mild CTE. Diagnosis was associated with older age (mean difference, 3.92 years; P < .001) and significantly more years of exposure to contact sports (11.6 vs. 8.8 years).
Among those with CTE, 71.4% played amateur sports, including football (60.9%), soccer (17.2%), hockey (7.8%), and wrestling (7%).
The cohort includes the first known American female athlete with CTE. Recruiting female brain donors has always been a challenge, Dr. McKee said. In this study, females comprised about 7% of the entire cohort and tended to be younger and play fewer years of a sport, compared with their male counterparts. All of that could lower their risk for CTE, Dr. McKee said.
“We don’t have enough brain donations to make any comments about differences between the genders, but we’ve always known that women can develop CTE,” she said. “It’s been reported after domestic violence and in an autistic woman who was a headbanger, so it was just a matter of time before we found our first case.”
Early stage of CTE?
Neuropathological analysis revealed neuronal p-tau aggregates in all CTE cases, a hallmark of the disease.
Young athletes with CTE had significantly more ventricular dilatation, suggesting atrophy or shrinkage of the brain, and more cavum septum pellucidum.
“I was surprised that even at this very young age group we could see structural changes to the gross pathology,” Dr. McKee said.
Investigators also found evidence of perivascular macrophages in the deep white matter, a microscopic change that correlated with CTE and years of play and indicates a breach of the blood-brain barrier that could allow pro-inflammatory molecules to enter the brain, setting up a neuroinflammatory response.
“Neuroinflammation is a very early change after repetitive head impacts, as well as in CTE,” Dr. McKee said. “This may be one of the mechanisms by which the inflammation starts, meaning microvascular injury might be an integral part of the pathogenesis of CTE.”
A message for clinicians
All athletes had symptoms of mood and neurobehavioral dysfunction common in people with RHIs. There were no significant differences in those clinical symptoms based on CTE diagnosis, which is likely related to the retrospective nature of the clinical evaluations, Dr. McKee said.
While the study leaves many questions about CTE in younger athletes unanswered, there is a message for clinicians and for patients in the findings, she said.
For clinicians, it’s important to note that “this young population of amateur athletes can be very symptomatic, and in all likelihood, a lot of these symptoms are reversible with proper care and management,” Dr. McKee said.
“For individual athletes, it’s important to note that 58% of this cohort did not have CTE, so just because you have these symptoms is not an indication that you have a neurodegenerative disease,” she added.
The study was funded by Andlinger Foundation, the National Football League, Mac Parkman Foundation, National Operating Committee on Standards for Athletic Equipment, and the Nick and Lynn Buoniconti Foundation, World Wrestling Entertainment, Alzheimer’s Association, National Institutes of Health, Concussion Legacy Foundation, U.S. Department of Defense and the U.S. Department of Veterans Affairs. Dr. McKee is a member of the Mackey-White Health and Safety Committee of the National Football League Players Association and reported receiving grants from the NIH and Department of Veteran Affairs and other funding from the Buoniconti Foundation and Mac Parkman Foundation during the conduct of the study.
A version of this article appeared on Medscape.com.
Analysis of brain tissue from athletes who were exposed to RHIs and died before the age of 30 revealed neuropathological evidence of shrinkage of the brain and microscopic changes that indicate a breach of the blood-brain barrier. The case series also identified the first known American female athlete with CTE.
Nearly all of those with CTE had a mild form of the disease and 71% played only at the amateur level in youth, high school, or college sports.
“A lot of people think CTE is a result of high-level, professional play such as football, ice hockey, and boxing, but it can affect amateur athletes and can affect people at a young age,” lead author Ann McKee, MD, professor of neurology and pathology and director of the Chronic Traumatic Encephalopathy Center at Boston University, said in an interview.
The findings were published online in JAMA Neurology.
A rare look
Brain donation at younger ages is rare, so most of what is known about CTE comes from studies in older athletes.
“We’ve always known that young people could develop this disease early after just amateur high school, youth, and college exposure, but this is the largest study of donor brains at this age,” Dr. McKee said.
The case series included 152 brains of athletes who played contact sports, experienced RHIs, and died before age 30. The tissues are part of the Understanding Neurologic Injury and Traumatic Encephalopathy (UNITE) Brain Bank and were donated between February 2008 and September 2022.
Researchers reviewed the donors’ medical records and conducted retrospective interviews with the donors’ next of kin to assess cognitive symptoms, mood disturbances, and neurobehavioral issues.
Donors died between the ages of 13 and 29 years, 92.8% were male and 73% were White. In 57.2% of the cases, suicide was the cause of death, with no difference between those with or without CTE.
CTE was neuropathologically diagnosed in 41.4% of athletes, using diagnostic criteria developed by the National Institute of Neurological Disorders and Stroke.
More than 95% had mild CTE. Diagnosis was associated with older age (mean difference, 3.92 years; P < .001) and significantly more years of exposure to contact sports (11.6 vs. 8.8 years).
Among those with CTE, 71.4% played amateur sports, including football (60.9%), soccer (17.2%), hockey (7.8%), and wrestling (7%).
The cohort includes the first known American female athlete with CTE. Recruiting female brain donors has always been a challenge, Dr. McKee said. In this study, females comprised about 7% of the entire cohort and tended to be younger and play fewer years of a sport, compared with their male counterparts. All of that could lower their risk for CTE, Dr. McKee said.
“We don’t have enough brain donations to make any comments about differences between the genders, but we’ve always known that women can develop CTE,” she said. “It’s been reported after domestic violence and in an autistic woman who was a headbanger, so it was just a matter of time before we found our first case.”
Early stage of CTE?
Neuropathological analysis revealed neuronal p-tau aggregates in all CTE cases, a hallmark of the disease.
Young athletes with CTE had significantly more ventricular dilatation, suggesting atrophy or shrinkage of the brain, and more cavum septum pellucidum.
“I was surprised that even at this very young age group we could see structural changes to the gross pathology,” Dr. McKee said.
Investigators also found evidence of perivascular macrophages in the deep white matter, a microscopic change that correlated with CTE and years of play and indicates a breach of the blood-brain barrier that could allow pro-inflammatory molecules to enter the brain, setting up a neuroinflammatory response.
“Neuroinflammation is a very early change after repetitive head impacts, as well as in CTE,” Dr. McKee said. “This may be one of the mechanisms by which the inflammation starts, meaning microvascular injury might be an integral part of the pathogenesis of CTE.”
A message for clinicians
All athletes had symptoms of mood and neurobehavioral dysfunction common in people with RHIs. There were no significant differences in those clinical symptoms based on CTE diagnosis, which is likely related to the retrospective nature of the clinical evaluations, Dr. McKee said.
While the study leaves many questions about CTE in younger athletes unanswered, there is a message for clinicians and for patients in the findings, she said.
For clinicians, it’s important to note that “this young population of amateur athletes can be very symptomatic, and in all likelihood, a lot of these symptoms are reversible with proper care and management,” Dr. McKee said.
“For individual athletes, it’s important to note that 58% of this cohort did not have CTE, so just because you have these symptoms is not an indication that you have a neurodegenerative disease,” she added.
The study was funded by Andlinger Foundation, the National Football League, Mac Parkman Foundation, National Operating Committee on Standards for Athletic Equipment, and the Nick and Lynn Buoniconti Foundation, World Wrestling Entertainment, Alzheimer’s Association, National Institutes of Health, Concussion Legacy Foundation, U.S. Department of Defense and the U.S. Department of Veterans Affairs. Dr. McKee is a member of the Mackey-White Health and Safety Committee of the National Football League Players Association and reported receiving grants from the NIH and Department of Veteran Affairs and other funding from the Buoniconti Foundation and Mac Parkman Foundation during the conduct of the study.
A version of this article appeared on Medscape.com.
Analysis of brain tissue from athletes who were exposed to RHIs and died before the age of 30 revealed neuropathological evidence of shrinkage of the brain and microscopic changes that indicate a breach of the blood-brain barrier. The case series also identified the first known American female athlete with CTE.
Nearly all of those with CTE had a mild form of the disease and 71% played only at the amateur level in youth, high school, or college sports.
“A lot of people think CTE is a result of high-level, professional play such as football, ice hockey, and boxing, but it can affect amateur athletes and can affect people at a young age,” lead author Ann McKee, MD, professor of neurology and pathology and director of the Chronic Traumatic Encephalopathy Center at Boston University, said in an interview.
The findings were published online in JAMA Neurology.
A rare look
Brain donation at younger ages is rare, so most of what is known about CTE comes from studies in older athletes.
“We’ve always known that young people could develop this disease early after just amateur high school, youth, and college exposure, but this is the largest study of donor brains at this age,” Dr. McKee said.
The case series included 152 brains of athletes who played contact sports, experienced RHIs, and died before age 30. The tissues are part of the Understanding Neurologic Injury and Traumatic Encephalopathy (UNITE) Brain Bank and were donated between February 2008 and September 2022.
Researchers reviewed the donors’ medical records and conducted retrospective interviews with the donors’ next of kin to assess cognitive symptoms, mood disturbances, and neurobehavioral issues.
Donors died between the ages of 13 and 29 years, 92.8% were male and 73% were White. In 57.2% of the cases, suicide was the cause of death, with no difference between those with or without CTE.
CTE was neuropathologically diagnosed in 41.4% of athletes, using diagnostic criteria developed by the National Institute of Neurological Disorders and Stroke.
More than 95% had mild CTE. Diagnosis was associated with older age (mean difference, 3.92 years; P < .001) and significantly more years of exposure to contact sports (11.6 vs. 8.8 years).
Among those with CTE, 71.4% played amateur sports, including football (60.9%), soccer (17.2%), hockey (7.8%), and wrestling (7%).
The cohort includes the first known American female athlete with CTE. Recruiting female brain donors has always been a challenge, Dr. McKee said. In this study, females comprised about 7% of the entire cohort and tended to be younger and play fewer years of a sport, compared with their male counterparts. All of that could lower their risk for CTE, Dr. McKee said.
“We don’t have enough brain donations to make any comments about differences between the genders, but we’ve always known that women can develop CTE,” she said. “It’s been reported after domestic violence and in an autistic woman who was a headbanger, so it was just a matter of time before we found our first case.”
Early stage of CTE?
Neuropathological analysis revealed neuronal p-tau aggregates in all CTE cases, a hallmark of the disease.
Young athletes with CTE had significantly more ventricular dilatation, suggesting atrophy or shrinkage of the brain, and more cavum septum pellucidum.
“I was surprised that even at this very young age group we could see structural changes to the gross pathology,” Dr. McKee said.
Investigators also found evidence of perivascular macrophages in the deep white matter, a microscopic change that correlated with CTE and years of play and indicates a breach of the blood-brain barrier that could allow pro-inflammatory molecules to enter the brain, setting up a neuroinflammatory response.
“Neuroinflammation is a very early change after repetitive head impacts, as well as in CTE,” Dr. McKee said. “This may be one of the mechanisms by which the inflammation starts, meaning microvascular injury might be an integral part of the pathogenesis of CTE.”
A message for clinicians
All athletes had symptoms of mood and neurobehavioral dysfunction common in people with RHIs. There were no significant differences in those clinical symptoms based on CTE diagnosis, which is likely related to the retrospective nature of the clinical evaluations, Dr. McKee said.
While the study leaves many questions about CTE in younger athletes unanswered, there is a message for clinicians and for patients in the findings, she said.
For clinicians, it’s important to note that “this young population of amateur athletes can be very symptomatic, and in all likelihood, a lot of these symptoms are reversible with proper care and management,” Dr. McKee said.
“For individual athletes, it’s important to note that 58% of this cohort did not have CTE, so just because you have these symptoms is not an indication that you have a neurodegenerative disease,” she added.
The study was funded by Andlinger Foundation, the National Football League, Mac Parkman Foundation, National Operating Committee on Standards for Athletic Equipment, and the Nick and Lynn Buoniconti Foundation, World Wrestling Entertainment, Alzheimer’s Association, National Institutes of Health, Concussion Legacy Foundation, U.S. Department of Defense and the U.S. Department of Veterans Affairs. Dr. McKee is a member of the Mackey-White Health and Safety Committee of the National Football League Players Association and reported receiving grants from the NIH and Department of Veteran Affairs and other funding from the Buoniconti Foundation and Mac Parkman Foundation during the conduct of the study.
A version of this article appeared on Medscape.com.
Could retinal changes be a harbinger of Parkinson’s?
Changes in retinal tissues known to be associated with Parkinson’s disease (PD) may occur up to 7 years before clinical symptoms of the disease appear, a new study suggests.
Researchers used artificial intelligence (AI) to analyze data from two population-level data sets and the world’s largest database of retinal images and associated clinical data to detect the retinal changes in patients with PD and in healthy individuals who developed the disease years later.
Prior research had shown that PD is associated with a thinning of the ganglion cell-inner plexiform layer (GCIPL) in the retina, something that investigators confirmed in this new study. But they also identified changes in the inner nuclear layer (INL), which is a new finding.
The study is the largest to date on retinal markers in PD and the first to show these changes in living patients.
“I think we are still several years away from converting these findings into individual level prediction for patients,” lead author, Siegfried Wagner, MD, MsC, Honorary Clinical Senior Research Fellow at Moorfields Eye Hospital and University College of London Institute of Ophthalmology in London, told this news organization. “The most important takeaway is that there are observable differences in the retina of individuals who go on to develop Parkinson’s disease.”
The findings were published online in Neurology.
Another look at OCT
Researchers used data from retinal eye scans taken by optical coherence tomography (OCT), a noninvasive three-dimensional imaging technology that is widely used by opticians.
Other studies have used OCT to detect retinal changes in multiple sclerosis and cognitive decline.
For this research, investigators identified markers in people with PD using ophthalmic imaging data from 700 patients and 105,770 controls who participated in the retrospective AlzEye study.
After adjustment for age, sex, ethnicity, hypertension, and diabetes, individuals with PD had significantly thinner GCIPL and reduced thickness of the INL.
To evaluate retinal changes in patients before a PD diagnosis, researchers then turned to 50,405 participants in the UK Biobank with no history of PD who received a retinal scan as part of their baseline visit. Of that group, 53 were diagnosed with PD during the study period.
Researchers found an association between new diagnoses of PD and reduced thickness of the GCIPL (hazard ratio [HR], 0.62; P = .002) and thinner INL, especially at the inferior subfield (HR, 0.66; P = .002). That association persisted even in people whose clinical symptoms developed within 2 years of the retinal scan.
“We wonder if the reduced INL thickness is indicating a direct dopaminergic impairment occurring within the inner retina,” Dr. Wagner said. “Dopaminergic amacrine cells only account for a small proportion of the cells in this layer but previous work in the laboratory shows observable abnormalities in Parkinson’s disease.”
Too early for diagnostics?
Commenting on the findings, Rebecca Gilbert, MD, PhD, chief scientific officer, American Parkinson Disease Association, noted that the changes in the retinal thickness identified in the study were too small to be useful in the clinic as a screening tool for early PD.
“In order for that to happen, the specificity and sensitivity needs to be established,” she said. “Both specificity and sensitivity need to be high enough so that the test can be used to give clinically meaningful results – and reliably tell an individual with PD that he or she does have the disease and individual without PD that he or she doesn’t have the disease.”
Authors of an accompanying editorial agreed. Valeria Koska, MD, and Philipp Albrecht, MD, both of Heinrich Heine University Düsseldorf in Germany, noted that though the effect sizes of retinal changes were small, the study “sets new standards for the role of retinal morphology as potential biomarker in neurodegenerative disease.”
The study was funded by Fight for Sight UK, Medical Research Council, UK Research & Innovation, Basque Health Department, and the Wellcome Trust Study. Dr. Wagner reported funding from the Medical Research Council and the Rank Prize. Dr. Gilbert is employed by the American Parkinson Disease Association. Dr. Albrecht has received grant and personal fees and nonfinancial support from Allergan, Biogen, Celgene, Ipsen, Janssen Cilag, Merck, Merz Pharmaceuticals, Novartis, Roche, and Teva, outside the submitted work. Dr. Koska reported no relevant disclosures.
A version of this article appeared on Medscape.com.
Changes in retinal tissues known to be associated with Parkinson’s disease (PD) may occur up to 7 years before clinical symptoms of the disease appear, a new study suggests.
Researchers used artificial intelligence (AI) to analyze data from two population-level data sets and the world’s largest database of retinal images and associated clinical data to detect the retinal changes in patients with PD and in healthy individuals who developed the disease years later.
Prior research had shown that PD is associated with a thinning of the ganglion cell-inner plexiform layer (GCIPL) in the retina, something that investigators confirmed in this new study. But they also identified changes in the inner nuclear layer (INL), which is a new finding.
The study is the largest to date on retinal markers in PD and the first to show these changes in living patients.
“I think we are still several years away from converting these findings into individual level prediction for patients,” lead author, Siegfried Wagner, MD, MsC, Honorary Clinical Senior Research Fellow at Moorfields Eye Hospital and University College of London Institute of Ophthalmology in London, told this news organization. “The most important takeaway is that there are observable differences in the retina of individuals who go on to develop Parkinson’s disease.”
The findings were published online in Neurology.
Another look at OCT
Researchers used data from retinal eye scans taken by optical coherence tomography (OCT), a noninvasive three-dimensional imaging technology that is widely used by opticians.
Other studies have used OCT to detect retinal changes in multiple sclerosis and cognitive decline.
For this research, investigators identified markers in people with PD using ophthalmic imaging data from 700 patients and 105,770 controls who participated in the retrospective AlzEye study.
After adjustment for age, sex, ethnicity, hypertension, and diabetes, individuals with PD had significantly thinner GCIPL and reduced thickness of the INL.
To evaluate retinal changes in patients before a PD diagnosis, researchers then turned to 50,405 participants in the UK Biobank with no history of PD who received a retinal scan as part of their baseline visit. Of that group, 53 were diagnosed with PD during the study period.
Researchers found an association between new diagnoses of PD and reduced thickness of the GCIPL (hazard ratio [HR], 0.62; P = .002) and thinner INL, especially at the inferior subfield (HR, 0.66; P = .002). That association persisted even in people whose clinical symptoms developed within 2 years of the retinal scan.
“We wonder if the reduced INL thickness is indicating a direct dopaminergic impairment occurring within the inner retina,” Dr. Wagner said. “Dopaminergic amacrine cells only account for a small proportion of the cells in this layer but previous work in the laboratory shows observable abnormalities in Parkinson’s disease.”
Too early for diagnostics?
Commenting on the findings, Rebecca Gilbert, MD, PhD, chief scientific officer, American Parkinson Disease Association, noted that the changes in the retinal thickness identified in the study were too small to be useful in the clinic as a screening tool for early PD.
“In order for that to happen, the specificity and sensitivity needs to be established,” she said. “Both specificity and sensitivity need to be high enough so that the test can be used to give clinically meaningful results – and reliably tell an individual with PD that he or she does have the disease and individual without PD that he or she doesn’t have the disease.”
Authors of an accompanying editorial agreed. Valeria Koska, MD, and Philipp Albrecht, MD, both of Heinrich Heine University Düsseldorf in Germany, noted that though the effect sizes of retinal changes were small, the study “sets new standards for the role of retinal morphology as potential biomarker in neurodegenerative disease.”
The study was funded by Fight for Sight UK, Medical Research Council, UK Research & Innovation, Basque Health Department, and the Wellcome Trust Study. Dr. Wagner reported funding from the Medical Research Council and the Rank Prize. Dr. Gilbert is employed by the American Parkinson Disease Association. Dr. Albrecht has received grant and personal fees and nonfinancial support from Allergan, Biogen, Celgene, Ipsen, Janssen Cilag, Merck, Merz Pharmaceuticals, Novartis, Roche, and Teva, outside the submitted work. Dr. Koska reported no relevant disclosures.
A version of this article appeared on Medscape.com.
Changes in retinal tissues known to be associated with Parkinson’s disease (PD) may occur up to 7 years before clinical symptoms of the disease appear, a new study suggests.
Researchers used artificial intelligence (AI) to analyze data from two population-level data sets and the world’s largest database of retinal images and associated clinical data to detect the retinal changes in patients with PD and in healthy individuals who developed the disease years later.
Prior research had shown that PD is associated with a thinning of the ganglion cell-inner plexiform layer (GCIPL) in the retina, something that investigators confirmed in this new study. But they also identified changes in the inner nuclear layer (INL), which is a new finding.
The study is the largest to date on retinal markers in PD and the first to show these changes in living patients.
“I think we are still several years away from converting these findings into individual level prediction for patients,” lead author, Siegfried Wagner, MD, MsC, Honorary Clinical Senior Research Fellow at Moorfields Eye Hospital and University College of London Institute of Ophthalmology in London, told this news organization. “The most important takeaway is that there are observable differences in the retina of individuals who go on to develop Parkinson’s disease.”
The findings were published online in Neurology.
Another look at OCT
Researchers used data from retinal eye scans taken by optical coherence tomography (OCT), a noninvasive three-dimensional imaging technology that is widely used by opticians.
Other studies have used OCT to detect retinal changes in multiple sclerosis and cognitive decline.
For this research, investigators identified markers in people with PD using ophthalmic imaging data from 700 patients and 105,770 controls who participated in the retrospective AlzEye study.
After adjustment for age, sex, ethnicity, hypertension, and diabetes, individuals with PD had significantly thinner GCIPL and reduced thickness of the INL.
To evaluate retinal changes in patients before a PD diagnosis, researchers then turned to 50,405 participants in the UK Biobank with no history of PD who received a retinal scan as part of their baseline visit. Of that group, 53 were diagnosed with PD during the study period.
Researchers found an association between new diagnoses of PD and reduced thickness of the GCIPL (hazard ratio [HR], 0.62; P = .002) and thinner INL, especially at the inferior subfield (HR, 0.66; P = .002). That association persisted even in people whose clinical symptoms developed within 2 years of the retinal scan.
“We wonder if the reduced INL thickness is indicating a direct dopaminergic impairment occurring within the inner retina,” Dr. Wagner said. “Dopaminergic amacrine cells only account for a small proportion of the cells in this layer but previous work in the laboratory shows observable abnormalities in Parkinson’s disease.”
Too early for diagnostics?
Commenting on the findings, Rebecca Gilbert, MD, PhD, chief scientific officer, American Parkinson Disease Association, noted that the changes in the retinal thickness identified in the study were too small to be useful in the clinic as a screening tool for early PD.
“In order for that to happen, the specificity and sensitivity needs to be established,” she said. “Both specificity and sensitivity need to be high enough so that the test can be used to give clinically meaningful results – and reliably tell an individual with PD that he or she does have the disease and individual without PD that he or she doesn’t have the disease.”
Authors of an accompanying editorial agreed. Valeria Koska, MD, and Philipp Albrecht, MD, both of Heinrich Heine University Düsseldorf in Germany, noted that though the effect sizes of retinal changes were small, the study “sets new standards for the role of retinal morphology as potential biomarker in neurodegenerative disease.”
The study was funded by Fight for Sight UK, Medical Research Council, UK Research & Innovation, Basque Health Department, and the Wellcome Trust Study. Dr. Wagner reported funding from the Medical Research Council and the Rank Prize. Dr. Gilbert is employed by the American Parkinson Disease Association. Dr. Albrecht has received grant and personal fees and nonfinancial support from Allergan, Biogen, Celgene, Ipsen, Janssen Cilag, Merck, Merz Pharmaceuticals, Novartis, Roche, and Teva, outside the submitted work. Dr. Koska reported no relevant disclosures.
A version of this article appeared on Medscape.com.
TBI tied to increased mental health diagnoses, time to suicide
Investigators also found that increases in new mental health diagnoses are significantly higher in soldiers with a history of TBI – in some cases, strikingly higher. For example, cases of substance use disorder rose by 100% among veterans with TBI compared to just 14.5% in those with no brain injury.
“We had had pieces of these findings for a long time but to be able to lay out this longitudinal story over time is the part that’s new and important to really switch the focus to people’s whole lives and things that happen over time, both psychological and physical,” lead author Lisa Brenner, PhD, director of the Veterans Health Administration (VHA) Rocky Mountain Mental Illness Research Education and Clinical Center, Aurora, Colo., said in an interview.
“If we take that life-course view, it’s a very different way about thinking about conceptualizing exposures and conceptualizing risk and it’s a different way of thinking about treatment and prevention,” added Dr. Brenner, professor of physical medicine and rehabilitation, psychiatry, and neurology at the University of Colorado, Aurora. “I think that definitely applies to civilian populations.”
The findings were published online in JAMA Network Open.
Largest, longest study to date
Researchers have long suspected that TBI and a higher rate of new mental illness and a shorter time to suicide are all somehow linked. But this study examined all three components longitudinally, in what is thought to be the largest and longest study on the topic to date, including more than 860,000 people who were followed for up to a decade.
Investigators studied health data from the Substance Use and Psychological Injury Combat Study database on 860,892 U.S. Army soldiers who returned from deployment in Iraq or Afghanistan between 2008 and 2014 and were 18-24 years old at the end of that deployment. They then examined new mental health diagnoses and suicide trends over time.
Nearly 109,000 (12.6%) experienced a TBI during deployment, and 2,695 had died by suicide through the end of 2018.
New-onset diagnoses of anxiety, mood disorders, posttraumatic stress disorder, alcohol use, and substance use disorder (SUD) after deployment were all more common in soldiers who experienced PTSD while serving compared with those with no history of TBI.
There was a 67.7% increase in mood disorders in participants with TBI compared with a 37.5% increase in those without TBI. The increase in new cases of alcohol use disorder was also greater in the TBI group (a 31.9% increase vs. a 10.3% increase).
But the sharpest difference was the increase in substance use disorder among those with TBI, which rose 100% compared with a 14.5% increase in solders with no history of TBI.
Sharp differences in time to suicide
Death by suicide was only slightly more common in those with TBI compared with those without (0.4% vs. 0.3%, respectively). But those with a brain injury committed suicide 21.3% sooner than did those without a head injury, after the researchers controlled for sex, age, race, ethnicity, and fiscal year of return from deployment.
Time to suicide was faster in those with a TBI and two or more new mental health diagnoses and fastest among those with TBI and a new SUD diagnosis, who took their own lives 62.8% faster than did those without a TBI.
The findings offer an important message to medical professionals in many different specialties, Dr. Brenner said.
“Folks in mental health probably have a lot of patients who have brain injury in their practice, and they don’t know it and that’s an important thing to know,” she said, adding that “neurologists should screen for depression and other mental health conditions and make sure those people have evidence-based treatments for those mental health conditions while they’re addressing the TBI-related symptoms.”
Applicable to civilians?
“The complex interplay between TBI, its potential effects on mental health, and risk of suicide remains a vexing focus of ongoing investigations and academic inquiry,” Ross Zafonte, DO, president of Spaulding Rehabilitation Hospital Network and professor and chair of physical medicine and rehabilitation at Harvard Medical School, Boston, and colleagues, wrote in an accompanying editorial.
The study builds on earlier work, they added, and praised the study’s longitudinal design and large cohort as key to the findings. The data on increased rates of new-onset substance use disorder, which was also associated with a faster time to suicide in the TBI group, were of particular interest.
“In this work, Brenner and colleagues identified substance use disorder as a key factor in faster time to suicide for active-duty service members with a history of TBI compared with those without TBI and theorized that a multiple stress or exposure burden may enhance risk,” they wrote. “This theory is reasonable and has been postulated among individuals with medical sequelae linked to TBI.”
However, the authors caution against applying these findings in military veterans to civilians.
“While this work is critical in the military population, caution should be given to avoid direct generalization to other populations, such as athletes, for whom the linkage to suicidal ideation is less understood,” they wrote.
The study was funded by National Institute of Mental Health and Office of the Director at National Institutes of Health. Dr. Brenner has received personal fees from Wolters Kluwer, Rand, American Psychological Association, and Oxford University Press and serves as a consultant to sports leagues via her university affiliation. Dr. Zafonte reported receiving royalties from Springer/Demos; serving as a member of the editorial boards of Journal of Neurotrauma and Frontiers in Neurology and scientific advisory boards of Myomo, Nanodiagnostics, Onecare.ai, and Kisbee; and evaluating patients in the MGH Brain and Body-TRUST Program, which is funded by the National Football League Players Association.
A version of this article first appeared on Medscape.com.
Investigators also found that increases in new mental health diagnoses are significantly higher in soldiers with a history of TBI – in some cases, strikingly higher. For example, cases of substance use disorder rose by 100% among veterans with TBI compared to just 14.5% in those with no brain injury.
“We had had pieces of these findings for a long time but to be able to lay out this longitudinal story over time is the part that’s new and important to really switch the focus to people’s whole lives and things that happen over time, both psychological and physical,” lead author Lisa Brenner, PhD, director of the Veterans Health Administration (VHA) Rocky Mountain Mental Illness Research Education and Clinical Center, Aurora, Colo., said in an interview.
“If we take that life-course view, it’s a very different way about thinking about conceptualizing exposures and conceptualizing risk and it’s a different way of thinking about treatment and prevention,” added Dr. Brenner, professor of physical medicine and rehabilitation, psychiatry, and neurology at the University of Colorado, Aurora. “I think that definitely applies to civilian populations.”
The findings were published online in JAMA Network Open.
Largest, longest study to date
Researchers have long suspected that TBI and a higher rate of new mental illness and a shorter time to suicide are all somehow linked. But this study examined all three components longitudinally, in what is thought to be the largest and longest study on the topic to date, including more than 860,000 people who were followed for up to a decade.
Investigators studied health data from the Substance Use and Psychological Injury Combat Study database on 860,892 U.S. Army soldiers who returned from deployment in Iraq or Afghanistan between 2008 and 2014 and were 18-24 years old at the end of that deployment. They then examined new mental health diagnoses and suicide trends over time.
Nearly 109,000 (12.6%) experienced a TBI during deployment, and 2,695 had died by suicide through the end of 2018.
New-onset diagnoses of anxiety, mood disorders, posttraumatic stress disorder, alcohol use, and substance use disorder (SUD) after deployment were all more common in soldiers who experienced PTSD while serving compared with those with no history of TBI.
There was a 67.7% increase in mood disorders in participants with TBI compared with a 37.5% increase in those without TBI. The increase in new cases of alcohol use disorder was also greater in the TBI group (a 31.9% increase vs. a 10.3% increase).
But the sharpest difference was the increase in substance use disorder among those with TBI, which rose 100% compared with a 14.5% increase in solders with no history of TBI.
Sharp differences in time to suicide
Death by suicide was only slightly more common in those with TBI compared with those without (0.4% vs. 0.3%, respectively). But those with a brain injury committed suicide 21.3% sooner than did those without a head injury, after the researchers controlled for sex, age, race, ethnicity, and fiscal year of return from deployment.
Time to suicide was faster in those with a TBI and two or more new mental health diagnoses and fastest among those with TBI and a new SUD diagnosis, who took their own lives 62.8% faster than did those without a TBI.
The findings offer an important message to medical professionals in many different specialties, Dr. Brenner said.
“Folks in mental health probably have a lot of patients who have brain injury in their practice, and they don’t know it and that’s an important thing to know,” she said, adding that “neurologists should screen for depression and other mental health conditions and make sure those people have evidence-based treatments for those mental health conditions while they’re addressing the TBI-related symptoms.”
Applicable to civilians?
“The complex interplay between TBI, its potential effects on mental health, and risk of suicide remains a vexing focus of ongoing investigations and academic inquiry,” Ross Zafonte, DO, president of Spaulding Rehabilitation Hospital Network and professor and chair of physical medicine and rehabilitation at Harvard Medical School, Boston, and colleagues, wrote in an accompanying editorial.
The study builds on earlier work, they added, and praised the study’s longitudinal design and large cohort as key to the findings. The data on increased rates of new-onset substance use disorder, which was also associated with a faster time to suicide in the TBI group, were of particular interest.
“In this work, Brenner and colleagues identified substance use disorder as a key factor in faster time to suicide for active-duty service members with a history of TBI compared with those without TBI and theorized that a multiple stress or exposure burden may enhance risk,” they wrote. “This theory is reasonable and has been postulated among individuals with medical sequelae linked to TBI.”
However, the authors caution against applying these findings in military veterans to civilians.
“While this work is critical in the military population, caution should be given to avoid direct generalization to other populations, such as athletes, for whom the linkage to suicidal ideation is less understood,” they wrote.
The study was funded by National Institute of Mental Health and Office of the Director at National Institutes of Health. Dr. Brenner has received personal fees from Wolters Kluwer, Rand, American Psychological Association, and Oxford University Press and serves as a consultant to sports leagues via her university affiliation. Dr. Zafonte reported receiving royalties from Springer/Demos; serving as a member of the editorial boards of Journal of Neurotrauma and Frontiers in Neurology and scientific advisory boards of Myomo, Nanodiagnostics, Onecare.ai, and Kisbee; and evaluating patients in the MGH Brain and Body-TRUST Program, which is funded by the National Football League Players Association.
A version of this article first appeared on Medscape.com.
Investigators also found that increases in new mental health diagnoses are significantly higher in soldiers with a history of TBI – in some cases, strikingly higher. For example, cases of substance use disorder rose by 100% among veterans with TBI compared to just 14.5% in those with no brain injury.
“We had had pieces of these findings for a long time but to be able to lay out this longitudinal story over time is the part that’s new and important to really switch the focus to people’s whole lives and things that happen over time, both psychological and physical,” lead author Lisa Brenner, PhD, director of the Veterans Health Administration (VHA) Rocky Mountain Mental Illness Research Education and Clinical Center, Aurora, Colo., said in an interview.
“If we take that life-course view, it’s a very different way about thinking about conceptualizing exposures and conceptualizing risk and it’s a different way of thinking about treatment and prevention,” added Dr. Brenner, professor of physical medicine and rehabilitation, psychiatry, and neurology at the University of Colorado, Aurora. “I think that definitely applies to civilian populations.”
The findings were published online in JAMA Network Open.
Largest, longest study to date
Researchers have long suspected that TBI and a higher rate of new mental illness and a shorter time to suicide are all somehow linked. But this study examined all three components longitudinally, in what is thought to be the largest and longest study on the topic to date, including more than 860,000 people who were followed for up to a decade.
Investigators studied health data from the Substance Use and Psychological Injury Combat Study database on 860,892 U.S. Army soldiers who returned from deployment in Iraq or Afghanistan between 2008 and 2014 and were 18-24 years old at the end of that deployment. They then examined new mental health diagnoses and suicide trends over time.
Nearly 109,000 (12.6%) experienced a TBI during deployment, and 2,695 had died by suicide through the end of 2018.
New-onset diagnoses of anxiety, mood disorders, posttraumatic stress disorder, alcohol use, and substance use disorder (SUD) after deployment were all more common in soldiers who experienced PTSD while serving compared with those with no history of TBI.
There was a 67.7% increase in mood disorders in participants with TBI compared with a 37.5% increase in those without TBI. The increase in new cases of alcohol use disorder was also greater in the TBI group (a 31.9% increase vs. a 10.3% increase).
But the sharpest difference was the increase in substance use disorder among those with TBI, which rose 100% compared with a 14.5% increase in solders with no history of TBI.
Sharp differences in time to suicide
Death by suicide was only slightly more common in those with TBI compared with those without (0.4% vs. 0.3%, respectively). But those with a brain injury committed suicide 21.3% sooner than did those without a head injury, after the researchers controlled for sex, age, race, ethnicity, and fiscal year of return from deployment.
Time to suicide was faster in those with a TBI and two or more new mental health diagnoses and fastest among those with TBI and a new SUD diagnosis, who took their own lives 62.8% faster than did those without a TBI.
The findings offer an important message to medical professionals in many different specialties, Dr. Brenner said.
“Folks in mental health probably have a lot of patients who have brain injury in their practice, and they don’t know it and that’s an important thing to know,” she said, adding that “neurologists should screen for depression and other mental health conditions and make sure those people have evidence-based treatments for those mental health conditions while they’re addressing the TBI-related symptoms.”
Applicable to civilians?
“The complex interplay between TBI, its potential effects on mental health, and risk of suicide remains a vexing focus of ongoing investigations and academic inquiry,” Ross Zafonte, DO, president of Spaulding Rehabilitation Hospital Network and professor and chair of physical medicine and rehabilitation at Harvard Medical School, Boston, and colleagues, wrote in an accompanying editorial.
The study builds on earlier work, they added, and praised the study’s longitudinal design and large cohort as key to the findings. The data on increased rates of new-onset substance use disorder, which was also associated with a faster time to suicide in the TBI group, were of particular interest.
“In this work, Brenner and colleagues identified substance use disorder as a key factor in faster time to suicide for active-duty service members with a history of TBI compared with those without TBI and theorized that a multiple stress or exposure burden may enhance risk,” they wrote. “This theory is reasonable and has been postulated among individuals with medical sequelae linked to TBI.”
However, the authors caution against applying these findings in military veterans to civilians.
“While this work is critical in the military population, caution should be given to avoid direct generalization to other populations, such as athletes, for whom the linkage to suicidal ideation is less understood,” they wrote.
The study was funded by National Institute of Mental Health and Office of the Director at National Institutes of Health. Dr. Brenner has received personal fees from Wolters Kluwer, Rand, American Psychological Association, and Oxford University Press and serves as a consultant to sports leagues via her university affiliation. Dr. Zafonte reported receiving royalties from Springer/Demos; serving as a member of the editorial boards of Journal of Neurotrauma and Frontiers in Neurology and scientific advisory boards of Myomo, Nanodiagnostics, Onecare.ai, and Kisbee; and evaluating patients in the MGH Brain and Body-TRUST Program, which is funded by the National Football League Players Association.
A version of this article first appeared on Medscape.com.
FROM JAMA NETWORK OPEN
Medications for opioid addiction significantly underutilized
Using data from the 2021 National Survey on Drug Use and Health (NSDUH), investigators found that of the 2.5 million adults with OUD in that year, 35.6% received some kind of substance abuse treatment, but only 22.3% received recommended medications for the condition, such as methadone, buprenorphine, or extended-release naltrexone.
“More than 80,000 people are dying of a drug overdose involving an opioid every year, while safe and effective medicines to treat opioid use disorder are sitting on the shelf unused,” senior author Wilson Compton, MD, MPE, deputy director of the National Institute on Drug Abuse (NIDA), said in a statement. “This study adds to the growing evidence that telehealth services are an important strategy that could help us bridge this gap, supporting the delivery of safe, effective, and lifesaving care for people with opioid use disorder.”
The findings were published online as a research letter in JAMA Network Open.
The study included 47,291 adults aged 18 years or older in the 2021 NSDUH, which provides nationally representative data of the U.S. civilian, noninstitutionalized population based on past-year OUD.
Men, people aged 35 years or older, urban residents, and non-Hispanic Whites were the most likely to receive medication for opioid use disorder (MOUD). MOUD use was more common among those who received substance use treatment via telehealth, those with severe OUD, and people with annual incomes below $50,000.
Black people, women, unemployed individuals, those living in rural areas, and people with past-year cannabis use disorder were less likely to receive MOUD.
“It is not a matter of whether we should address health disparities and inequities that many racial/ethnic minority groups face when trying to access substance use treatment,” lead author Christopher M. Jones, PharmD, MPH, DrPH, director of the National Center for Injury Prevention and Control in the Centers for Disease Control and Prevention, said in a statement. “We must address these issues if we hope to reverse the trend of increasing drug overdose deaths.”
The study was funded by the Centers for Disease Control and Prevention and the National Institutes of Health. Dr. Compton reported long-term stock holdings in General Electric, 3M Companies, and Pfizer outside the submitted work.
A version of this article first appeared on Medscape.com.
Using data from the 2021 National Survey on Drug Use and Health (NSDUH), investigators found that of the 2.5 million adults with OUD in that year, 35.6% received some kind of substance abuse treatment, but only 22.3% received recommended medications for the condition, such as methadone, buprenorphine, or extended-release naltrexone.
“More than 80,000 people are dying of a drug overdose involving an opioid every year, while safe and effective medicines to treat opioid use disorder are sitting on the shelf unused,” senior author Wilson Compton, MD, MPE, deputy director of the National Institute on Drug Abuse (NIDA), said in a statement. “This study adds to the growing evidence that telehealth services are an important strategy that could help us bridge this gap, supporting the delivery of safe, effective, and lifesaving care for people with opioid use disorder.”
The findings were published online as a research letter in JAMA Network Open.
The study included 47,291 adults aged 18 years or older in the 2021 NSDUH, which provides nationally representative data of the U.S. civilian, noninstitutionalized population based on past-year OUD.
Men, people aged 35 years or older, urban residents, and non-Hispanic Whites were the most likely to receive medication for opioid use disorder (MOUD). MOUD use was more common among those who received substance use treatment via telehealth, those with severe OUD, and people with annual incomes below $50,000.
Black people, women, unemployed individuals, those living in rural areas, and people with past-year cannabis use disorder were less likely to receive MOUD.
“It is not a matter of whether we should address health disparities and inequities that many racial/ethnic minority groups face when trying to access substance use treatment,” lead author Christopher M. Jones, PharmD, MPH, DrPH, director of the National Center for Injury Prevention and Control in the Centers for Disease Control and Prevention, said in a statement. “We must address these issues if we hope to reverse the trend of increasing drug overdose deaths.”
The study was funded by the Centers for Disease Control and Prevention and the National Institutes of Health. Dr. Compton reported long-term stock holdings in General Electric, 3M Companies, and Pfizer outside the submitted work.
A version of this article first appeared on Medscape.com.
Using data from the 2021 National Survey on Drug Use and Health (NSDUH), investigators found that of the 2.5 million adults with OUD in that year, 35.6% received some kind of substance abuse treatment, but only 22.3% received recommended medications for the condition, such as methadone, buprenorphine, or extended-release naltrexone.
“More than 80,000 people are dying of a drug overdose involving an opioid every year, while safe and effective medicines to treat opioid use disorder are sitting on the shelf unused,” senior author Wilson Compton, MD, MPE, deputy director of the National Institute on Drug Abuse (NIDA), said in a statement. “This study adds to the growing evidence that telehealth services are an important strategy that could help us bridge this gap, supporting the delivery of safe, effective, and lifesaving care for people with opioid use disorder.”
The findings were published online as a research letter in JAMA Network Open.
The study included 47,291 adults aged 18 years or older in the 2021 NSDUH, which provides nationally representative data of the U.S. civilian, noninstitutionalized population based on past-year OUD.
Men, people aged 35 years or older, urban residents, and non-Hispanic Whites were the most likely to receive medication for opioid use disorder (MOUD). MOUD use was more common among those who received substance use treatment via telehealth, those with severe OUD, and people with annual incomes below $50,000.
Black people, women, unemployed individuals, those living in rural areas, and people with past-year cannabis use disorder were less likely to receive MOUD.
“It is not a matter of whether we should address health disparities and inequities that many racial/ethnic minority groups face when trying to access substance use treatment,” lead author Christopher M. Jones, PharmD, MPH, DrPH, director of the National Center for Injury Prevention and Control in the Centers for Disease Control and Prevention, said in a statement. “We must address these issues if we hope to reverse the trend of increasing drug overdose deaths.”
The study was funded by the Centers for Disease Control and Prevention and the National Institutes of Health. Dr. Compton reported long-term stock holdings in General Electric, 3M Companies, and Pfizer outside the submitted work.
A version of this article first appeared on Medscape.com.
FROM JAMA NETWORK OPEN
Why genetic testing may be our best shot at progress in Parkinson’s disease
In 2017, Sanofi Genzyme launched a phase 2 clinical trial of a drug designed to target a specific genetic mutation in some patients with Parkinson’s disease. Researchers hoped the drug would slow or even stop disease progression.
Like many before it, the trial yielded disappointing results and the company shut it down in 2021. It was the latest in a string of unsuccessful clinical trials testing disease-modifying Parkinson’s disease drugs.
Although it failed, the Sanofi Genzyme study was different: It was the first to enroll patients with Parkinson’s disease who had a specific genotype and marked the earliest days of precision medicine and gene-specific drug development for the disease.
Once thought to play only a small role in a small number of patients with Parkinson’s disease,
“We’re about to enter this era of precision medicine for Parkinson’s disease, which makes genetic testing important,” said James Beck, PhD, senior vice president and chief scientific officer for the Parkinson’s Foundation.
“A number of companies have clinical trials or are in preparation for clinical trials to test some specific therapies that would depend upon people having a specific genetic mutation,” he said.
Today, at least four clinical trials of drugs that target specific Parkinson’s disease-related gene variants on LRRK2 and GBA are under way, and more are in the pipeline. Whether these drugs will be effective at modifying the course of the disease remains to be seen. First, the trials must enroll enough patients. And therein lies the challenge: Genetic testing isn’t part of routine Parkinson’s disease care and isn’t covered by most insurance policies. Most patients don’t know their genotype.
It’s a significant roadblock to the future of a precision medicine approach that is based on a patient’s individual genotype, which some experts argue offers the best shot at slowing disease progression.
“To enroll in clinical trials for precision drugs people with Parkinson’s disease have to be aware of their genetic status,” said Roy N. Alcalay, MD, chief of the movement disorders division at Tel Aviv Medical Center in Israel and part-time associate professor at Columbia University in New York. “How can a person with Parkinson’s and a LRRK2 mutation join a precision medicine trial for LRRK2 if she does not know she is a LRRK2 carrier?”
Free genetic testing
Previous studies have shown that some genetic variants increase the risk for Parkinson’s disease after exposure to environmental factors such as pesticides. Research has also shown that a patient’s genotype can predict survival time and that certain medications may prove more effective at slowing disease progression in patients with specific genotypes. All of this points to a significant role for genetics in a disorder that is rapidly increasing.
This makes expanding patient access to genetic testing even more important, Dr. Alcalay said, noting that it’s equally important that patients are informed of their genotype, something that doesn’t usually happen in blinded clinical trials.
To that end, Dr. Alcalay hopes a national genetics study he is leading will address access and need-to-know issues. PD GENEration, a project launched in 2019 by the Parkinson’s Foundation, offers patients free genetic testing for seven clinically relevant Parkinson’s disease-related genes.
Testing is done at home or in a nearby clinic and the results are shared with patients during a free genetic counseling session and with site investigators. Patient samples are stored in a genetic data bank that is open to researchers around the world.
“We surveyed clinical trialists in the Parkinson’s disease field prior to initiation of PD GENEration and estimated that over 90% of people with Parkinson’s disease prior to the effort were not aware of their genetic status,” Dr. Alcalay said.
“I think precision medicine in Parkinson’s disease will not happen without PD GENEration or similar efforts.”
‘Overwhelming’ patient interest
Participants in the study are screened for variants in seven genes known to be involved in Parkinson’s disease risk: GBA, LRRK2, PRKN, PINK1, SNCA, PARK7, and VPS35.
In less than 3 years, the study has already produced what is thought to be the largest genetic data bank of sequenced sets of Parkinson’s disease-risk genes made accessible to patients. Since the end of 2020, the first year of patient enrollment, the number of participants has increased from 676 to 10,515 and the number of participating clinical sites rose from 12 to 101.
The foundation has spent nearly $20 million on the project so far and plans to spend another $10 million to reach a goal of 15,000 patients. The study, which is funded by private donors, is so successful that the foundation has had to scale back enrollment.
“When we were at a peak, we had over 700 participants enrolling each month,” Dr. Beck said. Beginning in April, the program capped new sign-ups to 200 patients per month and created a waiting list for future enrollment. The waiting list is hundreds of patients long.
“The participants’ response to enroll in PD GENEration demonstrates there is an overwhelming interest by people with Parkinson’s disease to learn more about their genetic risk factors,” Dr. Alcalay said.
A research driver
Nearly 60% of participants enrolled so far are male and close to 80% are White. The average age is 69 years and 44% were diagnosed in the past 5 years. Close to 75% had never participated in a clinical trial.
Nearly 13% have tested positive for mutations on at least one of the seven target genes. Previous studies had suggested genetics were involved in only about 10% of cases.
The majority of those with positive results had early-onset Parkinson’s disease, high-risk ancestry, or a first-degree relative with the disease. However, 9% of people who tested positive weren’t in any of those categories.
Genetic information collected by the project is shared with the Global Parkinson’s Genetics Program (GP2), a resource program of the Aligning Science Across Parkinson’s initiative that is focused on the disease’s genetic architecture. Researchers around the world have access to GP2 data to study known gene variants and identify new ones.
PD GENEration participants can choose to be notified if they are carriers of gene variants discovered in the future.
“All DNA samples shared by participants are undergoing research-grade testing,” Dr. Beck said. “Not only do we want to be able to inform people with Parkinson’s disease about their genetic status, but we also want to be able to use this precious resource to further drive research into the genetics of Parkinson’s disease.”
Early success
Patient recruitment has long been one of the biggest challenges to any clinical trial’s success. Research suggests that 90% of all clinical trials fail to reach recruitment milestones in their allotted time frame and two-thirds of multicenter trials fold because too few patients sign up. Data from the Parkinson’s Foundation show that only about 1% of all patients with Parkinson’s disease participate in clinical trials.
Increasing those numbers is the primary goal of PD GENEration, Dr. Beck said. And there’s evidence it’s already paying off.
Earlier this year, one of the program’s participating clinical sites, Intermountain Health, in Salt Lake City, Utah, joined a phase 2 clinical trial of an experimental drug that targets a mutation on the GBA1 gene.
“One of the reasons we were able to participate was when we got the call about joining, we were able to say that we had patients with that specific gene mutation, and we could only say that because the patients had been genotyped through PD GENEration,” said Kathleen E. McKee, MD, director of movement disorders, associate medical director of neurosciences research, and PD GENEration principal investigator at Intermountain Health.
Since 2021, Dr. McKee has enrolled hundreds of patients in the foundation’s gene study and hopes to enroll even more. Few patients turn down the opportunity to participate, she added. Knowing their genotype has proven empowering for her patients, most of whom could not afford genetic testing on their own.
“Previously I would tell patients this is not going to change your immediate management,” Dr. McKee said. “Now I tell my patients that these trials are out there, it may actually change how I treat you and what I recommend.”
A version of this article appeared on Medscape.com.
In 2017, Sanofi Genzyme launched a phase 2 clinical trial of a drug designed to target a specific genetic mutation in some patients with Parkinson’s disease. Researchers hoped the drug would slow or even stop disease progression.
Like many before it, the trial yielded disappointing results and the company shut it down in 2021. It was the latest in a string of unsuccessful clinical trials testing disease-modifying Parkinson’s disease drugs.
Although it failed, the Sanofi Genzyme study was different: It was the first to enroll patients with Parkinson’s disease who had a specific genotype and marked the earliest days of precision medicine and gene-specific drug development for the disease.
Once thought to play only a small role in a small number of patients with Parkinson’s disease,
“We’re about to enter this era of precision medicine for Parkinson’s disease, which makes genetic testing important,” said James Beck, PhD, senior vice president and chief scientific officer for the Parkinson’s Foundation.
“A number of companies have clinical trials or are in preparation for clinical trials to test some specific therapies that would depend upon people having a specific genetic mutation,” he said.
Today, at least four clinical trials of drugs that target specific Parkinson’s disease-related gene variants on LRRK2 and GBA are under way, and more are in the pipeline. Whether these drugs will be effective at modifying the course of the disease remains to be seen. First, the trials must enroll enough patients. And therein lies the challenge: Genetic testing isn’t part of routine Parkinson’s disease care and isn’t covered by most insurance policies. Most patients don’t know their genotype.
It’s a significant roadblock to the future of a precision medicine approach that is based on a patient’s individual genotype, which some experts argue offers the best shot at slowing disease progression.
“To enroll in clinical trials for precision drugs people with Parkinson’s disease have to be aware of their genetic status,” said Roy N. Alcalay, MD, chief of the movement disorders division at Tel Aviv Medical Center in Israel and part-time associate professor at Columbia University in New York. “How can a person with Parkinson’s and a LRRK2 mutation join a precision medicine trial for LRRK2 if she does not know she is a LRRK2 carrier?”
Free genetic testing
Previous studies have shown that some genetic variants increase the risk for Parkinson’s disease after exposure to environmental factors such as pesticides. Research has also shown that a patient’s genotype can predict survival time and that certain medications may prove more effective at slowing disease progression in patients with specific genotypes. All of this points to a significant role for genetics in a disorder that is rapidly increasing.
This makes expanding patient access to genetic testing even more important, Dr. Alcalay said, noting that it’s equally important that patients are informed of their genotype, something that doesn’t usually happen in blinded clinical trials.
To that end, Dr. Alcalay hopes a national genetics study he is leading will address access and need-to-know issues. PD GENEration, a project launched in 2019 by the Parkinson’s Foundation, offers patients free genetic testing for seven clinically relevant Parkinson’s disease-related genes.
Testing is done at home or in a nearby clinic and the results are shared with patients during a free genetic counseling session and with site investigators. Patient samples are stored in a genetic data bank that is open to researchers around the world.
“We surveyed clinical trialists in the Parkinson’s disease field prior to initiation of PD GENEration and estimated that over 90% of people with Parkinson’s disease prior to the effort were not aware of their genetic status,” Dr. Alcalay said.
“I think precision medicine in Parkinson’s disease will not happen without PD GENEration or similar efforts.”
‘Overwhelming’ patient interest
Participants in the study are screened for variants in seven genes known to be involved in Parkinson’s disease risk: GBA, LRRK2, PRKN, PINK1, SNCA, PARK7, and VPS35.
In less than 3 years, the study has already produced what is thought to be the largest genetic data bank of sequenced sets of Parkinson’s disease-risk genes made accessible to patients. Since the end of 2020, the first year of patient enrollment, the number of participants has increased from 676 to 10,515 and the number of participating clinical sites rose from 12 to 101.
The foundation has spent nearly $20 million on the project so far and plans to spend another $10 million to reach a goal of 15,000 patients. The study, which is funded by private donors, is so successful that the foundation has had to scale back enrollment.
“When we were at a peak, we had over 700 participants enrolling each month,” Dr. Beck said. Beginning in April, the program capped new sign-ups to 200 patients per month and created a waiting list for future enrollment. The waiting list is hundreds of patients long.
“The participants’ response to enroll in PD GENEration demonstrates there is an overwhelming interest by people with Parkinson’s disease to learn more about their genetic risk factors,” Dr. Alcalay said.
A research driver
Nearly 60% of participants enrolled so far are male and close to 80% are White. The average age is 69 years and 44% were diagnosed in the past 5 years. Close to 75% had never participated in a clinical trial.
Nearly 13% have tested positive for mutations on at least one of the seven target genes. Previous studies had suggested genetics were involved in only about 10% of cases.
The majority of those with positive results had early-onset Parkinson’s disease, high-risk ancestry, or a first-degree relative with the disease. However, 9% of people who tested positive weren’t in any of those categories.
Genetic information collected by the project is shared with the Global Parkinson’s Genetics Program (GP2), a resource program of the Aligning Science Across Parkinson’s initiative that is focused on the disease’s genetic architecture. Researchers around the world have access to GP2 data to study known gene variants and identify new ones.
PD GENEration participants can choose to be notified if they are carriers of gene variants discovered in the future.
“All DNA samples shared by participants are undergoing research-grade testing,” Dr. Beck said. “Not only do we want to be able to inform people with Parkinson’s disease about their genetic status, but we also want to be able to use this precious resource to further drive research into the genetics of Parkinson’s disease.”
Early success
Patient recruitment has long been one of the biggest challenges to any clinical trial’s success. Research suggests that 90% of all clinical trials fail to reach recruitment milestones in their allotted time frame and two-thirds of multicenter trials fold because too few patients sign up. Data from the Parkinson’s Foundation show that only about 1% of all patients with Parkinson’s disease participate in clinical trials.
Increasing those numbers is the primary goal of PD GENEration, Dr. Beck said. And there’s evidence it’s already paying off.
Earlier this year, one of the program’s participating clinical sites, Intermountain Health, in Salt Lake City, Utah, joined a phase 2 clinical trial of an experimental drug that targets a mutation on the GBA1 gene.
“One of the reasons we were able to participate was when we got the call about joining, we were able to say that we had patients with that specific gene mutation, and we could only say that because the patients had been genotyped through PD GENEration,” said Kathleen E. McKee, MD, director of movement disorders, associate medical director of neurosciences research, and PD GENEration principal investigator at Intermountain Health.
Since 2021, Dr. McKee has enrolled hundreds of patients in the foundation’s gene study and hopes to enroll even more. Few patients turn down the opportunity to participate, she added. Knowing their genotype has proven empowering for her patients, most of whom could not afford genetic testing on their own.
“Previously I would tell patients this is not going to change your immediate management,” Dr. McKee said. “Now I tell my patients that these trials are out there, it may actually change how I treat you and what I recommend.”
A version of this article appeared on Medscape.com.
In 2017, Sanofi Genzyme launched a phase 2 clinical trial of a drug designed to target a specific genetic mutation in some patients with Parkinson’s disease. Researchers hoped the drug would slow or even stop disease progression.
Like many before it, the trial yielded disappointing results and the company shut it down in 2021. It was the latest in a string of unsuccessful clinical trials testing disease-modifying Parkinson’s disease drugs.
Although it failed, the Sanofi Genzyme study was different: It was the first to enroll patients with Parkinson’s disease who had a specific genotype and marked the earliest days of precision medicine and gene-specific drug development for the disease.
Once thought to play only a small role in a small number of patients with Parkinson’s disease,
“We’re about to enter this era of precision medicine for Parkinson’s disease, which makes genetic testing important,” said James Beck, PhD, senior vice president and chief scientific officer for the Parkinson’s Foundation.
“A number of companies have clinical trials or are in preparation for clinical trials to test some specific therapies that would depend upon people having a specific genetic mutation,” he said.
Today, at least four clinical trials of drugs that target specific Parkinson’s disease-related gene variants on LRRK2 and GBA are under way, and more are in the pipeline. Whether these drugs will be effective at modifying the course of the disease remains to be seen. First, the trials must enroll enough patients. And therein lies the challenge: Genetic testing isn’t part of routine Parkinson’s disease care and isn’t covered by most insurance policies. Most patients don’t know their genotype.
It’s a significant roadblock to the future of a precision medicine approach that is based on a patient’s individual genotype, which some experts argue offers the best shot at slowing disease progression.
“To enroll in clinical trials for precision drugs people with Parkinson’s disease have to be aware of their genetic status,” said Roy N. Alcalay, MD, chief of the movement disorders division at Tel Aviv Medical Center in Israel and part-time associate professor at Columbia University in New York. “How can a person with Parkinson’s and a LRRK2 mutation join a precision medicine trial for LRRK2 if she does not know she is a LRRK2 carrier?”
Free genetic testing
Previous studies have shown that some genetic variants increase the risk for Parkinson’s disease after exposure to environmental factors such as pesticides. Research has also shown that a patient’s genotype can predict survival time and that certain medications may prove more effective at slowing disease progression in patients with specific genotypes. All of this points to a significant role for genetics in a disorder that is rapidly increasing.
This makes expanding patient access to genetic testing even more important, Dr. Alcalay said, noting that it’s equally important that patients are informed of their genotype, something that doesn’t usually happen in blinded clinical trials.
To that end, Dr. Alcalay hopes a national genetics study he is leading will address access and need-to-know issues. PD GENEration, a project launched in 2019 by the Parkinson’s Foundation, offers patients free genetic testing for seven clinically relevant Parkinson’s disease-related genes.
Testing is done at home or in a nearby clinic and the results are shared with patients during a free genetic counseling session and with site investigators. Patient samples are stored in a genetic data bank that is open to researchers around the world.
“We surveyed clinical trialists in the Parkinson’s disease field prior to initiation of PD GENEration and estimated that over 90% of people with Parkinson’s disease prior to the effort were not aware of their genetic status,” Dr. Alcalay said.
“I think precision medicine in Parkinson’s disease will not happen without PD GENEration or similar efforts.”
‘Overwhelming’ patient interest
Participants in the study are screened for variants in seven genes known to be involved in Parkinson’s disease risk: GBA, LRRK2, PRKN, PINK1, SNCA, PARK7, and VPS35.
In less than 3 years, the study has already produced what is thought to be the largest genetic data bank of sequenced sets of Parkinson’s disease-risk genes made accessible to patients. Since the end of 2020, the first year of patient enrollment, the number of participants has increased from 676 to 10,515 and the number of participating clinical sites rose from 12 to 101.
The foundation has spent nearly $20 million on the project so far and plans to spend another $10 million to reach a goal of 15,000 patients. The study, which is funded by private donors, is so successful that the foundation has had to scale back enrollment.
“When we were at a peak, we had over 700 participants enrolling each month,” Dr. Beck said. Beginning in April, the program capped new sign-ups to 200 patients per month and created a waiting list for future enrollment. The waiting list is hundreds of patients long.
“The participants’ response to enroll in PD GENEration demonstrates there is an overwhelming interest by people with Parkinson’s disease to learn more about their genetic risk factors,” Dr. Alcalay said.
A research driver
Nearly 60% of participants enrolled so far are male and close to 80% are White. The average age is 69 years and 44% were diagnosed in the past 5 years. Close to 75% had never participated in a clinical trial.
Nearly 13% have tested positive for mutations on at least one of the seven target genes. Previous studies had suggested genetics were involved in only about 10% of cases.
The majority of those with positive results had early-onset Parkinson’s disease, high-risk ancestry, or a first-degree relative with the disease. However, 9% of people who tested positive weren’t in any of those categories.
Genetic information collected by the project is shared with the Global Parkinson’s Genetics Program (GP2), a resource program of the Aligning Science Across Parkinson’s initiative that is focused on the disease’s genetic architecture. Researchers around the world have access to GP2 data to study known gene variants and identify new ones.
PD GENEration participants can choose to be notified if they are carriers of gene variants discovered in the future.
“All DNA samples shared by participants are undergoing research-grade testing,” Dr. Beck said. “Not only do we want to be able to inform people with Parkinson’s disease about their genetic status, but we also want to be able to use this precious resource to further drive research into the genetics of Parkinson’s disease.”
Early success
Patient recruitment has long been one of the biggest challenges to any clinical trial’s success. Research suggests that 90% of all clinical trials fail to reach recruitment milestones in their allotted time frame and two-thirds of multicenter trials fold because too few patients sign up. Data from the Parkinson’s Foundation show that only about 1% of all patients with Parkinson’s disease participate in clinical trials.
Increasing those numbers is the primary goal of PD GENEration, Dr. Beck said. And there’s evidence it’s already paying off.
Earlier this year, one of the program’s participating clinical sites, Intermountain Health, in Salt Lake City, Utah, joined a phase 2 clinical trial of an experimental drug that targets a mutation on the GBA1 gene.
“One of the reasons we were able to participate was when we got the call about joining, we were able to say that we had patients with that specific gene mutation, and we could only say that because the patients had been genotyped through PD GENEration,” said Kathleen E. McKee, MD, director of movement disorders, associate medical director of neurosciences research, and PD GENEration principal investigator at Intermountain Health.
Since 2021, Dr. McKee has enrolled hundreds of patients in the foundation’s gene study and hopes to enroll even more. Few patients turn down the opportunity to participate, she added. Knowing their genotype has proven empowering for her patients, most of whom could not afford genetic testing on their own.
“Previously I would tell patients this is not going to change your immediate management,” Dr. McKee said. “Now I tell my patients that these trials are out there, it may actually change how I treat you and what I recommend.”
A version of this article appeared on Medscape.com.
No cognitive benefit from meditation, learning a language?
The findings are similar to results from another study published last year but are contrary to previous findings showing cognitive benefits for practicing meditation and learning a new language later in life.
“Based on existing literature, which has provided support for the efficacy of meditation and foreign language training in promoting cognition among older adults, perhaps the most surprising outcome of our study was the lack of evidence indicating cognitive benefits after 18 months of either intervention,” lead author Harriet Demnitz-King, MSc, a doctoral candidate at University College London, said in an interview. The findings were published online in JAMA Network Open.
Contradictory findings
For the study, 135 French-speaking, cognitively healthy people were randomized to English-language training, meditation, or a control group. All participants were aged 65 years or older, had been retired for at least 1 year, and had completed at least 7 years of education.
The meditation and English-language training interventions were both 18 months long and included a 2-hour weekly group session, daily home practice of at least 20 minutes, and 1-day intensive 5-hour practice.
Researchers found no significant changes in global cognition, episodic memory, executive function, or attention with either intervention, compared with the control group or to each other.
The findings contradict the researchers’ earlier work that found mindfulness meditation boosted cognitive function in older adults with subjective cognitive decline.
“We are still trying to reconcile these findings,” senior author Natalie Marchant, PhD, associate professor in the division of psychiatry at University College London, said. “It may be that mindfulness meditation may not improve cognition beyond normally functioning levels but may help to preserve cognition in the face of cognitive decline.”
This study was the longest randomized controlled trial in older adults to investigate the effects of non-native language learning on cognition, Dr. Marchant said.
“It may be that language-learning may buffer against age-related cognitive decline but does not boost cognition in high-functioning individuals,” Dr. Marchant said. “While language learning may not improve cognition, we do not want to discard the other possibility without first examining it.”
Dr. Marchant plans to follow participants for years to come to study that very question.
More to learn
The results harken to those of a study last year with a similar participant group and similar results. In that work, mindfulness meditation and exercise also failed to boost cognition in healthy adults. But that may not be the whole story, according to Eric Lenze, MD, professor and chair of psychiatry at Washington University School of Medicine, St. Louis.
Dr. Lenze was a lead author on that earlier research, known as the MEDEX trial, but was not involved with this study. He commented on the new findings for this news organization.
“People may read these results, and ours that were published in JAMA in December, as suggesting that lifestyle and cognitive interventions don’t work in older adults, but that’s not what this shows, in my opinion,” Dr. Lenze said. “It shows that we don’t understand the science of the aging brain as much as we would like to.”
Participants in most of these studies were mostly White, highly educated, and in good cognitive health, all characteristics that could have skewed these findings, he added.
“It may be that interventions to improve cognitive function in older adults would be more likely to help people who have more room to benefit,” Dr. Lenze said. “If you’re already highly educated, healthy, and cognitively normal, why should we expect that you could do even better than that?”
The Age-Well study was funded by European Union in Horizon 2020 program and Inserm, Région Normandie, Fondation d’entreprise MMA des Entrepreneurs du Futur. Dr. Marchant reports grants from Alzheimer’s Society and the U.K. Medical Research Council. Dr. Lenze reports funding from Takeda pharmaceuticals and has been a consultant for Pritikin Intensive Cardiac Rehabilitation.
A version of this article first appeared on Medscape.com.
The findings are similar to results from another study published last year but are contrary to previous findings showing cognitive benefits for practicing meditation and learning a new language later in life.
“Based on existing literature, which has provided support for the efficacy of meditation and foreign language training in promoting cognition among older adults, perhaps the most surprising outcome of our study was the lack of evidence indicating cognitive benefits after 18 months of either intervention,” lead author Harriet Demnitz-King, MSc, a doctoral candidate at University College London, said in an interview. The findings were published online in JAMA Network Open.
Contradictory findings
For the study, 135 French-speaking, cognitively healthy people were randomized to English-language training, meditation, or a control group. All participants were aged 65 years or older, had been retired for at least 1 year, and had completed at least 7 years of education.
The meditation and English-language training interventions were both 18 months long and included a 2-hour weekly group session, daily home practice of at least 20 minutes, and 1-day intensive 5-hour practice.
Researchers found no significant changes in global cognition, episodic memory, executive function, or attention with either intervention, compared with the control group or to each other.
The findings contradict the researchers’ earlier work that found mindfulness meditation boosted cognitive function in older adults with subjective cognitive decline.
“We are still trying to reconcile these findings,” senior author Natalie Marchant, PhD, associate professor in the division of psychiatry at University College London, said. “It may be that mindfulness meditation may not improve cognition beyond normally functioning levels but may help to preserve cognition in the face of cognitive decline.”
This study was the longest randomized controlled trial in older adults to investigate the effects of non-native language learning on cognition, Dr. Marchant said.
“It may be that language-learning may buffer against age-related cognitive decline but does not boost cognition in high-functioning individuals,” Dr. Marchant said. “While language learning may not improve cognition, we do not want to discard the other possibility without first examining it.”
Dr. Marchant plans to follow participants for years to come to study that very question.
More to learn
The results harken to those of a study last year with a similar participant group and similar results. In that work, mindfulness meditation and exercise also failed to boost cognition in healthy adults. But that may not be the whole story, according to Eric Lenze, MD, professor and chair of psychiatry at Washington University School of Medicine, St. Louis.
Dr. Lenze was a lead author on that earlier research, known as the MEDEX trial, but was not involved with this study. He commented on the new findings for this news organization.
“People may read these results, and ours that were published in JAMA in December, as suggesting that lifestyle and cognitive interventions don’t work in older adults, but that’s not what this shows, in my opinion,” Dr. Lenze said. “It shows that we don’t understand the science of the aging brain as much as we would like to.”
Participants in most of these studies were mostly White, highly educated, and in good cognitive health, all characteristics that could have skewed these findings, he added.
“It may be that interventions to improve cognitive function in older adults would be more likely to help people who have more room to benefit,” Dr. Lenze said. “If you’re already highly educated, healthy, and cognitively normal, why should we expect that you could do even better than that?”
The Age-Well study was funded by European Union in Horizon 2020 program and Inserm, Région Normandie, Fondation d’entreprise MMA des Entrepreneurs du Futur. Dr. Marchant reports grants from Alzheimer’s Society and the U.K. Medical Research Council. Dr. Lenze reports funding from Takeda pharmaceuticals and has been a consultant for Pritikin Intensive Cardiac Rehabilitation.
A version of this article first appeared on Medscape.com.
The findings are similar to results from another study published last year but are contrary to previous findings showing cognitive benefits for practicing meditation and learning a new language later in life.
“Based on existing literature, which has provided support for the efficacy of meditation and foreign language training in promoting cognition among older adults, perhaps the most surprising outcome of our study was the lack of evidence indicating cognitive benefits after 18 months of either intervention,” lead author Harriet Demnitz-King, MSc, a doctoral candidate at University College London, said in an interview. The findings were published online in JAMA Network Open.
Contradictory findings
For the study, 135 French-speaking, cognitively healthy people were randomized to English-language training, meditation, or a control group. All participants were aged 65 years or older, had been retired for at least 1 year, and had completed at least 7 years of education.
The meditation and English-language training interventions were both 18 months long and included a 2-hour weekly group session, daily home practice of at least 20 minutes, and 1-day intensive 5-hour practice.
Researchers found no significant changes in global cognition, episodic memory, executive function, or attention with either intervention, compared with the control group or to each other.
The findings contradict the researchers’ earlier work that found mindfulness meditation boosted cognitive function in older adults with subjective cognitive decline.
“We are still trying to reconcile these findings,” senior author Natalie Marchant, PhD, associate professor in the division of psychiatry at University College London, said. “It may be that mindfulness meditation may not improve cognition beyond normally functioning levels but may help to preserve cognition in the face of cognitive decline.”
This study was the longest randomized controlled trial in older adults to investigate the effects of non-native language learning on cognition, Dr. Marchant said.
“It may be that language-learning may buffer against age-related cognitive decline but does not boost cognition in high-functioning individuals,” Dr. Marchant said. “While language learning may not improve cognition, we do not want to discard the other possibility without first examining it.”
Dr. Marchant plans to follow participants for years to come to study that very question.
More to learn
The results harken to those of a study last year with a similar participant group and similar results. In that work, mindfulness meditation and exercise also failed to boost cognition in healthy adults. But that may not be the whole story, according to Eric Lenze, MD, professor and chair of psychiatry at Washington University School of Medicine, St. Louis.
Dr. Lenze was a lead author on that earlier research, known as the MEDEX trial, but was not involved with this study. He commented on the new findings for this news organization.
“People may read these results, and ours that were published in JAMA in December, as suggesting that lifestyle and cognitive interventions don’t work in older adults, but that’s not what this shows, in my opinion,” Dr. Lenze said. “It shows that we don’t understand the science of the aging brain as much as we would like to.”
Participants in most of these studies were mostly White, highly educated, and in good cognitive health, all characteristics that could have skewed these findings, he added.
“It may be that interventions to improve cognitive function in older adults would be more likely to help people who have more room to benefit,” Dr. Lenze said. “If you’re already highly educated, healthy, and cognitively normal, why should we expect that you could do even better than that?”
The Age-Well study was funded by European Union in Horizon 2020 program and Inserm, Région Normandie, Fondation d’entreprise MMA des Entrepreneurs du Futur. Dr. Marchant reports grants from Alzheimer’s Society and the U.K. Medical Research Council. Dr. Lenze reports funding from Takeda pharmaceuticals and has been a consultant for Pritikin Intensive Cardiac Rehabilitation.
A version of this article first appeared on Medscape.com.
FROM JAMA Network Open
Early MS treatment tied to a major reduction in severe disability
a new study suggests.
Patients who received early treatment had a 45% lower risk of reaching a disability score of 3 and a 60% lower risk of advancing to secondary progressive MS compared with those who began treatment 18 months or more after symptoms presented.
Those with a score of 3 can still walk unassisted but have moderate disability in one of eight areas, such as motor function, vision or thinking skills, or mild disability in three or four areas.
“With a very early treatment, within 6 months from the first symptoms and even before the MS diagnosis, we are now able to decrease long-term disability. This means the earlier the better – time is brain,” lead author Alvaro Cobo-Calvo, MD, PhD, clinical neurologists and researcher with the Multiple Sclerosis Center of Catalonia in Barcelona and the Universitat Autonoma de Barcelona, said in an interview.
The findings were published online in Neurology.
Measuring disability
The observational, retrospective study included people aged 50 years or younger who received MS treatment within 6 months of their first clinical demyelinating event (n = 194), 6-16 months later (n = 192), or more than 16 months after the initial symptoms presented (n = 194).
The investigators noted that this cohort is one of the few that is considered “deeply phenotyped,” meaning it is followed prospectively over time with strict quality controls and systematic data collection methods.
MRIs were done within 3-5 months of the first symptoms, again at 12 months after the first event, and every 5 years over a median 11.2-year follow-up.
Disability levels were measured using the Expanded Disability Status Scale, with scores ranging from 0-10 and higher scores indicating more disability.
Patients who received treatment within 6 months of first symptoms were 45% less likely to have a disability score of 3 by the end of the study than did those who received treatment more than 16 months after that first event (hazard ratio, 0.55; 95% confidence interval, 0.32-0.97).
The earliest-treatment group also had a 60% lower risk of advancing to secondary progressive MS than did people in the latest-treatment group (HR, 0.40; 95% CI, 0.19-0.85).
Better disease stability
The researchers also found that earlier treatment was associated with a 53% better chance of disease stability 1 year after initial treatment (HR, 0.47; 95% CI, 0.28-0.80).
The early-treatment group also had a lower disability progression rate and lower severe disability in a self-reported test, compared with those who were treated later.
The investigators also found that patients who received early treatment were at lower risk for disability, even those with a higher baseline radiologic burden.
Current guidelines recommend early treatment of MS, but it is unclear whether disease-modifying treatments (DMTs) should be prescribed after the first MS symptoms or after a definitive MS diagnosis.
Earlier studies often evaluated treatment efficacy after MS diagnosis. This study began tracking efficacy when therapy began after the first symptoms. In some cases, that was before a diagnosis was given.
“It is important to be cautious when starting treatment and we need to know if the patient will evolve to MS or if the patient is diagnosed with MS based on current McDonald criteria.
“In our study, 70% of patients had MS at the time of the first symptoms according to McDonald 201, but the remainder started treatment without an ‘official’ diagnosis but with an event highly suggestive of MS,” Dr. Cobo-Calvo said.
He added that very early treatment after first symptoms is key to preserving neurologic functionality.
Controversy remains
Adding MRI results as a clinical variable is a novel approach, but the MRI risk score used in the study is a new tool that has not yet been validated, the authors of an accompanying editorial noted.
“The results of this study show that in order to achieve a balance between compared groups, matching on MRI has little to add to good-quality balancing on patients’ clinical and demographic features,” wrote Erin Longbrake, MD, PhD, of the department of neurology, Yale University, New Haven, Conn., and Tomas Kalincik, MD, PhD, of the Neuroimmunology Centre, department of neurology, Royal Melbourne Hospital and the CORe unit, department of medicine, University of Melbourne.
Despite growing evidence pointing to improved outcomes from administering DMTs soon after diagnosis, the timing and sequence of therapy remains an area of controversy, they added.
“While these uncertain diagnostic scenarios may tempt neurologists to ‘wait and see,’ the data presented here remind us that these patients remain at risk of accumulating disability,” the authors wrote. “Neurologists must therefore remain vigilant to ensure that diagnosis is made promptly, that patients are followed up effectively and that effective treatments are used liberally.”
The study was funded by the European Regional Development Fund, Instituto de Salud Carlos III. Dr. Cobo-Calvo has received a grant from Instituto de Salud Carlos III. Dr. Longbrake has consulted for Genentech and NGM Bio and received research support from Biogen & Genentech. Dr. Kalincik has received conference travel support and/or speaker honoraria from WebMD Global, Eisai, Novartis, Biogen, Roche, Sanofi Genzyme, Teva, BioCSL, and Merck, and has received research or educational event support from Biogen, Novartis, Genzyme, Roche, Celgene, and Merck.
A version of this article first appeared on Medscape.com.
a new study suggests.
Patients who received early treatment had a 45% lower risk of reaching a disability score of 3 and a 60% lower risk of advancing to secondary progressive MS compared with those who began treatment 18 months or more after symptoms presented.
Those with a score of 3 can still walk unassisted but have moderate disability in one of eight areas, such as motor function, vision or thinking skills, or mild disability in three or four areas.
“With a very early treatment, within 6 months from the first symptoms and even before the MS diagnosis, we are now able to decrease long-term disability. This means the earlier the better – time is brain,” lead author Alvaro Cobo-Calvo, MD, PhD, clinical neurologists and researcher with the Multiple Sclerosis Center of Catalonia in Barcelona and the Universitat Autonoma de Barcelona, said in an interview.
The findings were published online in Neurology.
Measuring disability
The observational, retrospective study included people aged 50 years or younger who received MS treatment within 6 months of their first clinical demyelinating event (n = 194), 6-16 months later (n = 192), or more than 16 months after the initial symptoms presented (n = 194).
The investigators noted that this cohort is one of the few that is considered “deeply phenotyped,” meaning it is followed prospectively over time with strict quality controls and systematic data collection methods.
MRIs were done within 3-5 months of the first symptoms, again at 12 months after the first event, and every 5 years over a median 11.2-year follow-up.
Disability levels were measured using the Expanded Disability Status Scale, with scores ranging from 0-10 and higher scores indicating more disability.
Patients who received treatment within 6 months of first symptoms were 45% less likely to have a disability score of 3 by the end of the study than did those who received treatment more than 16 months after that first event (hazard ratio, 0.55; 95% confidence interval, 0.32-0.97).
The earliest-treatment group also had a 60% lower risk of advancing to secondary progressive MS than did people in the latest-treatment group (HR, 0.40; 95% CI, 0.19-0.85).
Better disease stability
The researchers also found that earlier treatment was associated with a 53% better chance of disease stability 1 year after initial treatment (HR, 0.47; 95% CI, 0.28-0.80).
The early-treatment group also had a lower disability progression rate and lower severe disability in a self-reported test, compared with those who were treated later.
The investigators also found that patients who received early treatment were at lower risk for disability, even those with a higher baseline radiologic burden.
Current guidelines recommend early treatment of MS, but it is unclear whether disease-modifying treatments (DMTs) should be prescribed after the first MS symptoms or after a definitive MS diagnosis.
Earlier studies often evaluated treatment efficacy after MS diagnosis. This study began tracking efficacy when therapy began after the first symptoms. In some cases, that was before a diagnosis was given.
“It is important to be cautious when starting treatment and we need to know if the patient will evolve to MS or if the patient is diagnosed with MS based on current McDonald criteria.
“In our study, 70% of patients had MS at the time of the first symptoms according to McDonald 201, but the remainder started treatment without an ‘official’ diagnosis but with an event highly suggestive of MS,” Dr. Cobo-Calvo said.
He added that very early treatment after first symptoms is key to preserving neurologic functionality.
Controversy remains
Adding MRI results as a clinical variable is a novel approach, but the MRI risk score used in the study is a new tool that has not yet been validated, the authors of an accompanying editorial noted.
“The results of this study show that in order to achieve a balance between compared groups, matching on MRI has little to add to good-quality balancing on patients’ clinical and demographic features,” wrote Erin Longbrake, MD, PhD, of the department of neurology, Yale University, New Haven, Conn., and Tomas Kalincik, MD, PhD, of the Neuroimmunology Centre, department of neurology, Royal Melbourne Hospital and the CORe unit, department of medicine, University of Melbourne.
Despite growing evidence pointing to improved outcomes from administering DMTs soon after diagnosis, the timing and sequence of therapy remains an area of controversy, they added.
“While these uncertain diagnostic scenarios may tempt neurologists to ‘wait and see,’ the data presented here remind us that these patients remain at risk of accumulating disability,” the authors wrote. “Neurologists must therefore remain vigilant to ensure that diagnosis is made promptly, that patients are followed up effectively and that effective treatments are used liberally.”
The study was funded by the European Regional Development Fund, Instituto de Salud Carlos III. Dr. Cobo-Calvo has received a grant from Instituto de Salud Carlos III. Dr. Longbrake has consulted for Genentech and NGM Bio and received research support from Biogen & Genentech. Dr. Kalincik has received conference travel support and/or speaker honoraria from WebMD Global, Eisai, Novartis, Biogen, Roche, Sanofi Genzyme, Teva, BioCSL, and Merck, and has received research or educational event support from Biogen, Novartis, Genzyme, Roche, Celgene, and Merck.
A version of this article first appeared on Medscape.com.
a new study suggests.
Patients who received early treatment had a 45% lower risk of reaching a disability score of 3 and a 60% lower risk of advancing to secondary progressive MS compared with those who began treatment 18 months or more after symptoms presented.
Those with a score of 3 can still walk unassisted but have moderate disability in one of eight areas, such as motor function, vision or thinking skills, or mild disability in three or four areas.
“With a very early treatment, within 6 months from the first symptoms and even before the MS diagnosis, we are now able to decrease long-term disability. This means the earlier the better – time is brain,” lead author Alvaro Cobo-Calvo, MD, PhD, clinical neurologists and researcher with the Multiple Sclerosis Center of Catalonia in Barcelona and the Universitat Autonoma de Barcelona, said in an interview.
The findings were published online in Neurology.
Measuring disability
The observational, retrospective study included people aged 50 years or younger who received MS treatment within 6 months of their first clinical demyelinating event (n = 194), 6-16 months later (n = 192), or more than 16 months after the initial symptoms presented (n = 194).
The investigators noted that this cohort is one of the few that is considered “deeply phenotyped,” meaning it is followed prospectively over time with strict quality controls and systematic data collection methods.
MRIs were done within 3-5 months of the first symptoms, again at 12 months after the first event, and every 5 years over a median 11.2-year follow-up.
Disability levels were measured using the Expanded Disability Status Scale, with scores ranging from 0-10 and higher scores indicating more disability.
Patients who received treatment within 6 months of first symptoms were 45% less likely to have a disability score of 3 by the end of the study than did those who received treatment more than 16 months after that first event (hazard ratio, 0.55; 95% confidence interval, 0.32-0.97).
The earliest-treatment group also had a 60% lower risk of advancing to secondary progressive MS than did people in the latest-treatment group (HR, 0.40; 95% CI, 0.19-0.85).
Better disease stability
The researchers also found that earlier treatment was associated with a 53% better chance of disease stability 1 year after initial treatment (HR, 0.47; 95% CI, 0.28-0.80).
The early-treatment group also had a lower disability progression rate and lower severe disability in a self-reported test, compared with those who were treated later.
The investigators also found that patients who received early treatment were at lower risk for disability, even those with a higher baseline radiologic burden.
Current guidelines recommend early treatment of MS, but it is unclear whether disease-modifying treatments (DMTs) should be prescribed after the first MS symptoms or after a definitive MS diagnosis.
Earlier studies often evaluated treatment efficacy after MS diagnosis. This study began tracking efficacy when therapy began after the first symptoms. In some cases, that was before a diagnosis was given.
“It is important to be cautious when starting treatment and we need to know if the patient will evolve to MS or if the patient is diagnosed with MS based on current McDonald criteria.
“In our study, 70% of patients had MS at the time of the first symptoms according to McDonald 201, but the remainder started treatment without an ‘official’ diagnosis but with an event highly suggestive of MS,” Dr. Cobo-Calvo said.
He added that very early treatment after first symptoms is key to preserving neurologic functionality.
Controversy remains
Adding MRI results as a clinical variable is a novel approach, but the MRI risk score used in the study is a new tool that has not yet been validated, the authors of an accompanying editorial noted.
“The results of this study show that in order to achieve a balance between compared groups, matching on MRI has little to add to good-quality balancing on patients’ clinical and demographic features,” wrote Erin Longbrake, MD, PhD, of the department of neurology, Yale University, New Haven, Conn., and Tomas Kalincik, MD, PhD, of the Neuroimmunology Centre, department of neurology, Royal Melbourne Hospital and the CORe unit, department of medicine, University of Melbourne.
Despite growing evidence pointing to improved outcomes from administering DMTs soon after diagnosis, the timing and sequence of therapy remains an area of controversy, they added.
“While these uncertain diagnostic scenarios may tempt neurologists to ‘wait and see,’ the data presented here remind us that these patients remain at risk of accumulating disability,” the authors wrote. “Neurologists must therefore remain vigilant to ensure that diagnosis is made promptly, that patients are followed up effectively and that effective treatments are used liberally.”
The study was funded by the European Regional Development Fund, Instituto de Salud Carlos III. Dr. Cobo-Calvo has received a grant from Instituto de Salud Carlos III. Dr. Longbrake has consulted for Genentech and NGM Bio and received research support from Biogen & Genentech. Dr. Kalincik has received conference travel support and/or speaker honoraria from WebMD Global, Eisai, Novartis, Biogen, Roche, Sanofi Genzyme, Teva, BioCSL, and Merck, and has received research or educational event support from Biogen, Novartis, Genzyme, Roche, Celgene, and Merck.
A version of this article first appeared on Medscape.com.
FROM NEUROLOGY
New international guidelines on opioid deprescribing
An expert panel of pain management clinicians has released what they say are the first international guidelines for general practitioners on opioid analgesic deprescribing in adults.
The recommendations describe best practices for stopping opioid therapy and emphasize slow tapering and individualized deprescribing plans tailored to each patient.
Developed by general practitioners, pain specialists, addiction specialists, pharmacists, registered nurses, consumers, and physiotherapists, the guidelines note that deprescribing may not be appropriate for every patient and that stopping abruptly can be associated with an increased risk of overdose.
“Internationally, we were seeing significant harms from opioids but also significant harms from unsolicited and abrupt opioid cessation,” said lead author Aili Langford, PhD, who conducted the study as a doctoral student at the University of Sydney. “It was clear that recommendations to support safe and person-centered opioid deprescribing were required.”
The findings were published online in the Medical Journal of Australia.
Deprescribing plan
The consensus guidelines include 11 recommendations for deprescribing in adult patients who take at least one opioid for any type of pain.
Recommendations include implementing a deprescribing plan when opioids are first prescribed and gradual and individualized deprescribing, with regular monitoring and review.
Clinicians should consider opioid deprescribing in patients who experience no clinically meaningful improvement in function, quality of life, or pain at high risk with opioid therapy, they note. Patients who are at high risk for opioid-related harm are also good candidates for deprescribing.
Stopping opioid therapy is not recommended for patients with severe opioid use disorder (OUD). In those patients, medication-assisted OUD treatment and other evidence-based interventions are recommended.
“Opioids can be effective in pain management,” co-author Carl Schneider, PhD, an associate professor of pharmacy at the University of Sydney, said in a press release. “However, over the longer term, the risk of harms may outweigh the benefits.”
A ‘global problem’
Commenting on the guidelines, Orman Trent Hall, DO, assistant professor of addiction medicine, department of psychiatry and behavioral health at the Ohio State University Wexner Medical Center, Columbus, said they are similar to recommendations published by the U.S. Centers for Disease Control and Prevention in 2016 and 2022 but offer additional information that could be helpful.
“This new guideline provides more explicit advice about tapering and withdrawal management, which may be useful to practitioners. The opioid crisis is a global problem, and while individual countries may require local solutions, the new international guideline may offer a framework for approaching this issue,” he said.
The guideline’s emphasis on the potential risks of deprescribing in some patients is also key, Dr. Hall added. Patients who are tapering off opioid therapy may have worsening pain and loss of function that can affect their quality of life.
“Patients may also experience psychological harm and increased risk of opioid use disorder and death by suicide following opioid deprescribing,” Dr. Hall said. “Therefore, it is important for providers to carefully weigh the risks of prescribing and deprescribing and engage patients with person-centered communication and shared decision-making.”
The work was funded by grants from the University of Sydney and the National Health and Medical Research Council. Full disclosures are available in the original article. Dr. Hall has provided expert opinion to the health care consultancy firm Lumanity and Emergent BioSolutions regarding the overdose crisis.
A version of this article originally appeared on Medscape.com.
An expert panel of pain management clinicians has released what they say are the first international guidelines for general practitioners on opioid analgesic deprescribing in adults.
The recommendations describe best practices for stopping opioid therapy and emphasize slow tapering and individualized deprescribing plans tailored to each patient.
Developed by general practitioners, pain specialists, addiction specialists, pharmacists, registered nurses, consumers, and physiotherapists, the guidelines note that deprescribing may not be appropriate for every patient and that stopping abruptly can be associated with an increased risk of overdose.
“Internationally, we were seeing significant harms from opioids but also significant harms from unsolicited and abrupt opioid cessation,” said lead author Aili Langford, PhD, who conducted the study as a doctoral student at the University of Sydney. “It was clear that recommendations to support safe and person-centered opioid deprescribing were required.”
The findings were published online in the Medical Journal of Australia.
Deprescribing plan
The consensus guidelines include 11 recommendations for deprescribing in adult patients who take at least one opioid for any type of pain.
Recommendations include implementing a deprescribing plan when opioids are first prescribed and gradual and individualized deprescribing, with regular monitoring and review.
Clinicians should consider opioid deprescribing in patients who experience no clinically meaningful improvement in function, quality of life, or pain at high risk with opioid therapy, they note. Patients who are at high risk for opioid-related harm are also good candidates for deprescribing.
Stopping opioid therapy is not recommended for patients with severe opioid use disorder (OUD). In those patients, medication-assisted OUD treatment and other evidence-based interventions are recommended.
“Opioids can be effective in pain management,” co-author Carl Schneider, PhD, an associate professor of pharmacy at the University of Sydney, said in a press release. “However, over the longer term, the risk of harms may outweigh the benefits.”
A ‘global problem’
Commenting on the guidelines, Orman Trent Hall, DO, assistant professor of addiction medicine, department of psychiatry and behavioral health at the Ohio State University Wexner Medical Center, Columbus, said they are similar to recommendations published by the U.S. Centers for Disease Control and Prevention in 2016 and 2022 but offer additional information that could be helpful.
“This new guideline provides more explicit advice about tapering and withdrawal management, which may be useful to practitioners. The opioid crisis is a global problem, and while individual countries may require local solutions, the new international guideline may offer a framework for approaching this issue,” he said.
The guideline’s emphasis on the potential risks of deprescribing in some patients is also key, Dr. Hall added. Patients who are tapering off opioid therapy may have worsening pain and loss of function that can affect their quality of life.
“Patients may also experience psychological harm and increased risk of opioid use disorder and death by suicide following opioid deprescribing,” Dr. Hall said. “Therefore, it is important for providers to carefully weigh the risks of prescribing and deprescribing and engage patients with person-centered communication and shared decision-making.”
The work was funded by grants from the University of Sydney and the National Health and Medical Research Council. Full disclosures are available in the original article. Dr. Hall has provided expert opinion to the health care consultancy firm Lumanity and Emergent BioSolutions regarding the overdose crisis.
A version of this article originally appeared on Medscape.com.
An expert panel of pain management clinicians has released what they say are the first international guidelines for general practitioners on opioid analgesic deprescribing in adults.
The recommendations describe best practices for stopping opioid therapy and emphasize slow tapering and individualized deprescribing plans tailored to each patient.
Developed by general practitioners, pain specialists, addiction specialists, pharmacists, registered nurses, consumers, and physiotherapists, the guidelines note that deprescribing may not be appropriate for every patient and that stopping abruptly can be associated with an increased risk of overdose.
“Internationally, we were seeing significant harms from opioids but also significant harms from unsolicited and abrupt opioid cessation,” said lead author Aili Langford, PhD, who conducted the study as a doctoral student at the University of Sydney. “It was clear that recommendations to support safe and person-centered opioid deprescribing were required.”
The findings were published online in the Medical Journal of Australia.
Deprescribing plan
The consensus guidelines include 11 recommendations for deprescribing in adult patients who take at least one opioid for any type of pain.
Recommendations include implementing a deprescribing plan when opioids are first prescribed and gradual and individualized deprescribing, with regular monitoring and review.
Clinicians should consider opioid deprescribing in patients who experience no clinically meaningful improvement in function, quality of life, or pain at high risk with opioid therapy, they note. Patients who are at high risk for opioid-related harm are also good candidates for deprescribing.
Stopping opioid therapy is not recommended for patients with severe opioid use disorder (OUD). In those patients, medication-assisted OUD treatment and other evidence-based interventions are recommended.
“Opioids can be effective in pain management,” co-author Carl Schneider, PhD, an associate professor of pharmacy at the University of Sydney, said in a press release. “However, over the longer term, the risk of harms may outweigh the benefits.”
A ‘global problem’
Commenting on the guidelines, Orman Trent Hall, DO, assistant professor of addiction medicine, department of psychiatry and behavioral health at the Ohio State University Wexner Medical Center, Columbus, said they are similar to recommendations published by the U.S. Centers for Disease Control and Prevention in 2016 and 2022 but offer additional information that could be helpful.
“This new guideline provides more explicit advice about tapering and withdrawal management, which may be useful to practitioners. The opioid crisis is a global problem, and while individual countries may require local solutions, the new international guideline may offer a framework for approaching this issue,” he said.
The guideline’s emphasis on the potential risks of deprescribing in some patients is also key, Dr. Hall added. Patients who are tapering off opioid therapy may have worsening pain and loss of function that can affect their quality of life.
“Patients may also experience psychological harm and increased risk of opioid use disorder and death by suicide following opioid deprescribing,” Dr. Hall said. “Therefore, it is important for providers to carefully weigh the risks of prescribing and deprescribing and engage patients with person-centered communication and shared decision-making.”
The work was funded by grants from the University of Sydney and the National Health and Medical Research Council. Full disclosures are available in the original article. Dr. Hall has provided expert opinion to the health care consultancy firm Lumanity and Emergent BioSolutions regarding the overdose crisis.
A version of this article originally appeared on Medscape.com.
Potential new treatment for REM sleep behavior disorder
Dual orexin receptor antagonists (DORAs), a class of drugs approved to treat insomnia, may also be effective for rapid eye movement sleep behavior disorder (RBD), a study suggests.
About 3 million people in the United States have RBD, which is often a precursor to Parkinson’s disease. People with the disorder act out their dreams by talking, flailing their arms and legs, punching, kicking, and exhibiting other behaviors while asleep.
Researchers used an animal model for the study, which they say is the first to identify a new form of treatment for RBD.
“REM behavior disorder is difficult to treat, and the treatments are mostly limited to clonazepam and melatonin,” which may have side effects, senior investigator Andrew Varga, MD, PhD, associate professor of pulmonary, critical care, and sleep medicine at the Icahn School of Medicine at Mount Sinai, New York, told this news organization. “We’re using something completely different, which raises the possibility this might be something useful for REM behavior disorders.”
The findings, with Mount Sinai assistant professor Korey Kam, PhD, as lead author, were published online in the Journal of Neuroscience.
A new model for RBD?
RBD can signal risk for synucleinopathies, a group of neurological conditions such as Parkinson’s disease that involve the formation of clumps of alpha-synuclein protein in the brain.
Prior research on RBD was done in synucleinopathy mouse models. For this study, however, researchers used a tauopathy mouse model to investigate how the abnormal accumulation of tau protein might affect RBD.
Researchers collected data on biophysical properties when the mice were awake and in REM and non-REM sleep. They examined length of sleep, transitions from waking to sleep, and how some factors are related to age.
Nearly a third of the older animals showed behaviors similar to REM sleep behavior disorder in humans, including chewing and limb extension.
But after researchers administered a DORA medication twice during a 24-hour period, they noted that the medication not only helped the animals fall asleep faster and for longer, it also reduced levels of dream enactment that are a hallmark of RBD.
The ‘bigger highlight’
Finding RBD behaviors in a tauopathy animal model was surprising, Dr. Varga said, because RBD has been previously linked to synucleinopathies. There was no known correlation between RBD and abnormal accumulation of tau.
Another unexpected finding was the detection of RBD in some of the younger animals, who had not yet shown evidence of tau accumulation.
“It appears to be a biomarker or a signature of something that’s going on that predicts the impending tauopathy at a time where there is very little, or no, tau pathology going on in the brain,” Dr. Varga said.
If RBD is an early predictor of future tau accumulation, the model could guide future prevention and treatment. However, the more important finding is the potential new treatment for the condition.
“The bigger highlight here is less about what’s causing the RBD [than about] what you can do to make it better,” he said.
The next step in the work is to study whether the effect of DORAs on RBD seen in this tauopathy mouse model is evidenced in other animals and whether it is effective in humans with RBD, Dr. Varga said.
The study was funded by the Alzheimer’s Association and Merck Investigator Studies Program. Dr. Kam, Dr. Varga, and coauthors report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Dual orexin receptor antagonists (DORAs), a class of drugs approved to treat insomnia, may also be effective for rapid eye movement sleep behavior disorder (RBD), a study suggests.
About 3 million people in the United States have RBD, which is often a precursor to Parkinson’s disease. People with the disorder act out their dreams by talking, flailing their arms and legs, punching, kicking, and exhibiting other behaviors while asleep.
Researchers used an animal model for the study, which they say is the first to identify a new form of treatment for RBD.
“REM behavior disorder is difficult to treat, and the treatments are mostly limited to clonazepam and melatonin,” which may have side effects, senior investigator Andrew Varga, MD, PhD, associate professor of pulmonary, critical care, and sleep medicine at the Icahn School of Medicine at Mount Sinai, New York, told this news organization. “We’re using something completely different, which raises the possibility this might be something useful for REM behavior disorders.”
The findings, with Mount Sinai assistant professor Korey Kam, PhD, as lead author, were published online in the Journal of Neuroscience.
A new model for RBD?
RBD can signal risk for synucleinopathies, a group of neurological conditions such as Parkinson’s disease that involve the formation of clumps of alpha-synuclein protein in the brain.
Prior research on RBD was done in synucleinopathy mouse models. For this study, however, researchers used a tauopathy mouse model to investigate how the abnormal accumulation of tau protein might affect RBD.
Researchers collected data on biophysical properties when the mice were awake and in REM and non-REM sleep. They examined length of sleep, transitions from waking to sleep, and how some factors are related to age.
Nearly a third of the older animals showed behaviors similar to REM sleep behavior disorder in humans, including chewing and limb extension.
But after researchers administered a DORA medication twice during a 24-hour period, they noted that the medication not only helped the animals fall asleep faster and for longer, it also reduced levels of dream enactment that are a hallmark of RBD.
The ‘bigger highlight’
Finding RBD behaviors in a tauopathy animal model was surprising, Dr. Varga said, because RBD has been previously linked to synucleinopathies. There was no known correlation between RBD and abnormal accumulation of tau.
Another unexpected finding was the detection of RBD in some of the younger animals, who had not yet shown evidence of tau accumulation.
“It appears to be a biomarker or a signature of something that’s going on that predicts the impending tauopathy at a time where there is very little, or no, tau pathology going on in the brain,” Dr. Varga said.
If RBD is an early predictor of future tau accumulation, the model could guide future prevention and treatment. However, the more important finding is the potential new treatment for the condition.
“The bigger highlight here is less about what’s causing the RBD [than about] what you can do to make it better,” he said.
The next step in the work is to study whether the effect of DORAs on RBD seen in this tauopathy mouse model is evidenced in other animals and whether it is effective in humans with RBD, Dr. Varga said.
The study was funded by the Alzheimer’s Association and Merck Investigator Studies Program. Dr. Kam, Dr. Varga, and coauthors report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Dual orexin receptor antagonists (DORAs), a class of drugs approved to treat insomnia, may also be effective for rapid eye movement sleep behavior disorder (RBD), a study suggests.
About 3 million people in the United States have RBD, which is often a precursor to Parkinson’s disease. People with the disorder act out their dreams by talking, flailing their arms and legs, punching, kicking, and exhibiting other behaviors while asleep.
Researchers used an animal model for the study, which they say is the first to identify a new form of treatment for RBD.
“REM behavior disorder is difficult to treat, and the treatments are mostly limited to clonazepam and melatonin,” which may have side effects, senior investigator Andrew Varga, MD, PhD, associate professor of pulmonary, critical care, and sleep medicine at the Icahn School of Medicine at Mount Sinai, New York, told this news organization. “We’re using something completely different, which raises the possibility this might be something useful for REM behavior disorders.”
The findings, with Mount Sinai assistant professor Korey Kam, PhD, as lead author, were published online in the Journal of Neuroscience.
A new model for RBD?
RBD can signal risk for synucleinopathies, a group of neurological conditions such as Parkinson’s disease that involve the formation of clumps of alpha-synuclein protein in the brain.
Prior research on RBD was done in synucleinopathy mouse models. For this study, however, researchers used a tauopathy mouse model to investigate how the abnormal accumulation of tau protein might affect RBD.
Researchers collected data on biophysical properties when the mice were awake and in REM and non-REM sleep. They examined length of sleep, transitions from waking to sleep, and how some factors are related to age.
Nearly a third of the older animals showed behaviors similar to REM sleep behavior disorder in humans, including chewing and limb extension.
But after researchers administered a DORA medication twice during a 24-hour period, they noted that the medication not only helped the animals fall asleep faster and for longer, it also reduced levels of dream enactment that are a hallmark of RBD.
The ‘bigger highlight’
Finding RBD behaviors in a tauopathy animal model was surprising, Dr. Varga said, because RBD has been previously linked to synucleinopathies. There was no known correlation between RBD and abnormal accumulation of tau.
Another unexpected finding was the detection of RBD in some of the younger animals, who had not yet shown evidence of tau accumulation.
“It appears to be a biomarker or a signature of something that’s going on that predicts the impending tauopathy at a time where there is very little, or no, tau pathology going on in the brain,” Dr. Varga said.
If RBD is an early predictor of future tau accumulation, the model could guide future prevention and treatment. However, the more important finding is the potential new treatment for the condition.
“The bigger highlight here is less about what’s causing the RBD [than about] what you can do to make it better,” he said.
The next step in the work is to study whether the effect of DORAs on RBD seen in this tauopathy mouse model is evidenced in other animals and whether it is effective in humans with RBD, Dr. Varga said.
The study was funded by the Alzheimer’s Association and Merck Investigator Studies Program. Dr. Kam, Dr. Varga, and coauthors report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM THE JOURNAL OF NEUROSCIENCE
Regular exercise may boost pain tolerance
new research suggests.
In a large observational study of more than 10,000 adults, researchers found those who consistently engage in moderate to vigorous physical activity over the 7- to 8-year study period reported the highest pain tolerance. However, the results also showed that even light exercise was associated with greater pain tolerance.
“There were indications that both total amount of physical activity over time, as well as the direction of change in activity level over time matters to how high your pain tolerance is,” lead investigator Anders Pedersen Årnes, PT, MPH, research fellow and adviser at the University Hospital of North Norway, affiliated with the University of Tromsø, said in an interview. “As an observational study, this points toward the possibility that increased physical activity might increase pain tolerance.”
The findings were published online in PLOS One.
Anything is better than nothing
The researchers drew from the prospective, population-based Tromsø health study, a health survey that draws on surveys conducted periodically since 1974 among residents in northern Norway.
The study included 10,732 participants who completed surveys in 2007-2008 and again in 2015-2016.
Data on physical activity, experimental pain tolerance, sex, sociodemographic covariates, and chronic pain was collected through questionnaires, biological samples and clinical examination.
Pain tolerance was measured using the cold-pressor test (CPT), in which participants submerge their hand in icy water for as long as possible.
CPT tolerance was 7%, 14%, and 16% higher respectively for light, moderate, and vigorous consistent exercise across the two surveys versus the sedentary group.
“Engaging in habitual physical activity in leisure time is associated with higher pain tolerance,” Mr. Årnes said. “Any kind of activity over time is better than being sedentary.”
The researchers also found that people who were sedentary at baseline who reported greater physical activity at follow-up also had higher pain tolerance than those who remained sedentary, although this finding was not statistically significant.
This highest pain tolerance was noted in people who engaged in moderate to vigorous exercise over time, with a 20.4-second longer performance in the CPT than those who were consistently sedentary (P < .001; 95% confidence interval, 13.7-27.1).
There was no significant difference in pain tolerance between men and women and all participants experienced a decline in tolerance over time.
“Results indicate that a positive change in physical activity level over time was associated with higher pain tolerance,” Mr. Årnes said. “Your total activity level might decide how much, as more seems to be better.”
More work needed
The long follow-up and large number of patients are two strengths of the study, Steven Cohen, MD, chief of pain medicine and professor of anesthesiology, neurology, physical medicine & rehabilitation and psychiatry at Johns Hopkins University, Baltimore, said in an interview.
“This study explored the relationship between general physical activity levels and one form of acute pain, but data from other studies show a benefit for other forms of pain,” said Dr. Cohen, who was not part of the research. “Taken together, this suggests that exercise is beneficial for individuals living with pain.”
The findings demonstrate an association between exercise and pain tolerance and other research has shown evidence of a cause-and-effect relationship, Dr. Cohen said. However, “more work is needed to determine what mediates these effects.”
Questions also remain about how exercise might impact tolerance or risk for chronic pain, he added.
Investigators are now working on a follow-up study of how the effect of exercise on pain tolerance might influence chronic pain risk, Mr. Årnes said.
The study received no specific funding. Mr. Årnes and Dr. Cohen reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
new research suggests.
In a large observational study of more than 10,000 adults, researchers found those who consistently engage in moderate to vigorous physical activity over the 7- to 8-year study period reported the highest pain tolerance. However, the results also showed that even light exercise was associated with greater pain tolerance.
“There were indications that both total amount of physical activity over time, as well as the direction of change in activity level over time matters to how high your pain tolerance is,” lead investigator Anders Pedersen Årnes, PT, MPH, research fellow and adviser at the University Hospital of North Norway, affiliated with the University of Tromsø, said in an interview. “As an observational study, this points toward the possibility that increased physical activity might increase pain tolerance.”
The findings were published online in PLOS One.
Anything is better than nothing
The researchers drew from the prospective, population-based Tromsø health study, a health survey that draws on surveys conducted periodically since 1974 among residents in northern Norway.
The study included 10,732 participants who completed surveys in 2007-2008 and again in 2015-2016.
Data on physical activity, experimental pain tolerance, sex, sociodemographic covariates, and chronic pain was collected through questionnaires, biological samples and clinical examination.
Pain tolerance was measured using the cold-pressor test (CPT), in which participants submerge their hand in icy water for as long as possible.
CPT tolerance was 7%, 14%, and 16% higher respectively for light, moderate, and vigorous consistent exercise across the two surveys versus the sedentary group.
“Engaging in habitual physical activity in leisure time is associated with higher pain tolerance,” Mr. Årnes said. “Any kind of activity over time is better than being sedentary.”
The researchers also found that people who were sedentary at baseline who reported greater physical activity at follow-up also had higher pain tolerance than those who remained sedentary, although this finding was not statistically significant.
This highest pain tolerance was noted in people who engaged in moderate to vigorous exercise over time, with a 20.4-second longer performance in the CPT than those who were consistently sedentary (P < .001; 95% confidence interval, 13.7-27.1).
There was no significant difference in pain tolerance between men and women and all participants experienced a decline in tolerance over time.
“Results indicate that a positive change in physical activity level over time was associated with higher pain tolerance,” Mr. Årnes said. “Your total activity level might decide how much, as more seems to be better.”
More work needed
The long follow-up and large number of patients are two strengths of the study, Steven Cohen, MD, chief of pain medicine and professor of anesthesiology, neurology, physical medicine & rehabilitation and psychiatry at Johns Hopkins University, Baltimore, said in an interview.
“This study explored the relationship between general physical activity levels and one form of acute pain, but data from other studies show a benefit for other forms of pain,” said Dr. Cohen, who was not part of the research. “Taken together, this suggests that exercise is beneficial for individuals living with pain.”
The findings demonstrate an association between exercise and pain tolerance and other research has shown evidence of a cause-and-effect relationship, Dr. Cohen said. However, “more work is needed to determine what mediates these effects.”
Questions also remain about how exercise might impact tolerance or risk for chronic pain, he added.
Investigators are now working on a follow-up study of how the effect of exercise on pain tolerance might influence chronic pain risk, Mr. Årnes said.
The study received no specific funding. Mr. Årnes and Dr. Cohen reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
new research suggests.
In a large observational study of more than 10,000 adults, researchers found those who consistently engage in moderate to vigorous physical activity over the 7- to 8-year study period reported the highest pain tolerance. However, the results also showed that even light exercise was associated with greater pain tolerance.
“There were indications that both total amount of physical activity over time, as well as the direction of change in activity level over time matters to how high your pain tolerance is,” lead investigator Anders Pedersen Årnes, PT, MPH, research fellow and adviser at the University Hospital of North Norway, affiliated with the University of Tromsø, said in an interview. “As an observational study, this points toward the possibility that increased physical activity might increase pain tolerance.”
The findings were published online in PLOS One.
Anything is better than nothing
The researchers drew from the prospective, population-based Tromsø health study, a health survey that draws on surveys conducted periodically since 1974 among residents in northern Norway.
The study included 10,732 participants who completed surveys in 2007-2008 and again in 2015-2016.
Data on physical activity, experimental pain tolerance, sex, sociodemographic covariates, and chronic pain was collected through questionnaires, biological samples and clinical examination.
Pain tolerance was measured using the cold-pressor test (CPT), in which participants submerge their hand in icy water for as long as possible.
CPT tolerance was 7%, 14%, and 16% higher respectively for light, moderate, and vigorous consistent exercise across the two surveys versus the sedentary group.
“Engaging in habitual physical activity in leisure time is associated with higher pain tolerance,” Mr. Årnes said. “Any kind of activity over time is better than being sedentary.”
The researchers also found that people who were sedentary at baseline who reported greater physical activity at follow-up also had higher pain tolerance than those who remained sedentary, although this finding was not statistically significant.
This highest pain tolerance was noted in people who engaged in moderate to vigorous exercise over time, with a 20.4-second longer performance in the CPT than those who were consistently sedentary (P < .001; 95% confidence interval, 13.7-27.1).
There was no significant difference in pain tolerance between men and women and all participants experienced a decline in tolerance over time.
“Results indicate that a positive change in physical activity level over time was associated with higher pain tolerance,” Mr. Årnes said. “Your total activity level might decide how much, as more seems to be better.”
More work needed
The long follow-up and large number of patients are two strengths of the study, Steven Cohen, MD, chief of pain medicine and professor of anesthesiology, neurology, physical medicine & rehabilitation and psychiatry at Johns Hopkins University, Baltimore, said in an interview.
“This study explored the relationship between general physical activity levels and one form of acute pain, but data from other studies show a benefit for other forms of pain,” said Dr. Cohen, who was not part of the research. “Taken together, this suggests that exercise is beneficial for individuals living with pain.”
The findings demonstrate an association between exercise and pain tolerance and other research has shown evidence of a cause-and-effect relationship, Dr. Cohen said. However, “more work is needed to determine what mediates these effects.”
Questions also remain about how exercise might impact tolerance or risk for chronic pain, he added.
Investigators are now working on a follow-up study of how the effect of exercise on pain tolerance might influence chronic pain risk, Mr. Årnes said.
The study received no specific funding. Mr. Årnes and Dr. Cohen reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM PLOS ONE