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New Data Support Viagra for Alzheimer’s Prevention
The large real-world analysis of patient data from two databases showed a 30%-54% reduced prevalence in Alzheimer’s disease among patients who took sildenafil (Viagra) than those who did not, after adjusting for potential confounding factors.
This observation was further supported by mechanistic studies showing decreased neurotoxic protein levels in brain cells exposed to the phosphodiesterase type 5 inhibitor (PDE5i).
“Our findings provide further weight to repurposing this existing FDA-approved drug as a novel treatment for Alzheimer’s, which is in great need of new therapies,” Feixiong Cheng, PhD, director of the Cleveland Clinic Genome Center, who led the research, said in a news release.
“We used artificial intelligence to integrate data across multiple domains which all indicated sildenafil’s potential against this devastating neurological disease,” Dr. Cheng noted.
The study was published online in the Journal of Alzheimer’s Disease.
Neuroprotective?
Using real-world patient data from the MarketScan Medicare Supplemental database (2012-2017) and the Clinformatics database (2007-2020), the researchers conducted propensity score-stratified analyses after adjusting for gender, age, race, and comorbidities.
They searched for all individuals with pharmacy claims for sildenafil or four comparator drugs — bumetanide, furosemide, spironolactone, and nifedipine. Results showed that sildenafil use was associated with reduced likelihood of Alzheimer’s disease relative to the control drugs.
For example, sildenafil use was associated with a 54% reduced incidence of Alzheimer’s disease in MarketScan (hazard ratio [HR], 0.46; 95% CI, 0.32-0.66) and a 30% reduced prevalence of Alzheimer’s disease in Clinformatics (HR, 0.70; 95% CI, 0.49-1.00) compared with spironolactone.
The findings support a study published earlier this year that found a potential protective effect of PDE5i treatment on Alzheimer’s disease risk.
However, this research and the current study are contradicted by another paper published in Brain Communications in late 2022 which showed no such link between ED meds and reduced Alzheimer’s disease risk.
The investigators also found that sildenafil reduces tau hyperphosphorylation (pTau181 and pTau205) in a dose-dependent manner in both familial and sporadic Alzheimer’s disease patient induced pluripotent stem cell (iPSC)-derived neurons.
They further demonstrated through RNA-sequencing data analysis that sildenafil specifically targets Alzheimer’s disease related genes and pathobiological pathways, mechanistically supporting the beneficial effect of sildenafil in Alzheimer’s disease.
“We believe our findings provide the evidence needed for clinical trials to further examine the potential effectiveness of sildenafil in patients with Alzheimer’s disease,” Dr. Cheng said.
The study was primarily supported by the National Institute on Aging (NIA) and the National Institute of Neurological Disorders and Stroke (NINDS). Dr. Cheng had no relevant disclosures.
A version of this article appeared on Medscape.com.
The large real-world analysis of patient data from two databases showed a 30%-54% reduced prevalence in Alzheimer’s disease among patients who took sildenafil (Viagra) than those who did not, after adjusting for potential confounding factors.
This observation was further supported by mechanistic studies showing decreased neurotoxic protein levels in brain cells exposed to the phosphodiesterase type 5 inhibitor (PDE5i).
“Our findings provide further weight to repurposing this existing FDA-approved drug as a novel treatment for Alzheimer’s, which is in great need of new therapies,” Feixiong Cheng, PhD, director of the Cleveland Clinic Genome Center, who led the research, said in a news release.
“We used artificial intelligence to integrate data across multiple domains which all indicated sildenafil’s potential against this devastating neurological disease,” Dr. Cheng noted.
The study was published online in the Journal of Alzheimer’s Disease.
Neuroprotective?
Using real-world patient data from the MarketScan Medicare Supplemental database (2012-2017) and the Clinformatics database (2007-2020), the researchers conducted propensity score-stratified analyses after adjusting for gender, age, race, and comorbidities.
They searched for all individuals with pharmacy claims for sildenafil or four comparator drugs — bumetanide, furosemide, spironolactone, and nifedipine. Results showed that sildenafil use was associated with reduced likelihood of Alzheimer’s disease relative to the control drugs.
For example, sildenafil use was associated with a 54% reduced incidence of Alzheimer’s disease in MarketScan (hazard ratio [HR], 0.46; 95% CI, 0.32-0.66) and a 30% reduced prevalence of Alzheimer’s disease in Clinformatics (HR, 0.70; 95% CI, 0.49-1.00) compared with spironolactone.
The findings support a study published earlier this year that found a potential protective effect of PDE5i treatment on Alzheimer’s disease risk.
However, this research and the current study are contradicted by another paper published in Brain Communications in late 2022 which showed no such link between ED meds and reduced Alzheimer’s disease risk.
The investigators also found that sildenafil reduces tau hyperphosphorylation (pTau181 and pTau205) in a dose-dependent manner in both familial and sporadic Alzheimer’s disease patient induced pluripotent stem cell (iPSC)-derived neurons.
They further demonstrated through RNA-sequencing data analysis that sildenafil specifically targets Alzheimer’s disease related genes and pathobiological pathways, mechanistically supporting the beneficial effect of sildenafil in Alzheimer’s disease.
“We believe our findings provide the evidence needed for clinical trials to further examine the potential effectiveness of sildenafil in patients with Alzheimer’s disease,” Dr. Cheng said.
The study was primarily supported by the National Institute on Aging (NIA) and the National Institute of Neurological Disorders and Stroke (NINDS). Dr. Cheng had no relevant disclosures.
A version of this article appeared on Medscape.com.
The large real-world analysis of patient data from two databases showed a 30%-54% reduced prevalence in Alzheimer’s disease among patients who took sildenafil (Viagra) than those who did not, after adjusting for potential confounding factors.
This observation was further supported by mechanistic studies showing decreased neurotoxic protein levels in brain cells exposed to the phosphodiesterase type 5 inhibitor (PDE5i).
“Our findings provide further weight to repurposing this existing FDA-approved drug as a novel treatment for Alzheimer’s, which is in great need of new therapies,” Feixiong Cheng, PhD, director of the Cleveland Clinic Genome Center, who led the research, said in a news release.
“We used artificial intelligence to integrate data across multiple domains which all indicated sildenafil’s potential against this devastating neurological disease,” Dr. Cheng noted.
The study was published online in the Journal of Alzheimer’s Disease.
Neuroprotective?
Using real-world patient data from the MarketScan Medicare Supplemental database (2012-2017) and the Clinformatics database (2007-2020), the researchers conducted propensity score-stratified analyses after adjusting for gender, age, race, and comorbidities.
They searched for all individuals with pharmacy claims for sildenafil or four comparator drugs — bumetanide, furosemide, spironolactone, and nifedipine. Results showed that sildenafil use was associated with reduced likelihood of Alzheimer’s disease relative to the control drugs.
For example, sildenafil use was associated with a 54% reduced incidence of Alzheimer’s disease in MarketScan (hazard ratio [HR], 0.46; 95% CI, 0.32-0.66) and a 30% reduced prevalence of Alzheimer’s disease in Clinformatics (HR, 0.70; 95% CI, 0.49-1.00) compared with spironolactone.
The findings support a study published earlier this year that found a potential protective effect of PDE5i treatment on Alzheimer’s disease risk.
However, this research and the current study are contradicted by another paper published in Brain Communications in late 2022 which showed no such link between ED meds and reduced Alzheimer’s disease risk.
The investigators also found that sildenafil reduces tau hyperphosphorylation (pTau181 and pTau205) in a dose-dependent manner in both familial and sporadic Alzheimer’s disease patient induced pluripotent stem cell (iPSC)-derived neurons.
They further demonstrated through RNA-sequencing data analysis that sildenafil specifically targets Alzheimer’s disease related genes and pathobiological pathways, mechanistically supporting the beneficial effect of sildenafil in Alzheimer’s disease.
“We believe our findings provide the evidence needed for clinical trials to further examine the potential effectiveness of sildenafil in patients with Alzheimer’s disease,” Dr. Cheng said.
The study was primarily supported by the National Institute on Aging (NIA) and the National Institute of Neurological Disorders and Stroke (NINDS). Dr. Cheng had no relevant disclosures.
A version of this article appeared on Medscape.com.
FROM THE JOURNAL OF ALZHEIMER’S RESEARCH
Air Pollution Tied to Greater Amyloid Burden in the Brain
TOPLINE:
, a new postmortem study showed.
METHODOLOGY:
- Investigators examined the brain tissue of 224 people living in the Atlanta area who agreed to donate their brains after death (average age of death, 76 years) for the presence of amyloid plaques and tau tangles.
- They also studied the amount of fine particulate matter < 2.5 microns (PM2.5) from traffic-related air pollution at participants’ home addresses at 1, 3, and 5 years before death.
- The presence of the APOE e4 gene was examined for evidence of any effect on the relationship between air pollution and evidence of Alzheimer’s disease (AD).
TAKEAWAY:
The average level of exposure in the year before death was 1.32 µg/m3 and 1.35 µg/m3 in the 3 years before death.
People with 1 µg/m3 higher PM2.5 exposure in the year before death were nearly twice as likely to have higher levels of plaques (odds ratio [OR], 1.92; 95% CI, 1.12-3.30), while those with higher exposure in the 3 years before death were 87% more likely to have higher levels of plaques (OR, 1.87; 95% CI, 1.01-3.17).
A little more than half (56%) of the sample were positive for the APOE e4 genotype, but the strongest association between pollution and neuropathology markers was for noncarriers of the genotype, although this relationship did not reach statistical significance.
IN PRACTICE:
“More research is needed to establish causality for the association between PM2.5 and AD, including epidemiologic and mechanistic studies. Future studies should also investigate the association between PM2.5 and other dementia-related pathologies, including cerebrovascular pathology,” the study authors wrote.
SOURCE:
Anke Hüls, PhD, of Emory University in Atlanta, led the study, which was published online on February 21, 2024, in Neurology.
LIMITATIONS:
The sample was not population-based but a convenience sample composed mostly of highly educated White participants.
DISCLOSURES:
The study was funded by the National Institute of Environmental Health Sciences, the Goizueta Alzheimer’s Disease Research Center, the National Institute on Aging, and the National Institutes of Health. There were no relevant disclosures.
A version of this article appeared on Medscape.com.
TOPLINE:
, a new postmortem study showed.
METHODOLOGY:
- Investigators examined the brain tissue of 224 people living in the Atlanta area who agreed to donate their brains after death (average age of death, 76 years) for the presence of amyloid plaques and tau tangles.
- They also studied the amount of fine particulate matter < 2.5 microns (PM2.5) from traffic-related air pollution at participants’ home addresses at 1, 3, and 5 years before death.
- The presence of the APOE e4 gene was examined for evidence of any effect on the relationship between air pollution and evidence of Alzheimer’s disease (AD).
TAKEAWAY:
The average level of exposure in the year before death was 1.32 µg/m3 and 1.35 µg/m3 in the 3 years before death.
People with 1 µg/m3 higher PM2.5 exposure in the year before death were nearly twice as likely to have higher levels of plaques (odds ratio [OR], 1.92; 95% CI, 1.12-3.30), while those with higher exposure in the 3 years before death were 87% more likely to have higher levels of plaques (OR, 1.87; 95% CI, 1.01-3.17).
A little more than half (56%) of the sample were positive for the APOE e4 genotype, but the strongest association between pollution and neuropathology markers was for noncarriers of the genotype, although this relationship did not reach statistical significance.
IN PRACTICE:
“More research is needed to establish causality for the association between PM2.5 and AD, including epidemiologic and mechanistic studies. Future studies should also investigate the association between PM2.5 and other dementia-related pathologies, including cerebrovascular pathology,” the study authors wrote.
SOURCE:
Anke Hüls, PhD, of Emory University in Atlanta, led the study, which was published online on February 21, 2024, in Neurology.
LIMITATIONS:
The sample was not population-based but a convenience sample composed mostly of highly educated White participants.
DISCLOSURES:
The study was funded by the National Institute of Environmental Health Sciences, the Goizueta Alzheimer’s Disease Research Center, the National Institute on Aging, and the National Institutes of Health. There were no relevant disclosures.
A version of this article appeared on Medscape.com.
TOPLINE:
, a new postmortem study showed.
METHODOLOGY:
- Investigators examined the brain tissue of 224 people living in the Atlanta area who agreed to donate their brains after death (average age of death, 76 years) for the presence of amyloid plaques and tau tangles.
- They also studied the amount of fine particulate matter < 2.5 microns (PM2.5) from traffic-related air pollution at participants’ home addresses at 1, 3, and 5 years before death.
- The presence of the APOE e4 gene was examined for evidence of any effect on the relationship between air pollution and evidence of Alzheimer’s disease (AD).
TAKEAWAY:
The average level of exposure in the year before death was 1.32 µg/m3 and 1.35 µg/m3 in the 3 years before death.
People with 1 µg/m3 higher PM2.5 exposure in the year before death were nearly twice as likely to have higher levels of plaques (odds ratio [OR], 1.92; 95% CI, 1.12-3.30), while those with higher exposure in the 3 years before death were 87% more likely to have higher levels of plaques (OR, 1.87; 95% CI, 1.01-3.17).
A little more than half (56%) of the sample were positive for the APOE e4 genotype, but the strongest association between pollution and neuropathology markers was for noncarriers of the genotype, although this relationship did not reach statistical significance.
IN PRACTICE:
“More research is needed to establish causality for the association between PM2.5 and AD, including epidemiologic and mechanistic studies. Future studies should also investigate the association between PM2.5 and other dementia-related pathologies, including cerebrovascular pathology,” the study authors wrote.
SOURCE:
Anke Hüls, PhD, of Emory University in Atlanta, led the study, which was published online on February 21, 2024, in Neurology.
LIMITATIONS:
The sample was not population-based but a convenience sample composed mostly of highly educated White participants.
DISCLOSURES:
The study was funded by the National Institute of Environmental Health Sciences, the Goizueta Alzheimer’s Disease Research Center, the National Institute on Aging, and the National Institutes of Health. There were no relevant disclosures.
A version of this article appeared on Medscape.com.
A New Biomarker of Brain Injury?
Posttraumatic headache (PTH) is associated with an increase in iron accumulation in certain brain regions , notably those involved in the pain network, early research shows.
The findings come on the heels of previous research showing patients with iron accumulation in certain brain regions don’t respond as well to treatment, study investigator, Simona Nikolova, PhD, assistant professor of neurology, Mayo Clinic, Phoenix, Arizona, told this news organization.
“This is really important, and doctors need to be aware of it. If you have a patient who is not responding to treatment, then you know what to look at,” she said.
The findings (Abstract #3379) will be presented on April 15 at the American Academy of Neurology (AAN) 2024 Annual Meeting.
Dose Effect
The study included 60 people with acute PTH due to mTBI. Most were White, and almost half had sustained a concussion due to a fall, with about 30% injured in a vehicle accident and a smaller number injured during a fight.
The mean number of lifetime mTBIs was 2.4, although participants had sustained as many as five or six and as few as one. The mean time from the most recent mTBI was 25 days, and the mean score on the Sport Concussion Assessment Tool (SCAT), which measures postconcussion symptom severity, was 29.
Most in the mTBI group (43) had migraine or probable migraine, and 14 had tension-type headaches. Mean headache frequency was 81%.
Researchers matched these patients with 60 controls without concussion or headache. Because iron accumulation is age-related, they tried to eliminate this covariant by pairing each participant with mTBI with an age- and sex-matched control.
All participants underwent a type of brain MRI known as T2* weighted sequence that can identify brain iron accumulation, a marker of neural injury.
Investigators found that the PTH group had significantly higher levels of iron accumulation in several areas of the brain, most of which are part of a “pain network” that includes about 63 areas of the brain, Dr. Nikolova said.
The study wasn’t designed to determine how much more iron accumulation mTBI patients had vs controls.
“We can’t say it was twice as much or three times as much; we can only say it was significant. Measuring concentrations in PTH patients and comparing that with controls is something we haven’t don’t yet,” said Dr. Nikolova.
Areas of the brain with increased iron accumulation, included the periaqueductal gray (PAG), anterior cingulated cortex, and supramarginal gyrus.
Research suggests patients with migraine who have elevated levels of iron in the PAG have a poorer response to botulinum toxin treatment. An earlier study by the same team showed a poorer response to the calcitonin gene-related peptide inhibitor erenumab in migraine patients with elevated iron in the PAG.
Researchers discovered that those with more lifetime TBIs had higher iron accumulation in the right gyrus rectus and right putamen vs those with fewer injuries and that headache frequency was associated with iron accumulation in the posterior corona radiata, bilateral temporal, right frontal, bilateral supplemental motor area, left fusiform, right hippocampus, sagittal striatum, and left cerebellum.
Surprising Result
The investigators also found a link between time since the most recent mTBI and iron accumulation in the bilateral temporal, right hippocampus, posterior and superior corona radiata, bilateral thalamus, right precuneus and cuneus, right lingual, and right cerebellum.
“The more time that passed since the concussion occurred, the more likely that people had higher iron levels,” said Dr. Nikolova.
It’s perhaps to be expected that the length of time since injury is linked to iron accumulation in the brain as iron accumulates over time. But even those whose injury was relatively recent had higher amounts of iron, which Dr. Nikolova said was “surprising.”
“We thought iron accumulates over time so we were thinking maybe we should be doing a longitudinal study to see what happens, but we see definite iron accumulation due to injury shortly after the injury,” she said.
There was no association between iron accumulation and symptom severity as measured by SCAT scores.
Questions Remain
It’s unclear why iron accumulates after an injury or what the ramifications are of this accumulation, Dr. Nikolova noted.
The imaging used in the study doesn’t distinguish between “bound” iron found after a hemorrhage and “free” iron in the brain. The free iron type has been shown to be increased after TBI and is “the stuff you should be afraid of,” Dr. Nikolova said.
Iron’s role in the metabolic process is important, but must be closely regulated, she said. Even a small accumulation can lead to oxidative stress.
Researchers are investigating whether the findings would be similar in mTBI but no headache and want to increase the number of study participants. A larger, more diverse sample would allow them to probe other questions, including whether iron accumulation is different in men and women. More data could also eventually lead to iron accumulation becoming a biomarker for concussion and PTH, Dr. Nikolova said.
“If you know a certain person has that biomarker, you might be able to administer a drug or some therapeutic procedure to prevent that iron from continuing to accumulate in the brain.”
Chelation drugs and other therapies may clear iron from the body but not necessarily from the brain.
Commenting on the study for this news organization, Frank Conidi, MD, director, Florida Center for Headache and Sports Neurology, Port St. Lucie , said that the study supports the hypothesis that concussion “is not a benign process for the brain, and the cumulative effect of repetitive head injury can result in permanent brain injury.”
He said that he found the accumulation of iron in cortical structures particularly interesting. This, he said, differs from most current research that suggests head trauma mainly results in damage to white matter tracts.
He prefers the term “concussion” over “mild traumatic brain injury” which was used in the study. “Recent guidelines, including some that I’ve been involved with, have defined mild traumatic brain injury as a more permanent process,” he said.
The study was supported by the US Department of Defense and National Institutes of Health. No relevant conflicts of interest were disclosed.
A version of this article appeared on Medscape.com.
Posttraumatic headache (PTH) is associated with an increase in iron accumulation in certain brain regions , notably those involved in the pain network, early research shows.
The findings come on the heels of previous research showing patients with iron accumulation in certain brain regions don’t respond as well to treatment, study investigator, Simona Nikolova, PhD, assistant professor of neurology, Mayo Clinic, Phoenix, Arizona, told this news organization.
“This is really important, and doctors need to be aware of it. If you have a patient who is not responding to treatment, then you know what to look at,” she said.
The findings (Abstract #3379) will be presented on April 15 at the American Academy of Neurology (AAN) 2024 Annual Meeting.
Dose Effect
The study included 60 people with acute PTH due to mTBI. Most were White, and almost half had sustained a concussion due to a fall, with about 30% injured in a vehicle accident and a smaller number injured during a fight.
The mean number of lifetime mTBIs was 2.4, although participants had sustained as many as five or six and as few as one. The mean time from the most recent mTBI was 25 days, and the mean score on the Sport Concussion Assessment Tool (SCAT), which measures postconcussion symptom severity, was 29.
Most in the mTBI group (43) had migraine or probable migraine, and 14 had tension-type headaches. Mean headache frequency was 81%.
Researchers matched these patients with 60 controls without concussion or headache. Because iron accumulation is age-related, they tried to eliminate this covariant by pairing each participant with mTBI with an age- and sex-matched control.
All participants underwent a type of brain MRI known as T2* weighted sequence that can identify brain iron accumulation, a marker of neural injury.
Investigators found that the PTH group had significantly higher levels of iron accumulation in several areas of the brain, most of which are part of a “pain network” that includes about 63 areas of the brain, Dr. Nikolova said.
The study wasn’t designed to determine how much more iron accumulation mTBI patients had vs controls.
“We can’t say it was twice as much or three times as much; we can only say it was significant. Measuring concentrations in PTH patients and comparing that with controls is something we haven’t don’t yet,” said Dr. Nikolova.
Areas of the brain with increased iron accumulation, included the periaqueductal gray (PAG), anterior cingulated cortex, and supramarginal gyrus.
Research suggests patients with migraine who have elevated levels of iron in the PAG have a poorer response to botulinum toxin treatment. An earlier study by the same team showed a poorer response to the calcitonin gene-related peptide inhibitor erenumab in migraine patients with elevated iron in the PAG.
Researchers discovered that those with more lifetime TBIs had higher iron accumulation in the right gyrus rectus and right putamen vs those with fewer injuries and that headache frequency was associated with iron accumulation in the posterior corona radiata, bilateral temporal, right frontal, bilateral supplemental motor area, left fusiform, right hippocampus, sagittal striatum, and left cerebellum.
Surprising Result
The investigators also found a link between time since the most recent mTBI and iron accumulation in the bilateral temporal, right hippocampus, posterior and superior corona radiata, bilateral thalamus, right precuneus and cuneus, right lingual, and right cerebellum.
“The more time that passed since the concussion occurred, the more likely that people had higher iron levels,” said Dr. Nikolova.
It’s perhaps to be expected that the length of time since injury is linked to iron accumulation in the brain as iron accumulates over time. But even those whose injury was relatively recent had higher amounts of iron, which Dr. Nikolova said was “surprising.”
“We thought iron accumulates over time so we were thinking maybe we should be doing a longitudinal study to see what happens, but we see definite iron accumulation due to injury shortly after the injury,” she said.
There was no association between iron accumulation and symptom severity as measured by SCAT scores.
Questions Remain
It’s unclear why iron accumulates after an injury or what the ramifications are of this accumulation, Dr. Nikolova noted.
The imaging used in the study doesn’t distinguish between “bound” iron found after a hemorrhage and “free” iron in the brain. The free iron type has been shown to be increased after TBI and is “the stuff you should be afraid of,” Dr. Nikolova said.
Iron’s role in the metabolic process is important, but must be closely regulated, she said. Even a small accumulation can lead to oxidative stress.
Researchers are investigating whether the findings would be similar in mTBI but no headache and want to increase the number of study participants. A larger, more diverse sample would allow them to probe other questions, including whether iron accumulation is different in men and women. More data could also eventually lead to iron accumulation becoming a biomarker for concussion and PTH, Dr. Nikolova said.
“If you know a certain person has that biomarker, you might be able to administer a drug or some therapeutic procedure to prevent that iron from continuing to accumulate in the brain.”
Chelation drugs and other therapies may clear iron from the body but not necessarily from the brain.
Commenting on the study for this news organization, Frank Conidi, MD, director, Florida Center for Headache and Sports Neurology, Port St. Lucie , said that the study supports the hypothesis that concussion “is not a benign process for the brain, and the cumulative effect of repetitive head injury can result in permanent brain injury.”
He said that he found the accumulation of iron in cortical structures particularly interesting. This, he said, differs from most current research that suggests head trauma mainly results in damage to white matter tracts.
He prefers the term “concussion” over “mild traumatic brain injury” which was used in the study. “Recent guidelines, including some that I’ve been involved with, have defined mild traumatic brain injury as a more permanent process,” he said.
The study was supported by the US Department of Defense and National Institutes of Health. No relevant conflicts of interest were disclosed.
A version of this article appeared on Medscape.com.
Posttraumatic headache (PTH) is associated with an increase in iron accumulation in certain brain regions , notably those involved in the pain network, early research shows.
The findings come on the heels of previous research showing patients with iron accumulation in certain brain regions don’t respond as well to treatment, study investigator, Simona Nikolova, PhD, assistant professor of neurology, Mayo Clinic, Phoenix, Arizona, told this news organization.
“This is really important, and doctors need to be aware of it. If you have a patient who is not responding to treatment, then you know what to look at,” she said.
The findings (Abstract #3379) will be presented on April 15 at the American Academy of Neurology (AAN) 2024 Annual Meeting.
Dose Effect
The study included 60 people with acute PTH due to mTBI. Most were White, and almost half had sustained a concussion due to a fall, with about 30% injured in a vehicle accident and a smaller number injured during a fight.
The mean number of lifetime mTBIs was 2.4, although participants had sustained as many as five or six and as few as one. The mean time from the most recent mTBI was 25 days, and the mean score on the Sport Concussion Assessment Tool (SCAT), which measures postconcussion symptom severity, was 29.
Most in the mTBI group (43) had migraine or probable migraine, and 14 had tension-type headaches. Mean headache frequency was 81%.
Researchers matched these patients with 60 controls without concussion or headache. Because iron accumulation is age-related, they tried to eliminate this covariant by pairing each participant with mTBI with an age- and sex-matched control.
All participants underwent a type of brain MRI known as T2* weighted sequence that can identify brain iron accumulation, a marker of neural injury.
Investigators found that the PTH group had significantly higher levels of iron accumulation in several areas of the brain, most of which are part of a “pain network” that includes about 63 areas of the brain, Dr. Nikolova said.
The study wasn’t designed to determine how much more iron accumulation mTBI patients had vs controls.
“We can’t say it was twice as much or three times as much; we can only say it was significant. Measuring concentrations in PTH patients and comparing that with controls is something we haven’t don’t yet,” said Dr. Nikolova.
Areas of the brain with increased iron accumulation, included the periaqueductal gray (PAG), anterior cingulated cortex, and supramarginal gyrus.
Research suggests patients with migraine who have elevated levels of iron in the PAG have a poorer response to botulinum toxin treatment. An earlier study by the same team showed a poorer response to the calcitonin gene-related peptide inhibitor erenumab in migraine patients with elevated iron in the PAG.
Researchers discovered that those with more lifetime TBIs had higher iron accumulation in the right gyrus rectus and right putamen vs those with fewer injuries and that headache frequency was associated with iron accumulation in the posterior corona radiata, bilateral temporal, right frontal, bilateral supplemental motor area, left fusiform, right hippocampus, sagittal striatum, and left cerebellum.
Surprising Result
The investigators also found a link between time since the most recent mTBI and iron accumulation in the bilateral temporal, right hippocampus, posterior and superior corona radiata, bilateral thalamus, right precuneus and cuneus, right lingual, and right cerebellum.
“The more time that passed since the concussion occurred, the more likely that people had higher iron levels,” said Dr. Nikolova.
It’s perhaps to be expected that the length of time since injury is linked to iron accumulation in the brain as iron accumulates over time. But even those whose injury was relatively recent had higher amounts of iron, which Dr. Nikolova said was “surprising.”
“We thought iron accumulates over time so we were thinking maybe we should be doing a longitudinal study to see what happens, but we see definite iron accumulation due to injury shortly after the injury,” she said.
There was no association between iron accumulation and symptom severity as measured by SCAT scores.
Questions Remain
It’s unclear why iron accumulates after an injury or what the ramifications are of this accumulation, Dr. Nikolova noted.
The imaging used in the study doesn’t distinguish between “bound” iron found after a hemorrhage and “free” iron in the brain. The free iron type has been shown to be increased after TBI and is “the stuff you should be afraid of,” Dr. Nikolova said.
Iron’s role in the metabolic process is important, but must be closely regulated, she said. Even a small accumulation can lead to oxidative stress.
Researchers are investigating whether the findings would be similar in mTBI but no headache and want to increase the number of study participants. A larger, more diverse sample would allow them to probe other questions, including whether iron accumulation is different in men and women. More data could also eventually lead to iron accumulation becoming a biomarker for concussion and PTH, Dr. Nikolova said.
“If you know a certain person has that biomarker, you might be able to administer a drug or some therapeutic procedure to prevent that iron from continuing to accumulate in the brain.”
Chelation drugs and other therapies may clear iron from the body but not necessarily from the brain.
Commenting on the study for this news organization, Frank Conidi, MD, director, Florida Center for Headache and Sports Neurology, Port St. Lucie , said that the study supports the hypothesis that concussion “is not a benign process for the brain, and the cumulative effect of repetitive head injury can result in permanent brain injury.”
He said that he found the accumulation of iron in cortical structures particularly interesting. This, he said, differs from most current research that suggests head trauma mainly results in damage to white matter tracts.
He prefers the term “concussion” over “mild traumatic brain injury” which was used in the study. “Recent guidelines, including some that I’ve been involved with, have defined mild traumatic brain injury as a more permanent process,” he said.
The study was supported by the US Department of Defense and National Institutes of Health. No relevant conflicts of interest were disclosed.
A version of this article appeared on Medscape.com.
Promising New Wearable Could Retrain the Brain After Stroke
A new and deceptively simple advance in chronic stroke treatment could be a vibrating glove.
Researchers at Stanford University and Georgia Tech have developed a wearable device that straps around the wrist and hand, delivering subtle vibrations (akin to a vibrating cellphone) that may relieve spasticity as well as or better than the standard Botox injections.
“The vibro-tactile stimulation can be used at home, and we’re hoping it can be relatively low cost,” said senior study author Allison Okamura, PhD, a mechanical engineer at Stanford University, Stanford, California.
For now, the device is available only to clinical trial patients. But the researchers hope to get the glove into — or rather onto — more patients’ hands within a few years. A recent grant from the National Science Foundation’s Convergence Accelerator program could help pave the way to a commercial product. The team also hopes to expand access in the meantime through larger clinical trials with patients in additional locations.
The work builds on accumulating research exploring vibration and other stimulation therapies as treatments for neurological conditions. Other vibrating gloves have helped reduce involuntary movement for patients with Parkinson’s. And the University of Kansas Medical Center, Kansas City, will soon trial the Food and Drug Administration–approved vagal nerve stimulator, an implantable device intended to treat motor function in stroke survivors. Dr. Okamura noted that devices use “different types of vibration patterns and intensities,” depending on the disease state they target.
Spasticity often develops or worsens months after a stroke. By then, patients may have run out of insurance coverage for rehabilitation. And the effectiveness of Botox injections can “wear out over time,” Dr. Okamura said.
In a clinical trial, patients wore the device for 3 hours a day for 8 weeks, while doing their usual activities. The researchers continued testing their spasticity for 2 more weeks.
How Vibro-Tactile Stimulation May Rewire the Brain
The device originated at Georgia Tech, where Dr. Okamura’s postdoctoral research fellow Caitlyn Seim, PhD, was using vibro-tactile stimulation (VTS) to teach people skills, such as playing the piano, using touch-feedback training. The team decided to target spasticity, which VTS had helped in previousstudies of in-clinic (non-wearable) devices.
How does the device work? The researchers point to neuroplasticity, the ability of neurons to create new synapses or strengthen existing ones in the brain.
“The stimulation is sending additional sensory signals to the brain, which helps the brain interpret and reconnect any lost circuits,” Dr. Okamura said.
Spasticity is driven by “an imbalance in the excitatory drive to the muscles,” she continued. This can lead to worsening contractions, until a hand closes into a fist or a foot curls up. (The team has also done preliminary research on a similar device for foot spasticity, which they hope to continue developing.) Previous studies by Okamura and others suggest that vibration stimulation may prevent these contractions, both in the short and long term.
“Immediately, we do see some softening of the muscles,” Dr. Okamura said. “But in our longer-term study, where we compared to Botox, I also think that the vibration may be retraining the brain to send inhibitory signals. And that can restore balance that’s lost due to the damaged neural circuits from a stroke.”
When the team did a separate study comparing the effects of muscle and skin stimulation, they hypothesized that the vibration could be having a biomechanical effect on the muscle. Instead, they found that stimulating the skin had a greater impact — a “somewhat unexpected” result, Dr. Okamura said. That led them to the brain.
“Stimulating the skin is really about creating sensory signals that get sent to the brain,” Dr. Okamura said, “which is why we think it’s actually a brain-retraining effect and not a direct biomechanical effect.”
What’s Next?
The researchers are seeking funding for longer-term clinical studies to find out if effects persist beyond 2 weeks. They also want to explore how long and often patients should wear the glove for best results.
The researchers also want to study how movement might enhance the effects of the device.
“One of the treatments for spasticity — medications aside, this vibration machine aside — is more exercise, more passive range of motion,” said Oluwole O. Awosika, MD, associate professor at the University of Cincinnati College of Medicine, who was not involved in the study. “It would have been nice to have a control group that didn’t get any of this stimulation or that was only encouraged to do 3 hours of movement a day. What would the difference be?”
Dr. Awosika also wondered how easy it would be for stroke patients without in-home assistance to use the device. “Sometimes wearing these devices requires someone to put it on,” he said.
Of course, if all goes well, patients wouldn’t have to deal with that forever. “The dream would be that you reach true rehabilitation, which is no longer needing the device,” Dr. Okamura said.
A version of this article appeared on Medscape.com.
A new and deceptively simple advance in chronic stroke treatment could be a vibrating glove.
Researchers at Stanford University and Georgia Tech have developed a wearable device that straps around the wrist and hand, delivering subtle vibrations (akin to a vibrating cellphone) that may relieve spasticity as well as or better than the standard Botox injections.
“The vibro-tactile stimulation can be used at home, and we’re hoping it can be relatively low cost,” said senior study author Allison Okamura, PhD, a mechanical engineer at Stanford University, Stanford, California.
For now, the device is available only to clinical trial patients. But the researchers hope to get the glove into — or rather onto — more patients’ hands within a few years. A recent grant from the National Science Foundation’s Convergence Accelerator program could help pave the way to a commercial product. The team also hopes to expand access in the meantime through larger clinical trials with patients in additional locations.
The work builds on accumulating research exploring vibration and other stimulation therapies as treatments for neurological conditions. Other vibrating gloves have helped reduce involuntary movement for patients with Parkinson’s. And the University of Kansas Medical Center, Kansas City, will soon trial the Food and Drug Administration–approved vagal nerve stimulator, an implantable device intended to treat motor function in stroke survivors. Dr. Okamura noted that devices use “different types of vibration patterns and intensities,” depending on the disease state they target.
Spasticity often develops or worsens months after a stroke. By then, patients may have run out of insurance coverage for rehabilitation. And the effectiveness of Botox injections can “wear out over time,” Dr. Okamura said.
In a clinical trial, patients wore the device for 3 hours a day for 8 weeks, while doing their usual activities. The researchers continued testing their spasticity for 2 more weeks.
How Vibro-Tactile Stimulation May Rewire the Brain
The device originated at Georgia Tech, where Dr. Okamura’s postdoctoral research fellow Caitlyn Seim, PhD, was using vibro-tactile stimulation (VTS) to teach people skills, such as playing the piano, using touch-feedback training. The team decided to target spasticity, which VTS had helped in previousstudies of in-clinic (non-wearable) devices.
How does the device work? The researchers point to neuroplasticity, the ability of neurons to create new synapses or strengthen existing ones in the brain.
“The stimulation is sending additional sensory signals to the brain, which helps the brain interpret and reconnect any lost circuits,” Dr. Okamura said.
Spasticity is driven by “an imbalance in the excitatory drive to the muscles,” she continued. This can lead to worsening contractions, until a hand closes into a fist or a foot curls up. (The team has also done preliminary research on a similar device for foot spasticity, which they hope to continue developing.) Previous studies by Okamura and others suggest that vibration stimulation may prevent these contractions, both in the short and long term.
“Immediately, we do see some softening of the muscles,” Dr. Okamura said. “But in our longer-term study, where we compared to Botox, I also think that the vibration may be retraining the brain to send inhibitory signals. And that can restore balance that’s lost due to the damaged neural circuits from a stroke.”
When the team did a separate study comparing the effects of muscle and skin stimulation, they hypothesized that the vibration could be having a biomechanical effect on the muscle. Instead, they found that stimulating the skin had a greater impact — a “somewhat unexpected” result, Dr. Okamura said. That led them to the brain.
“Stimulating the skin is really about creating sensory signals that get sent to the brain,” Dr. Okamura said, “which is why we think it’s actually a brain-retraining effect and not a direct biomechanical effect.”
What’s Next?
The researchers are seeking funding for longer-term clinical studies to find out if effects persist beyond 2 weeks. They also want to explore how long and often patients should wear the glove for best results.
The researchers also want to study how movement might enhance the effects of the device.
“One of the treatments for spasticity — medications aside, this vibration machine aside — is more exercise, more passive range of motion,” said Oluwole O. Awosika, MD, associate professor at the University of Cincinnati College of Medicine, who was not involved in the study. “It would have been nice to have a control group that didn’t get any of this stimulation or that was only encouraged to do 3 hours of movement a day. What would the difference be?”
Dr. Awosika also wondered how easy it would be for stroke patients without in-home assistance to use the device. “Sometimes wearing these devices requires someone to put it on,” he said.
Of course, if all goes well, patients wouldn’t have to deal with that forever. “The dream would be that you reach true rehabilitation, which is no longer needing the device,” Dr. Okamura said.
A version of this article appeared on Medscape.com.
A new and deceptively simple advance in chronic stroke treatment could be a vibrating glove.
Researchers at Stanford University and Georgia Tech have developed a wearable device that straps around the wrist and hand, delivering subtle vibrations (akin to a vibrating cellphone) that may relieve spasticity as well as or better than the standard Botox injections.
“The vibro-tactile stimulation can be used at home, and we’re hoping it can be relatively low cost,” said senior study author Allison Okamura, PhD, a mechanical engineer at Stanford University, Stanford, California.
For now, the device is available only to clinical trial patients. But the researchers hope to get the glove into — or rather onto — more patients’ hands within a few years. A recent grant from the National Science Foundation’s Convergence Accelerator program could help pave the way to a commercial product. The team also hopes to expand access in the meantime through larger clinical trials with patients in additional locations.
The work builds on accumulating research exploring vibration and other stimulation therapies as treatments for neurological conditions. Other vibrating gloves have helped reduce involuntary movement for patients with Parkinson’s. And the University of Kansas Medical Center, Kansas City, will soon trial the Food and Drug Administration–approved vagal nerve stimulator, an implantable device intended to treat motor function in stroke survivors. Dr. Okamura noted that devices use “different types of vibration patterns and intensities,” depending on the disease state they target.
Spasticity often develops or worsens months after a stroke. By then, patients may have run out of insurance coverage for rehabilitation. And the effectiveness of Botox injections can “wear out over time,” Dr. Okamura said.
In a clinical trial, patients wore the device for 3 hours a day for 8 weeks, while doing their usual activities. The researchers continued testing their spasticity for 2 more weeks.
How Vibro-Tactile Stimulation May Rewire the Brain
The device originated at Georgia Tech, where Dr. Okamura’s postdoctoral research fellow Caitlyn Seim, PhD, was using vibro-tactile stimulation (VTS) to teach people skills, such as playing the piano, using touch-feedback training. The team decided to target spasticity, which VTS had helped in previousstudies of in-clinic (non-wearable) devices.
How does the device work? The researchers point to neuroplasticity, the ability of neurons to create new synapses or strengthen existing ones in the brain.
“The stimulation is sending additional sensory signals to the brain, which helps the brain interpret and reconnect any lost circuits,” Dr. Okamura said.
Spasticity is driven by “an imbalance in the excitatory drive to the muscles,” she continued. This can lead to worsening contractions, until a hand closes into a fist or a foot curls up. (The team has also done preliminary research on a similar device for foot spasticity, which they hope to continue developing.) Previous studies by Okamura and others suggest that vibration stimulation may prevent these contractions, both in the short and long term.
“Immediately, we do see some softening of the muscles,” Dr. Okamura said. “But in our longer-term study, where we compared to Botox, I also think that the vibration may be retraining the brain to send inhibitory signals. And that can restore balance that’s lost due to the damaged neural circuits from a stroke.”
When the team did a separate study comparing the effects of muscle and skin stimulation, they hypothesized that the vibration could be having a biomechanical effect on the muscle. Instead, they found that stimulating the skin had a greater impact — a “somewhat unexpected” result, Dr. Okamura said. That led them to the brain.
“Stimulating the skin is really about creating sensory signals that get sent to the brain,” Dr. Okamura said, “which is why we think it’s actually a brain-retraining effect and not a direct biomechanical effect.”
What’s Next?
The researchers are seeking funding for longer-term clinical studies to find out if effects persist beyond 2 weeks. They also want to explore how long and often patients should wear the glove for best results.
The researchers also want to study how movement might enhance the effects of the device.
“One of the treatments for spasticity — medications aside, this vibration machine aside — is more exercise, more passive range of motion,” said Oluwole O. Awosika, MD, associate professor at the University of Cincinnati College of Medicine, who was not involved in the study. “It would have been nice to have a control group that didn’t get any of this stimulation or that was only encouraged to do 3 hours of movement a day. What would the difference be?”
Dr. Awosika also wondered how easy it would be for stroke patients without in-home assistance to use the device. “Sometimes wearing these devices requires someone to put it on,” he said.
Of course, if all goes well, patients wouldn’t have to deal with that forever. “The dream would be that you reach true rehabilitation, which is no longer needing the device,” Dr. Okamura said.
A version of this article appeared on Medscape.com.
‘Remarkable’ Study Tracks Timeline of Biomarker Changes 20 Years Before Alzheimer’s disease
, something that hasn’t previously been extensively investigated in longitudinal studies.
By analyzing cerebral spinal fluid (CSF), as well as cognitive and brain imaging assessments conducted every few years for two decades, researchers were able to plot the course of changing levels of amyloid-beta 42 (Abeta42), phosphorylated tau 181 (p-tau181), and neurofilament light chain (NfL) in adults with Alzheimer’s disease and mark when those levels began to deviate from those of adults without Alzheimer’s disease.
Levels of Abeta42 in CSF and the ratio of Abeta42 to Abeta40 in people who developed Alzheimer’s disease diverged from those of peers who remained cognitively normal at 18 years and 14 years, respectively, before clinical signs of disease appeared.
The level of p-tau181 in CSF increased 11 years before disease onset, and NfL levels, a measure of neurodegeneration, increased 9 years before diagnosis.
These changes were followed by hippocampal atrophy and cognitive decline a few years later.
The results also show “an apparent accelerated change in concentrations of CSF biomarkers followed by a slowing of this change up to the time of diagnosis,” report the authors, led by Jianping Jia, MD, PhD, with the Innovation Center for Neurological Disorders, Xuanwu Hospital, Capital Medical University, Beijing, China.
The study was published online in The New England Journal of Medicine.
Time Course of Biomarker Changes
Dr. Jia and colleagues conducted a nested case-control study within the China Cognition and Aging Study (COAST). They matched 648 adults who developed Alzheimer’s disease to 648 who remained cognitively normal. CSF, cognitive, and brain imaging assessments were performed every 2-3 years for a median of about 20 years.
Within both groups, men slightly outnumbered women. At baseline, CSF biomarker levels, cognitive scores, and hippocampal volumes were similar in the two groups. Adults who developed Alzheimer’s disease were more likely than their matched controls to be carriers of the APOE epsilon-4 allele (37% vs 20%).
In terms of CSF Abeta42, the level of this biomarker in those who developed Alzheimer’s disease diverged from the level in controls an estimated 18 years before clinical diagnosis. At that time, the level was lower by a mean 59.13 pg/mL in the Alzheimer’s disease group.
A difference in the ratio of CSF Abeta42 to Abeta40 between the two groups appeared an estimated 14 years before the diagnosis of Alzheimer’s disease (difference in mean values, −0.01 pg/mL).
Differences between the two groups in CSF p-tau181 and total tau concentrations were apparent roughly 11 and 10 years before diagnosis, respectively. At those times, the mean differences in p-tau181 and total tau concentrations were 7.10 pg/mL and 87.10 pg/mL, respectively.
In terms of NfL, a difference between the groups was observed 9 years before diagnosis, with its trajectory progressively deviating from the concentrations observed in cognitively normal groups at that time, to a final mean difference in NfL of 228.29 pg/mL.
Bilateral hippocampal volume decreased with age in both groups. However, the decrease began to differ between the two groups 8 years before Alzheimer’s disease diagnosis, at which time volume was lower by 358.94 mm3 in the Alzheimer’s disease group compared with the control group.
Average Clinical Dementia Rating–Sum of Boxes (CDR-SB) scores in the Alzheimer’s disease group began to worsen compared with the control group at about 6 years before diagnosis.
As Alzheimer’s disease progressed, changes in CSF biomarkers increased before reaching a plateau.
Important Contribution
In a linked editorial, Richard Mayeux, MD, Department of Neurology, Columbia University, New York, said the importance of this work “cannot be overstated. Knowledge of the timing of these physiological events is critical to provide clinicians with useful starting points for prevention and therapeutic strategies.”
Dr. Mayeux said this “remarkable” longitudinal study spanning 2 decades “not only confirms the hypotheses of previous investigators but extends and validates the sequence of changes” in sporadic Alzheimer’s disease.
Dr. Mayeux acknowledged that one might consider the finding in this study to be limited owing to the inclusion of only individuals of Han Chinese ancestry.
However, longitudinal studies of plasma biomarkers in individuals of Asian, European, African, and Hispanic ancestry have shown similar trends in biomarker changes preceding the onset of Alzheimer’s disease, he noted.
“Ethnic variation in these biomarkers is known, but that fact does not lessen the effect of the results reported. It merely highlights that similar studies must continue and must be inclusive of other groups,” Dr. Mayeux concluded.
The study had no commercial funding. Disclosures for authors and editorialist are available at NEJM.org.
A version of this article appeared on Medscape.com.
, something that hasn’t previously been extensively investigated in longitudinal studies.
By analyzing cerebral spinal fluid (CSF), as well as cognitive and brain imaging assessments conducted every few years for two decades, researchers were able to plot the course of changing levels of amyloid-beta 42 (Abeta42), phosphorylated tau 181 (p-tau181), and neurofilament light chain (NfL) in adults with Alzheimer’s disease and mark when those levels began to deviate from those of adults without Alzheimer’s disease.
Levels of Abeta42 in CSF and the ratio of Abeta42 to Abeta40 in people who developed Alzheimer’s disease diverged from those of peers who remained cognitively normal at 18 years and 14 years, respectively, before clinical signs of disease appeared.
The level of p-tau181 in CSF increased 11 years before disease onset, and NfL levels, a measure of neurodegeneration, increased 9 years before diagnosis.
These changes were followed by hippocampal atrophy and cognitive decline a few years later.
The results also show “an apparent accelerated change in concentrations of CSF biomarkers followed by a slowing of this change up to the time of diagnosis,” report the authors, led by Jianping Jia, MD, PhD, with the Innovation Center for Neurological Disorders, Xuanwu Hospital, Capital Medical University, Beijing, China.
The study was published online in The New England Journal of Medicine.
Time Course of Biomarker Changes
Dr. Jia and colleagues conducted a nested case-control study within the China Cognition and Aging Study (COAST). They matched 648 adults who developed Alzheimer’s disease to 648 who remained cognitively normal. CSF, cognitive, and brain imaging assessments were performed every 2-3 years for a median of about 20 years.
Within both groups, men slightly outnumbered women. At baseline, CSF biomarker levels, cognitive scores, and hippocampal volumes were similar in the two groups. Adults who developed Alzheimer’s disease were more likely than their matched controls to be carriers of the APOE epsilon-4 allele (37% vs 20%).
In terms of CSF Abeta42, the level of this biomarker in those who developed Alzheimer’s disease diverged from the level in controls an estimated 18 years before clinical diagnosis. At that time, the level was lower by a mean 59.13 pg/mL in the Alzheimer’s disease group.
A difference in the ratio of CSF Abeta42 to Abeta40 between the two groups appeared an estimated 14 years before the diagnosis of Alzheimer’s disease (difference in mean values, −0.01 pg/mL).
Differences between the two groups in CSF p-tau181 and total tau concentrations were apparent roughly 11 and 10 years before diagnosis, respectively. At those times, the mean differences in p-tau181 and total tau concentrations were 7.10 pg/mL and 87.10 pg/mL, respectively.
In terms of NfL, a difference between the groups was observed 9 years before diagnosis, with its trajectory progressively deviating from the concentrations observed in cognitively normal groups at that time, to a final mean difference in NfL of 228.29 pg/mL.
Bilateral hippocampal volume decreased with age in both groups. However, the decrease began to differ between the two groups 8 years before Alzheimer’s disease diagnosis, at which time volume was lower by 358.94 mm3 in the Alzheimer’s disease group compared with the control group.
Average Clinical Dementia Rating–Sum of Boxes (CDR-SB) scores in the Alzheimer’s disease group began to worsen compared with the control group at about 6 years before diagnosis.
As Alzheimer’s disease progressed, changes in CSF biomarkers increased before reaching a plateau.
Important Contribution
In a linked editorial, Richard Mayeux, MD, Department of Neurology, Columbia University, New York, said the importance of this work “cannot be overstated. Knowledge of the timing of these physiological events is critical to provide clinicians with useful starting points for prevention and therapeutic strategies.”
Dr. Mayeux said this “remarkable” longitudinal study spanning 2 decades “not only confirms the hypotheses of previous investigators but extends and validates the sequence of changes” in sporadic Alzheimer’s disease.
Dr. Mayeux acknowledged that one might consider the finding in this study to be limited owing to the inclusion of only individuals of Han Chinese ancestry.
However, longitudinal studies of plasma biomarkers in individuals of Asian, European, African, and Hispanic ancestry have shown similar trends in biomarker changes preceding the onset of Alzheimer’s disease, he noted.
“Ethnic variation in these biomarkers is known, but that fact does not lessen the effect of the results reported. It merely highlights that similar studies must continue and must be inclusive of other groups,” Dr. Mayeux concluded.
The study had no commercial funding. Disclosures for authors and editorialist are available at NEJM.org.
A version of this article appeared on Medscape.com.
, something that hasn’t previously been extensively investigated in longitudinal studies.
By analyzing cerebral spinal fluid (CSF), as well as cognitive and brain imaging assessments conducted every few years for two decades, researchers were able to plot the course of changing levels of amyloid-beta 42 (Abeta42), phosphorylated tau 181 (p-tau181), and neurofilament light chain (NfL) in adults with Alzheimer’s disease and mark when those levels began to deviate from those of adults without Alzheimer’s disease.
Levels of Abeta42 in CSF and the ratio of Abeta42 to Abeta40 in people who developed Alzheimer’s disease diverged from those of peers who remained cognitively normal at 18 years and 14 years, respectively, before clinical signs of disease appeared.
The level of p-tau181 in CSF increased 11 years before disease onset, and NfL levels, a measure of neurodegeneration, increased 9 years before diagnosis.
These changes were followed by hippocampal atrophy and cognitive decline a few years later.
The results also show “an apparent accelerated change in concentrations of CSF biomarkers followed by a slowing of this change up to the time of diagnosis,” report the authors, led by Jianping Jia, MD, PhD, with the Innovation Center for Neurological Disorders, Xuanwu Hospital, Capital Medical University, Beijing, China.
The study was published online in The New England Journal of Medicine.
Time Course of Biomarker Changes
Dr. Jia and colleagues conducted a nested case-control study within the China Cognition and Aging Study (COAST). They matched 648 adults who developed Alzheimer’s disease to 648 who remained cognitively normal. CSF, cognitive, and brain imaging assessments were performed every 2-3 years for a median of about 20 years.
Within both groups, men slightly outnumbered women. At baseline, CSF biomarker levels, cognitive scores, and hippocampal volumes were similar in the two groups. Adults who developed Alzheimer’s disease were more likely than their matched controls to be carriers of the APOE epsilon-4 allele (37% vs 20%).
In terms of CSF Abeta42, the level of this biomarker in those who developed Alzheimer’s disease diverged from the level in controls an estimated 18 years before clinical diagnosis. At that time, the level was lower by a mean 59.13 pg/mL in the Alzheimer’s disease group.
A difference in the ratio of CSF Abeta42 to Abeta40 between the two groups appeared an estimated 14 years before the diagnosis of Alzheimer’s disease (difference in mean values, −0.01 pg/mL).
Differences between the two groups in CSF p-tau181 and total tau concentrations were apparent roughly 11 and 10 years before diagnosis, respectively. At those times, the mean differences in p-tau181 and total tau concentrations were 7.10 pg/mL and 87.10 pg/mL, respectively.
In terms of NfL, a difference between the groups was observed 9 years before diagnosis, with its trajectory progressively deviating from the concentrations observed in cognitively normal groups at that time, to a final mean difference in NfL of 228.29 pg/mL.
Bilateral hippocampal volume decreased with age in both groups. However, the decrease began to differ between the two groups 8 years before Alzheimer’s disease diagnosis, at which time volume was lower by 358.94 mm3 in the Alzheimer’s disease group compared with the control group.
Average Clinical Dementia Rating–Sum of Boxes (CDR-SB) scores in the Alzheimer’s disease group began to worsen compared with the control group at about 6 years before diagnosis.
As Alzheimer’s disease progressed, changes in CSF biomarkers increased before reaching a plateau.
Important Contribution
In a linked editorial, Richard Mayeux, MD, Department of Neurology, Columbia University, New York, said the importance of this work “cannot be overstated. Knowledge of the timing of these physiological events is critical to provide clinicians with useful starting points for prevention and therapeutic strategies.”
Dr. Mayeux said this “remarkable” longitudinal study spanning 2 decades “not only confirms the hypotheses of previous investigators but extends and validates the sequence of changes” in sporadic Alzheimer’s disease.
Dr. Mayeux acknowledged that one might consider the finding in this study to be limited owing to the inclusion of only individuals of Han Chinese ancestry.
However, longitudinal studies of plasma biomarkers in individuals of Asian, European, African, and Hispanic ancestry have shown similar trends in biomarker changes preceding the onset of Alzheimer’s disease, he noted.
“Ethnic variation in these biomarkers is known, but that fact does not lessen the effect of the results reported. It merely highlights that similar studies must continue and must be inclusive of other groups,” Dr. Mayeux concluded.
The study had no commercial funding. Disclosures for authors and editorialist are available at NEJM.org.
A version of this article appeared on Medscape.com.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
5 Interesting Neurology Studies
This transcript has been edited for clarity.
Dear colleagues, I’m Christoph Diener from the medical faculty of University Duisburg-Essen in Germany. Today I would like to tell you about five interesting studies that were published in January 2024.
Long COVID
I would like to start with long COVID. There is an ongoing discussion about whether this condition — which means symptoms like dizziness, vertigo, fatigue, headache, and cognitive impairment that persist for more than 6 months — is either a consequence of the infection, functional symptoms, psychosomatic disease, or a depression.
There is an important paper that came out in Science. The group investigated 39 controls and 113 patients who had COVID-19. At 6 months, 40 of them had long COVID. The researchers repeatedly measured more than 6500 proteins in serum. The patients with long COVID had a significant increase in complement activation, which persisted even beyond 6 months. These patients also showed increased tissue lesion markers in the blood and activation of the endothelium.
Also, they had increased platelet activation and autoantibodies with increased anti-cytomegalovirus and anti-Epstein-Barr virus immunoglobulins. These are very strong indicators that COVID-19 leads to long-term changes in our immune system, and different activations of complement factors could explain the variety of symptoms that these patients display. Whether this has consequences for treatment is unclear at the moment.
Parkinson’s Classification
Let me come to another issue, which is the future treatment of Parkinson’s disease, covered in a paper in The Lancet Neurology. I think you are all aware that once patients display symptoms like rigidity, bradykinesia, or tremor, it’s most probably too late for neuroprotective therapy because 70% of the dopaminergic neurons are already dead.
The authors propose a new biological diagnosis of the disease in the preclinical state. This early preclinical diagnosis has three components. One is to show the presence of synuclein either in skin biopsy or in serum. The second is proof of neurodegeneration either by MRI or by PET imaging. The third involves genetic markers.
On top of this, we know that we have preclinical manifestations of Parkinson’s disease, like REM sleep disorders, autonomic disturbances, and cognitive impairment. With this new classification, we should be able to identify the preclinical phase of Parkinson’s disease and include these patients in future trials for neuroprotection.
Niemann-Pick Disease
My third study, in The New England Journal of Medicine, deals with Niemann-Pick disease type C (Trial of N-Acetyl-l-Leucine in Niemann–Pick Disease Type C. This is a rare autosomal recessive disorder that involves impaired lysosomal storage. This disease, which manifests usually in childhood, goes along with systemic, psychiatric, and neurologic abnormalities, and in particular, ataxia. Until now, there has been only one therapy, with miglustat. which has many side effects.
The group of authors found a new therapeutic approach with N-acetyl-L-leucine, which primarily increases mitochondrial energy production. This was a small, placebo-controlled, crossover trial with 2 x 12 weeks of treatment. This new compound showed efficacy and was very well tolerated. This shows that we definitely need long-term studies with this new, well-tolerated drug in this rare disease.
Anticoagulation in Subclinical AF
My fourth study comes from the stroke-prevention field, published in The New England Journal of Medicine. I think you are aware of subclinical atrail fibrillation. These are high-frequency episodes in ECG, usually identified by pacemakers or ECG monitoring systems. The international ARTESIA study included more than 4000 patients randomized either to apixaban 5 mg twice daily or aspirin 81 mg.
After 3.5 years, the investigators showed a small but significant decrease in the rate of stroke, with a relative risk reduction of 37%, but also, unfortunately, a significantly increased risk for major bleeding with apixaban. This means that we need a careful discussion with the patient, the family, and the GP to decide whether these patients should be anticoagulated or not.
Migraine and Depression
My final study, published in the European Journal of Neurology, deals with the comorbidity of depression and migraine. This study in the Netherlands included 108 patients treated with erenumab and 90 with fremanezumab; 68 were controls.
They used two depression scales. They showed that treatment with the monoclonal antibodies improved at least one of the two depression scales. I think this is an important study because it indicates that you can improve comorbid depression in people with severe migraine, even if this study did not show a correlation between the reduction in monthly migraine days and the improvement of depression.
What we learned for clinical practice is that we have to identify depression in people with migraine and we have to deal with it. Whether it’s with the treatment of monoclonal antibodies or antidepressant therapy doesn’t really matter.
Dear colleagues, we had interesting studies this month. I think the most spectacular one was published in Science on long COVID. Thank you very much for listening and watching. I’m Christoph Diener from University Duisburg-Essen.
Dr. Diener is Professor, Department of Neurology, Stroke Center-Headache Center, University Duisburg-Essen, Essen, Germany. He disclosed ties with Abbott; Addex Pharma; Alder; Allergan; Almirall; Amgen; Autonomic Technology; AstraZeneca; Bayer Vital; Berlin Chemie; Bristol-Myers Squibb; Boehringer Ingelheim; Chordate; CoAxia; Corimmun; Covidien; Coherex; CoLucid; Daiichi-Sankyo; D-Pharml Electrocore; Fresenius; GlaxoSmithKline; Grunenthal; Janssen-Cilag; Labrys Biologics Lilly; La Roche; 3M Medica; MSD; Medtronic; Menarini; MindFrame; Minster; Neuroscore; Neurobiological Technologies; Novartis; Novo-Nordisk; Johnson & Johnson; Knoll; Paion; Parke-Davis; Pierre Fabre; Pfizer Inc; Schaper and Brummer; sanofi-aventis; Schering-Plough; Servier; Solvay; Syngis; St. Jude; Talecris; Thrombogenics; WebMD Global; Weber and Weber; Wyeth; and Yamanouchi.
A version of this article appeared on Medscape.com.
This transcript has been edited for clarity.
Dear colleagues, I’m Christoph Diener from the medical faculty of University Duisburg-Essen in Germany. Today I would like to tell you about five interesting studies that were published in January 2024.
Long COVID
I would like to start with long COVID. There is an ongoing discussion about whether this condition — which means symptoms like dizziness, vertigo, fatigue, headache, and cognitive impairment that persist for more than 6 months — is either a consequence of the infection, functional symptoms, psychosomatic disease, or a depression.
There is an important paper that came out in Science. The group investigated 39 controls and 113 patients who had COVID-19. At 6 months, 40 of them had long COVID. The researchers repeatedly measured more than 6500 proteins in serum. The patients with long COVID had a significant increase in complement activation, which persisted even beyond 6 months. These patients also showed increased tissue lesion markers in the blood and activation of the endothelium.
Also, they had increased platelet activation and autoantibodies with increased anti-cytomegalovirus and anti-Epstein-Barr virus immunoglobulins. These are very strong indicators that COVID-19 leads to long-term changes in our immune system, and different activations of complement factors could explain the variety of symptoms that these patients display. Whether this has consequences for treatment is unclear at the moment.
Parkinson’s Classification
Let me come to another issue, which is the future treatment of Parkinson’s disease, covered in a paper in The Lancet Neurology. I think you are all aware that once patients display symptoms like rigidity, bradykinesia, or tremor, it’s most probably too late for neuroprotective therapy because 70% of the dopaminergic neurons are already dead.
The authors propose a new biological diagnosis of the disease in the preclinical state. This early preclinical diagnosis has three components. One is to show the presence of synuclein either in skin biopsy or in serum. The second is proof of neurodegeneration either by MRI or by PET imaging. The third involves genetic markers.
On top of this, we know that we have preclinical manifestations of Parkinson’s disease, like REM sleep disorders, autonomic disturbances, and cognitive impairment. With this new classification, we should be able to identify the preclinical phase of Parkinson’s disease and include these patients in future trials for neuroprotection.
Niemann-Pick Disease
My third study, in The New England Journal of Medicine, deals with Niemann-Pick disease type C (Trial of N-Acetyl-l-Leucine in Niemann–Pick Disease Type C. This is a rare autosomal recessive disorder that involves impaired lysosomal storage. This disease, which manifests usually in childhood, goes along with systemic, psychiatric, and neurologic abnormalities, and in particular, ataxia. Until now, there has been only one therapy, with miglustat. which has many side effects.
The group of authors found a new therapeutic approach with N-acetyl-L-leucine, which primarily increases mitochondrial energy production. This was a small, placebo-controlled, crossover trial with 2 x 12 weeks of treatment. This new compound showed efficacy and was very well tolerated. This shows that we definitely need long-term studies with this new, well-tolerated drug in this rare disease.
Anticoagulation in Subclinical AF
My fourth study comes from the stroke-prevention field, published in The New England Journal of Medicine. I think you are aware of subclinical atrail fibrillation. These are high-frequency episodes in ECG, usually identified by pacemakers or ECG monitoring systems. The international ARTESIA study included more than 4000 patients randomized either to apixaban 5 mg twice daily or aspirin 81 mg.
After 3.5 years, the investigators showed a small but significant decrease in the rate of stroke, with a relative risk reduction of 37%, but also, unfortunately, a significantly increased risk for major bleeding with apixaban. This means that we need a careful discussion with the patient, the family, and the GP to decide whether these patients should be anticoagulated or not.
Migraine and Depression
My final study, published in the European Journal of Neurology, deals with the comorbidity of depression and migraine. This study in the Netherlands included 108 patients treated with erenumab and 90 with fremanezumab; 68 were controls.
They used two depression scales. They showed that treatment with the monoclonal antibodies improved at least one of the two depression scales. I think this is an important study because it indicates that you can improve comorbid depression in people with severe migraine, even if this study did not show a correlation between the reduction in monthly migraine days and the improvement of depression.
What we learned for clinical practice is that we have to identify depression in people with migraine and we have to deal with it. Whether it’s with the treatment of monoclonal antibodies or antidepressant therapy doesn’t really matter.
Dear colleagues, we had interesting studies this month. I think the most spectacular one was published in Science on long COVID. Thank you very much for listening and watching. I’m Christoph Diener from University Duisburg-Essen.
Dr. Diener is Professor, Department of Neurology, Stroke Center-Headache Center, University Duisburg-Essen, Essen, Germany. He disclosed ties with Abbott; Addex Pharma; Alder; Allergan; Almirall; Amgen; Autonomic Technology; AstraZeneca; Bayer Vital; Berlin Chemie; Bristol-Myers Squibb; Boehringer Ingelheim; Chordate; CoAxia; Corimmun; Covidien; Coherex; CoLucid; Daiichi-Sankyo; D-Pharml Electrocore; Fresenius; GlaxoSmithKline; Grunenthal; Janssen-Cilag; Labrys Biologics Lilly; La Roche; 3M Medica; MSD; Medtronic; Menarini; MindFrame; Minster; Neuroscore; Neurobiological Technologies; Novartis; Novo-Nordisk; Johnson & Johnson; Knoll; Paion; Parke-Davis; Pierre Fabre; Pfizer Inc; Schaper and Brummer; sanofi-aventis; Schering-Plough; Servier; Solvay; Syngis; St. Jude; Talecris; Thrombogenics; WebMD Global; Weber and Weber; Wyeth; and Yamanouchi.
A version of this article appeared on Medscape.com.
This transcript has been edited for clarity.
Dear colleagues, I’m Christoph Diener from the medical faculty of University Duisburg-Essen in Germany. Today I would like to tell you about five interesting studies that were published in January 2024.
Long COVID
I would like to start with long COVID. There is an ongoing discussion about whether this condition — which means symptoms like dizziness, vertigo, fatigue, headache, and cognitive impairment that persist for more than 6 months — is either a consequence of the infection, functional symptoms, psychosomatic disease, or a depression.
There is an important paper that came out in Science. The group investigated 39 controls and 113 patients who had COVID-19. At 6 months, 40 of them had long COVID. The researchers repeatedly measured more than 6500 proteins in serum. The patients with long COVID had a significant increase in complement activation, which persisted even beyond 6 months. These patients also showed increased tissue lesion markers in the blood and activation of the endothelium.
Also, they had increased platelet activation and autoantibodies with increased anti-cytomegalovirus and anti-Epstein-Barr virus immunoglobulins. These are very strong indicators that COVID-19 leads to long-term changes in our immune system, and different activations of complement factors could explain the variety of symptoms that these patients display. Whether this has consequences for treatment is unclear at the moment.
Parkinson’s Classification
Let me come to another issue, which is the future treatment of Parkinson’s disease, covered in a paper in The Lancet Neurology. I think you are all aware that once patients display symptoms like rigidity, bradykinesia, or tremor, it’s most probably too late for neuroprotective therapy because 70% of the dopaminergic neurons are already dead.
The authors propose a new biological diagnosis of the disease in the preclinical state. This early preclinical diagnosis has three components. One is to show the presence of synuclein either in skin biopsy or in serum. The second is proof of neurodegeneration either by MRI or by PET imaging. The third involves genetic markers.
On top of this, we know that we have preclinical manifestations of Parkinson’s disease, like REM sleep disorders, autonomic disturbances, and cognitive impairment. With this new classification, we should be able to identify the preclinical phase of Parkinson’s disease and include these patients in future trials for neuroprotection.
Niemann-Pick Disease
My third study, in The New England Journal of Medicine, deals with Niemann-Pick disease type C (Trial of N-Acetyl-l-Leucine in Niemann–Pick Disease Type C. This is a rare autosomal recessive disorder that involves impaired lysosomal storage. This disease, which manifests usually in childhood, goes along with systemic, psychiatric, and neurologic abnormalities, and in particular, ataxia. Until now, there has been only one therapy, with miglustat. which has many side effects.
The group of authors found a new therapeutic approach with N-acetyl-L-leucine, which primarily increases mitochondrial energy production. This was a small, placebo-controlled, crossover trial with 2 x 12 weeks of treatment. This new compound showed efficacy and was very well tolerated. This shows that we definitely need long-term studies with this new, well-tolerated drug in this rare disease.
Anticoagulation in Subclinical AF
My fourth study comes from the stroke-prevention field, published in The New England Journal of Medicine. I think you are aware of subclinical atrail fibrillation. These are high-frequency episodes in ECG, usually identified by pacemakers or ECG monitoring systems. The international ARTESIA study included more than 4000 patients randomized either to apixaban 5 mg twice daily or aspirin 81 mg.
After 3.5 years, the investigators showed a small but significant decrease in the rate of stroke, with a relative risk reduction of 37%, but also, unfortunately, a significantly increased risk for major bleeding with apixaban. This means that we need a careful discussion with the patient, the family, and the GP to decide whether these patients should be anticoagulated or not.
Migraine and Depression
My final study, published in the European Journal of Neurology, deals with the comorbidity of depression and migraine. This study in the Netherlands included 108 patients treated with erenumab and 90 with fremanezumab; 68 were controls.
They used two depression scales. They showed that treatment with the monoclonal antibodies improved at least one of the two depression scales. I think this is an important study because it indicates that you can improve comorbid depression in people with severe migraine, even if this study did not show a correlation between the reduction in monthly migraine days and the improvement of depression.
What we learned for clinical practice is that we have to identify depression in people with migraine and we have to deal with it. Whether it’s with the treatment of monoclonal antibodies or antidepressant therapy doesn’t really matter.
Dear colleagues, we had interesting studies this month. I think the most spectacular one was published in Science on long COVID. Thank you very much for listening and watching. I’m Christoph Diener from University Duisburg-Essen.
Dr. Diener is Professor, Department of Neurology, Stroke Center-Headache Center, University Duisburg-Essen, Essen, Germany. He disclosed ties with Abbott; Addex Pharma; Alder; Allergan; Almirall; Amgen; Autonomic Technology; AstraZeneca; Bayer Vital; Berlin Chemie; Bristol-Myers Squibb; Boehringer Ingelheim; Chordate; CoAxia; Corimmun; Covidien; Coherex; CoLucid; Daiichi-Sankyo; D-Pharml Electrocore; Fresenius; GlaxoSmithKline; Grunenthal; Janssen-Cilag; Labrys Biologics Lilly; La Roche; 3M Medica; MSD; Medtronic; Menarini; MindFrame; Minster; Neuroscore; Neurobiological Technologies; Novartis; Novo-Nordisk; Johnson & Johnson; Knoll; Paion; Parke-Davis; Pierre Fabre; Pfizer Inc; Schaper and Brummer; sanofi-aventis; Schering-Plough; Servier; Solvay; Syngis; St. Jude; Talecris; Thrombogenics; WebMD Global; Weber and Weber; Wyeth; and Yamanouchi.
A version of this article appeared on Medscape.com.
FDA Removes Harmful Chemicals From Food Packaging
Issued on February 28, 2024, “this means the major source of dietary exposure to PFAS from food packaging like fast-food wrappers, microwave popcorn bags, take-out paperboard containers, and pet food bags is being eliminated,” the FDA said in a statement.
In 2020, the FDA had secured commitments from manufacturers to stop selling products containing PFAS used in the food packaging for grease-proofing. “Today’s announcement marks the fulfillment of these voluntary commitments,” according to the agency.
PFAS, a class of thousands of chemicals also called “forever chemicals” are widely used in consumer and industrial products. People may be exposed via contaminated food packaging (although perhaps no longer in the United States) or occupationally. Studies have found that some PFAS disrupt hormones including estrogen and testosterone, whereas others may impair thyroid function.
Endocrine Society Report Sounds the Alarm About PFAS and Others
The FDA’s announcement came just 2 days after the Endocrine Society issued a new alarm about the human health dangers from environmental EDCs including PFAS in a report covering the latest science.
“Endocrine disrupting chemicals” are individual substances or mixtures that can interfere with natural hormonal function, leading to disease or even death. Many are ubiquitous in the modern environment and contribute to a wide range of human diseases.
The new report Endocrine Disrupting Chemicals: Threats to Human Health was issued jointly with the International Pollutants Elimination Network (IPEN), a global advocacy organization. It’s an update to the Endocrine Society’s 2015 report, providing new data on the endocrine-disrupting substances previously covered and adding four EDCs not discussed in that document: Pesticides, plastics, PFAS, and children’s products containing arsenic.
At a briefing held during the United Nations Environment Assembly meeting in Nairobi, Kenya, last week, the new report’s lead author Andrea C. Gore, PhD, of the University of Texas at Austin, noted, “A well-established body of scientific research indicates that endocrine-disrupting chemicals that are part of our daily lives are making us more susceptible to reproductive disorders, cancer, diabetes, obesity, heart disease, and other serious health conditions.”
Added Dr. Gore, who is also a member of the Endocrine Society’s Board of Directors, “These chemicals pose particularly serious risks to pregnant women and children. Now is the time for the UN Environment Assembly and other global policymakers to take action to address this threat to public health.”
While the science has been emerging rapidly, global and national chemical control policies haven’t kept up, the authors said. Of particular concern is that EDCs behave differently from other chemicals in many ways, including that even very low-dose exposures can pose health threats, but policies thus far haven’t dealt with that aspect.
Moreover, “the effects of low doses cannot be predicted by the effects observed at high doses. This means there may be no safe dose for exposure to EDCs,” according to the report.
Exposures can come from household products, including furniture, toys, and food packages, as well as electronics building materials and cosmetics. These chemicals are also in the outdoor environment, via pesticides, air pollution, and industrial waste.
“IPEN and the Endocrine Society call for chemical regulations based on the most modern scientific understanding of how hormones act and how EDCs can perturb these actions. We work to educate policy makers in global, regional, and national government assemblies and help ensure that regulations correlate with current scientific understanding,” they said in the report.
New Data on Four Classes of EDCs
Chapters of the report summarized the latest information about the science of EDCs and their links to endocrine disease and real-world exposure. It included a special section about “EDCs throughout the plastics life cycle” and a summary of the links between EDCs and climate change.
The report reviewed three pesticides, including the world’s most heavily applied herbicide, glycophosphate. Exposures can occur directly from the air, water, dust, and food residues. Recent data linked glycophosphate to adverse reproductive health outcomes.
Two toxic plastic chemicals, phthalates and bisphenols, are present in personal care products, among others. Emerging evidence links them with impaired neurodevelopment, leading to impaired cognitive function, learning, attention, and impulsivity.
Arsenic has long been linked to human health conditions including cancer, but more recent evidence finds it can disrupt multiple endocrine systems and lead to metabolic conditions including diabetes, reproductive dysfunction, and cardiovascular and neurocognitive conditions.
The special section about plastics noted that they are made from fossil fuels and chemicals, including many toxic substances that are known or suspected EDCs. People who live near plastic production facilities or waste dumps may be at greatest risk, but anyone can be exposed using any plastic product. Plastic waste disposal is increasingly problematic and often foisted on lower- and middle-income countries.
‘Additional Education and Awareness-Raising Among Stakeholders Remain Necessary’
Policies aimed at reducing human health risks from EDCs have included the 2022 Plastics Treaty, a resolution adopted by 175 countries at the United Nations Environmental Assembly that “may be a significant step toward global control of plastics and elimination of threats from exposures to EDCs in plastics,” the report said.
The authors added, “While significant progress has been made in recent years connecting scientific advances on EDCs with health-protective policies, additional education and awareness-raising among stakeholders remain necessary to achieve a safer and more sustainable environment that minimizes exposure to these harmful chemicals.”
The document was produced with financial contributions from the Government of Sweden, the Tides Foundation, Passport Foundation, and other donors.
A version of this article appeared on Medscape.com.
Issued on February 28, 2024, “this means the major source of dietary exposure to PFAS from food packaging like fast-food wrappers, microwave popcorn bags, take-out paperboard containers, and pet food bags is being eliminated,” the FDA said in a statement.
In 2020, the FDA had secured commitments from manufacturers to stop selling products containing PFAS used in the food packaging for grease-proofing. “Today’s announcement marks the fulfillment of these voluntary commitments,” according to the agency.
PFAS, a class of thousands of chemicals also called “forever chemicals” are widely used in consumer and industrial products. People may be exposed via contaminated food packaging (although perhaps no longer in the United States) or occupationally. Studies have found that some PFAS disrupt hormones including estrogen and testosterone, whereas others may impair thyroid function.
Endocrine Society Report Sounds the Alarm About PFAS and Others
The FDA’s announcement came just 2 days after the Endocrine Society issued a new alarm about the human health dangers from environmental EDCs including PFAS in a report covering the latest science.
“Endocrine disrupting chemicals” are individual substances or mixtures that can interfere with natural hormonal function, leading to disease or even death. Many are ubiquitous in the modern environment and contribute to a wide range of human diseases.
The new report Endocrine Disrupting Chemicals: Threats to Human Health was issued jointly with the International Pollutants Elimination Network (IPEN), a global advocacy organization. It’s an update to the Endocrine Society’s 2015 report, providing new data on the endocrine-disrupting substances previously covered and adding four EDCs not discussed in that document: Pesticides, plastics, PFAS, and children’s products containing arsenic.
At a briefing held during the United Nations Environment Assembly meeting in Nairobi, Kenya, last week, the new report’s lead author Andrea C. Gore, PhD, of the University of Texas at Austin, noted, “A well-established body of scientific research indicates that endocrine-disrupting chemicals that are part of our daily lives are making us more susceptible to reproductive disorders, cancer, diabetes, obesity, heart disease, and other serious health conditions.”
Added Dr. Gore, who is also a member of the Endocrine Society’s Board of Directors, “These chemicals pose particularly serious risks to pregnant women and children. Now is the time for the UN Environment Assembly and other global policymakers to take action to address this threat to public health.”
While the science has been emerging rapidly, global and national chemical control policies haven’t kept up, the authors said. Of particular concern is that EDCs behave differently from other chemicals in many ways, including that even very low-dose exposures can pose health threats, but policies thus far haven’t dealt with that aspect.
Moreover, “the effects of low doses cannot be predicted by the effects observed at high doses. This means there may be no safe dose for exposure to EDCs,” according to the report.
Exposures can come from household products, including furniture, toys, and food packages, as well as electronics building materials and cosmetics. These chemicals are also in the outdoor environment, via pesticides, air pollution, and industrial waste.
“IPEN and the Endocrine Society call for chemical regulations based on the most modern scientific understanding of how hormones act and how EDCs can perturb these actions. We work to educate policy makers in global, regional, and national government assemblies and help ensure that regulations correlate with current scientific understanding,” they said in the report.
New Data on Four Classes of EDCs
Chapters of the report summarized the latest information about the science of EDCs and their links to endocrine disease and real-world exposure. It included a special section about “EDCs throughout the plastics life cycle” and a summary of the links between EDCs and climate change.
The report reviewed three pesticides, including the world’s most heavily applied herbicide, glycophosphate. Exposures can occur directly from the air, water, dust, and food residues. Recent data linked glycophosphate to adverse reproductive health outcomes.
Two toxic plastic chemicals, phthalates and bisphenols, are present in personal care products, among others. Emerging evidence links them with impaired neurodevelopment, leading to impaired cognitive function, learning, attention, and impulsivity.
Arsenic has long been linked to human health conditions including cancer, but more recent evidence finds it can disrupt multiple endocrine systems and lead to metabolic conditions including diabetes, reproductive dysfunction, and cardiovascular and neurocognitive conditions.
The special section about plastics noted that they are made from fossil fuels and chemicals, including many toxic substances that are known or suspected EDCs. People who live near plastic production facilities or waste dumps may be at greatest risk, but anyone can be exposed using any plastic product. Plastic waste disposal is increasingly problematic and often foisted on lower- and middle-income countries.
‘Additional Education and Awareness-Raising Among Stakeholders Remain Necessary’
Policies aimed at reducing human health risks from EDCs have included the 2022 Plastics Treaty, a resolution adopted by 175 countries at the United Nations Environmental Assembly that “may be a significant step toward global control of plastics and elimination of threats from exposures to EDCs in plastics,” the report said.
The authors added, “While significant progress has been made in recent years connecting scientific advances on EDCs with health-protective policies, additional education and awareness-raising among stakeholders remain necessary to achieve a safer and more sustainable environment that minimizes exposure to these harmful chemicals.”
The document was produced with financial contributions from the Government of Sweden, the Tides Foundation, Passport Foundation, and other donors.
A version of this article appeared on Medscape.com.
Issued on February 28, 2024, “this means the major source of dietary exposure to PFAS from food packaging like fast-food wrappers, microwave popcorn bags, take-out paperboard containers, and pet food bags is being eliminated,” the FDA said in a statement.
In 2020, the FDA had secured commitments from manufacturers to stop selling products containing PFAS used in the food packaging for grease-proofing. “Today’s announcement marks the fulfillment of these voluntary commitments,” according to the agency.
PFAS, a class of thousands of chemicals also called “forever chemicals” are widely used in consumer and industrial products. People may be exposed via contaminated food packaging (although perhaps no longer in the United States) or occupationally. Studies have found that some PFAS disrupt hormones including estrogen and testosterone, whereas others may impair thyroid function.
Endocrine Society Report Sounds the Alarm About PFAS and Others
The FDA’s announcement came just 2 days after the Endocrine Society issued a new alarm about the human health dangers from environmental EDCs including PFAS in a report covering the latest science.
“Endocrine disrupting chemicals” are individual substances or mixtures that can interfere with natural hormonal function, leading to disease or even death. Many are ubiquitous in the modern environment and contribute to a wide range of human diseases.
The new report Endocrine Disrupting Chemicals: Threats to Human Health was issued jointly with the International Pollutants Elimination Network (IPEN), a global advocacy organization. It’s an update to the Endocrine Society’s 2015 report, providing new data on the endocrine-disrupting substances previously covered and adding four EDCs not discussed in that document: Pesticides, plastics, PFAS, and children’s products containing arsenic.
At a briefing held during the United Nations Environment Assembly meeting in Nairobi, Kenya, last week, the new report’s lead author Andrea C. Gore, PhD, of the University of Texas at Austin, noted, “A well-established body of scientific research indicates that endocrine-disrupting chemicals that are part of our daily lives are making us more susceptible to reproductive disorders, cancer, diabetes, obesity, heart disease, and other serious health conditions.”
Added Dr. Gore, who is also a member of the Endocrine Society’s Board of Directors, “These chemicals pose particularly serious risks to pregnant women and children. Now is the time for the UN Environment Assembly and other global policymakers to take action to address this threat to public health.”
While the science has been emerging rapidly, global and national chemical control policies haven’t kept up, the authors said. Of particular concern is that EDCs behave differently from other chemicals in many ways, including that even very low-dose exposures can pose health threats, but policies thus far haven’t dealt with that aspect.
Moreover, “the effects of low doses cannot be predicted by the effects observed at high doses. This means there may be no safe dose for exposure to EDCs,” according to the report.
Exposures can come from household products, including furniture, toys, and food packages, as well as electronics building materials and cosmetics. These chemicals are also in the outdoor environment, via pesticides, air pollution, and industrial waste.
“IPEN and the Endocrine Society call for chemical regulations based on the most modern scientific understanding of how hormones act and how EDCs can perturb these actions. We work to educate policy makers in global, regional, and national government assemblies and help ensure that regulations correlate with current scientific understanding,” they said in the report.
New Data on Four Classes of EDCs
Chapters of the report summarized the latest information about the science of EDCs and their links to endocrine disease and real-world exposure. It included a special section about “EDCs throughout the plastics life cycle” and a summary of the links between EDCs and climate change.
The report reviewed three pesticides, including the world’s most heavily applied herbicide, glycophosphate. Exposures can occur directly from the air, water, dust, and food residues. Recent data linked glycophosphate to adverse reproductive health outcomes.
Two toxic plastic chemicals, phthalates and bisphenols, are present in personal care products, among others. Emerging evidence links them with impaired neurodevelopment, leading to impaired cognitive function, learning, attention, and impulsivity.
Arsenic has long been linked to human health conditions including cancer, but more recent evidence finds it can disrupt multiple endocrine systems and lead to metabolic conditions including diabetes, reproductive dysfunction, and cardiovascular and neurocognitive conditions.
The special section about plastics noted that they are made from fossil fuels and chemicals, including many toxic substances that are known or suspected EDCs. People who live near plastic production facilities or waste dumps may be at greatest risk, but anyone can be exposed using any plastic product. Plastic waste disposal is increasingly problematic and often foisted on lower- and middle-income countries.
‘Additional Education and Awareness-Raising Among Stakeholders Remain Necessary’
Policies aimed at reducing human health risks from EDCs have included the 2022 Plastics Treaty, a resolution adopted by 175 countries at the United Nations Environmental Assembly that “may be a significant step toward global control of plastics and elimination of threats from exposures to EDCs in plastics,” the report said.
The authors added, “While significant progress has been made in recent years connecting scientific advances on EDCs with health-protective policies, additional education and awareness-raising among stakeholders remain necessary to achieve a safer and more sustainable environment that minimizes exposure to these harmful chemicals.”
The document was produced with financial contributions from the Government of Sweden, the Tides Foundation, Passport Foundation, and other donors.
A version of this article appeared on Medscape.com.
Galantamine Supplements Found Mislabeled, Contaminated
TOPLINE:
Galantamine purchased as a dietary supplement may be more likely to contain bacterial contaminants and an incorrect amount of the product vs when it is prescribed as a generic drug, new research showed.
METHODOLOGY:
- Galantamine, a plant alkaloid, is approved for treating mild to moderate Alzheimer’s dementia but is also marketed as a dietary supplement for cognitive enhancement.
- In June 2023, researchers purchased all 10 galantamine dietary supplements available on Amazon.com that had a Supplement Facts panel.
- In September 2023, they acquired all 11 generic immediate-release formulations of prescription galantamine available in the United States.
- They analyzed the content of galantamine in each product using ultrahigh-performance liquid chromatography-mass spectrometry and quantified any microorganisms present.
TAKEAWAY:
- Generic galantamine drugs were found to contain 97.5%-104.2% of the labeled content, with no microbial contamination.
- , according to the authors of the study.
IN PRACTICE:
“Clinicians should query patients with memory concerns about the use of dietary supplements and advise patients not to use galantamine supplements,” the researchers wrote.
SOURCE:
The corresponding author of the study was Pieter A. Cohen, MD, with Broadway Clinic, Cambridge Health Alliance, in Somerville, Massachusetts. The paper was published online as a research letter in JAMA.
LIMITATIONS:
The products were purchased at a single point in time and may not reflect current options, the researchers noted. The generalizability of the findings to other supplement ingredients or generic drugs is unknown.
DISCLOSURES:
Dr. Cohen has received grants from the Consumers Union and PEW Charitable Trust and personal fees from UpToDate and the Centers for Disease Control and Prevention. He has been sued by a supplement company in a case where the jury found in his favor.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
A version of this article appeared on Medscape.com.
TOPLINE:
Galantamine purchased as a dietary supplement may be more likely to contain bacterial contaminants and an incorrect amount of the product vs when it is prescribed as a generic drug, new research showed.
METHODOLOGY:
- Galantamine, a plant alkaloid, is approved for treating mild to moderate Alzheimer’s dementia but is also marketed as a dietary supplement for cognitive enhancement.
- In June 2023, researchers purchased all 10 galantamine dietary supplements available on Amazon.com that had a Supplement Facts panel.
- In September 2023, they acquired all 11 generic immediate-release formulations of prescription galantamine available in the United States.
- They analyzed the content of galantamine in each product using ultrahigh-performance liquid chromatography-mass spectrometry and quantified any microorganisms present.
TAKEAWAY:
- Generic galantamine drugs were found to contain 97.5%-104.2% of the labeled content, with no microbial contamination.
- , according to the authors of the study.
IN PRACTICE:
“Clinicians should query patients with memory concerns about the use of dietary supplements and advise patients not to use galantamine supplements,” the researchers wrote.
SOURCE:
The corresponding author of the study was Pieter A. Cohen, MD, with Broadway Clinic, Cambridge Health Alliance, in Somerville, Massachusetts. The paper was published online as a research letter in JAMA.
LIMITATIONS:
The products were purchased at a single point in time and may not reflect current options, the researchers noted. The generalizability of the findings to other supplement ingredients or generic drugs is unknown.
DISCLOSURES:
Dr. Cohen has received grants from the Consumers Union and PEW Charitable Trust and personal fees from UpToDate and the Centers for Disease Control and Prevention. He has been sued by a supplement company in a case where the jury found in his favor.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
A version of this article appeared on Medscape.com.
TOPLINE:
Galantamine purchased as a dietary supplement may be more likely to contain bacterial contaminants and an incorrect amount of the product vs when it is prescribed as a generic drug, new research showed.
METHODOLOGY:
- Galantamine, a plant alkaloid, is approved for treating mild to moderate Alzheimer’s dementia but is also marketed as a dietary supplement for cognitive enhancement.
- In June 2023, researchers purchased all 10 galantamine dietary supplements available on Amazon.com that had a Supplement Facts panel.
- In September 2023, they acquired all 11 generic immediate-release formulations of prescription galantamine available in the United States.
- They analyzed the content of galantamine in each product using ultrahigh-performance liquid chromatography-mass spectrometry and quantified any microorganisms present.
TAKEAWAY:
- Generic galantamine drugs were found to contain 97.5%-104.2% of the labeled content, with no microbial contamination.
- , according to the authors of the study.
IN PRACTICE:
“Clinicians should query patients with memory concerns about the use of dietary supplements and advise patients not to use galantamine supplements,” the researchers wrote.
SOURCE:
The corresponding author of the study was Pieter A. Cohen, MD, with Broadway Clinic, Cambridge Health Alliance, in Somerville, Massachusetts. The paper was published online as a research letter in JAMA.
LIMITATIONS:
The products were purchased at a single point in time and may not reflect current options, the researchers noted. The generalizability of the findings to other supplement ingredients or generic drugs is unknown.
DISCLOSURES:
Dr. Cohen has received grants from the Consumers Union and PEW Charitable Trust and personal fees from UpToDate and the Centers for Disease Control and Prevention. He has been sued by a supplement company in a case where the jury found in his favor.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
A version of this article appeared on Medscape.com.
Moderate to Severe TBI Linked to Brain Cancer Risk
Moderate, severe, and penetrating traumatic brain injury (TBI) is associated with an elevated risk of developing brain cancer, new research suggested. However, mild TBI appears to confer no increased risk.
In a large cohort of post-9/11 US veterans, those who suffered moderate/severe TBI had a nearly twofold increased risk for a subsequent brain cancer diagnosis, while those with penetrating TBI had a greater than threefold increased risk.
“While the absolute number of brain cancer diagnoses was small, these diagnoses are associated with profoundly poor outcomes. Further research of this rare but devastating condition is needed to better identify those at risk and develop screening protocols,” wrote investigators led by Ian Stewart, MD, with the Uniformed Services University of Health Sciences, Bethesda, Maryland.
The study was published online on February 15 in JAMA Network Open.
Common War Wound
TBI is one of the most common battlefield wounds among veterans of the Iraq and Afghanistan wars. But evidence to date on the potential association of TBI with the subsequent risk for brain cancer is conflicting, the authors noted.
To investigate further, they reviewed the records of nearly 2 million mostly male US veterans of the Iraq and Afghanistan wars. A total of 449,880 people experienced TBI, which was mild in 385,848 cases, moderate/severe in 46,859 cases, and penetrating in 17,173 cases.
During a median follow-up of 7.2 years, brain cancer occurred in 318 veterans without TBI (0.02%), 80 with mild TBI (0.02%), 17 with moderate/severe TBI (0.04%), and 10 or fewer with penetrating TBI (0.06% or less).
There was a stepwise increase in brain cancer incidence with worse TBI severity. Crude incidence rates per 100,000 person-years were 3.06 for no TBI, 2.85 for mild TBI, 4.88 for moderate/severe TBI, and 10.34 for penetrating TBI.
In the fully adjusted model, moderate/severe TBI showed a near-doubling of brain cancer risk vs no TBI (adjusted hazard ratio [aHR], 1.90; 95% CI, 1.16-3.12), while penetrating TBI was associated with a greater than tripling of risk (aHR, 3.33; 95% CI, 1.71-6.49). There was no significantly increased risk after mild TBI.
There are plausible biological mechanisms linking TBI to brain cancer, the authors noted, including alterations in metabolism, inflammation, astrocyte proliferation, and stem cell migration and differentiation.
They caution that with few female veterans and a predominantly young cohort, the findings may not extend to the general population.
Meaningful New Data
In an accompanying editorial, Elie Massaad, MD, MSc, and Ali Kiapour, PhD, MMSc, Massachusetts General Hospital, Boston, noted that federal data show glioblastoma, the most aggressive malignant brain tumor, is the third leading cause of cancer-related death among active duty personnel.
“Post-9/11 veterans deployed to Iraq, Afghanistan, and elsewhere face a 26% higher glioblastoma rate vs the general public, with an average age of onset decades earlier than in broader populations,” they wrote.
Overall, they noted this new research provides “meaningful data clarifying associations between combat-related TBI severity and subsequent brain cancer risk among post-9/11 veterans.
“Elucidating potential connections between battlefield trauma and longer-term health outcomes is imperative to inform prevention and care approaches for those who have served,” they added.
This study was supported by the Assistant Secretary of Defense for Health Affairs endorsed by the Department of Defense through the Psychological Health/Traumatic Brain Injury Research Program Long-Term Impact of Military Relevant Brain Injury Consortium. The authors and editorialists had declared no relevant conflicts of interest.
A version of this article appeared on Medscape.com.
Moderate, severe, and penetrating traumatic brain injury (TBI) is associated with an elevated risk of developing brain cancer, new research suggested. However, mild TBI appears to confer no increased risk.
In a large cohort of post-9/11 US veterans, those who suffered moderate/severe TBI had a nearly twofold increased risk for a subsequent brain cancer diagnosis, while those with penetrating TBI had a greater than threefold increased risk.
“While the absolute number of brain cancer diagnoses was small, these diagnoses are associated with profoundly poor outcomes. Further research of this rare but devastating condition is needed to better identify those at risk and develop screening protocols,” wrote investigators led by Ian Stewart, MD, with the Uniformed Services University of Health Sciences, Bethesda, Maryland.
The study was published online on February 15 in JAMA Network Open.
Common War Wound
TBI is one of the most common battlefield wounds among veterans of the Iraq and Afghanistan wars. But evidence to date on the potential association of TBI with the subsequent risk for brain cancer is conflicting, the authors noted.
To investigate further, they reviewed the records of nearly 2 million mostly male US veterans of the Iraq and Afghanistan wars. A total of 449,880 people experienced TBI, which was mild in 385,848 cases, moderate/severe in 46,859 cases, and penetrating in 17,173 cases.
During a median follow-up of 7.2 years, brain cancer occurred in 318 veterans without TBI (0.02%), 80 with mild TBI (0.02%), 17 with moderate/severe TBI (0.04%), and 10 or fewer with penetrating TBI (0.06% or less).
There was a stepwise increase in brain cancer incidence with worse TBI severity. Crude incidence rates per 100,000 person-years were 3.06 for no TBI, 2.85 for mild TBI, 4.88 for moderate/severe TBI, and 10.34 for penetrating TBI.
In the fully adjusted model, moderate/severe TBI showed a near-doubling of brain cancer risk vs no TBI (adjusted hazard ratio [aHR], 1.90; 95% CI, 1.16-3.12), while penetrating TBI was associated with a greater than tripling of risk (aHR, 3.33; 95% CI, 1.71-6.49). There was no significantly increased risk after mild TBI.
There are plausible biological mechanisms linking TBI to brain cancer, the authors noted, including alterations in metabolism, inflammation, astrocyte proliferation, and stem cell migration and differentiation.
They caution that with few female veterans and a predominantly young cohort, the findings may not extend to the general population.
Meaningful New Data
In an accompanying editorial, Elie Massaad, MD, MSc, and Ali Kiapour, PhD, MMSc, Massachusetts General Hospital, Boston, noted that federal data show glioblastoma, the most aggressive malignant brain tumor, is the third leading cause of cancer-related death among active duty personnel.
“Post-9/11 veterans deployed to Iraq, Afghanistan, and elsewhere face a 26% higher glioblastoma rate vs the general public, with an average age of onset decades earlier than in broader populations,” they wrote.
Overall, they noted this new research provides “meaningful data clarifying associations between combat-related TBI severity and subsequent brain cancer risk among post-9/11 veterans.
“Elucidating potential connections between battlefield trauma and longer-term health outcomes is imperative to inform prevention and care approaches for those who have served,” they added.
This study was supported by the Assistant Secretary of Defense for Health Affairs endorsed by the Department of Defense through the Psychological Health/Traumatic Brain Injury Research Program Long-Term Impact of Military Relevant Brain Injury Consortium. The authors and editorialists had declared no relevant conflicts of interest.
A version of this article appeared on Medscape.com.
Moderate, severe, and penetrating traumatic brain injury (TBI) is associated with an elevated risk of developing brain cancer, new research suggested. However, mild TBI appears to confer no increased risk.
In a large cohort of post-9/11 US veterans, those who suffered moderate/severe TBI had a nearly twofold increased risk for a subsequent brain cancer diagnosis, while those with penetrating TBI had a greater than threefold increased risk.
“While the absolute number of brain cancer diagnoses was small, these diagnoses are associated with profoundly poor outcomes. Further research of this rare but devastating condition is needed to better identify those at risk and develop screening protocols,” wrote investigators led by Ian Stewart, MD, with the Uniformed Services University of Health Sciences, Bethesda, Maryland.
The study was published online on February 15 in JAMA Network Open.
Common War Wound
TBI is one of the most common battlefield wounds among veterans of the Iraq and Afghanistan wars. But evidence to date on the potential association of TBI with the subsequent risk for brain cancer is conflicting, the authors noted.
To investigate further, they reviewed the records of nearly 2 million mostly male US veterans of the Iraq and Afghanistan wars. A total of 449,880 people experienced TBI, which was mild in 385,848 cases, moderate/severe in 46,859 cases, and penetrating in 17,173 cases.
During a median follow-up of 7.2 years, brain cancer occurred in 318 veterans without TBI (0.02%), 80 with mild TBI (0.02%), 17 with moderate/severe TBI (0.04%), and 10 or fewer with penetrating TBI (0.06% or less).
There was a stepwise increase in brain cancer incidence with worse TBI severity. Crude incidence rates per 100,000 person-years were 3.06 for no TBI, 2.85 for mild TBI, 4.88 for moderate/severe TBI, and 10.34 for penetrating TBI.
In the fully adjusted model, moderate/severe TBI showed a near-doubling of brain cancer risk vs no TBI (adjusted hazard ratio [aHR], 1.90; 95% CI, 1.16-3.12), while penetrating TBI was associated with a greater than tripling of risk (aHR, 3.33; 95% CI, 1.71-6.49). There was no significantly increased risk after mild TBI.
There are plausible biological mechanisms linking TBI to brain cancer, the authors noted, including alterations in metabolism, inflammation, astrocyte proliferation, and stem cell migration and differentiation.
They caution that with few female veterans and a predominantly young cohort, the findings may not extend to the general population.
Meaningful New Data
In an accompanying editorial, Elie Massaad, MD, MSc, and Ali Kiapour, PhD, MMSc, Massachusetts General Hospital, Boston, noted that federal data show glioblastoma, the most aggressive malignant brain tumor, is the third leading cause of cancer-related death among active duty personnel.
“Post-9/11 veterans deployed to Iraq, Afghanistan, and elsewhere face a 26% higher glioblastoma rate vs the general public, with an average age of onset decades earlier than in broader populations,” they wrote.
Overall, they noted this new research provides “meaningful data clarifying associations between combat-related TBI severity and subsequent brain cancer risk among post-9/11 veterans.
“Elucidating potential connections between battlefield trauma and longer-term health outcomes is imperative to inform prevention and care approaches for those who have served,” they added.
This study was supported by the Assistant Secretary of Defense for Health Affairs endorsed by the Department of Defense through the Psychological Health/Traumatic Brain Injury Research Program Long-Term Impact of Military Relevant Brain Injury Consortium. The authors and editorialists had declared no relevant conflicts of interest.
A version of this article appeared on Medscape.com.
Does the Internet Protect the Elderly From Cognitive Decline?
Several cross-sectional and longitudinal studies (though with relatively short follow-up periods) suggest that regular Internet use helps maintain cognitive reserve, although some observers have voiced skepticism. This hypothesis is particularly relevant for older patients facing the potentially detrimental effects of brain aging. According to some studies, memory, cognitive performance, and verbal reasoning tend to be better preserved among Internet users.
Several factors come into play, including socioeconomic disparities, socio-educational level, and generational differences, since Internet usage varies qualitatively and quantitatively with age. Older patients theoretically have more limited Internet usage. Under these conditions, the effect on cognitive functions would likely be modest compared with generations who were immersed in digital technology early on and tend to overuse it. After a certain age, accelerated brain aging would weigh much more heavily than any potential positive effects of the Internet. It is worth noting that the negative effects of Internet use have mainly been studied in young subjects, thus there is a lack of data concerning older patients.
Nearly 20,000 Participants
These considerations highlight the significance of a longitudinal cohort study that included 18,154 adults aged 50-64.9 years who were free from any dementia at baseline. These adults were participating in the Health and Retirement Study. The median follow-up period was 7.9 years, and follow-up extended to 17.1 years in some cases. Given that adults with better cognitive health are likely to self-select as regular users, the propensity score method was employed to control for this nonrandom factor using inverse probability weighting.
The risk for dementia based on initial Internet use was estimated using the Cox proportional hazards model, incorporating potentially late entry into the workforce and several covariables. Interactions with education level, gender, generation, and ethnic origin were also considered. Cumulative Internet exposure in terms of regular periodic use throughout life was included in the statistical analysis, as well as the hours spent on this activity each day. The analyses were conducted from September 2021 to November 2022.
Risk Nearly Halved
Regular Internet use was associated with a reduced risk for dementia, compared with irregular use. The hazard ratio (HR) for dementia was estimated at 0.57. After adjustment for the nonrandom factor of self-selection, this association persisted, and the HR decreased to 0.54. Accounting for baseline cognitive decline did not substantially change these results and yielded an HR of 0.62. The difference in risk between regular and irregular users was not altered by considering potential confounding factors such as education level, ethnic origin, gender, or generation. The longer the cumulative exposure over life, the lower the risk for dementia during follow-up.
The relationship between dementia risk and daily Internet usage hours seems to follow a U-shaped curve, with the lowest risk observed for durations between 0.1 and 2 hours. However, these estimates did not reach statistical significance because of the small sample size analyzed.
The risk for dementia appears to be approximately twice as low among regular Internet users compared with nonusers. This hypothesis deserves serious consideration because of the large sample size and long follow-up duration, as well as careful consideration of as many potential confounding factors as possible. Potential negative effects remain to be clarified as the study was not designed to detect them. The results of previous studies suggest that Internet usage should be moderate for optimal benefit, with approximately 2 hours per day being the most suitable duration, regardless of age, until proven otherwise.
This story was translated from JIM, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
Several cross-sectional and longitudinal studies (though with relatively short follow-up periods) suggest that regular Internet use helps maintain cognitive reserve, although some observers have voiced skepticism. This hypothesis is particularly relevant for older patients facing the potentially detrimental effects of brain aging. According to some studies, memory, cognitive performance, and verbal reasoning tend to be better preserved among Internet users.
Several factors come into play, including socioeconomic disparities, socio-educational level, and generational differences, since Internet usage varies qualitatively and quantitatively with age. Older patients theoretically have more limited Internet usage. Under these conditions, the effect on cognitive functions would likely be modest compared with generations who were immersed in digital technology early on and tend to overuse it. After a certain age, accelerated brain aging would weigh much more heavily than any potential positive effects of the Internet. It is worth noting that the negative effects of Internet use have mainly been studied in young subjects, thus there is a lack of data concerning older patients.
Nearly 20,000 Participants
These considerations highlight the significance of a longitudinal cohort study that included 18,154 adults aged 50-64.9 years who were free from any dementia at baseline. These adults were participating in the Health and Retirement Study. The median follow-up period was 7.9 years, and follow-up extended to 17.1 years in some cases. Given that adults with better cognitive health are likely to self-select as regular users, the propensity score method was employed to control for this nonrandom factor using inverse probability weighting.
The risk for dementia based on initial Internet use was estimated using the Cox proportional hazards model, incorporating potentially late entry into the workforce and several covariables. Interactions with education level, gender, generation, and ethnic origin were also considered. Cumulative Internet exposure in terms of regular periodic use throughout life was included in the statistical analysis, as well as the hours spent on this activity each day. The analyses were conducted from September 2021 to November 2022.
Risk Nearly Halved
Regular Internet use was associated with a reduced risk for dementia, compared with irregular use. The hazard ratio (HR) for dementia was estimated at 0.57. After adjustment for the nonrandom factor of self-selection, this association persisted, and the HR decreased to 0.54. Accounting for baseline cognitive decline did not substantially change these results and yielded an HR of 0.62. The difference in risk between regular and irregular users was not altered by considering potential confounding factors such as education level, ethnic origin, gender, or generation. The longer the cumulative exposure over life, the lower the risk for dementia during follow-up.
The relationship between dementia risk and daily Internet usage hours seems to follow a U-shaped curve, with the lowest risk observed for durations between 0.1 and 2 hours. However, these estimates did not reach statistical significance because of the small sample size analyzed.
The risk for dementia appears to be approximately twice as low among regular Internet users compared with nonusers. This hypothesis deserves serious consideration because of the large sample size and long follow-up duration, as well as careful consideration of as many potential confounding factors as possible. Potential negative effects remain to be clarified as the study was not designed to detect them. The results of previous studies suggest that Internet usage should be moderate for optimal benefit, with approximately 2 hours per day being the most suitable duration, regardless of age, until proven otherwise.
This story was translated from JIM, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
Several cross-sectional and longitudinal studies (though with relatively short follow-up periods) suggest that regular Internet use helps maintain cognitive reserve, although some observers have voiced skepticism. This hypothesis is particularly relevant for older patients facing the potentially detrimental effects of brain aging. According to some studies, memory, cognitive performance, and verbal reasoning tend to be better preserved among Internet users.
Several factors come into play, including socioeconomic disparities, socio-educational level, and generational differences, since Internet usage varies qualitatively and quantitatively with age. Older patients theoretically have more limited Internet usage. Under these conditions, the effect on cognitive functions would likely be modest compared with generations who were immersed in digital technology early on and tend to overuse it. After a certain age, accelerated brain aging would weigh much more heavily than any potential positive effects of the Internet. It is worth noting that the negative effects of Internet use have mainly been studied in young subjects, thus there is a lack of data concerning older patients.
Nearly 20,000 Participants
These considerations highlight the significance of a longitudinal cohort study that included 18,154 adults aged 50-64.9 years who were free from any dementia at baseline. These adults were participating in the Health and Retirement Study. The median follow-up period was 7.9 years, and follow-up extended to 17.1 years in some cases. Given that adults with better cognitive health are likely to self-select as regular users, the propensity score method was employed to control for this nonrandom factor using inverse probability weighting.
The risk for dementia based on initial Internet use was estimated using the Cox proportional hazards model, incorporating potentially late entry into the workforce and several covariables. Interactions with education level, gender, generation, and ethnic origin were also considered. Cumulative Internet exposure in terms of regular periodic use throughout life was included in the statistical analysis, as well as the hours spent on this activity each day. The analyses were conducted from September 2021 to November 2022.
Risk Nearly Halved
Regular Internet use was associated with a reduced risk for dementia, compared with irregular use. The hazard ratio (HR) for dementia was estimated at 0.57. After adjustment for the nonrandom factor of self-selection, this association persisted, and the HR decreased to 0.54. Accounting for baseline cognitive decline did not substantially change these results and yielded an HR of 0.62. The difference in risk between regular and irregular users was not altered by considering potential confounding factors such as education level, ethnic origin, gender, or generation. The longer the cumulative exposure over life, the lower the risk for dementia during follow-up.
The relationship between dementia risk and daily Internet usage hours seems to follow a U-shaped curve, with the lowest risk observed for durations between 0.1 and 2 hours. However, these estimates did not reach statistical significance because of the small sample size analyzed.
The risk for dementia appears to be approximately twice as low among regular Internet users compared with nonusers. This hypothesis deserves serious consideration because of the large sample size and long follow-up duration, as well as careful consideration of as many potential confounding factors as possible. Potential negative effects remain to be clarified as the study was not designed to detect them. The results of previous studies suggest that Internet usage should be moderate for optimal benefit, with approximately 2 hours per day being the most suitable duration, regardless of age, until proven otherwise.
This story was translated from JIM, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.