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Study casts doubt on safety, efficacy of L-serine supplementation for AD
When given to patients with AD, L-serine supplements could be driving abnormally increased serine levels in the brain even higher, potentially accelerating neuronal death, according to study author Xu Chen, PhD, of the University of California, San Diego, and colleagues.
This conclusion conflicts with a 2020 study by Juliette Le Douce, PhD, and colleagues, who reported that oral L-serine supplementation may act as a “ready-to-use therapy” for AD, based on their findings that patients with AD had low levels of PHGDH, an enzyme necessary for synthesizing serine, and AD-like mice had low levels of serine.
Writing in Cell Metabolism, Dr. Chen and colleagues framed the present study, and their findings, in this context.
“In contrast to the work of Le Douce et al., here we report that PHGDH mRNA and protein levels are increased in the brains of two mouse models of AD and/or tauopathy, and are also progressively increased in human brains with no, early, and late AD pathology, as well as in people with no, asymptomatic, and symptomatic AD,” they wrote.
They suggested adjusting clinical recommendations for L-serine, the form of the amino acid commonly found in supplements. In the body, L-serine is converted to D-serine, which acts on the NMDA receptor (NMDAR).
‘Long-term use of D-serine contributes to neuronal death’ suggests research
“We feel oral L-serine as a ready-to-use therapy to AD warrants precaution,” Dr. Chen and colleagues wrote. “This is because despite being a cognitive enhancer, some [research] suggests that long-term use of D-serine contributes to neuronal death in AD through excitotoxicity. Furthermore, D-serine, as a co-agonist of NMDAR, would be expected to oppose NMDAR antagonists, which have proven clinical benefits in treating AD.”
According to principal author Sheng Zhong, PhD, of the University of California, San Diego, “Research is needed to test if targeting PHGDH can ameliorate cognitive decline in AD.”
Dr. Zhong also noted that the present findings support the “promise of using a specific RNA in blood as a biomarker for early detection of Alzheimer’s disease.” This approach is currently being validated at UCSD Shiley-Marcos Alzheimer’s Disease Research Center, he added.
Roles of PHGDH and serine in Alzheimer’s disease require further study
Commenting on both studies, Steve W. Barger, PhD, of the University of Arkansas for Medical Sciences, Little Rock, suggested that more work is needed to better understand the roles of PHGDH and serine in AD before clinical applications can be considered.
“In the end, these two studies fail to provide the clarity we need in designing evidence-based therapeutic hypotheses,” Dr. Barger said in an interview. “We still do not have a firm grasp on the role that D-serine plays in AD. Indeed, the evidence regarding even a single enzyme contributing to its levels is ambiguous.”
Dr. Barger, who has published extensively on the topic of neuronal death, with a particular focus on Alzheimer’s disease, noted that “determination of what happens to D-serine levels in AD has been of interest for decades,” but levels of the amino acid have been notoriously challenging to measure because “D-serine can disappear rapidly from the brain and its fluids after death.”
While Dr. Le Douce and colleagues did measure levels of serine in mice, Dr. Barger noted that the study by Dr. Chen and colleagues was conducted with more “quantitatively rigorous methods.” Even though Dr. Chen and colleagues “did not assay the levels of D-serine itself ... the implication of their findings is that PHGDH is poised to elevate this critical neurotransmitter,” leading to their conclusion that serine supplementation is “potentially dangerous.”
At this point, it may be too early to tell, according to Dr. Barger.
He suggested that conclusions drawn from PHGDH levels alone are “always limited,” and conclusions based on serine levels may be equally dubious, considering that the activities and effects of serine “are quite complex,” and may be influenced by other physiologic processes, including the effects of gut bacteria.
Instead, Dr. Barger suggested that changes in PHGDH and serine may be interpreted as signals coming from a more relevant process upstream: glucose metabolism.
“What we can say confidently is that the glucose metabolism that PHGDH connects to D-serine is most definitely a factor in AD,” he said. “Countless studies have documented what now appears to be a universal decline in glucose delivery to the cerebral cortex, even before frank dementia sets in.”
Dr. Barger noted that declining glucose delivery coincides with some of the earliest events in the development of AD, perhaps “linking accumulation of amyloid β-peptide to subsequent neurofibrillary tangles and tissue atrophy.”
Dr. Barger’s own work recently demonstrated that AD is associated with “an irregularity in the insertion of a specific glucose transporter (GLUT1) into the cell surface” of astrocytes.
“It could be more effective to direct therapeutic interventions at these events lying upstream of PHGDH or serine,” he concluded.
The study was partly supported by a Kreuger v. Wyeth research award. The investigators and Dr. Barger reported no conflicts of interest.
When given to patients with AD, L-serine supplements could be driving abnormally increased serine levels in the brain even higher, potentially accelerating neuronal death, according to study author Xu Chen, PhD, of the University of California, San Diego, and colleagues.
This conclusion conflicts with a 2020 study by Juliette Le Douce, PhD, and colleagues, who reported that oral L-serine supplementation may act as a “ready-to-use therapy” for AD, based on their findings that patients with AD had low levels of PHGDH, an enzyme necessary for synthesizing serine, and AD-like mice had low levels of serine.
Writing in Cell Metabolism, Dr. Chen and colleagues framed the present study, and their findings, in this context.
“In contrast to the work of Le Douce et al., here we report that PHGDH mRNA and protein levels are increased in the brains of two mouse models of AD and/or tauopathy, and are also progressively increased in human brains with no, early, and late AD pathology, as well as in people with no, asymptomatic, and symptomatic AD,” they wrote.
They suggested adjusting clinical recommendations for L-serine, the form of the amino acid commonly found in supplements. In the body, L-serine is converted to D-serine, which acts on the NMDA receptor (NMDAR).
‘Long-term use of D-serine contributes to neuronal death’ suggests research
“We feel oral L-serine as a ready-to-use therapy to AD warrants precaution,” Dr. Chen and colleagues wrote. “This is because despite being a cognitive enhancer, some [research] suggests that long-term use of D-serine contributes to neuronal death in AD through excitotoxicity. Furthermore, D-serine, as a co-agonist of NMDAR, would be expected to oppose NMDAR antagonists, which have proven clinical benefits in treating AD.”
According to principal author Sheng Zhong, PhD, of the University of California, San Diego, “Research is needed to test if targeting PHGDH can ameliorate cognitive decline in AD.”
Dr. Zhong also noted that the present findings support the “promise of using a specific RNA in blood as a biomarker for early detection of Alzheimer’s disease.” This approach is currently being validated at UCSD Shiley-Marcos Alzheimer’s Disease Research Center, he added.
Roles of PHGDH and serine in Alzheimer’s disease require further study
Commenting on both studies, Steve W. Barger, PhD, of the University of Arkansas for Medical Sciences, Little Rock, suggested that more work is needed to better understand the roles of PHGDH and serine in AD before clinical applications can be considered.
“In the end, these two studies fail to provide the clarity we need in designing evidence-based therapeutic hypotheses,” Dr. Barger said in an interview. “We still do not have a firm grasp on the role that D-serine plays in AD. Indeed, the evidence regarding even a single enzyme contributing to its levels is ambiguous.”
Dr. Barger, who has published extensively on the topic of neuronal death, with a particular focus on Alzheimer’s disease, noted that “determination of what happens to D-serine levels in AD has been of interest for decades,” but levels of the amino acid have been notoriously challenging to measure because “D-serine can disappear rapidly from the brain and its fluids after death.”
While Dr. Le Douce and colleagues did measure levels of serine in mice, Dr. Barger noted that the study by Dr. Chen and colleagues was conducted with more “quantitatively rigorous methods.” Even though Dr. Chen and colleagues “did not assay the levels of D-serine itself ... the implication of their findings is that PHGDH is poised to elevate this critical neurotransmitter,” leading to their conclusion that serine supplementation is “potentially dangerous.”
At this point, it may be too early to tell, according to Dr. Barger.
He suggested that conclusions drawn from PHGDH levels alone are “always limited,” and conclusions based on serine levels may be equally dubious, considering that the activities and effects of serine “are quite complex,” and may be influenced by other physiologic processes, including the effects of gut bacteria.
Instead, Dr. Barger suggested that changes in PHGDH and serine may be interpreted as signals coming from a more relevant process upstream: glucose metabolism.
“What we can say confidently is that the glucose metabolism that PHGDH connects to D-serine is most definitely a factor in AD,” he said. “Countless studies have documented what now appears to be a universal decline in glucose delivery to the cerebral cortex, even before frank dementia sets in.”
Dr. Barger noted that declining glucose delivery coincides with some of the earliest events in the development of AD, perhaps “linking accumulation of amyloid β-peptide to subsequent neurofibrillary tangles and tissue atrophy.”
Dr. Barger’s own work recently demonstrated that AD is associated with “an irregularity in the insertion of a specific glucose transporter (GLUT1) into the cell surface” of astrocytes.
“It could be more effective to direct therapeutic interventions at these events lying upstream of PHGDH or serine,” he concluded.
The study was partly supported by a Kreuger v. Wyeth research award. The investigators and Dr. Barger reported no conflicts of interest.
When given to patients with AD, L-serine supplements could be driving abnormally increased serine levels in the brain even higher, potentially accelerating neuronal death, according to study author Xu Chen, PhD, of the University of California, San Diego, and colleagues.
This conclusion conflicts with a 2020 study by Juliette Le Douce, PhD, and colleagues, who reported that oral L-serine supplementation may act as a “ready-to-use therapy” for AD, based on their findings that patients with AD had low levels of PHGDH, an enzyme necessary for synthesizing serine, and AD-like mice had low levels of serine.
Writing in Cell Metabolism, Dr. Chen and colleagues framed the present study, and their findings, in this context.
“In contrast to the work of Le Douce et al., here we report that PHGDH mRNA and protein levels are increased in the brains of two mouse models of AD and/or tauopathy, and are also progressively increased in human brains with no, early, and late AD pathology, as well as in people with no, asymptomatic, and symptomatic AD,” they wrote.
They suggested adjusting clinical recommendations for L-serine, the form of the amino acid commonly found in supplements. In the body, L-serine is converted to D-serine, which acts on the NMDA receptor (NMDAR).
‘Long-term use of D-serine contributes to neuronal death’ suggests research
“We feel oral L-serine as a ready-to-use therapy to AD warrants precaution,” Dr. Chen and colleagues wrote. “This is because despite being a cognitive enhancer, some [research] suggests that long-term use of D-serine contributes to neuronal death in AD through excitotoxicity. Furthermore, D-serine, as a co-agonist of NMDAR, would be expected to oppose NMDAR antagonists, which have proven clinical benefits in treating AD.”
According to principal author Sheng Zhong, PhD, of the University of California, San Diego, “Research is needed to test if targeting PHGDH can ameliorate cognitive decline in AD.”
Dr. Zhong also noted that the present findings support the “promise of using a specific RNA in blood as a biomarker for early detection of Alzheimer’s disease.” This approach is currently being validated at UCSD Shiley-Marcos Alzheimer’s Disease Research Center, he added.
Roles of PHGDH and serine in Alzheimer’s disease require further study
Commenting on both studies, Steve W. Barger, PhD, of the University of Arkansas for Medical Sciences, Little Rock, suggested that more work is needed to better understand the roles of PHGDH and serine in AD before clinical applications can be considered.
“In the end, these two studies fail to provide the clarity we need in designing evidence-based therapeutic hypotheses,” Dr. Barger said in an interview. “We still do not have a firm grasp on the role that D-serine plays in AD. Indeed, the evidence regarding even a single enzyme contributing to its levels is ambiguous.”
Dr. Barger, who has published extensively on the topic of neuronal death, with a particular focus on Alzheimer’s disease, noted that “determination of what happens to D-serine levels in AD has been of interest for decades,” but levels of the amino acid have been notoriously challenging to measure because “D-serine can disappear rapidly from the brain and its fluids after death.”
While Dr. Le Douce and colleagues did measure levels of serine in mice, Dr. Barger noted that the study by Dr. Chen and colleagues was conducted with more “quantitatively rigorous methods.” Even though Dr. Chen and colleagues “did not assay the levels of D-serine itself ... the implication of their findings is that PHGDH is poised to elevate this critical neurotransmitter,” leading to their conclusion that serine supplementation is “potentially dangerous.”
At this point, it may be too early to tell, according to Dr. Barger.
He suggested that conclusions drawn from PHGDH levels alone are “always limited,” and conclusions based on serine levels may be equally dubious, considering that the activities and effects of serine “are quite complex,” and may be influenced by other physiologic processes, including the effects of gut bacteria.
Instead, Dr. Barger suggested that changes in PHGDH and serine may be interpreted as signals coming from a more relevant process upstream: glucose metabolism.
“What we can say confidently is that the glucose metabolism that PHGDH connects to D-serine is most definitely a factor in AD,” he said. “Countless studies have documented what now appears to be a universal decline in glucose delivery to the cerebral cortex, even before frank dementia sets in.”
Dr. Barger noted that declining glucose delivery coincides with some of the earliest events in the development of AD, perhaps “linking accumulation of amyloid β-peptide to subsequent neurofibrillary tangles and tissue atrophy.”
Dr. Barger’s own work recently demonstrated that AD is associated with “an irregularity in the insertion of a specific glucose transporter (GLUT1) into the cell surface” of astrocytes.
“It could be more effective to direct therapeutic interventions at these events lying upstream of PHGDH or serine,” he concluded.
The study was partly supported by a Kreuger v. Wyeth research award. The investigators and Dr. Barger reported no conflicts of interest.
FROM CELL METABOLISM
Higher industriousness reduces risk of predementia syndrome in older adults
Higher industriousness was associated with a 25% reduced risk of concurrent motoric cognitive risk syndrome (MCR), based on data from approximately 6,000 individuals.
Previous research supports an association between conscientiousness and a lower risk of MCR, a form of predementia that involves slow gait speed and cognitive complaints, wrote Yannick Stephan, PhD, of the University of Montpellier (France), and colleagues. However, the specific facets of conscientiousness that impact MCR have not been examined.
In a study published in the Journal of Psychiatric Research, the authors reviewed data from 6,001 dementia-free adults aged 65-99 years who were enrolled in the Health and Retirement Study, a nationally representative longitudinal study of adults aged 50 years and older in the United States.
Baseline data were collected between 2008 and 2010, and participants were assessed for MCR at follow-up points during 2012-2014 and 2016-2018. Six facets of conscientiousness were assessed using a 24-item scale that has been used in previous studies. The six facets were industriousness, self-control, order, traditionalism, virtue, and responsibility. The researchers controlled for variables including demographic factors, cognition, physical activity, disease burden, depressive symptoms, and body mass index.
Overall, increased industriousness was significantly associated with a lower likelihood of concurrent MCR (odds ratio, 0.75) and a reduced risk of incident MCR (hazard ratio, 0.63,; P < .001 for both).
The conscientiousness facets of order, self-control, and responsibility also were associated with a lower likelihood of both concurrent and incident MCR, with ORs ranging from 0.82-0.88 for concurrent and HRs ranging from 0.72-0.82 for incident.
Traditionalism and virtue were significantly associated with a lower risk of incident MCR, but not concurrent MCR (HR, 0.84; P < .01 for both).
The mechanism of action for the association may be explained by several cognitive, health-related, behavioral, and psychological pathways, the researchers wrote. With regard to industriousness, the relationship could be partly explained by cognition, physical activity, disease burden, BMI, and depressive symptoms. However, industriousness also has been associated with a reduced risk of systemic inflammation, which may in turn reduce MCR risk. Also, data suggest that industriousness and MCR share a common genetic cause.
The study findings were limited by several factors including the observational design and the positive selection effect from patients with complete follow-up data, as these patients likely have higher levels of order, industriousness, and responsibility, the researchers noted. However, the results support those from previous studies and were strengthened by the large sample and examination of six facets of conscientiousness.
“This study thus provides a more detailed understanding of the specific components of conscientiousness that are associated with risk of MCR among older adults,” and the facets could be targeted in interventions to reduce both MCR and dementia, they concluded.
The Health and Retirement Study is supported by the National Institute on Aging and conducted by the University of Michigan. The current study was supported in part by the National Institutes of Health. The researchers had no financial conflicts to disclose.
Higher industriousness was associated with a 25% reduced risk of concurrent motoric cognitive risk syndrome (MCR), based on data from approximately 6,000 individuals.
Previous research supports an association between conscientiousness and a lower risk of MCR, a form of predementia that involves slow gait speed and cognitive complaints, wrote Yannick Stephan, PhD, of the University of Montpellier (France), and colleagues. However, the specific facets of conscientiousness that impact MCR have not been examined.
In a study published in the Journal of Psychiatric Research, the authors reviewed data from 6,001 dementia-free adults aged 65-99 years who were enrolled in the Health and Retirement Study, a nationally representative longitudinal study of adults aged 50 years and older in the United States.
Baseline data were collected between 2008 and 2010, and participants were assessed for MCR at follow-up points during 2012-2014 and 2016-2018. Six facets of conscientiousness were assessed using a 24-item scale that has been used in previous studies. The six facets were industriousness, self-control, order, traditionalism, virtue, and responsibility. The researchers controlled for variables including demographic factors, cognition, physical activity, disease burden, depressive symptoms, and body mass index.
Overall, increased industriousness was significantly associated with a lower likelihood of concurrent MCR (odds ratio, 0.75) and a reduced risk of incident MCR (hazard ratio, 0.63,; P < .001 for both).
The conscientiousness facets of order, self-control, and responsibility also were associated with a lower likelihood of both concurrent and incident MCR, with ORs ranging from 0.82-0.88 for concurrent and HRs ranging from 0.72-0.82 for incident.
Traditionalism and virtue were significantly associated with a lower risk of incident MCR, but not concurrent MCR (HR, 0.84; P < .01 for both).
The mechanism of action for the association may be explained by several cognitive, health-related, behavioral, and psychological pathways, the researchers wrote. With regard to industriousness, the relationship could be partly explained by cognition, physical activity, disease burden, BMI, and depressive symptoms. However, industriousness also has been associated with a reduced risk of systemic inflammation, which may in turn reduce MCR risk. Also, data suggest that industriousness and MCR share a common genetic cause.
The study findings were limited by several factors including the observational design and the positive selection effect from patients with complete follow-up data, as these patients likely have higher levels of order, industriousness, and responsibility, the researchers noted. However, the results support those from previous studies and were strengthened by the large sample and examination of six facets of conscientiousness.
“This study thus provides a more detailed understanding of the specific components of conscientiousness that are associated with risk of MCR among older adults,” and the facets could be targeted in interventions to reduce both MCR and dementia, they concluded.
The Health and Retirement Study is supported by the National Institute on Aging and conducted by the University of Michigan. The current study was supported in part by the National Institutes of Health. The researchers had no financial conflicts to disclose.
Higher industriousness was associated with a 25% reduced risk of concurrent motoric cognitive risk syndrome (MCR), based on data from approximately 6,000 individuals.
Previous research supports an association between conscientiousness and a lower risk of MCR, a form of predementia that involves slow gait speed and cognitive complaints, wrote Yannick Stephan, PhD, of the University of Montpellier (France), and colleagues. However, the specific facets of conscientiousness that impact MCR have not been examined.
In a study published in the Journal of Psychiatric Research, the authors reviewed data from 6,001 dementia-free adults aged 65-99 years who were enrolled in the Health and Retirement Study, a nationally representative longitudinal study of adults aged 50 years and older in the United States.
Baseline data were collected between 2008 and 2010, and participants were assessed for MCR at follow-up points during 2012-2014 and 2016-2018. Six facets of conscientiousness were assessed using a 24-item scale that has been used in previous studies. The six facets were industriousness, self-control, order, traditionalism, virtue, and responsibility. The researchers controlled for variables including demographic factors, cognition, physical activity, disease burden, depressive symptoms, and body mass index.
Overall, increased industriousness was significantly associated with a lower likelihood of concurrent MCR (odds ratio, 0.75) and a reduced risk of incident MCR (hazard ratio, 0.63,; P < .001 for both).
The conscientiousness facets of order, self-control, and responsibility also were associated with a lower likelihood of both concurrent and incident MCR, with ORs ranging from 0.82-0.88 for concurrent and HRs ranging from 0.72-0.82 for incident.
Traditionalism and virtue were significantly associated with a lower risk of incident MCR, but not concurrent MCR (HR, 0.84; P < .01 for both).
The mechanism of action for the association may be explained by several cognitive, health-related, behavioral, and psychological pathways, the researchers wrote. With regard to industriousness, the relationship could be partly explained by cognition, physical activity, disease burden, BMI, and depressive symptoms. However, industriousness also has been associated with a reduced risk of systemic inflammation, which may in turn reduce MCR risk. Also, data suggest that industriousness and MCR share a common genetic cause.
The study findings were limited by several factors including the observational design and the positive selection effect from patients with complete follow-up data, as these patients likely have higher levels of order, industriousness, and responsibility, the researchers noted. However, the results support those from previous studies and were strengthened by the large sample and examination of six facets of conscientiousness.
“This study thus provides a more detailed understanding of the specific components of conscientiousness that are associated with risk of MCR among older adults,” and the facets could be targeted in interventions to reduce both MCR and dementia, they concluded.
The Health and Retirement Study is supported by the National Institute on Aging and conducted by the University of Michigan. The current study was supported in part by the National Institutes of Health. The researchers had no financial conflicts to disclose.
FROM PSYCHIATRIC RESEARCH
Best antioxidants to prevent age-related dementia identified?
Investigators found that individuals with the highest serum levels of lutein + zeaxanthin and beta-cryptoxanthin at baseline were less likely to have dementia decades later than were their peers with lower levels of these antioxidants.
Lutein and zeaxanthin are found in green leafy vegetables such as kale, spinach, broccoli, and peas. Beta-cryptoxanthin is found in fruits such as oranges, papaya, tangerines, and persimmons.
“Antioxidants may help protect the brain from oxidative stress, which can cause cell damage,” first author May A. Beydoun, PhD, with the National Institute on Aging (NIA), said in a news release.
“This is the first nationally representative study to analyze blood levels of antioxidants in relation to dementia risk,” NIA scientific director Luigi Ferrucci, MD, said in an interview.
“Blood test results may be more representative of the actual antioxidant level than a person’s report of what kind of foods they regularly consume,” Dr. Ferrucci added.
The study was published online in Neurology.
Reduced dementia risk
The researchers tested associations and interactions of serum vitamins A, C and E, and total and individual serum carotenoids and interactions with incident Alzheimer’s disease (AD) and all-cause dementia.
They analyzed data from 7,283 participants in the Third National Health and Nutrition Examination Survey (NHANES III) who were at least 45 years old at baseline and followed for an average of 16-17 years.
They found serum levels of lutein + zeaxanthin were associated with reduced risk of all-cause dementia among people aged 65 and older in models adjusted for lifestyle.
For lutein + zeaxanthin, every standard deviation (SD) increase (roughly 15.4 µmol/liter) was associated with a 7% decrease in risk for dementia (hazard ratio [HR] 0.93; 95% confidence interval [CI], 0.87-0.99, P = .037). This association was attenuated somewhat after adjustment for socioeconomic status.
Serum levels of beta-cryptoxanthin showed a “strong” inverse relationship with all-cause dementia in age- and sex-adjusted models.
For beta-cryptoxanthin, every SD increase (roughly 8.6 µmol/liter) was associated with a 14% reduced risk for dementia in people aged 45 and older (HR, 0.86; 95% CI, 0.80-0.93, P < .001) and 65 and older (HR, 0.86; 95% CI, 0.80-0.93, P = .001).
This relationship remained strong in models adjusted for sociodemographic and socioeconomic factors but attenuated in subsequent models.
No associations were found for lycopene, alpha-carotene, beta-carotene, or vitamins A, C, or E in the fully adjusted models.
Antagonistic interactions were observed for vitamin A and alpha-carotene, vitamin A and beta-carotene, vitamin E and lycopene, and lycopene and beta-carotene, suggesting putative protective effects of one antioxidant at lower levels of the other, the researchers noted.
“This analysis of an observational study found that the most important carotenoids in potentially protecting the brain may be lutein + zeaxanthin and beta-cryptoxanthin. However, randomized controlled trials are needed to prove causality,” said Dr. Ferrucci.
“Experts do not yet know the daily level of antioxidant intake to promote healthy aging of the brain. More research is needed to establish the necessary level of antioxidant intake – through the diet and/or supplements – to promote brain health and healthy aging,” he added.
An important step forward
In an accompanying editorial, Babak Hooshmand, MD, PhD, and Miia Kivipelto, MD, PhD, with Karolinska Institute, Stockholm, noted that while nutrition and dietary components are “potential targets” for dementia risk reduction, observational studies to date have reported “inconsistent findings.”
This study is “an important step towards exploring the complex relationship between antioxidants and dementia because it accounts for factors that could possibly influence the associations and considers interactions between different components,” they wrote.
The findings are “challenging,” they added, because they may lead to the hypothesis that inhibition of oxidative damage by antioxidants might have beneficial effects on preventing dementia.
However, clinical trials of antioxidant supplementation have been mainly “disappointing” and a recent Cochrane review found a lack of evidence for supplement use to preserve cognitive function or prevent dementia, Dr. Hooshmand and Dr. Kivipelto noted.
They added that the study contributes to the belief that antioxidants don’t act independently of each other or other factors, including socioeconomic status and lifestyle, in the mediation of dementia risk.
“A careful examination of the evidence is required to learn how antioxidants influence the complex pathology of dementia, because it appears to be more to it than meets the eye,”they concluded.
The research was supported in part by the Intramural Research Program of the National Institutes of Health and the National Institute on Aging. Dr. Beydoun, Dr. Ferrucci, and Dr. Hooshmand report no relevant disclosures. Dr. Kivipelto has supported advisory boards for Combinostics, Roche, and Biogen.
A version of this article first appeared on Medscape.com.
Investigators found that individuals with the highest serum levels of lutein + zeaxanthin and beta-cryptoxanthin at baseline were less likely to have dementia decades later than were their peers with lower levels of these antioxidants.
Lutein and zeaxanthin are found in green leafy vegetables such as kale, spinach, broccoli, and peas. Beta-cryptoxanthin is found in fruits such as oranges, papaya, tangerines, and persimmons.
“Antioxidants may help protect the brain from oxidative stress, which can cause cell damage,” first author May A. Beydoun, PhD, with the National Institute on Aging (NIA), said in a news release.
“This is the first nationally representative study to analyze blood levels of antioxidants in relation to dementia risk,” NIA scientific director Luigi Ferrucci, MD, said in an interview.
“Blood test results may be more representative of the actual antioxidant level than a person’s report of what kind of foods they regularly consume,” Dr. Ferrucci added.
The study was published online in Neurology.
Reduced dementia risk
The researchers tested associations and interactions of serum vitamins A, C and E, and total and individual serum carotenoids and interactions with incident Alzheimer’s disease (AD) and all-cause dementia.
They analyzed data from 7,283 participants in the Third National Health and Nutrition Examination Survey (NHANES III) who were at least 45 years old at baseline and followed for an average of 16-17 years.
They found serum levels of lutein + zeaxanthin were associated with reduced risk of all-cause dementia among people aged 65 and older in models adjusted for lifestyle.
For lutein + zeaxanthin, every standard deviation (SD) increase (roughly 15.4 µmol/liter) was associated with a 7% decrease in risk for dementia (hazard ratio [HR] 0.93; 95% confidence interval [CI], 0.87-0.99, P = .037). This association was attenuated somewhat after adjustment for socioeconomic status.
Serum levels of beta-cryptoxanthin showed a “strong” inverse relationship with all-cause dementia in age- and sex-adjusted models.
For beta-cryptoxanthin, every SD increase (roughly 8.6 µmol/liter) was associated with a 14% reduced risk for dementia in people aged 45 and older (HR, 0.86; 95% CI, 0.80-0.93, P < .001) and 65 and older (HR, 0.86; 95% CI, 0.80-0.93, P = .001).
This relationship remained strong in models adjusted for sociodemographic and socioeconomic factors but attenuated in subsequent models.
No associations were found for lycopene, alpha-carotene, beta-carotene, or vitamins A, C, or E in the fully adjusted models.
Antagonistic interactions were observed for vitamin A and alpha-carotene, vitamin A and beta-carotene, vitamin E and lycopene, and lycopene and beta-carotene, suggesting putative protective effects of one antioxidant at lower levels of the other, the researchers noted.
“This analysis of an observational study found that the most important carotenoids in potentially protecting the brain may be lutein + zeaxanthin and beta-cryptoxanthin. However, randomized controlled trials are needed to prove causality,” said Dr. Ferrucci.
“Experts do not yet know the daily level of antioxidant intake to promote healthy aging of the brain. More research is needed to establish the necessary level of antioxidant intake – through the diet and/or supplements – to promote brain health and healthy aging,” he added.
An important step forward
In an accompanying editorial, Babak Hooshmand, MD, PhD, and Miia Kivipelto, MD, PhD, with Karolinska Institute, Stockholm, noted that while nutrition and dietary components are “potential targets” for dementia risk reduction, observational studies to date have reported “inconsistent findings.”
This study is “an important step towards exploring the complex relationship between antioxidants and dementia because it accounts for factors that could possibly influence the associations and considers interactions between different components,” they wrote.
The findings are “challenging,” they added, because they may lead to the hypothesis that inhibition of oxidative damage by antioxidants might have beneficial effects on preventing dementia.
However, clinical trials of antioxidant supplementation have been mainly “disappointing” and a recent Cochrane review found a lack of evidence for supplement use to preserve cognitive function or prevent dementia, Dr. Hooshmand and Dr. Kivipelto noted.
They added that the study contributes to the belief that antioxidants don’t act independently of each other or other factors, including socioeconomic status and lifestyle, in the mediation of dementia risk.
“A careful examination of the evidence is required to learn how antioxidants influence the complex pathology of dementia, because it appears to be more to it than meets the eye,”they concluded.
The research was supported in part by the Intramural Research Program of the National Institutes of Health and the National Institute on Aging. Dr. Beydoun, Dr. Ferrucci, and Dr. Hooshmand report no relevant disclosures. Dr. Kivipelto has supported advisory boards for Combinostics, Roche, and Biogen.
A version of this article first appeared on Medscape.com.
Investigators found that individuals with the highest serum levels of lutein + zeaxanthin and beta-cryptoxanthin at baseline were less likely to have dementia decades later than were their peers with lower levels of these antioxidants.
Lutein and zeaxanthin are found in green leafy vegetables such as kale, spinach, broccoli, and peas. Beta-cryptoxanthin is found in fruits such as oranges, papaya, tangerines, and persimmons.
“Antioxidants may help protect the brain from oxidative stress, which can cause cell damage,” first author May A. Beydoun, PhD, with the National Institute on Aging (NIA), said in a news release.
“This is the first nationally representative study to analyze blood levels of antioxidants in relation to dementia risk,” NIA scientific director Luigi Ferrucci, MD, said in an interview.
“Blood test results may be more representative of the actual antioxidant level than a person’s report of what kind of foods they regularly consume,” Dr. Ferrucci added.
The study was published online in Neurology.
Reduced dementia risk
The researchers tested associations and interactions of serum vitamins A, C and E, and total and individual serum carotenoids and interactions with incident Alzheimer’s disease (AD) and all-cause dementia.
They analyzed data from 7,283 participants in the Third National Health and Nutrition Examination Survey (NHANES III) who were at least 45 years old at baseline and followed for an average of 16-17 years.
They found serum levels of lutein + zeaxanthin were associated with reduced risk of all-cause dementia among people aged 65 and older in models adjusted for lifestyle.
For lutein + zeaxanthin, every standard deviation (SD) increase (roughly 15.4 µmol/liter) was associated with a 7% decrease in risk for dementia (hazard ratio [HR] 0.93; 95% confidence interval [CI], 0.87-0.99, P = .037). This association was attenuated somewhat after adjustment for socioeconomic status.
Serum levels of beta-cryptoxanthin showed a “strong” inverse relationship with all-cause dementia in age- and sex-adjusted models.
For beta-cryptoxanthin, every SD increase (roughly 8.6 µmol/liter) was associated with a 14% reduced risk for dementia in people aged 45 and older (HR, 0.86; 95% CI, 0.80-0.93, P < .001) and 65 and older (HR, 0.86; 95% CI, 0.80-0.93, P = .001).
This relationship remained strong in models adjusted for sociodemographic and socioeconomic factors but attenuated in subsequent models.
No associations were found for lycopene, alpha-carotene, beta-carotene, or vitamins A, C, or E in the fully adjusted models.
Antagonistic interactions were observed for vitamin A and alpha-carotene, vitamin A and beta-carotene, vitamin E and lycopene, and lycopene and beta-carotene, suggesting putative protective effects of one antioxidant at lower levels of the other, the researchers noted.
“This analysis of an observational study found that the most important carotenoids in potentially protecting the brain may be lutein + zeaxanthin and beta-cryptoxanthin. However, randomized controlled trials are needed to prove causality,” said Dr. Ferrucci.
“Experts do not yet know the daily level of antioxidant intake to promote healthy aging of the brain. More research is needed to establish the necessary level of antioxidant intake – through the diet and/or supplements – to promote brain health and healthy aging,” he added.
An important step forward
In an accompanying editorial, Babak Hooshmand, MD, PhD, and Miia Kivipelto, MD, PhD, with Karolinska Institute, Stockholm, noted that while nutrition and dietary components are “potential targets” for dementia risk reduction, observational studies to date have reported “inconsistent findings.”
This study is “an important step towards exploring the complex relationship between antioxidants and dementia because it accounts for factors that could possibly influence the associations and considers interactions between different components,” they wrote.
The findings are “challenging,” they added, because they may lead to the hypothesis that inhibition of oxidative damage by antioxidants might have beneficial effects on preventing dementia.
However, clinical trials of antioxidant supplementation have been mainly “disappointing” and a recent Cochrane review found a lack of evidence for supplement use to preserve cognitive function or prevent dementia, Dr. Hooshmand and Dr. Kivipelto noted.
They added that the study contributes to the belief that antioxidants don’t act independently of each other or other factors, including socioeconomic status and lifestyle, in the mediation of dementia risk.
“A careful examination of the evidence is required to learn how antioxidants influence the complex pathology of dementia, because it appears to be more to it than meets the eye,”they concluded.
The research was supported in part by the Intramural Research Program of the National Institutes of Health and the National Institute on Aging. Dr. Beydoun, Dr. Ferrucci, and Dr. Hooshmand report no relevant disclosures. Dr. Kivipelto has supported advisory boards for Combinostics, Roche, and Biogen.
A version of this article first appeared on Medscape.com.
FROM NEUROLOGY
Residential green space linked to better cognitive function
Exposure to green space may boost cognitive function, new research suggests.
This association may be explained by a reduction in depression, researchers note. Scores for overall cognition and psychomotor speed/attention among women with high green-space exposure were equivalent to those of women an average of 1.2 years younger, they add.
“Despite the fact that the women in our study were relatively younger than those in previous studies, we were still able to detect protective associations between green space and cognition,” lead author Marcia Pescador Jimenez, PhD, assistant professor of epidemiology, Boston University School of Public Health, told this news organization.
“This may signal the public health importance of green space and the important clinical implications at the population level,” she said.
The findings were published online in JAMA Network Open.
Better psychomotor speed, attention
Recent studies on the benefits of green space have shown a link between higher exposure and reduced risks for schizophrenia and ischemic stroke. Other studies have explored the link between green space and dementia and Alzheimer’s disease.
Cognitive function in middle age is associated with subsequent dementia, so Dr. Jimenez said she and her colleagues wanted to analyze the effect of residential green space on cognitive function in middle-aged women.
The study included 13,594 women (median age, 61.2 years) who are participants in the ongoing Nurses’ Health Study II, one of the largest studies to examine risk factors for chronic illness in women.
To calculate the amount of green space, researchers used the Normalized Difference Vegetation Index (NDVI), a satellite-based indicator of green vegetation around a residential address. The data were based on each participant’s 2013 residence.
After adjusting for age at assessment, race, and childhood, adulthood, and neighborhood socioeconomic status, green space was associated with higher scores on the global CogState composite (mean difference per interquartile range in green space, 0.05; 95% confidence interval, .02-.07) and psychomotor speed and attention (mean difference in score, 0.05 standard units; 95% CI, .02-.08) scales.
There was no association between green-space exposure and learning and working memory. Investigators also found no differences based on urbanicity, suggesting the benefits were similar for urban versus rural settings.
Specific to cognitive domains
“We were surprised to see that while our study found that higher levels of residential green space were associated with higher scores on processing speed and attention and on overall cognition, we also found that higher levels of residential green space were not associated with learning/working memory battery scores,” Dr. Jimenez said.
“This is actually in-line with previous research suggesting differing associations between green space and cognition based on the cognitive domain examined,” she added.
About 98% of participants were White, limiting the generalizability of the findings, the researchers note. There was also no information on proximity to or size of green space, or how much time individuals spent in the green space and what kinds of activities they engaged in.
Dr. Jimenez said projects examining the amount of time of green-space exposure are underway.
In addition, the researchers found lower rates of depression might contribute to the cognitive benefits associated with green-space exposure, explaining 3.95% (95% CI, .35%-7.55%) of the association between green space and psychomotor speed/attention and 6.3% (95% CI, .77%-11.81%) of the association between green space and overall cognition.
Reduced air pollution and increased physical activity, which are other factors often thought to contribute to the cognitive benefits of green space, were not significant in this study.
‘Interesting and novel’
Commenting on the findings, Payam Dadvand, MD, PhD, associate research professor, Barcelona Institute for Global Health, called the finding that depression may mediate green-space benefits “quite interesting and novel.”
“The results of this study, given its large sample size and its geographical coverage, adds to an emerging body of evidence on the beneficial association of exposure to green space on aging, and in particular, cognitive aging in older adults,” said Dr. Dadvand, who was not involved with the research.
The study was funded by the National Institutes of Health. Dr. Jimenez and Dr. Dadvand have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Exposure to green space may boost cognitive function, new research suggests.
This association may be explained by a reduction in depression, researchers note. Scores for overall cognition and psychomotor speed/attention among women with high green-space exposure were equivalent to those of women an average of 1.2 years younger, they add.
“Despite the fact that the women in our study were relatively younger than those in previous studies, we were still able to detect protective associations between green space and cognition,” lead author Marcia Pescador Jimenez, PhD, assistant professor of epidemiology, Boston University School of Public Health, told this news organization.
“This may signal the public health importance of green space and the important clinical implications at the population level,” she said.
The findings were published online in JAMA Network Open.
Better psychomotor speed, attention
Recent studies on the benefits of green space have shown a link between higher exposure and reduced risks for schizophrenia and ischemic stroke. Other studies have explored the link between green space and dementia and Alzheimer’s disease.
Cognitive function in middle age is associated with subsequent dementia, so Dr. Jimenez said she and her colleagues wanted to analyze the effect of residential green space on cognitive function in middle-aged women.
The study included 13,594 women (median age, 61.2 years) who are participants in the ongoing Nurses’ Health Study II, one of the largest studies to examine risk factors for chronic illness in women.
To calculate the amount of green space, researchers used the Normalized Difference Vegetation Index (NDVI), a satellite-based indicator of green vegetation around a residential address. The data were based on each participant’s 2013 residence.
After adjusting for age at assessment, race, and childhood, adulthood, and neighborhood socioeconomic status, green space was associated with higher scores on the global CogState composite (mean difference per interquartile range in green space, 0.05; 95% confidence interval, .02-.07) and psychomotor speed and attention (mean difference in score, 0.05 standard units; 95% CI, .02-.08) scales.
There was no association between green-space exposure and learning and working memory. Investigators also found no differences based on urbanicity, suggesting the benefits were similar for urban versus rural settings.
Specific to cognitive domains
“We were surprised to see that while our study found that higher levels of residential green space were associated with higher scores on processing speed and attention and on overall cognition, we also found that higher levels of residential green space were not associated with learning/working memory battery scores,” Dr. Jimenez said.
“This is actually in-line with previous research suggesting differing associations between green space and cognition based on the cognitive domain examined,” she added.
About 98% of participants were White, limiting the generalizability of the findings, the researchers note. There was also no information on proximity to or size of green space, or how much time individuals spent in the green space and what kinds of activities they engaged in.
Dr. Jimenez said projects examining the amount of time of green-space exposure are underway.
In addition, the researchers found lower rates of depression might contribute to the cognitive benefits associated with green-space exposure, explaining 3.95% (95% CI, .35%-7.55%) of the association between green space and psychomotor speed/attention and 6.3% (95% CI, .77%-11.81%) of the association between green space and overall cognition.
Reduced air pollution and increased physical activity, which are other factors often thought to contribute to the cognitive benefits of green space, were not significant in this study.
‘Interesting and novel’
Commenting on the findings, Payam Dadvand, MD, PhD, associate research professor, Barcelona Institute for Global Health, called the finding that depression may mediate green-space benefits “quite interesting and novel.”
“The results of this study, given its large sample size and its geographical coverage, adds to an emerging body of evidence on the beneficial association of exposure to green space on aging, and in particular, cognitive aging in older adults,” said Dr. Dadvand, who was not involved with the research.
The study was funded by the National Institutes of Health. Dr. Jimenez and Dr. Dadvand have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Exposure to green space may boost cognitive function, new research suggests.
This association may be explained by a reduction in depression, researchers note. Scores for overall cognition and psychomotor speed/attention among women with high green-space exposure were equivalent to those of women an average of 1.2 years younger, they add.
“Despite the fact that the women in our study were relatively younger than those in previous studies, we were still able to detect protective associations between green space and cognition,” lead author Marcia Pescador Jimenez, PhD, assistant professor of epidemiology, Boston University School of Public Health, told this news organization.
“This may signal the public health importance of green space and the important clinical implications at the population level,” she said.
The findings were published online in JAMA Network Open.
Better psychomotor speed, attention
Recent studies on the benefits of green space have shown a link between higher exposure and reduced risks for schizophrenia and ischemic stroke. Other studies have explored the link between green space and dementia and Alzheimer’s disease.
Cognitive function in middle age is associated with subsequent dementia, so Dr. Jimenez said she and her colleagues wanted to analyze the effect of residential green space on cognitive function in middle-aged women.
The study included 13,594 women (median age, 61.2 years) who are participants in the ongoing Nurses’ Health Study II, one of the largest studies to examine risk factors for chronic illness in women.
To calculate the amount of green space, researchers used the Normalized Difference Vegetation Index (NDVI), a satellite-based indicator of green vegetation around a residential address. The data were based on each participant’s 2013 residence.
After adjusting for age at assessment, race, and childhood, adulthood, and neighborhood socioeconomic status, green space was associated with higher scores on the global CogState composite (mean difference per interquartile range in green space, 0.05; 95% confidence interval, .02-.07) and psychomotor speed and attention (mean difference in score, 0.05 standard units; 95% CI, .02-.08) scales.
There was no association between green-space exposure and learning and working memory. Investigators also found no differences based on urbanicity, suggesting the benefits were similar for urban versus rural settings.
Specific to cognitive domains
“We were surprised to see that while our study found that higher levels of residential green space were associated with higher scores on processing speed and attention and on overall cognition, we also found that higher levels of residential green space were not associated with learning/working memory battery scores,” Dr. Jimenez said.
“This is actually in-line with previous research suggesting differing associations between green space and cognition based on the cognitive domain examined,” she added.
About 98% of participants were White, limiting the generalizability of the findings, the researchers note. There was also no information on proximity to or size of green space, or how much time individuals spent in the green space and what kinds of activities they engaged in.
Dr. Jimenez said projects examining the amount of time of green-space exposure are underway.
In addition, the researchers found lower rates of depression might contribute to the cognitive benefits associated with green-space exposure, explaining 3.95% (95% CI, .35%-7.55%) of the association between green space and psychomotor speed/attention and 6.3% (95% CI, .77%-11.81%) of the association between green space and overall cognition.
Reduced air pollution and increased physical activity, which are other factors often thought to contribute to the cognitive benefits of green space, were not significant in this study.
‘Interesting and novel’
Commenting on the findings, Payam Dadvand, MD, PhD, associate research professor, Barcelona Institute for Global Health, called the finding that depression may mediate green-space benefits “quite interesting and novel.”
“The results of this study, given its large sample size and its geographical coverage, adds to an emerging body of evidence on the beneficial association of exposure to green space on aging, and in particular, cognitive aging in older adults,” said Dr. Dadvand, who was not involved with the research.
The study was funded by the National Institutes of Health. Dr. Jimenez and Dr. Dadvand have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FDA clears diagnostic test for early Alzheimer’s
The Lumipulse G β-Amyloid Ratio 1-42/1-40 (Fujirebio Diagnostics) test detects amyloid plaques associated with AD in adults age 55 or older who are under investigation for AD and other causes of cognitive decline.
“The availability of an in vitro diagnostic test that can potentially eliminate the need for time-consuming and expensive [positron emission tomography (PET)] scans is great news for individuals and families concerned with the possibility of an Alzheimer’s disease diagnosis,” Jeff Shuren, MD, JD, director of the FDA’s Center for Devices and Radiological Health, said in a statement.
“With the Lumipulse test, there is a new option that can typically be completed the same day and can give doctors the same information regarding brain amyloid status, without the radiation risk, to help determine if a patient’s cognitive impairment is due to Alzheimer’s disease,” he added.
In its statement, the FDA notes that there is an “unmet need for a reliable and safe test that can accurately identify patients with amyloid plaques consistent with Alzheimer’s disease.”
The agency goes on to state that this new test may eliminate the need to use PET brain scans, a “potentially costly and cumbersome option” to visualize amyloid plaques for the diagnosis of AD.
The Lumipulse test measures the ratio of β-amyloid 1-42 and β-amyloid 1-40 concentrations in human cerebral spinal fluid (CSF). A positive Lumipulse G β-amyloid Ratio (1-42/1-40) test result is consistent with the presence of amyloid plaques, similar to that revealed in a PET scan. A negative result is consistent with a negative amyloid PET scan result.
However, the FDA notes that the test is not a stand-alone assay and should be used in conjunction with other clinical evaluations and additional tests to determine treatment options.
The FDA reports that it evaluated the safety and efficacy of the test in a clinical study of 292 CSF samples from the Alzheimer’s Disease Neuroimaging Initiative sample bank.
The samples were tested by the Lumipulse G β-amyloid Ratio (1-42/1-40) and compared with amyloid PET scan results. In this clinical study, 97% of individuals with Lumipulse G β-amyloid Ratio (1-42/1-40) positive results had the presence of amyloid plaques by PET scan and 84% of individuals with negative results had a negative amyloid PET scan.
The risks associated with the Lumipulse G β-amyloid Ratio (1-42/1-40) test are mainly the possibility of false-positive and false-negative test results.
False-positive results, in conjunction with other clinical information, could lead to an inappropriate diagnosis of, and unnecessary treatment for AD.
False-negative test results could result in additional unnecessary diagnostic tests and potential delay in effective treatment for AD.
The FDA reviewed the device through the De Novo premarket review pathway, a regulatory pathway for low- to moderate-risk devices of a new type.
The agency says this action “creates a new regulatory classification, which means that subsequent devices of the same type with the same intended use may go through FDA’s 510(k) premarket process, whereby devices can obtain marketing authorization by demonstrating substantial equivalence to a predicate device.”
The Lumipulse G β-amyloid Ratio (1-42/1-40) was granted Breakthrough Device designation, a process designed to expedite the development and review of devices that may provide for more effective treatment or diagnosis of life-threatening or irreversibly debilitating diseases or conditions.
A version of this article first appeared on Medscape.com.
The Lumipulse G β-Amyloid Ratio 1-42/1-40 (Fujirebio Diagnostics) test detects amyloid plaques associated with AD in adults age 55 or older who are under investigation for AD and other causes of cognitive decline.
“The availability of an in vitro diagnostic test that can potentially eliminate the need for time-consuming and expensive [positron emission tomography (PET)] scans is great news for individuals and families concerned with the possibility of an Alzheimer’s disease diagnosis,” Jeff Shuren, MD, JD, director of the FDA’s Center for Devices and Radiological Health, said in a statement.
“With the Lumipulse test, there is a new option that can typically be completed the same day and can give doctors the same information regarding brain amyloid status, without the radiation risk, to help determine if a patient’s cognitive impairment is due to Alzheimer’s disease,” he added.
In its statement, the FDA notes that there is an “unmet need for a reliable and safe test that can accurately identify patients with amyloid plaques consistent with Alzheimer’s disease.”
The agency goes on to state that this new test may eliminate the need to use PET brain scans, a “potentially costly and cumbersome option” to visualize amyloid plaques for the diagnosis of AD.
The Lumipulse test measures the ratio of β-amyloid 1-42 and β-amyloid 1-40 concentrations in human cerebral spinal fluid (CSF). A positive Lumipulse G β-amyloid Ratio (1-42/1-40) test result is consistent with the presence of amyloid plaques, similar to that revealed in a PET scan. A negative result is consistent with a negative amyloid PET scan result.
However, the FDA notes that the test is not a stand-alone assay and should be used in conjunction with other clinical evaluations and additional tests to determine treatment options.
The FDA reports that it evaluated the safety and efficacy of the test in a clinical study of 292 CSF samples from the Alzheimer’s Disease Neuroimaging Initiative sample bank.
The samples were tested by the Lumipulse G β-amyloid Ratio (1-42/1-40) and compared with amyloid PET scan results. In this clinical study, 97% of individuals with Lumipulse G β-amyloid Ratio (1-42/1-40) positive results had the presence of amyloid plaques by PET scan and 84% of individuals with negative results had a negative amyloid PET scan.
The risks associated with the Lumipulse G β-amyloid Ratio (1-42/1-40) test are mainly the possibility of false-positive and false-negative test results.
False-positive results, in conjunction with other clinical information, could lead to an inappropriate diagnosis of, and unnecessary treatment for AD.
False-negative test results could result in additional unnecessary diagnostic tests and potential delay in effective treatment for AD.
The FDA reviewed the device through the De Novo premarket review pathway, a regulatory pathway for low- to moderate-risk devices of a new type.
The agency says this action “creates a new regulatory classification, which means that subsequent devices of the same type with the same intended use may go through FDA’s 510(k) premarket process, whereby devices can obtain marketing authorization by demonstrating substantial equivalence to a predicate device.”
The Lumipulse G β-amyloid Ratio (1-42/1-40) was granted Breakthrough Device designation, a process designed to expedite the development and review of devices that may provide for more effective treatment or diagnosis of life-threatening or irreversibly debilitating diseases or conditions.
A version of this article first appeared on Medscape.com.
The Lumipulse G β-Amyloid Ratio 1-42/1-40 (Fujirebio Diagnostics) test detects amyloid plaques associated with AD in adults age 55 or older who are under investigation for AD and other causes of cognitive decline.
“The availability of an in vitro diagnostic test that can potentially eliminate the need for time-consuming and expensive [positron emission tomography (PET)] scans is great news for individuals and families concerned with the possibility of an Alzheimer’s disease diagnosis,” Jeff Shuren, MD, JD, director of the FDA’s Center for Devices and Radiological Health, said in a statement.
“With the Lumipulse test, there is a new option that can typically be completed the same day and can give doctors the same information regarding brain amyloid status, without the radiation risk, to help determine if a patient’s cognitive impairment is due to Alzheimer’s disease,” he added.
In its statement, the FDA notes that there is an “unmet need for a reliable and safe test that can accurately identify patients with amyloid plaques consistent with Alzheimer’s disease.”
The agency goes on to state that this new test may eliminate the need to use PET brain scans, a “potentially costly and cumbersome option” to visualize amyloid plaques for the diagnosis of AD.
The Lumipulse test measures the ratio of β-amyloid 1-42 and β-amyloid 1-40 concentrations in human cerebral spinal fluid (CSF). A positive Lumipulse G β-amyloid Ratio (1-42/1-40) test result is consistent with the presence of amyloid plaques, similar to that revealed in a PET scan. A negative result is consistent with a negative amyloid PET scan result.
However, the FDA notes that the test is not a stand-alone assay and should be used in conjunction with other clinical evaluations and additional tests to determine treatment options.
The FDA reports that it evaluated the safety and efficacy of the test in a clinical study of 292 CSF samples from the Alzheimer’s Disease Neuroimaging Initiative sample bank.
The samples were tested by the Lumipulse G β-amyloid Ratio (1-42/1-40) and compared with amyloid PET scan results. In this clinical study, 97% of individuals with Lumipulse G β-amyloid Ratio (1-42/1-40) positive results had the presence of amyloid plaques by PET scan and 84% of individuals with negative results had a negative amyloid PET scan.
The risks associated with the Lumipulse G β-amyloid Ratio (1-42/1-40) test are mainly the possibility of false-positive and false-negative test results.
False-positive results, in conjunction with other clinical information, could lead to an inappropriate diagnosis of, and unnecessary treatment for AD.
False-negative test results could result in additional unnecessary diagnostic tests and potential delay in effective treatment for AD.
The FDA reviewed the device through the De Novo premarket review pathway, a regulatory pathway for low- to moderate-risk devices of a new type.
The agency says this action “creates a new regulatory classification, which means that subsequent devices of the same type with the same intended use may go through FDA’s 510(k) premarket process, whereby devices can obtain marketing authorization by demonstrating substantial equivalence to a predicate device.”
The Lumipulse G β-amyloid Ratio (1-42/1-40) was granted Breakthrough Device designation, a process designed to expedite the development and review of devices that may provide for more effective treatment or diagnosis of life-threatening or irreversibly debilitating diseases or conditions.
A version of this article first appeared on Medscape.com.
Seven hours of sleep is ideal for middle aged and older
Sleep disturbances are common in older age, and previous studies have shown associations between too much or too little sleep and increased risk of cognitive decline, but the ideal amount of sleep for preserving mental health has not been well described, according to the authors of the new paper.
In the study published in Nature Aging, the team of researchers from China and the United Kingdom reviewed data from the UK Biobank, a national database of individuals in the United Kingdom that includes cognitive assessments, mental health questionnaires, and brain imaging data, as well as genetic information.
Sleep is important for physical and psychological health, and also serves a neuroprotective function by clearing waste products from the brain, lead author Yuzhu Li of Fudan University, Shanghai, China, and colleagues wrote.
The study population included 498,277 participants, aged 38-73 years, who completed touchscreen questionnaires about sleep duration between 2006 and 2010. The average age at baseline was 56.5 years, 54% were female, and the mean sleep duration was 7.15 hours.
The researchers also reviewed brain imaging data and genetic data from 39,692 participants in 2014 to examine the relationships between sleep duration and brain structure and between sleep duration and genetic risk. In addition, 156,884 participants completed an online follow-up mental health questionnaire in 2016-2017 to assess the longitudinal impact of sleep on mental health.
Both excessive and insufficient sleep was associated with impaired cognitive performance, evidenced by the U-shaped curve found by the researchers in their data analysis, which used quadratic associations.
Specific cognitive functions including pair matching, trail making, prospective memory, and reaction time were significantly impaired with too much or too little sleep, the researchers said. “This demonstrated the positive association of both insufficient and excessive sleep duration with inferior performance on cognitive tasks.”
When the researchers analyzed the association between sleep duration and mental health, sleep duration also showed a U-shaped association with symptoms of anxiety, depression, mental distress, mania, and self-harm, while well-being showed an inverted U-shape. All associations between sleep duration and mental health were statistically significant after controlling for confounding variables (P < .001).
On further analysis (using two-line tests), the researchers determined that consistent sleep duration of approximately 7 hours per night was optimal for cognitive performance and for good mental health.
The researchers also used neuroimaging data to examine the relationship between sleep duration and brain structure. Overall, greater changes were seen in the regions of the brain involved in cognitive processing and memory.
“The most significant cortical volumes nonlinearly associated with sleep duration included the precentral cortex, the superior frontal gyrus, the lateral orbitofrontal cortex, the pars orbitalis, the frontal pole, and the middle temporal cortex,” the researchers wrote (P < .05 for all).
The association between sleep duration and cognitive function diminished among individuals older than 65 years, compared with those aged approximately 40 years, which suggests that optimal sleep duration may be more beneficial in middle age, the researchers noted. However, no similar impact of age was seen for mental health. For brain structure, the nonlinear relationship between sleep duration and cortical volumes was greatest in those aged 44-59 years, and gradually flattened with older age.
Research supports sleep discussions with patients
“Primary care physicians can use this study in their discussions with middle-aged and older patients to recommend optimal sleep duration and measures to achieve this sleep target,” Noel Deep, MD, a general internist in group practice in Antigo, Wisc., who was not involved in the study, said in an interview.
“This study is important because it demonstrated that both inadequate and excessive sleep patterns were associated with cognitive and mental health changes,” said Dr. Deep. “It supported previous observations of cognitive decline and mental health disorders being linked to disturbed sleep. But this study was unique because it provides data supporting an optimal sleep duration of 7 hours and the ill effects of both insufficient and excessive sleep duration.
“The usual thought process has been to assume that older individuals may not require as much sleep as the younger individuals, but this study supports an optimal time duration of sleep of 7 hours that benefits the older individuals. It was also interesting to note the mental health effects caused by the inadequate and excessive sleep durations,” he added.
As for additional research, “I would like to look into the quality of the sleep, in addition to the duration of sleep,” said Dr. Deep. For example, whether the excessive sleep was caused by poor quality sleep or fragmented sleep leading to the structural and subsequent cognitive decline.
Study limitations
“The current study relied on self-reporting of the sleep duration and was not observed and recorded data,” Dr. Deep noted. “It would also be beneficial to not only rely on healthy volunteers reporting the sleep duration, but also obtain sleep data from individuals with known brain disorders.”
The study findings were limited by several other factors, including the use of total sleep duration only, without other measures of sleep hygiene, the researchers noted. More research is needed to investigate the mechanisms driving the association between too much and not enough sleep and poor mental health and cognitive function.
The study was supported by the National Key R&D Program of China, the Shanghai Municipal Science and Technology Major Project, the Shanghai Center for Brain Science and Brain-Inspired Technology, the 111 Project, the National Natural Sciences Foundation of China and the Shanghai Rising Star Program.
The researchers had no financial conflicts to disclose. Dr. Deep had no financial conflicts to disclose, but serves on the editorial advisory board of Internal Medicine News.
Sleep disturbances are common in older age, and previous studies have shown associations between too much or too little sleep and increased risk of cognitive decline, but the ideal amount of sleep for preserving mental health has not been well described, according to the authors of the new paper.
In the study published in Nature Aging, the team of researchers from China and the United Kingdom reviewed data from the UK Biobank, a national database of individuals in the United Kingdom that includes cognitive assessments, mental health questionnaires, and brain imaging data, as well as genetic information.
Sleep is important for physical and psychological health, and also serves a neuroprotective function by clearing waste products from the brain, lead author Yuzhu Li of Fudan University, Shanghai, China, and colleagues wrote.
The study population included 498,277 participants, aged 38-73 years, who completed touchscreen questionnaires about sleep duration between 2006 and 2010. The average age at baseline was 56.5 years, 54% were female, and the mean sleep duration was 7.15 hours.
The researchers also reviewed brain imaging data and genetic data from 39,692 participants in 2014 to examine the relationships between sleep duration and brain structure and between sleep duration and genetic risk. In addition, 156,884 participants completed an online follow-up mental health questionnaire in 2016-2017 to assess the longitudinal impact of sleep on mental health.
Both excessive and insufficient sleep was associated with impaired cognitive performance, evidenced by the U-shaped curve found by the researchers in their data analysis, which used quadratic associations.
Specific cognitive functions including pair matching, trail making, prospective memory, and reaction time were significantly impaired with too much or too little sleep, the researchers said. “This demonstrated the positive association of both insufficient and excessive sleep duration with inferior performance on cognitive tasks.”
When the researchers analyzed the association between sleep duration and mental health, sleep duration also showed a U-shaped association with symptoms of anxiety, depression, mental distress, mania, and self-harm, while well-being showed an inverted U-shape. All associations between sleep duration and mental health were statistically significant after controlling for confounding variables (P < .001).
On further analysis (using two-line tests), the researchers determined that consistent sleep duration of approximately 7 hours per night was optimal for cognitive performance and for good mental health.
The researchers also used neuroimaging data to examine the relationship between sleep duration and brain structure. Overall, greater changes were seen in the regions of the brain involved in cognitive processing and memory.
“The most significant cortical volumes nonlinearly associated with sleep duration included the precentral cortex, the superior frontal gyrus, the lateral orbitofrontal cortex, the pars orbitalis, the frontal pole, and the middle temporal cortex,” the researchers wrote (P < .05 for all).
The association between sleep duration and cognitive function diminished among individuals older than 65 years, compared with those aged approximately 40 years, which suggests that optimal sleep duration may be more beneficial in middle age, the researchers noted. However, no similar impact of age was seen for mental health. For brain structure, the nonlinear relationship between sleep duration and cortical volumes was greatest in those aged 44-59 years, and gradually flattened with older age.
Research supports sleep discussions with patients
“Primary care physicians can use this study in their discussions with middle-aged and older patients to recommend optimal sleep duration and measures to achieve this sleep target,” Noel Deep, MD, a general internist in group practice in Antigo, Wisc., who was not involved in the study, said in an interview.
“This study is important because it demonstrated that both inadequate and excessive sleep patterns were associated with cognitive and mental health changes,” said Dr. Deep. “It supported previous observations of cognitive decline and mental health disorders being linked to disturbed sleep. But this study was unique because it provides data supporting an optimal sleep duration of 7 hours and the ill effects of both insufficient and excessive sleep duration.
“The usual thought process has been to assume that older individuals may not require as much sleep as the younger individuals, but this study supports an optimal time duration of sleep of 7 hours that benefits the older individuals. It was also interesting to note the mental health effects caused by the inadequate and excessive sleep durations,” he added.
As for additional research, “I would like to look into the quality of the sleep, in addition to the duration of sleep,” said Dr. Deep. For example, whether the excessive sleep was caused by poor quality sleep or fragmented sleep leading to the structural and subsequent cognitive decline.
Study limitations
“The current study relied on self-reporting of the sleep duration and was not observed and recorded data,” Dr. Deep noted. “It would also be beneficial to not only rely on healthy volunteers reporting the sleep duration, but also obtain sleep data from individuals with known brain disorders.”
The study findings were limited by several other factors, including the use of total sleep duration only, without other measures of sleep hygiene, the researchers noted. More research is needed to investigate the mechanisms driving the association between too much and not enough sleep and poor mental health and cognitive function.
The study was supported by the National Key R&D Program of China, the Shanghai Municipal Science and Technology Major Project, the Shanghai Center for Brain Science and Brain-Inspired Technology, the 111 Project, the National Natural Sciences Foundation of China and the Shanghai Rising Star Program.
The researchers had no financial conflicts to disclose. Dr. Deep had no financial conflicts to disclose, but serves on the editorial advisory board of Internal Medicine News.
Sleep disturbances are common in older age, and previous studies have shown associations between too much or too little sleep and increased risk of cognitive decline, but the ideal amount of sleep for preserving mental health has not been well described, according to the authors of the new paper.
In the study published in Nature Aging, the team of researchers from China and the United Kingdom reviewed data from the UK Biobank, a national database of individuals in the United Kingdom that includes cognitive assessments, mental health questionnaires, and brain imaging data, as well as genetic information.
Sleep is important for physical and psychological health, and also serves a neuroprotective function by clearing waste products from the brain, lead author Yuzhu Li of Fudan University, Shanghai, China, and colleagues wrote.
The study population included 498,277 participants, aged 38-73 years, who completed touchscreen questionnaires about sleep duration between 2006 and 2010. The average age at baseline was 56.5 years, 54% were female, and the mean sleep duration was 7.15 hours.
The researchers also reviewed brain imaging data and genetic data from 39,692 participants in 2014 to examine the relationships between sleep duration and brain structure and between sleep duration and genetic risk. In addition, 156,884 participants completed an online follow-up mental health questionnaire in 2016-2017 to assess the longitudinal impact of sleep on mental health.
Both excessive and insufficient sleep was associated with impaired cognitive performance, evidenced by the U-shaped curve found by the researchers in their data analysis, which used quadratic associations.
Specific cognitive functions including pair matching, trail making, prospective memory, and reaction time were significantly impaired with too much or too little sleep, the researchers said. “This demonstrated the positive association of both insufficient and excessive sleep duration with inferior performance on cognitive tasks.”
When the researchers analyzed the association between sleep duration and mental health, sleep duration also showed a U-shaped association with symptoms of anxiety, depression, mental distress, mania, and self-harm, while well-being showed an inverted U-shape. All associations between sleep duration and mental health were statistically significant after controlling for confounding variables (P < .001).
On further analysis (using two-line tests), the researchers determined that consistent sleep duration of approximately 7 hours per night was optimal for cognitive performance and for good mental health.
The researchers also used neuroimaging data to examine the relationship between sleep duration and brain structure. Overall, greater changes were seen in the regions of the brain involved in cognitive processing and memory.
“The most significant cortical volumes nonlinearly associated with sleep duration included the precentral cortex, the superior frontal gyrus, the lateral orbitofrontal cortex, the pars orbitalis, the frontal pole, and the middle temporal cortex,” the researchers wrote (P < .05 for all).
The association between sleep duration and cognitive function diminished among individuals older than 65 years, compared with those aged approximately 40 years, which suggests that optimal sleep duration may be more beneficial in middle age, the researchers noted. However, no similar impact of age was seen for mental health. For brain structure, the nonlinear relationship between sleep duration and cortical volumes was greatest in those aged 44-59 years, and gradually flattened with older age.
Research supports sleep discussions with patients
“Primary care physicians can use this study in their discussions with middle-aged and older patients to recommend optimal sleep duration and measures to achieve this sleep target,” Noel Deep, MD, a general internist in group practice in Antigo, Wisc., who was not involved in the study, said in an interview.
“This study is important because it demonstrated that both inadequate and excessive sleep patterns were associated with cognitive and mental health changes,” said Dr. Deep. “It supported previous observations of cognitive decline and mental health disorders being linked to disturbed sleep. But this study was unique because it provides data supporting an optimal sleep duration of 7 hours and the ill effects of both insufficient and excessive sleep duration.
“The usual thought process has been to assume that older individuals may not require as much sleep as the younger individuals, but this study supports an optimal time duration of sleep of 7 hours that benefits the older individuals. It was also interesting to note the mental health effects caused by the inadequate and excessive sleep durations,” he added.
As for additional research, “I would like to look into the quality of the sleep, in addition to the duration of sleep,” said Dr. Deep. For example, whether the excessive sleep was caused by poor quality sleep or fragmented sleep leading to the structural and subsequent cognitive decline.
Study limitations
“The current study relied on self-reporting of the sleep duration and was not observed and recorded data,” Dr. Deep noted. “It would also be beneficial to not only rely on healthy volunteers reporting the sleep duration, but also obtain sleep data from individuals with known brain disorders.”
The study findings were limited by several other factors, including the use of total sleep duration only, without other measures of sleep hygiene, the researchers noted. More research is needed to investigate the mechanisms driving the association between too much and not enough sleep and poor mental health and cognitive function.
The study was supported by the National Key R&D Program of China, the Shanghai Municipal Science and Technology Major Project, the Shanghai Center for Brain Science and Brain-Inspired Technology, the 111 Project, the National Natural Sciences Foundation of China and the Shanghai Rising Star Program.
The researchers had no financial conflicts to disclose. Dr. Deep had no financial conflicts to disclose, but serves on the editorial advisory board of Internal Medicine News.
FROM NATURE AGING
Severe COVID-19 adds 20 years of cognitive aging: Study
adding that the impairment is “equivalent to losing 10 IQ points.”
In their study, published in eClinicalMedicine, a team of scientists from the University of Cambridge and Imperial College London said there is growing evidence that COVID-19 can cause lasting cognitive and mental health problems. Patients report fatigue, “brain fog,” problems recalling words, sleep disturbances, anxiety, and even posttraumatic stress disorder months after infection.
The researchers analyzed data from 46 individuals who received critical care for COVID-19 at Addenbrooke’s Hospital between March and July 2020 (27 females, 19 males, mean age 51 years, 16 of whom had mechanical ventilation) and were recruited to the NIHR COVID-19 BioResource project.
At an average of 6 months after acute COVID-19 illness, the study participants underwent detailed computerized cognitive tests via the Cognitron platform, comprising eight tasks deployed on an iPad measuring mental function such as memory, attention, and reasoning. Also assessed were anxiety, depression, and posttraumatic stress disorder via standard mood, anxiety, and posttraumatic stress scales – specifically the Generalized Anxiety Disorder 7 (GAD-7), the Patient Health Questionnaire 9 (PHQ-9), and the PTSD Checklist for Diagnostic and Statistical Manual of Mental Disorders 5 (PCL-5). Their data were compared against 460 controls – matched for age, sex, education, and first language – and the pattern of deficits across tasks was qualitatively compared with normal age-related decline and early-stage dementia.
Less accurate and slower response times
The authors highlighted how this was the first time a “rigorous assessment and comparison” had been carried out in relation to the after-effects of severe COVID-19.
“Cognitive impairment is common to a wide range of neurological disorders, including dementia, and even routine aging, but the patterns we saw – the cognitive ‘fingerprint’ of COVID-19 – was distinct from all of these,” said David Menon, MD, division of anesthesia at the University of Cambridge, England, and the study’s senior author.
The scientists found that COVID-19 survivors were less accurate and had slower response times than the control population, and added that survivors scored particularly poorly on verbal analogical reasoning and showed slower processing speeds.
Critically, the scale of the cognitive deficits correlated with acute illness severity, but not fatigue or mental health status at the time of cognitive assessment, said the authors.
Recovery ‘at best gradual’
The effects were strongest for those with more severe acute illness, and who required mechanical ventilation, said the authors, who found that acute illness severity was “better at predicting the cognitive deficits.”
The authors pointed out how these deficits were still detectable when patients were followed up 6 months later, and that, although patients’ scores and reaction times began to improve over time, any recovery was “at best gradual” and likely to be influenced by factors such as illness severity and its neurological or psychological impacts.
“We followed some patients up as late as 10 months after their acute infection, so were able to see a very slow improvement,” Dr. Menon said. He explained how, while this improvement was not statistically significant, it was “at least heading in the right direction.”
However, he warned it is very possible that some of these individuals “will never fully recover.”
The cognitive deficits observed may be due to several factors in combination, said the authors, including inadequate oxygen or blood supply to the brain, blockage of large or small blood vessels due to clotting, and microscopic bleeds. They highlighted how the most important mechanism, however, may be “damage caused by the body’s own inflammatory response and immune system.”
Adam Hampshire, PhD, of the department of brain sciences at Imperial College London, one of the study’s authors, described how around 40,000 people have been through intensive care with COVID-19 in England alone, with many more despite having been very sick not admitted to hospital. This means there is a “large number of people out there still experiencing problems with cognition many months later,” he said. “We urgently need to look at what can be done to help these people.”
A version of this article first appeared on Univadis.
adding that the impairment is “equivalent to losing 10 IQ points.”
In their study, published in eClinicalMedicine, a team of scientists from the University of Cambridge and Imperial College London said there is growing evidence that COVID-19 can cause lasting cognitive and mental health problems. Patients report fatigue, “brain fog,” problems recalling words, sleep disturbances, anxiety, and even posttraumatic stress disorder months after infection.
The researchers analyzed data from 46 individuals who received critical care for COVID-19 at Addenbrooke’s Hospital between March and July 2020 (27 females, 19 males, mean age 51 years, 16 of whom had mechanical ventilation) and were recruited to the NIHR COVID-19 BioResource project.
At an average of 6 months after acute COVID-19 illness, the study participants underwent detailed computerized cognitive tests via the Cognitron platform, comprising eight tasks deployed on an iPad measuring mental function such as memory, attention, and reasoning. Also assessed were anxiety, depression, and posttraumatic stress disorder via standard mood, anxiety, and posttraumatic stress scales – specifically the Generalized Anxiety Disorder 7 (GAD-7), the Patient Health Questionnaire 9 (PHQ-9), and the PTSD Checklist for Diagnostic and Statistical Manual of Mental Disorders 5 (PCL-5). Their data were compared against 460 controls – matched for age, sex, education, and first language – and the pattern of deficits across tasks was qualitatively compared with normal age-related decline and early-stage dementia.
Less accurate and slower response times
The authors highlighted how this was the first time a “rigorous assessment and comparison” had been carried out in relation to the after-effects of severe COVID-19.
“Cognitive impairment is common to a wide range of neurological disorders, including dementia, and even routine aging, but the patterns we saw – the cognitive ‘fingerprint’ of COVID-19 – was distinct from all of these,” said David Menon, MD, division of anesthesia at the University of Cambridge, England, and the study’s senior author.
The scientists found that COVID-19 survivors were less accurate and had slower response times than the control population, and added that survivors scored particularly poorly on verbal analogical reasoning and showed slower processing speeds.
Critically, the scale of the cognitive deficits correlated with acute illness severity, but not fatigue or mental health status at the time of cognitive assessment, said the authors.
Recovery ‘at best gradual’
The effects were strongest for those with more severe acute illness, and who required mechanical ventilation, said the authors, who found that acute illness severity was “better at predicting the cognitive deficits.”
The authors pointed out how these deficits were still detectable when patients were followed up 6 months later, and that, although patients’ scores and reaction times began to improve over time, any recovery was “at best gradual” and likely to be influenced by factors such as illness severity and its neurological or psychological impacts.
“We followed some patients up as late as 10 months after their acute infection, so were able to see a very slow improvement,” Dr. Menon said. He explained how, while this improvement was not statistically significant, it was “at least heading in the right direction.”
However, he warned it is very possible that some of these individuals “will never fully recover.”
The cognitive deficits observed may be due to several factors in combination, said the authors, including inadequate oxygen or blood supply to the brain, blockage of large or small blood vessels due to clotting, and microscopic bleeds. They highlighted how the most important mechanism, however, may be “damage caused by the body’s own inflammatory response and immune system.”
Adam Hampshire, PhD, of the department of brain sciences at Imperial College London, one of the study’s authors, described how around 40,000 people have been through intensive care with COVID-19 in England alone, with many more despite having been very sick not admitted to hospital. This means there is a “large number of people out there still experiencing problems with cognition many months later,” he said. “We urgently need to look at what can be done to help these people.”
A version of this article first appeared on Univadis.
adding that the impairment is “equivalent to losing 10 IQ points.”
In their study, published in eClinicalMedicine, a team of scientists from the University of Cambridge and Imperial College London said there is growing evidence that COVID-19 can cause lasting cognitive and mental health problems. Patients report fatigue, “brain fog,” problems recalling words, sleep disturbances, anxiety, and even posttraumatic stress disorder months after infection.
The researchers analyzed data from 46 individuals who received critical care for COVID-19 at Addenbrooke’s Hospital between March and July 2020 (27 females, 19 males, mean age 51 years, 16 of whom had mechanical ventilation) and were recruited to the NIHR COVID-19 BioResource project.
At an average of 6 months after acute COVID-19 illness, the study participants underwent detailed computerized cognitive tests via the Cognitron platform, comprising eight tasks deployed on an iPad measuring mental function such as memory, attention, and reasoning. Also assessed were anxiety, depression, and posttraumatic stress disorder via standard mood, anxiety, and posttraumatic stress scales – specifically the Generalized Anxiety Disorder 7 (GAD-7), the Patient Health Questionnaire 9 (PHQ-9), and the PTSD Checklist for Diagnostic and Statistical Manual of Mental Disorders 5 (PCL-5). Their data were compared against 460 controls – matched for age, sex, education, and first language – and the pattern of deficits across tasks was qualitatively compared with normal age-related decline and early-stage dementia.
Less accurate and slower response times
The authors highlighted how this was the first time a “rigorous assessment and comparison” had been carried out in relation to the after-effects of severe COVID-19.
“Cognitive impairment is common to a wide range of neurological disorders, including dementia, and even routine aging, but the patterns we saw – the cognitive ‘fingerprint’ of COVID-19 – was distinct from all of these,” said David Menon, MD, division of anesthesia at the University of Cambridge, England, and the study’s senior author.
The scientists found that COVID-19 survivors were less accurate and had slower response times than the control population, and added that survivors scored particularly poorly on verbal analogical reasoning and showed slower processing speeds.
Critically, the scale of the cognitive deficits correlated with acute illness severity, but not fatigue or mental health status at the time of cognitive assessment, said the authors.
Recovery ‘at best gradual’
The effects were strongest for those with more severe acute illness, and who required mechanical ventilation, said the authors, who found that acute illness severity was “better at predicting the cognitive deficits.”
The authors pointed out how these deficits were still detectable when patients were followed up 6 months later, and that, although patients’ scores and reaction times began to improve over time, any recovery was “at best gradual” and likely to be influenced by factors such as illness severity and its neurological or psychological impacts.
“We followed some patients up as late as 10 months after their acute infection, so were able to see a very slow improvement,” Dr. Menon said. He explained how, while this improvement was not statistically significant, it was “at least heading in the right direction.”
However, he warned it is very possible that some of these individuals “will never fully recover.”
The cognitive deficits observed may be due to several factors in combination, said the authors, including inadequate oxygen or blood supply to the brain, blockage of large or small blood vessels due to clotting, and microscopic bleeds. They highlighted how the most important mechanism, however, may be “damage caused by the body’s own inflammatory response and immune system.”
Adam Hampshire, PhD, of the department of brain sciences at Imperial College London, one of the study’s authors, described how around 40,000 people have been through intensive care with COVID-19 in England alone, with many more despite having been very sick not admitted to hospital. This means there is a “large number of people out there still experiencing problems with cognition many months later,” he said. “We urgently need to look at what can be done to help these people.”
A version of this article first appeared on Univadis.
FROM ECLINICAL MEDICINE
Cutting dementia risk in AFib: Does rhythm control strategy matter?
The risk for dementia goes up in patients with atrial fibrillation (AFib), but some evidence suggests that risk can be blunted with therapies that restore sinus rhythm. However, a new cohort study suggests that the treatment effect’s magnitude might depend on the rhythm control strategy. It hinted that AFib catheter ablation might be more effective than pharmacologic rhythm control alone at cutting the risk for dementia.
The case-matched study of more than 38,000 adults with AFib saw a 41% reduction (P < .0001) in risk for dementia among those who underwent catheter ablation after attempted rhythm control with antiarrhythmic drugs (AAD), compared with those managed with pharmacologic rhythm control therapy alone.
The observational study comprising 20 years of data comes with big limitations and can’t say for sure whether catheter ablation is better than AAD-only at cutting the dementia risk in AFib. But it and other evidence support the idea, which has yet to be explored in a randomized fashion.
In a secondary finding, the analysis showed a similar reduction in dementia risk from catheter ablation, compared with AAD, in women and in men by 40% and 45%, respectively (P < .0001 for both). The findings are particularly relevant “given the higher life-long risk of dementia among women and the lower likelihood that women will be offered ablation, which has been demonstrated repeatedly,” Emily P. Zeitler, MD, MHS, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, told this news organization. “I think this is another reason to try to be more generous in offering ablation to women.”
Management of AFib certainly evolved in important ways from 2000 to 2021, the period covered by the study. But a sensitivity analysis based on data from 2010 to 2021 showed “no meaningful differences” in the results, said Dr. Zeitler, who is slated to present the findings April 30 at the Heart Rhythm Society 2022 Scientific Sessions, conducted virtually and live in San Francisco.
Dr. Zeitler acknowledged that the observational study, even with its propensity-matched ablation and AAD cohorts, can only hint at a preference for ablation over AAD for lowering risk for AFib-associated dementia. “We know there’s unmeasured and unfixable confounding between those two groups, so we see this really as hypothesis-generating.”
It was “a well-done analysis,” and the conclusion that the dementia risk was lower with catheter ablation is “absolutely correct,” but only as far as the study and its limitations allow, agreed David Conen, MD, MPH, McMaster University, Hamilton, Ontario, who is not a coauthor.
“Even with propensity matching, you can get rid of some sorts of confounding, but you can never get rid of all selection bias issues.” That, he said when interviewed, takes randomized trials.
Dr. Conen, who is studying cognitive decline in AFib as a SWISS-AF trial principal investigator, pointed to a secondary finding of the analysis as evidence for such confounding. He said the ablation group’s nearly 50% drop (P < .0001) in competing risk for death, compared with patients managed with AAD, isn’t plausible.
The finding “strongly suggests these people were healthier and that there’s some sort of selection bias. They were at lower risk of death, they were at lower risk of dementia, and they were probably also at lower risk of stroke, myocardial infarction, thrombosis, and cancer because they were just probably a little healthier than the others,” Dr. Conen said. The ablation and AAD groups “were two very different populations from the get-go.”
The analysis was based on U.S. insurance and Medicare claims data from AFib patients who either underwent catheter ablation after at least one AAD trial or filled prescriptions for at least two different antiarrhythmic agents in the year after AFib diagnosis. Patients with history of dementia, catheter or surgical AFib ablation, or a valve procedure were excluded.
The ablation and AAD-only groups each consisted of 19,066 patients after propensity matching, and the groups were balanced with respect to age, sex, type of insurance, CHA2DS2-VASc scores, and use of renin-angiotensin-system inhibitors, oral anticoagulants, and antiplatelets.
The overall risk for dementia was 1.9% for the ablation group and 3.3% for AAD-only patients (hazard ratio, 0.59; 95% confidence interval, 0.52-0.67). Corresponding HRs by sex were 0.55 (95% CI, 0.46-0.66) for men and 0.60 (95% CI, 0.50-0.72) for women.
The competing risk for death was also significantly decreased in the ablation group (HR, 0.51; 95% CI, 0.46-0.55).
Dr. Zeitler pointed to a randomized trial now in the early stages called Neurocognition and Greater Maintenance of Sinus Rhythm in Atrial Fibrillation, or NOGGIN-AF, which will explore relationships between rhythm control therapy and dementia in patients with AFib, whether catheter ablation or AAD can mitigate that risk, and whether either strategy works better than the other, among other goals.
“I’m optimistic,” she said, “and I think it’s going to add to the growing motivations to get patients ablated more quickly and more broadly.”
The analysis was funded by Biosense-Webster. Dr. Zeitler discloses consulting for Biosense-Webster and Arena Pharmaceuticals (now Pfizer); fees for speaking from Medtronic; and receiving research support from Boston Scientific, Sanofi, and Biosense-Webster. Dr. Conen has previously reported receiving speaker fees from Servier Canada.
A version of this article first appeared on Medscape.com.
The risk for dementia goes up in patients with atrial fibrillation (AFib), but some evidence suggests that risk can be blunted with therapies that restore sinus rhythm. However, a new cohort study suggests that the treatment effect’s magnitude might depend on the rhythm control strategy. It hinted that AFib catheter ablation might be more effective than pharmacologic rhythm control alone at cutting the risk for dementia.
The case-matched study of more than 38,000 adults with AFib saw a 41% reduction (P < .0001) in risk for dementia among those who underwent catheter ablation after attempted rhythm control with antiarrhythmic drugs (AAD), compared with those managed with pharmacologic rhythm control therapy alone.
The observational study comprising 20 years of data comes with big limitations and can’t say for sure whether catheter ablation is better than AAD-only at cutting the dementia risk in AFib. But it and other evidence support the idea, which has yet to be explored in a randomized fashion.
In a secondary finding, the analysis showed a similar reduction in dementia risk from catheter ablation, compared with AAD, in women and in men by 40% and 45%, respectively (P < .0001 for both). The findings are particularly relevant “given the higher life-long risk of dementia among women and the lower likelihood that women will be offered ablation, which has been demonstrated repeatedly,” Emily P. Zeitler, MD, MHS, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, told this news organization. “I think this is another reason to try to be more generous in offering ablation to women.”
Management of AFib certainly evolved in important ways from 2000 to 2021, the period covered by the study. But a sensitivity analysis based on data from 2010 to 2021 showed “no meaningful differences” in the results, said Dr. Zeitler, who is slated to present the findings April 30 at the Heart Rhythm Society 2022 Scientific Sessions, conducted virtually and live in San Francisco.
Dr. Zeitler acknowledged that the observational study, even with its propensity-matched ablation and AAD cohorts, can only hint at a preference for ablation over AAD for lowering risk for AFib-associated dementia. “We know there’s unmeasured and unfixable confounding between those two groups, so we see this really as hypothesis-generating.”
It was “a well-done analysis,” and the conclusion that the dementia risk was lower with catheter ablation is “absolutely correct,” but only as far as the study and its limitations allow, agreed David Conen, MD, MPH, McMaster University, Hamilton, Ontario, who is not a coauthor.
“Even with propensity matching, you can get rid of some sorts of confounding, but you can never get rid of all selection bias issues.” That, he said when interviewed, takes randomized trials.
Dr. Conen, who is studying cognitive decline in AFib as a SWISS-AF trial principal investigator, pointed to a secondary finding of the analysis as evidence for such confounding. He said the ablation group’s nearly 50% drop (P < .0001) in competing risk for death, compared with patients managed with AAD, isn’t plausible.
The finding “strongly suggests these people were healthier and that there’s some sort of selection bias. They were at lower risk of death, they were at lower risk of dementia, and they were probably also at lower risk of stroke, myocardial infarction, thrombosis, and cancer because they were just probably a little healthier than the others,” Dr. Conen said. The ablation and AAD groups “were two very different populations from the get-go.”
The analysis was based on U.S. insurance and Medicare claims data from AFib patients who either underwent catheter ablation after at least one AAD trial or filled prescriptions for at least two different antiarrhythmic agents in the year after AFib diagnosis. Patients with history of dementia, catheter or surgical AFib ablation, or a valve procedure were excluded.
The ablation and AAD-only groups each consisted of 19,066 patients after propensity matching, and the groups were balanced with respect to age, sex, type of insurance, CHA2DS2-VASc scores, and use of renin-angiotensin-system inhibitors, oral anticoagulants, and antiplatelets.
The overall risk for dementia was 1.9% for the ablation group and 3.3% for AAD-only patients (hazard ratio, 0.59; 95% confidence interval, 0.52-0.67). Corresponding HRs by sex were 0.55 (95% CI, 0.46-0.66) for men and 0.60 (95% CI, 0.50-0.72) for women.
The competing risk for death was also significantly decreased in the ablation group (HR, 0.51; 95% CI, 0.46-0.55).
Dr. Zeitler pointed to a randomized trial now in the early stages called Neurocognition and Greater Maintenance of Sinus Rhythm in Atrial Fibrillation, or NOGGIN-AF, which will explore relationships between rhythm control therapy and dementia in patients with AFib, whether catheter ablation or AAD can mitigate that risk, and whether either strategy works better than the other, among other goals.
“I’m optimistic,” she said, “and I think it’s going to add to the growing motivations to get patients ablated more quickly and more broadly.”
The analysis was funded by Biosense-Webster. Dr. Zeitler discloses consulting for Biosense-Webster and Arena Pharmaceuticals (now Pfizer); fees for speaking from Medtronic; and receiving research support from Boston Scientific, Sanofi, and Biosense-Webster. Dr. Conen has previously reported receiving speaker fees from Servier Canada.
A version of this article first appeared on Medscape.com.
The risk for dementia goes up in patients with atrial fibrillation (AFib), but some evidence suggests that risk can be blunted with therapies that restore sinus rhythm. However, a new cohort study suggests that the treatment effect’s magnitude might depend on the rhythm control strategy. It hinted that AFib catheter ablation might be more effective than pharmacologic rhythm control alone at cutting the risk for dementia.
The case-matched study of more than 38,000 adults with AFib saw a 41% reduction (P < .0001) in risk for dementia among those who underwent catheter ablation after attempted rhythm control with antiarrhythmic drugs (AAD), compared with those managed with pharmacologic rhythm control therapy alone.
The observational study comprising 20 years of data comes with big limitations and can’t say for sure whether catheter ablation is better than AAD-only at cutting the dementia risk in AFib. But it and other evidence support the idea, which has yet to be explored in a randomized fashion.
In a secondary finding, the analysis showed a similar reduction in dementia risk from catheter ablation, compared with AAD, in women and in men by 40% and 45%, respectively (P < .0001 for both). The findings are particularly relevant “given the higher life-long risk of dementia among women and the lower likelihood that women will be offered ablation, which has been demonstrated repeatedly,” Emily P. Zeitler, MD, MHS, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, told this news organization. “I think this is another reason to try to be more generous in offering ablation to women.”
Management of AFib certainly evolved in important ways from 2000 to 2021, the period covered by the study. But a sensitivity analysis based on data from 2010 to 2021 showed “no meaningful differences” in the results, said Dr. Zeitler, who is slated to present the findings April 30 at the Heart Rhythm Society 2022 Scientific Sessions, conducted virtually and live in San Francisco.
Dr. Zeitler acknowledged that the observational study, even with its propensity-matched ablation and AAD cohorts, can only hint at a preference for ablation over AAD for lowering risk for AFib-associated dementia. “We know there’s unmeasured and unfixable confounding between those two groups, so we see this really as hypothesis-generating.”
It was “a well-done analysis,” and the conclusion that the dementia risk was lower with catheter ablation is “absolutely correct,” but only as far as the study and its limitations allow, agreed David Conen, MD, MPH, McMaster University, Hamilton, Ontario, who is not a coauthor.
“Even with propensity matching, you can get rid of some sorts of confounding, but you can never get rid of all selection bias issues.” That, he said when interviewed, takes randomized trials.
Dr. Conen, who is studying cognitive decline in AFib as a SWISS-AF trial principal investigator, pointed to a secondary finding of the analysis as evidence for such confounding. He said the ablation group’s nearly 50% drop (P < .0001) in competing risk for death, compared with patients managed with AAD, isn’t plausible.
The finding “strongly suggests these people were healthier and that there’s some sort of selection bias. They were at lower risk of death, they were at lower risk of dementia, and they were probably also at lower risk of stroke, myocardial infarction, thrombosis, and cancer because they were just probably a little healthier than the others,” Dr. Conen said. The ablation and AAD groups “were two very different populations from the get-go.”
The analysis was based on U.S. insurance and Medicare claims data from AFib patients who either underwent catheter ablation after at least one AAD trial or filled prescriptions for at least two different antiarrhythmic agents in the year after AFib diagnosis. Patients with history of dementia, catheter or surgical AFib ablation, or a valve procedure were excluded.
The ablation and AAD-only groups each consisted of 19,066 patients after propensity matching, and the groups were balanced with respect to age, sex, type of insurance, CHA2DS2-VASc scores, and use of renin-angiotensin-system inhibitors, oral anticoagulants, and antiplatelets.
The overall risk for dementia was 1.9% for the ablation group and 3.3% for AAD-only patients (hazard ratio, 0.59; 95% confidence interval, 0.52-0.67). Corresponding HRs by sex were 0.55 (95% CI, 0.46-0.66) for men and 0.60 (95% CI, 0.50-0.72) for women.
The competing risk for death was also significantly decreased in the ablation group (HR, 0.51; 95% CI, 0.46-0.55).
Dr. Zeitler pointed to a randomized trial now in the early stages called Neurocognition and Greater Maintenance of Sinus Rhythm in Atrial Fibrillation, or NOGGIN-AF, which will explore relationships between rhythm control therapy and dementia in patients with AFib, whether catheter ablation or AAD can mitigate that risk, and whether either strategy works better than the other, among other goals.
“I’m optimistic,” she said, “and I think it’s going to add to the growing motivations to get patients ablated more quickly and more broadly.”
The analysis was funded by Biosense-Webster. Dr. Zeitler discloses consulting for Biosense-Webster and Arena Pharmaceuticals (now Pfizer); fees for speaking from Medtronic; and receiving research support from Boston Scientific, Sanofi, and Biosense-Webster. Dr. Conen has previously reported receiving speaker fees from Servier Canada.
A version of this article first appeared on Medscape.com.
Cutting dementia risk in atrial fibrillation: Does rhythm control strategy matter?
The risk for dementia goes up in patients with atrial fibrillation (AFib), but some evidence suggests that risk can be blunted with therapies that restore sinus rhythm. But a new cohort study suggests that the treatment effect’s magnitude might depend on the rhythm control strategy. It hinted that AFib catheter ablation might be more effective than pharmacologic rhythm control alone at cutting the risk for dementia.
The case-matched study of more than 38,000 adults with AFib saw a 41% reduction (P < .0001) in risk for dementia among those who underwent catheter ablation after attempted rhythm control with antiarrhythmic drugs (AAD), compared with those managed with pharmacologic rhythm control therapy alone.
The observational study comprising 20 years of data comes with big limitations and can’t say for sure whether catheter ablation is better than AAD alone at cutting the dementia risk in AFib. But it and other evidence support the idea, which has yet to be explored in a randomized fashion.
In a secondary finding, the analysis showed a similar reduction in dementia risk from catheter ablation, compared with AAD, in women and in men by 40% and 45%, respectively (P < .0001 for both). The findings are particularly relevant “given the higher life-long risk of dementia among women and the lower likelihood that women will be offered ablation, which has been demonstrated repeatedly,” Emily P. Zeitler, MD, MHS, Dartmouth-Hitchcock Medical Center, Lebanon, N.H., said in an interview. “I think this is another reason to try to be more generous in offering ablation to women.”
Management of AFib certainly evolved in important ways from 2000 to 2021, the period covered by the study. But a sensitivity analysis based on data from 2010 to 2021 showed “no meaningful differences” in the results, said Dr. Zeitler, who is slated to present the findings at the annual scientific sessions of the Heart Rhythm Society.
Dr. Zeitler acknowledged that the observational study, even with its propensity-matched ablation and AAD cohorts, can only hint at a preference for ablation over AAD for lowering risk for AFib-associated dementia. “We know there’s unmeasured and unfixable confounding between those two groups, so we see this really as hypothesis-generating.”
It was “a well-done analysis,” and the conclusion that the dementia risk was lower with catheter ablation is “absolutely correct,” but only as far as the study and its limitations allow, agreed David Conen, MD, MPH, McMaster University, Hamilton, Ont., who is not a coauthor.
“Even with propensity matching, you can get rid of some sorts of confounding, but you can never get rid of all selection bias issues.” That, he said when interviewed, takes randomized trials.
Dr. Conen, who is studying cognitive decline in AFib as a SWISS-AF trial principal investigator, pointed to a secondary finding of the analysis as evidence for such confounding. He said the ablation group’s nearly 50% drop (P < .0001) in competing risk for death, compared with patients managed with AAD, isn’t plausible.
The finding “strongly suggests these people were healthier and that there’s some sort of selection bias. They were at lower risk of death, they were at lower risk of dementia, and they were probably also at lower risk of stroke, myocardial infarction, thrombosis, and cancer because they were just probably a little healthier than the others,” Dr. Conen said. The ablation and AAD groups “were two very different populations from the get-go.”
The analysis was based on U.S. insurance and Medicare claims data from AFib patients who either underwent catheter ablation after at least one AAD trial or filled prescriptions for at least two different antiarrhythmic agents in the year after AFib diagnosis. Patients with history of dementia, catheter or surgical AFib ablation, or a valve procedure were excluded.
The ablation and AAD-only groups each consisted of 19,066 patients after propensity matching, and the groups were balanced with respect to age, sex, type of insurance, CHA2DS2-VASc scores, and use of renin-angiotensin system inhibitors, oral anticoagulants, and antiplatelets.
The overall risk for dementia was 1.9% for the ablation group and 3.3% for AAD-only patients (hazard ratio, 0.59; 95% confidence interval, 0.52-0.67). Corresponding HRs by sex were 0.55 (95% CI, 0.46-0.66) for men and 0.60 (95% CI, 0.50-0.72) for women.
The competing risk for death was also significantly decreased in the ablation group (HR, 0.51; 95% CI, 0.46-0.55).
Dr. Zeitler pointed to a randomized trial now in the early stages called Neurocognition and Greater Maintenance of Sinus Rhythm in Atrial Fibrillation, or NOGGIN-AF, which will explore relationships between rhythm control therapy and dementia in patients with AFib, whether catheter ablation or AAD can mitigate that risk, and whether either strategy works better than the other, among other goals.
“I’m optimistic,” she said, “and I think it’s going to add to the growing motivations to get patients ablated more quickly and more broadly.”
The analysis was funded by Biosense-Webster. Dr. Zeitler disclosed consulting for Biosense-Webster and Arena Pharmaceuticals (now Pfizer); fees for speaking from Medtronic; and receiving research support from Boston Scientific, Sanofi, and Biosense-Webster. Dr. Conen has previously reported receiving speaker fees from Servier Canada.
A version of this article first appeared on Medscape.com.
The risk for dementia goes up in patients with atrial fibrillation (AFib), but some evidence suggests that risk can be blunted with therapies that restore sinus rhythm. But a new cohort study suggests that the treatment effect’s magnitude might depend on the rhythm control strategy. It hinted that AFib catheter ablation might be more effective than pharmacologic rhythm control alone at cutting the risk for dementia.
The case-matched study of more than 38,000 adults with AFib saw a 41% reduction (P < .0001) in risk for dementia among those who underwent catheter ablation after attempted rhythm control with antiarrhythmic drugs (AAD), compared with those managed with pharmacologic rhythm control therapy alone.
The observational study comprising 20 years of data comes with big limitations and can’t say for sure whether catheter ablation is better than AAD alone at cutting the dementia risk in AFib. But it and other evidence support the idea, which has yet to be explored in a randomized fashion.
In a secondary finding, the analysis showed a similar reduction in dementia risk from catheter ablation, compared with AAD, in women and in men by 40% and 45%, respectively (P < .0001 for both). The findings are particularly relevant “given the higher life-long risk of dementia among women and the lower likelihood that women will be offered ablation, which has been demonstrated repeatedly,” Emily P. Zeitler, MD, MHS, Dartmouth-Hitchcock Medical Center, Lebanon, N.H., said in an interview. “I think this is another reason to try to be more generous in offering ablation to women.”
Management of AFib certainly evolved in important ways from 2000 to 2021, the period covered by the study. But a sensitivity analysis based on data from 2010 to 2021 showed “no meaningful differences” in the results, said Dr. Zeitler, who is slated to present the findings at the annual scientific sessions of the Heart Rhythm Society.
Dr. Zeitler acknowledged that the observational study, even with its propensity-matched ablation and AAD cohorts, can only hint at a preference for ablation over AAD for lowering risk for AFib-associated dementia. “We know there’s unmeasured and unfixable confounding between those two groups, so we see this really as hypothesis-generating.”
It was “a well-done analysis,” and the conclusion that the dementia risk was lower with catheter ablation is “absolutely correct,” but only as far as the study and its limitations allow, agreed David Conen, MD, MPH, McMaster University, Hamilton, Ont., who is not a coauthor.
“Even with propensity matching, you can get rid of some sorts of confounding, but you can never get rid of all selection bias issues.” That, he said when interviewed, takes randomized trials.
Dr. Conen, who is studying cognitive decline in AFib as a SWISS-AF trial principal investigator, pointed to a secondary finding of the analysis as evidence for such confounding. He said the ablation group’s nearly 50% drop (P < .0001) in competing risk for death, compared with patients managed with AAD, isn’t plausible.
The finding “strongly suggests these people were healthier and that there’s some sort of selection bias. They were at lower risk of death, they were at lower risk of dementia, and they were probably also at lower risk of stroke, myocardial infarction, thrombosis, and cancer because they were just probably a little healthier than the others,” Dr. Conen said. The ablation and AAD groups “were two very different populations from the get-go.”
The analysis was based on U.S. insurance and Medicare claims data from AFib patients who either underwent catheter ablation after at least one AAD trial or filled prescriptions for at least two different antiarrhythmic agents in the year after AFib diagnosis. Patients with history of dementia, catheter or surgical AFib ablation, or a valve procedure were excluded.
The ablation and AAD-only groups each consisted of 19,066 patients after propensity matching, and the groups were balanced with respect to age, sex, type of insurance, CHA2DS2-VASc scores, and use of renin-angiotensin system inhibitors, oral anticoagulants, and antiplatelets.
The overall risk for dementia was 1.9% for the ablation group and 3.3% for AAD-only patients (hazard ratio, 0.59; 95% confidence interval, 0.52-0.67). Corresponding HRs by sex were 0.55 (95% CI, 0.46-0.66) for men and 0.60 (95% CI, 0.50-0.72) for women.
The competing risk for death was also significantly decreased in the ablation group (HR, 0.51; 95% CI, 0.46-0.55).
Dr. Zeitler pointed to a randomized trial now in the early stages called Neurocognition and Greater Maintenance of Sinus Rhythm in Atrial Fibrillation, or NOGGIN-AF, which will explore relationships between rhythm control therapy and dementia in patients with AFib, whether catheter ablation or AAD can mitigate that risk, and whether either strategy works better than the other, among other goals.
“I’m optimistic,” she said, “and I think it’s going to add to the growing motivations to get patients ablated more quickly and more broadly.”
The analysis was funded by Biosense-Webster. Dr. Zeitler disclosed consulting for Biosense-Webster and Arena Pharmaceuticals (now Pfizer); fees for speaking from Medtronic; and receiving research support from Boston Scientific, Sanofi, and Biosense-Webster. Dr. Conen has previously reported receiving speaker fees from Servier Canada.
A version of this article first appeared on Medscape.com.
The risk for dementia goes up in patients with atrial fibrillation (AFib), but some evidence suggests that risk can be blunted with therapies that restore sinus rhythm. But a new cohort study suggests that the treatment effect’s magnitude might depend on the rhythm control strategy. It hinted that AFib catheter ablation might be more effective than pharmacologic rhythm control alone at cutting the risk for dementia.
The case-matched study of more than 38,000 adults with AFib saw a 41% reduction (P < .0001) in risk for dementia among those who underwent catheter ablation after attempted rhythm control with antiarrhythmic drugs (AAD), compared with those managed with pharmacologic rhythm control therapy alone.
The observational study comprising 20 years of data comes with big limitations and can’t say for sure whether catheter ablation is better than AAD alone at cutting the dementia risk in AFib. But it and other evidence support the idea, which has yet to be explored in a randomized fashion.
In a secondary finding, the analysis showed a similar reduction in dementia risk from catheter ablation, compared with AAD, in women and in men by 40% and 45%, respectively (P < .0001 for both). The findings are particularly relevant “given the higher life-long risk of dementia among women and the lower likelihood that women will be offered ablation, which has been demonstrated repeatedly,” Emily P. Zeitler, MD, MHS, Dartmouth-Hitchcock Medical Center, Lebanon, N.H., said in an interview. “I think this is another reason to try to be more generous in offering ablation to women.”
Management of AFib certainly evolved in important ways from 2000 to 2021, the period covered by the study. But a sensitivity analysis based on data from 2010 to 2021 showed “no meaningful differences” in the results, said Dr. Zeitler, who is slated to present the findings at the annual scientific sessions of the Heart Rhythm Society.
Dr. Zeitler acknowledged that the observational study, even with its propensity-matched ablation and AAD cohorts, can only hint at a preference for ablation over AAD for lowering risk for AFib-associated dementia. “We know there’s unmeasured and unfixable confounding between those two groups, so we see this really as hypothesis-generating.”
It was “a well-done analysis,” and the conclusion that the dementia risk was lower with catheter ablation is “absolutely correct,” but only as far as the study and its limitations allow, agreed David Conen, MD, MPH, McMaster University, Hamilton, Ont., who is not a coauthor.
“Even with propensity matching, you can get rid of some sorts of confounding, but you can never get rid of all selection bias issues.” That, he said when interviewed, takes randomized trials.
Dr. Conen, who is studying cognitive decline in AFib as a SWISS-AF trial principal investigator, pointed to a secondary finding of the analysis as evidence for such confounding. He said the ablation group’s nearly 50% drop (P < .0001) in competing risk for death, compared with patients managed with AAD, isn’t plausible.
The finding “strongly suggests these people were healthier and that there’s some sort of selection bias. They were at lower risk of death, they were at lower risk of dementia, and they were probably also at lower risk of stroke, myocardial infarction, thrombosis, and cancer because they were just probably a little healthier than the others,” Dr. Conen said. The ablation and AAD groups “were two very different populations from the get-go.”
The analysis was based on U.S. insurance and Medicare claims data from AFib patients who either underwent catheter ablation after at least one AAD trial or filled prescriptions for at least two different antiarrhythmic agents in the year after AFib diagnosis. Patients with history of dementia, catheter or surgical AFib ablation, or a valve procedure were excluded.
The ablation and AAD-only groups each consisted of 19,066 patients after propensity matching, and the groups were balanced with respect to age, sex, type of insurance, CHA2DS2-VASc scores, and use of renin-angiotensin system inhibitors, oral anticoagulants, and antiplatelets.
The overall risk for dementia was 1.9% for the ablation group and 3.3% for AAD-only patients (hazard ratio, 0.59; 95% confidence interval, 0.52-0.67). Corresponding HRs by sex were 0.55 (95% CI, 0.46-0.66) for men and 0.60 (95% CI, 0.50-0.72) for women.
The competing risk for death was also significantly decreased in the ablation group (HR, 0.51; 95% CI, 0.46-0.55).
Dr. Zeitler pointed to a randomized trial now in the early stages called Neurocognition and Greater Maintenance of Sinus Rhythm in Atrial Fibrillation, or NOGGIN-AF, which will explore relationships between rhythm control therapy and dementia in patients with AFib, whether catheter ablation or AAD can mitigate that risk, and whether either strategy works better than the other, among other goals.
“I’m optimistic,” she said, “and I think it’s going to add to the growing motivations to get patients ablated more quickly and more broadly.”
The analysis was funded by Biosense-Webster. Dr. Zeitler disclosed consulting for Biosense-Webster and Arena Pharmaceuticals (now Pfizer); fees for speaking from Medtronic; and receiving research support from Boston Scientific, Sanofi, and Biosense-Webster. Dr. Conen has previously reported receiving speaker fees from Servier Canada.
A version of this article first appeared on Medscape.com.
HEART RHYTHM 2022
Traumatic brain injury linked to ‘striking’ risk for CVD, diabetes, brain disorders
Mild traumatic brain injury (TBI) is linked to a significantly increased risk for a host of subsequent cardiovascular, endocrine, neurologic, and psychiatric disorders, new research shows.
Incidence of hypertension, coronary heart disease, diabetes, stroke, depression, and dementia all began to increase soon after the brain injury and persisted over a decade in both mild and moderate to severe TBI.
Researchers found the multisystem comorbidities in all age groups, including in patients as young as 18. They also found that patients who developed multiple postinjury problems had higher mortality during the decade-long follow-up.
The findings suggest patients with TBI may require longer follow-up and proactive screening for multisystem disease, regardless of age or injury severity.
“The fact that both patients with mild and moderate to severe injuries both had long-term ongoing associations with comorbidities that continued over time and that they are cardiovascular, endocrine, neurologic, and behavioral health oriented was pretty striking,” study author Ross Zafonte, DO, PhD, president of Spaulding Rehab Hospital and professor and chair of physical medicine and rehab at Harvard Medical School, both in Boston, told this news organization.
The study was published online in JAMA Network Open.
Injury severity not a factor
An estimated 2.8 million individuals in the United States experience TBI every year. Worldwide, the figure may be as high as 74 million.
Studies have long suggested a link between brain injury and subsequent neurologic disorders, but research suggesting a possible link to cardiovascular and endocrine problems has recently gained attention.
Building on a 2021 study that showed increased incidence of cardiovascular issues following a concussion, the researchers examined medical records of previously healthy patients treated for TBI between 2000 and 2015 who also had at least 1 follow-up visit between 6 months and 10 years after the initial injury.
Researchers analyzed data from 13,053 individuals – 4,351 with mild injury (mTBI), 4351 with moderate to severe injury (msTBI), and 4351 with no TBI. The most common cause of injury was a fall. Patients with sports-related injuries were excluded.
Incidence of hypertension was significantly higher among patients with mTBI (hazard ratio, 2.5; 95% confidence interval, 2.1-2.9) and msTBI (HR, 2.4; 95% CI, 2.0-2.9), compared with the unaffected group. Risk for other cardiovascular problems, including hyperlipidemia, obesity, and coronary artery disease, were also higher in the affected groups.
TBI patients also reported higher incidence of endocrine diseases, including diabetes (mTBI: HR, 1.9; 95% CI, 1.4-2.7; msTBI: HR, 1.9; 95% CI, 1.4-2.6). Elevated risk for ischemic stroke or transient ischemic attack was also increased (mTBI: HR, 2.2; 95% CI, 1.4-3.3; msTBI: HR, 3.6; 95% CI, 2.4-5.3).
Regardless of injury severity, patients with TBI had a higher risk for neurologic and psychiatric diseases, particularly depression, dementia, and psychotic disorders. “This tells us that mild TBI is not clean of events,” Dr. Zafonte said.
Surprising rate of comorbidity in youth
Investigators found increased risk for posttrauma comorbidities in all age groups, but researchers were struck by the high rates in younger patients, aged 18-40. Compared with age-matched individuals with no TBI history, hypertension risk was nearly six times higher in those with mTBI (HR, 5.9; 95% CI, 3.9-9.1) and nearly four times higher in patients with msTBI (HR, 3.9; 95% CI, 2.5-6.1).
Rates of hyperlipidemia and diabetes were also higher in younger patients in the mTBI group and posttraumatic seizures and psychiatric disorders were elevated regardless of TBI severity.
Overall, patients with msTBI, but not those with mTBI, were at higher risk for mortality, compared with the unexposed group (432 deaths [9.9%] vs. 250 deaths [5.7%]; P < .001).
“It’s clear that what we may be dealing with is that it holds up even for the younger people,” Dr. Zafonte said. “We used to think brain injury risk is worse in the severe cases, which it is, and it’s worse later on among those who are older, which it is. But our younger folks don’t get away either.”
While the study offers associations between TBI and multisystem health problems, Dr. Zafonte said it’s impossible to say at this point whether the brain injury caused the increased risk for cardiovascular or endocrine problems. Other organ injuries sustained in the trauma may be a contributing factor.
“Further data is needed to elucidate the mechanism and the causative relationships, which we do not have here,” he said.
Many of the postinjury comorbidities emerged a median of 3.5 years after TBI, regardless of severity. But some of the cardiovascular and psychiatric conditions emerged far sooner than that.
That’s important because research suggests less than half of patients with TBI receive follow-up care.
“It does make sense for folks who are interacting with people who’ve had a TBI to be suspicious of medical comorbidities relatively early on, within the first couple of years,” Dr. Zafonte said.
In an invited commentary, Vijay Krishnamoorthy, MD, MPH, PhD, Duke University, Durham, N.C., and Monica S. Vavilala, MD, University of Washington, Seattle, highlight some of the study’s limitations, including a lack of information on comorbidity severity and the lack of a matched group of patients who experienced non-head trauma.
Despite those limitations, the study offers important information on how TBI may affect organs beyond the brain, they noted.
“These observations, if replicated in future studies, raise intriguing implications in the future care of patients with TBI, including heightened chronic disease-screening measures and possibly enhanced guidelines for chronic extracranial organ system care for patients who experience TBI,” Dr. Krishnamoorthy and Dr. Vavilala wrote.
The study received no specific funding. Dr. Zafonte reported having received personal fees from Springer/Demos, serving on scientific advisory boards for Myomo and OnCare and has received funding from the Football Players Health Study at Harvard, funded in part by the National Football League Players Association. Dr. Krishnamoorthy and Dr. Vavilala disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Mild traumatic brain injury (TBI) is linked to a significantly increased risk for a host of subsequent cardiovascular, endocrine, neurologic, and psychiatric disorders, new research shows.
Incidence of hypertension, coronary heart disease, diabetes, stroke, depression, and dementia all began to increase soon after the brain injury and persisted over a decade in both mild and moderate to severe TBI.
Researchers found the multisystem comorbidities in all age groups, including in patients as young as 18. They also found that patients who developed multiple postinjury problems had higher mortality during the decade-long follow-up.
The findings suggest patients with TBI may require longer follow-up and proactive screening for multisystem disease, regardless of age or injury severity.
“The fact that both patients with mild and moderate to severe injuries both had long-term ongoing associations with comorbidities that continued over time and that they are cardiovascular, endocrine, neurologic, and behavioral health oriented was pretty striking,” study author Ross Zafonte, DO, PhD, president of Spaulding Rehab Hospital and professor and chair of physical medicine and rehab at Harvard Medical School, both in Boston, told this news organization.
The study was published online in JAMA Network Open.
Injury severity not a factor
An estimated 2.8 million individuals in the United States experience TBI every year. Worldwide, the figure may be as high as 74 million.
Studies have long suggested a link between brain injury and subsequent neurologic disorders, but research suggesting a possible link to cardiovascular and endocrine problems has recently gained attention.
Building on a 2021 study that showed increased incidence of cardiovascular issues following a concussion, the researchers examined medical records of previously healthy patients treated for TBI between 2000 and 2015 who also had at least 1 follow-up visit between 6 months and 10 years after the initial injury.
Researchers analyzed data from 13,053 individuals – 4,351 with mild injury (mTBI), 4351 with moderate to severe injury (msTBI), and 4351 with no TBI. The most common cause of injury was a fall. Patients with sports-related injuries were excluded.
Incidence of hypertension was significantly higher among patients with mTBI (hazard ratio, 2.5; 95% confidence interval, 2.1-2.9) and msTBI (HR, 2.4; 95% CI, 2.0-2.9), compared with the unaffected group. Risk for other cardiovascular problems, including hyperlipidemia, obesity, and coronary artery disease, were also higher in the affected groups.
TBI patients also reported higher incidence of endocrine diseases, including diabetes (mTBI: HR, 1.9; 95% CI, 1.4-2.7; msTBI: HR, 1.9; 95% CI, 1.4-2.6). Elevated risk for ischemic stroke or transient ischemic attack was also increased (mTBI: HR, 2.2; 95% CI, 1.4-3.3; msTBI: HR, 3.6; 95% CI, 2.4-5.3).
Regardless of injury severity, patients with TBI had a higher risk for neurologic and psychiatric diseases, particularly depression, dementia, and psychotic disorders. “This tells us that mild TBI is not clean of events,” Dr. Zafonte said.
Surprising rate of comorbidity in youth
Investigators found increased risk for posttrauma comorbidities in all age groups, but researchers were struck by the high rates in younger patients, aged 18-40. Compared with age-matched individuals with no TBI history, hypertension risk was nearly six times higher in those with mTBI (HR, 5.9; 95% CI, 3.9-9.1) and nearly four times higher in patients with msTBI (HR, 3.9; 95% CI, 2.5-6.1).
Rates of hyperlipidemia and diabetes were also higher in younger patients in the mTBI group and posttraumatic seizures and psychiatric disorders were elevated regardless of TBI severity.
Overall, patients with msTBI, but not those with mTBI, were at higher risk for mortality, compared with the unexposed group (432 deaths [9.9%] vs. 250 deaths [5.7%]; P < .001).
“It’s clear that what we may be dealing with is that it holds up even for the younger people,” Dr. Zafonte said. “We used to think brain injury risk is worse in the severe cases, which it is, and it’s worse later on among those who are older, which it is. But our younger folks don’t get away either.”
While the study offers associations between TBI and multisystem health problems, Dr. Zafonte said it’s impossible to say at this point whether the brain injury caused the increased risk for cardiovascular or endocrine problems. Other organ injuries sustained in the trauma may be a contributing factor.
“Further data is needed to elucidate the mechanism and the causative relationships, which we do not have here,” he said.
Many of the postinjury comorbidities emerged a median of 3.5 years after TBI, regardless of severity. But some of the cardiovascular and psychiatric conditions emerged far sooner than that.
That’s important because research suggests less than half of patients with TBI receive follow-up care.
“It does make sense for folks who are interacting with people who’ve had a TBI to be suspicious of medical comorbidities relatively early on, within the first couple of years,” Dr. Zafonte said.
In an invited commentary, Vijay Krishnamoorthy, MD, MPH, PhD, Duke University, Durham, N.C., and Monica S. Vavilala, MD, University of Washington, Seattle, highlight some of the study’s limitations, including a lack of information on comorbidity severity and the lack of a matched group of patients who experienced non-head trauma.
Despite those limitations, the study offers important information on how TBI may affect organs beyond the brain, they noted.
“These observations, if replicated in future studies, raise intriguing implications in the future care of patients with TBI, including heightened chronic disease-screening measures and possibly enhanced guidelines for chronic extracranial organ system care for patients who experience TBI,” Dr. Krishnamoorthy and Dr. Vavilala wrote.
The study received no specific funding. Dr. Zafonte reported having received personal fees from Springer/Demos, serving on scientific advisory boards for Myomo and OnCare and has received funding from the Football Players Health Study at Harvard, funded in part by the National Football League Players Association. Dr. Krishnamoorthy and Dr. Vavilala disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Mild traumatic brain injury (TBI) is linked to a significantly increased risk for a host of subsequent cardiovascular, endocrine, neurologic, and psychiatric disorders, new research shows.
Incidence of hypertension, coronary heart disease, diabetes, stroke, depression, and dementia all began to increase soon after the brain injury and persisted over a decade in both mild and moderate to severe TBI.
Researchers found the multisystem comorbidities in all age groups, including in patients as young as 18. They also found that patients who developed multiple postinjury problems had higher mortality during the decade-long follow-up.
The findings suggest patients with TBI may require longer follow-up and proactive screening for multisystem disease, regardless of age or injury severity.
“The fact that both patients with mild and moderate to severe injuries both had long-term ongoing associations with comorbidities that continued over time and that they are cardiovascular, endocrine, neurologic, and behavioral health oriented was pretty striking,” study author Ross Zafonte, DO, PhD, president of Spaulding Rehab Hospital and professor and chair of physical medicine and rehab at Harvard Medical School, both in Boston, told this news organization.
The study was published online in JAMA Network Open.
Injury severity not a factor
An estimated 2.8 million individuals in the United States experience TBI every year. Worldwide, the figure may be as high as 74 million.
Studies have long suggested a link between brain injury and subsequent neurologic disorders, but research suggesting a possible link to cardiovascular and endocrine problems has recently gained attention.
Building on a 2021 study that showed increased incidence of cardiovascular issues following a concussion, the researchers examined medical records of previously healthy patients treated for TBI between 2000 and 2015 who also had at least 1 follow-up visit between 6 months and 10 years after the initial injury.
Researchers analyzed data from 13,053 individuals – 4,351 with mild injury (mTBI), 4351 with moderate to severe injury (msTBI), and 4351 with no TBI. The most common cause of injury was a fall. Patients with sports-related injuries were excluded.
Incidence of hypertension was significantly higher among patients with mTBI (hazard ratio, 2.5; 95% confidence interval, 2.1-2.9) and msTBI (HR, 2.4; 95% CI, 2.0-2.9), compared with the unaffected group. Risk for other cardiovascular problems, including hyperlipidemia, obesity, and coronary artery disease, were also higher in the affected groups.
TBI patients also reported higher incidence of endocrine diseases, including diabetes (mTBI: HR, 1.9; 95% CI, 1.4-2.7; msTBI: HR, 1.9; 95% CI, 1.4-2.6). Elevated risk for ischemic stroke or transient ischemic attack was also increased (mTBI: HR, 2.2; 95% CI, 1.4-3.3; msTBI: HR, 3.6; 95% CI, 2.4-5.3).
Regardless of injury severity, patients with TBI had a higher risk for neurologic and psychiatric diseases, particularly depression, dementia, and psychotic disorders. “This tells us that mild TBI is not clean of events,” Dr. Zafonte said.
Surprising rate of comorbidity in youth
Investigators found increased risk for posttrauma comorbidities in all age groups, but researchers were struck by the high rates in younger patients, aged 18-40. Compared with age-matched individuals with no TBI history, hypertension risk was nearly six times higher in those with mTBI (HR, 5.9; 95% CI, 3.9-9.1) and nearly four times higher in patients with msTBI (HR, 3.9; 95% CI, 2.5-6.1).
Rates of hyperlipidemia and diabetes were also higher in younger patients in the mTBI group and posttraumatic seizures and psychiatric disorders were elevated regardless of TBI severity.
Overall, patients with msTBI, but not those with mTBI, were at higher risk for mortality, compared with the unexposed group (432 deaths [9.9%] vs. 250 deaths [5.7%]; P < .001).
“It’s clear that what we may be dealing with is that it holds up even for the younger people,” Dr. Zafonte said. “We used to think brain injury risk is worse in the severe cases, which it is, and it’s worse later on among those who are older, which it is. But our younger folks don’t get away either.”
While the study offers associations between TBI and multisystem health problems, Dr. Zafonte said it’s impossible to say at this point whether the brain injury caused the increased risk for cardiovascular or endocrine problems. Other organ injuries sustained in the trauma may be a contributing factor.
“Further data is needed to elucidate the mechanism and the causative relationships, which we do not have here,” he said.
Many of the postinjury comorbidities emerged a median of 3.5 years after TBI, regardless of severity. But some of the cardiovascular and psychiatric conditions emerged far sooner than that.
That’s important because research suggests less than half of patients with TBI receive follow-up care.
“It does make sense for folks who are interacting with people who’ve had a TBI to be suspicious of medical comorbidities relatively early on, within the first couple of years,” Dr. Zafonte said.
In an invited commentary, Vijay Krishnamoorthy, MD, MPH, PhD, Duke University, Durham, N.C., and Monica S. Vavilala, MD, University of Washington, Seattle, highlight some of the study’s limitations, including a lack of information on comorbidity severity and the lack of a matched group of patients who experienced non-head trauma.
Despite those limitations, the study offers important information on how TBI may affect organs beyond the brain, they noted.
“These observations, if replicated in future studies, raise intriguing implications in the future care of patients with TBI, including heightened chronic disease-screening measures and possibly enhanced guidelines for chronic extracranial organ system care for patients who experience TBI,” Dr. Krishnamoorthy and Dr. Vavilala wrote.
The study received no specific funding. Dr. Zafonte reported having received personal fees from Springer/Demos, serving on scientific advisory boards for Myomo and OnCare and has received funding from the Football Players Health Study at Harvard, funded in part by the National Football League Players Association. Dr. Krishnamoorthy and Dr. Vavilala disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM JAMA NETWORK OPEN