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Alzheimer’s Transmissible Via Stem Cell Transplantation?
Studies in preclinical models hint that familial Alzheimer’s disease (AD) may be transmissible via bone marrow transplant, but the researchers and outside experts caution against making the immediate leap to humans.
These pathologic features included compromised blood-brain barrier integrity, heightened cerebral vascular neoangiogenesis, elevated brain-associated beta-amyloid levels, and cognitive impairment.
In addition, symptoms of cognitive decline presented rapidly — 6 months after transplant in the APP-knockout mice and 9 months in the wild-type mice vs 12 months shown previously in AD transgenic mice.
“Contrary to prevailing beliefs regarding AD occurring solely in familial or sporadic forms, our study reveals an unexpected transplantable form of AD in a preclinical model, suggesting potential iatrogenic transmission in AD patients,” the investigators, led by Wilfred Jefferies, DPhil, write.
Although this is probably an “infrequent” occurrence, it’s still “concerning,” Dr. Jefferies told this news organization, and it suggests that “human donors of blood, tissue, organ, and stem cells should be screened to prevent its inadvertent transfer of disease during blood product transfusions and cellular therapies.”
The study was published March 28 in Stem Cell Reports.
Intriguing, but Limited Human Relevance
The researchers note the study also demonstrates that beta-amyloid accumulation originating outside of the central nervous system contributes to AD pathology, providing an opportunity for the development of new biomarkers for AD.
Several experts weighed in on this research in a statement from the UK-based nonprofit and independent Science Media Centre (SMC).
David Curtis, MBBS, MD, PhD, with University College London’s Genetics Institute, United Kingdom, noted that the study suggests that “theoretically there could be a risk of acquiring Alzheimer’s disease if one received a stem cell transplant from somebody carrying the severe, familial form of the disease. However, this form is extremely rare so in practice the risk seems low and there are many safeguards around stem cell transplantation. I do not see that the risks extend to other areas such as organ transplantation or blood transfusion because these procedures do not involve large numbers of stem cells which can go on to form glial cells.”
Paul Morgan, PhD, with UK Dementia Research Institute Cardiff, Cardiff University, said the study is “scientifically intriguing” in demonstrating in this “very specific experimental situation, that bone marrow cells are sufficient to transfer the gene and the disease. Relevance to human organ and cell transplant is limited.”
Morgan cautioned against making the “gargantuan leap to propose that tissue, organ and cell transplantation, and even blood transfusion, carry a risk of transferring Alzheimer’s disease and other neuropathologies in man.”
Bart De Strooper, MD, PhD, with University College London, agreed. “There is not sufficient evidence here to suggest that anyone receiving a bone marrow transplant is at risk of developing Alzheimer’s disease as a result of the procedure, and nobody should forgo a transplant for this reason,” he said in the SMC release.
The study had no specific funding. The authors hold equity in the start-up company, Cava Healthcare, which possesses intellectual property related to these findings. This had no role in the study design, data collection, analysis, or interpretation of data, or in the writing of the paper. Morgan, De Strooper, and Curtis have no relevant disclosures.
A version of this article appeared on Medscape.com.
Studies in preclinical models hint that familial Alzheimer’s disease (AD) may be transmissible via bone marrow transplant, but the researchers and outside experts caution against making the immediate leap to humans.
These pathologic features included compromised blood-brain barrier integrity, heightened cerebral vascular neoangiogenesis, elevated brain-associated beta-amyloid levels, and cognitive impairment.
In addition, symptoms of cognitive decline presented rapidly — 6 months after transplant in the APP-knockout mice and 9 months in the wild-type mice vs 12 months shown previously in AD transgenic mice.
“Contrary to prevailing beliefs regarding AD occurring solely in familial or sporadic forms, our study reveals an unexpected transplantable form of AD in a preclinical model, suggesting potential iatrogenic transmission in AD patients,” the investigators, led by Wilfred Jefferies, DPhil, write.
Although this is probably an “infrequent” occurrence, it’s still “concerning,” Dr. Jefferies told this news organization, and it suggests that “human donors of blood, tissue, organ, and stem cells should be screened to prevent its inadvertent transfer of disease during blood product transfusions and cellular therapies.”
The study was published March 28 in Stem Cell Reports.
Intriguing, but Limited Human Relevance
The researchers note the study also demonstrates that beta-amyloid accumulation originating outside of the central nervous system contributes to AD pathology, providing an opportunity for the development of new biomarkers for AD.
Several experts weighed in on this research in a statement from the UK-based nonprofit and independent Science Media Centre (SMC).
David Curtis, MBBS, MD, PhD, with University College London’s Genetics Institute, United Kingdom, noted that the study suggests that “theoretically there could be a risk of acquiring Alzheimer’s disease if one received a stem cell transplant from somebody carrying the severe, familial form of the disease. However, this form is extremely rare so in practice the risk seems low and there are many safeguards around stem cell transplantation. I do not see that the risks extend to other areas such as organ transplantation or blood transfusion because these procedures do not involve large numbers of stem cells which can go on to form glial cells.”
Paul Morgan, PhD, with UK Dementia Research Institute Cardiff, Cardiff University, said the study is “scientifically intriguing” in demonstrating in this “very specific experimental situation, that bone marrow cells are sufficient to transfer the gene and the disease. Relevance to human organ and cell transplant is limited.”
Morgan cautioned against making the “gargantuan leap to propose that tissue, organ and cell transplantation, and even blood transfusion, carry a risk of transferring Alzheimer’s disease and other neuropathologies in man.”
Bart De Strooper, MD, PhD, with University College London, agreed. “There is not sufficient evidence here to suggest that anyone receiving a bone marrow transplant is at risk of developing Alzheimer’s disease as a result of the procedure, and nobody should forgo a transplant for this reason,” he said in the SMC release.
The study had no specific funding. The authors hold equity in the start-up company, Cava Healthcare, which possesses intellectual property related to these findings. This had no role in the study design, data collection, analysis, or interpretation of data, or in the writing of the paper. Morgan, De Strooper, and Curtis have no relevant disclosures.
A version of this article appeared on Medscape.com.
Studies in preclinical models hint that familial Alzheimer’s disease (AD) may be transmissible via bone marrow transplant, but the researchers and outside experts caution against making the immediate leap to humans.
These pathologic features included compromised blood-brain barrier integrity, heightened cerebral vascular neoangiogenesis, elevated brain-associated beta-amyloid levels, and cognitive impairment.
In addition, symptoms of cognitive decline presented rapidly — 6 months after transplant in the APP-knockout mice and 9 months in the wild-type mice vs 12 months shown previously in AD transgenic mice.
“Contrary to prevailing beliefs regarding AD occurring solely in familial or sporadic forms, our study reveals an unexpected transplantable form of AD in a preclinical model, suggesting potential iatrogenic transmission in AD patients,” the investigators, led by Wilfred Jefferies, DPhil, write.
Although this is probably an “infrequent” occurrence, it’s still “concerning,” Dr. Jefferies told this news organization, and it suggests that “human donors of blood, tissue, organ, and stem cells should be screened to prevent its inadvertent transfer of disease during blood product transfusions and cellular therapies.”
The study was published March 28 in Stem Cell Reports.
Intriguing, but Limited Human Relevance
The researchers note the study also demonstrates that beta-amyloid accumulation originating outside of the central nervous system contributes to AD pathology, providing an opportunity for the development of new biomarkers for AD.
Several experts weighed in on this research in a statement from the UK-based nonprofit and independent Science Media Centre (SMC).
David Curtis, MBBS, MD, PhD, with University College London’s Genetics Institute, United Kingdom, noted that the study suggests that “theoretically there could be a risk of acquiring Alzheimer’s disease if one received a stem cell transplant from somebody carrying the severe, familial form of the disease. However, this form is extremely rare so in practice the risk seems low and there are many safeguards around stem cell transplantation. I do not see that the risks extend to other areas such as organ transplantation or blood transfusion because these procedures do not involve large numbers of stem cells which can go on to form glial cells.”
Paul Morgan, PhD, with UK Dementia Research Institute Cardiff, Cardiff University, said the study is “scientifically intriguing” in demonstrating in this “very specific experimental situation, that bone marrow cells are sufficient to transfer the gene and the disease. Relevance to human organ and cell transplant is limited.”
Morgan cautioned against making the “gargantuan leap to propose that tissue, organ and cell transplantation, and even blood transfusion, carry a risk of transferring Alzheimer’s disease and other neuropathologies in man.”
Bart De Strooper, MD, PhD, with University College London, agreed. “There is not sufficient evidence here to suggest that anyone receiving a bone marrow transplant is at risk of developing Alzheimer’s disease as a result of the procedure, and nobody should forgo a transplant for this reason,” he said in the SMC release.
The study had no specific funding. The authors hold equity in the start-up company, Cava Healthcare, which possesses intellectual property related to these findings. This had no role in the study design, data collection, analysis, or interpretation of data, or in the writing of the paper. Morgan, De Strooper, and Curtis have no relevant disclosures.
A version of this article appeared on Medscape.com.
FROM STEM CELL REPORTS
Human Brains Are Getting Bigger: Good News for Dementia Risk?
A secular trends analysis using brain imaging data from the long-running Framingham Heart Study revealed an increase in intracranial volume (ICV), cortical gray matter, white matter, and hippocampal volumes, as well as cortical surface area in people born in the 1970s versus those born in the 1930s.
“We hypothesize that the increased size of the brain will lead to increased ‘reserve’ against the diseases of aging, consequently reducing overall risk of dementia,” said Charles DeCarli, MD, director of the Alzheimer’s Disease Research Center and Imaging of Dementia and Aging Laboratory, Department of Neurology and Center for Neuroscience, University of California at Davis.
The study was published online in JAMA Neurology.
Dementia Protection?
An earlier report from the Framingham Heart Study suggested that dementia incidence is declining.
“This difference occurred among persons with at least a high school education and was not affected by differences in vascular risk. Our work was stimulated by this finding and the possibility that differences in brain size might be occurring over the three generations of the Framingham Heart Study which might explain an increased resilience to dementia,” said Dr. DeCarli.
The cross-sectional study used data from 3226 Framingham participants (53% women) born in the decades 1930–1970. None had dementia or a history of stroke. At a mean age of 57.7 years, they underwent brain MRI.
Compared with the 1930s birth decade, the 1970s birth decade had a 6.6% greater ICV (1321 mL vs 1234 mL), 7.7% greater white matter volume (476.3 mL vs 441.9 mL), 5.7% greater hippocampal volume (6.69 mL vs 6.51 mL), and 14.9% greater cortical surface area (2222 cm2 vs 1933 cm2).
Cortical thickness was thinner by 21% over the same period, coinciding with larger intracranial volume, cerebral white matter volume, and cortical surface area.
“We were surprised to find that the brain is getting larger, but the cortex is thinning very slightly. The apparent thinning of the cortex is related to the increased need for expansion of the cortical ribbon. This is based on hypotheses related to the effects of evolution and cortical development designed to make neuronal integration most efficient,” said Dr. DeCarli.
Repeat analysis applied to a subgroup of 1145 individuals of similar age range born in the 1940s (mean age, 60 years) and 1950s (mean age, 59 years) resulted in similar findings.
“These findings likely reflect both secular improvements in early life environmental influences through health, social-cultural, and educational factors, as well as secular improvements in modifiable dementia risk factors leading to better brain health and reserve,” the authors wrote.
While the effects observed are “likely to be small at the level of the individual, they are likely to be substantial at the population level, adding to growing literature that suggests optimized brain development and ideal health through modification of risk factors could substantially modify the effect of common neurodegenerative diseases such as stroke and Alzheiemer’s disease on dementia incidence,” they added.
Limitations included the predominately non-Hispanic White, healthy, and well-educated population that is the Framingham cohort, which is not representative of the broader US population. The cross-sectional nature of the study also limited causal inference.
Exciting Work
“If these results are confirmed by others and the observed differences by decade are as large as those reported, it has important implications for aging and dementia studies,” Prashanthi Lemuria, PhD, with Mayo Clinic, Rochester, Minnesota, wrote in an accompanying editorial.
“First, studies that use brain charts for the human life span to understand the mechanisms of aging, by stitching together data from individuals across the decades, are significantly overestimating the degree of brain health decline using volumes across the life span because the baseline brain health in individuals who are in their older decades is likely lower to begin with,” Dr. Lemuria noted.
“Second, cortical thickness measurements, often used in dementia studies as a cross-sectional marker for neurodegeneration, showed greatest decline due to secular trends and are not scaled for ICV. Therefore, these should be traded in favor of gray matter volumes after consideration of ICV to estimate the true degree of neurodegeneration,” Dr. Vemuri added.
The data also suggest that longitudinal imaging study designs should be preferred when testing hypotheses on brain health, Dr. Vemuri wrote.
Although this work is “exciting and will bring attention to secular trends in brain health, much work is yet to be done to validate and replicate these findings and, more importantly, understand the mechanistic basis of these trends,” she added.
“Do these secular trends in improvement of brain health underlie the decrease in dementia risk? The jury may be still out, but the authors are commended for investigating new avenues,” Dr. Vemuri concluded.
Support for this research was provided by the National Institute on Aging and the National Institute on Neurological Disorders and Stroke and the National Institutes of Health. Dr. DeCarli reported serving as a consultant to Novartis on a safety study of heart failure during the conduct of the study and receiving consultant fees from Eisai and Novo Nordisk outside the submitted work. Dr. Lemuria had no disclosures.
A version of this article appeared on Medscape.com.
A secular trends analysis using brain imaging data from the long-running Framingham Heart Study revealed an increase in intracranial volume (ICV), cortical gray matter, white matter, and hippocampal volumes, as well as cortical surface area in people born in the 1970s versus those born in the 1930s.
“We hypothesize that the increased size of the brain will lead to increased ‘reserve’ against the diseases of aging, consequently reducing overall risk of dementia,” said Charles DeCarli, MD, director of the Alzheimer’s Disease Research Center and Imaging of Dementia and Aging Laboratory, Department of Neurology and Center for Neuroscience, University of California at Davis.
The study was published online in JAMA Neurology.
Dementia Protection?
An earlier report from the Framingham Heart Study suggested that dementia incidence is declining.
“This difference occurred among persons with at least a high school education and was not affected by differences in vascular risk. Our work was stimulated by this finding and the possibility that differences in brain size might be occurring over the three generations of the Framingham Heart Study which might explain an increased resilience to dementia,” said Dr. DeCarli.
The cross-sectional study used data from 3226 Framingham participants (53% women) born in the decades 1930–1970. None had dementia or a history of stroke. At a mean age of 57.7 years, they underwent brain MRI.
Compared with the 1930s birth decade, the 1970s birth decade had a 6.6% greater ICV (1321 mL vs 1234 mL), 7.7% greater white matter volume (476.3 mL vs 441.9 mL), 5.7% greater hippocampal volume (6.69 mL vs 6.51 mL), and 14.9% greater cortical surface area (2222 cm2 vs 1933 cm2).
Cortical thickness was thinner by 21% over the same period, coinciding with larger intracranial volume, cerebral white matter volume, and cortical surface area.
“We were surprised to find that the brain is getting larger, but the cortex is thinning very slightly. The apparent thinning of the cortex is related to the increased need for expansion of the cortical ribbon. This is based on hypotheses related to the effects of evolution and cortical development designed to make neuronal integration most efficient,” said Dr. DeCarli.
Repeat analysis applied to a subgroup of 1145 individuals of similar age range born in the 1940s (mean age, 60 years) and 1950s (mean age, 59 years) resulted in similar findings.
“These findings likely reflect both secular improvements in early life environmental influences through health, social-cultural, and educational factors, as well as secular improvements in modifiable dementia risk factors leading to better brain health and reserve,” the authors wrote.
While the effects observed are “likely to be small at the level of the individual, they are likely to be substantial at the population level, adding to growing literature that suggests optimized brain development and ideal health through modification of risk factors could substantially modify the effect of common neurodegenerative diseases such as stroke and Alzheiemer’s disease on dementia incidence,” they added.
Limitations included the predominately non-Hispanic White, healthy, and well-educated population that is the Framingham cohort, which is not representative of the broader US population. The cross-sectional nature of the study also limited causal inference.
Exciting Work
“If these results are confirmed by others and the observed differences by decade are as large as those reported, it has important implications for aging and dementia studies,” Prashanthi Lemuria, PhD, with Mayo Clinic, Rochester, Minnesota, wrote in an accompanying editorial.
“First, studies that use brain charts for the human life span to understand the mechanisms of aging, by stitching together data from individuals across the decades, are significantly overestimating the degree of brain health decline using volumes across the life span because the baseline brain health in individuals who are in their older decades is likely lower to begin with,” Dr. Lemuria noted.
“Second, cortical thickness measurements, often used in dementia studies as a cross-sectional marker for neurodegeneration, showed greatest decline due to secular trends and are not scaled for ICV. Therefore, these should be traded in favor of gray matter volumes after consideration of ICV to estimate the true degree of neurodegeneration,” Dr. Vemuri added.
The data also suggest that longitudinal imaging study designs should be preferred when testing hypotheses on brain health, Dr. Vemuri wrote.
Although this work is “exciting and will bring attention to secular trends in brain health, much work is yet to be done to validate and replicate these findings and, more importantly, understand the mechanistic basis of these trends,” she added.
“Do these secular trends in improvement of brain health underlie the decrease in dementia risk? The jury may be still out, but the authors are commended for investigating new avenues,” Dr. Vemuri concluded.
Support for this research was provided by the National Institute on Aging and the National Institute on Neurological Disorders and Stroke and the National Institutes of Health. Dr. DeCarli reported serving as a consultant to Novartis on a safety study of heart failure during the conduct of the study and receiving consultant fees from Eisai and Novo Nordisk outside the submitted work. Dr. Lemuria had no disclosures.
A version of this article appeared on Medscape.com.
A secular trends analysis using brain imaging data from the long-running Framingham Heart Study revealed an increase in intracranial volume (ICV), cortical gray matter, white matter, and hippocampal volumes, as well as cortical surface area in people born in the 1970s versus those born in the 1930s.
“We hypothesize that the increased size of the brain will lead to increased ‘reserve’ against the diseases of aging, consequently reducing overall risk of dementia,” said Charles DeCarli, MD, director of the Alzheimer’s Disease Research Center and Imaging of Dementia and Aging Laboratory, Department of Neurology and Center for Neuroscience, University of California at Davis.
The study was published online in JAMA Neurology.
Dementia Protection?
An earlier report from the Framingham Heart Study suggested that dementia incidence is declining.
“This difference occurred among persons with at least a high school education and was not affected by differences in vascular risk. Our work was stimulated by this finding and the possibility that differences in brain size might be occurring over the three generations of the Framingham Heart Study which might explain an increased resilience to dementia,” said Dr. DeCarli.
The cross-sectional study used data from 3226 Framingham participants (53% women) born in the decades 1930–1970. None had dementia or a history of stroke. At a mean age of 57.7 years, they underwent brain MRI.
Compared with the 1930s birth decade, the 1970s birth decade had a 6.6% greater ICV (1321 mL vs 1234 mL), 7.7% greater white matter volume (476.3 mL vs 441.9 mL), 5.7% greater hippocampal volume (6.69 mL vs 6.51 mL), and 14.9% greater cortical surface area (2222 cm2 vs 1933 cm2).
Cortical thickness was thinner by 21% over the same period, coinciding with larger intracranial volume, cerebral white matter volume, and cortical surface area.
“We were surprised to find that the brain is getting larger, but the cortex is thinning very slightly. The apparent thinning of the cortex is related to the increased need for expansion of the cortical ribbon. This is based on hypotheses related to the effects of evolution and cortical development designed to make neuronal integration most efficient,” said Dr. DeCarli.
Repeat analysis applied to a subgroup of 1145 individuals of similar age range born in the 1940s (mean age, 60 years) and 1950s (mean age, 59 years) resulted in similar findings.
“These findings likely reflect both secular improvements in early life environmental influences through health, social-cultural, and educational factors, as well as secular improvements in modifiable dementia risk factors leading to better brain health and reserve,” the authors wrote.
While the effects observed are “likely to be small at the level of the individual, they are likely to be substantial at the population level, adding to growing literature that suggests optimized brain development and ideal health through modification of risk factors could substantially modify the effect of common neurodegenerative diseases such as stroke and Alzheiemer’s disease on dementia incidence,” they added.
Limitations included the predominately non-Hispanic White, healthy, and well-educated population that is the Framingham cohort, which is not representative of the broader US population. The cross-sectional nature of the study also limited causal inference.
Exciting Work
“If these results are confirmed by others and the observed differences by decade are as large as those reported, it has important implications for aging and dementia studies,” Prashanthi Lemuria, PhD, with Mayo Clinic, Rochester, Minnesota, wrote in an accompanying editorial.
“First, studies that use brain charts for the human life span to understand the mechanisms of aging, by stitching together data from individuals across the decades, are significantly overestimating the degree of brain health decline using volumes across the life span because the baseline brain health in individuals who are in their older decades is likely lower to begin with,” Dr. Lemuria noted.
“Second, cortical thickness measurements, often used in dementia studies as a cross-sectional marker for neurodegeneration, showed greatest decline due to secular trends and are not scaled for ICV. Therefore, these should be traded in favor of gray matter volumes after consideration of ICV to estimate the true degree of neurodegeneration,” Dr. Vemuri added.
The data also suggest that longitudinal imaging study designs should be preferred when testing hypotheses on brain health, Dr. Vemuri wrote.
Although this work is “exciting and will bring attention to secular trends in brain health, much work is yet to be done to validate and replicate these findings and, more importantly, understand the mechanistic basis of these trends,” she added.
“Do these secular trends in improvement of brain health underlie the decrease in dementia risk? The jury may be still out, but the authors are commended for investigating new avenues,” Dr. Vemuri concluded.
Support for this research was provided by the National Institute on Aging and the National Institute on Neurological Disorders and Stroke and the National Institutes of Health. Dr. DeCarli reported serving as a consultant to Novartis on a safety study of heart failure during the conduct of the study and receiving consultant fees from Eisai and Novo Nordisk outside the submitted work. Dr. Lemuria had no disclosures.
A version of this article appeared on Medscape.com.
FROM JAMA NEUROLOGY
Alzheimer’s Prevalence Predicted to Double by 2050
An estimated 6.9 million older adults are living with Alzheimer’s disease (AD) in the United States, and another 200,000 people under age 65 have younger-onset AD, new data showed.
The report also included sobering statistics on AD-related mortality — which increased 141% between 2001 and 2021 — and described “dementia neurology deserts” that will leave some states with less than 10 neurologists per 10,000 people with dementia as early as 2025. The shortages extend to other specialties, clinical professionals, and direct care workers, the report authors wrote.
“Dementia healthcare is a complex maze composed of primary care providers, specialists, social services, medication management, and caregiver support,” Sam Fazio, PhD, senior director, psychosocial research and quality care, Alzheimer’s Association, said in a press release.
“As the number of individuals living with Alzheimer’s continues to grow, ensuring patients, their caregivers, and families have a clear understanding of how to navigate dementia care resources is critical to improving health outcomes,” Dr. Fazio added.
The “2024 Alzheimer’s Disease Facts and Figures” study and accompanying report “Mapping a Better Future for Dementia Care Navigation” were published online on March 20 by the Alzheimer’s Association and will appear in the May issue of Alzheimer’s & Dementia.
Significant Increase in Mortality
The number of people over 65 with AD rose slightly in 2024 to 6.9 million from 6.7 million in 2023. The number of younger-onset AD cases remained roughly the same.
States and counties in the eastern and southeastern United States have the highest percentage of people over 65 with AD, with the District of Columbia reporting 16.8% and New York, Florida, and Mississippi between 12.5% and 12.7%. Alaska has the lowest with 8.8%.
Based on an analysis of death certificate data, the number of deaths from AD increased 141% between 2000 and 2021, while deaths from heart disease — the number-one cause of death — decreased 2.1%. Among people aged 70, 61% of those with AD are expected to die before age 80 compared with 30% of those without AD.
The cost of health and long-term care for people with AD has also risen, the data suggested, with a projected total for 2024 of $360 billion, a $15 billion increase since 2023. That figure does not include unpaid caregiving by family and friends, which the report valued at nearly $350 billion.
With the prevalence of AD expected to rise — the report projected 11.2 million by 2040 and 12.7 million by 2050 — mortality, morbidity, and healthcare costs will only continue to go up. Without new treatments and advancements in care, study authors estimated the cost will reach $1 trillion in 2050.
The report also waded into the issue of workforce deficits. Between 2012 and 2022, the number of direct care workers in the United States increased from 3.2 million to 4.8 million. Study authors estimated more than 1 million additional direct care workers will be needed before 2031.
There is a shortage of clinicians as well, especially for geriatricians, specially trained family physicians, or board-certified internists who can screen for, detect, and diagnose possible dementia. The National Center for Health Workforce Analysis (NCHWA) determined shortages in that specialty began a decade ago, and the projected need for geriatricians is expected to far exceed the supply in every region of the United States by 2050.
The NCHWA also projected a shortfall of neurologists by 2025. The report listed 20 US states as “dementia neurology deserts,” meaning they’re projected to have fewer than 10 neurologists per 10,000 people with dementia in 2025.
Several factors may contribute to the scarcity of specialists. In addition to an aging population, contributors include lower pay for geriatricians and neurologists compared with other specialists, an inadequate number of clinician educators with relevant specialties on faculties of health professional schools, and limited incentives to choose these specialties.
Underestimating a ‘Serious Problem’
The report “probably underestimates” the “serious problem with dementia specialty care in the United States,” David S. Knopman, MD, professor of neurology, Mayo Clinic, Rochester, Minnesota, told this news organization.
Given the complexity of managing treatments for AD, such as the monoclonal antibody lecanemab, or those for dementia with Lewy bodies, “my sense is that very few geriatricians are likely to take an active role in dementia care,” said Dr. Knopman.
Very few neurologists have specialty training in dementia diagnosis and care, he added, and neurologists who do specialize in dementia are generally located exclusively in tertiary medical centers.
“While neurologists are more likely to be able to diagnose dementia subtypes compared to geriatricians or general internists or family physicians, non-specialty neurologists are also unlikely to have the expertise to manage lecanemab therapy or to deal with diagnosis and management of dementia subtypes,” Dr. Knopman said.
“Filling the pipeline with new trainees is going to take a long, long time,” he added.
As it stands, most dementia diagnoses are not made by specialists. The report cited a study of Medicare beneficiaries that found 85% of people living with dementia were diagnosed by providers such as primary care physicians (PCPs).
Barriers to Care
Although screening is now a reimbursable service by Medicare, PCPs experience numerous barriers to detecting cognitive impairment and diagnosing dementia. Routinely used cognitive assessments are time-consuming and labor-intensive, making them challenging to use in a busy clinical setting.
“Even if dementia is diagnosed, providers sometimes wait to disclose this information to the patient due to diagnostic uncertainty, time constraints, stigma, and fear of causing emotional distress,” the authors wrote.
A previous survey by the Alzheimer’s Association uncovered a high degree of uncertainty and discomfort among PCPs in making a dementia diagnosis. While almost a third reported referring patients to specialists, 55% said there were not enough geriatricians and other specialists in their area to meet the demand.
In tackling the theme of dementia care navigation, the report included a survey of 1204 nonphysician healthcare workers, including nurses, physician assistants, and social workers.
About 60% believed the US healthcare system isn’t effectively helping patients and families navigate the system and that training in dementia care navigation is lacking and not standardized. Respondents also said nonmedical professionals are best suited to help people with dementia and their caregivers navigate care.
Respondents identified a range of barriers that make navigating dementia care difficult for patients and families. More than three in four (77%) identified a lack of community-based resources as a barrier. And 70% called out restrictions in current payment models as a barrier, with 41% saying this was the greatest barrier.
Alternative Model
In July, the Centers for Medicare & Medicaid Services will launch a pilot model in dementia care management, the Guiding an Improved Dementia Experience. The program will test a monthly per-patient payment model as a fee-for-service replacement.
Healthcare providers who participate in the program will deliver supportive services to people living with dementia and provide access to a care navigator to help patients and caregivers access services and support.
“There is growing momentum in this country to enhance dementia care navigation,” Dr. Fazio said in the release. “Dementia care navigation programs have shown they can be a huge benefit to people living with dementia and their caregivers.”
These programs are unfortunately not widespread across the country, but the Alzheimer’s Association hopes this report “will be a catalyst for change,” Dr. Fazio added.
A separate survey of dementia caregivers found they would overwhelmingly welcome navigator support. The vast majority (97%) said they would find navigation services helpful.
Such services may also go a long way to alleviating stresses involved in dementia caregiving, a top stressor being care coordination, the report noted. Seven in 10 caregiver survey respondents (70%) reported coordinating care is stressful. More than half (53%) said navigating healthcare is difficult, and two-thirds (66%) said they have difficulty finding resources and supports.
Around-the-clock support in addition to care coordination and help understanding their care recipient’s condition are among the top services dementia caregiver respondents cited as being most helpful.
Dr. Knopman reported no relevant conflicts of interest.
A version of this article appeared on Medscape.com.
An estimated 6.9 million older adults are living with Alzheimer’s disease (AD) in the United States, and another 200,000 people under age 65 have younger-onset AD, new data showed.
The report also included sobering statistics on AD-related mortality — which increased 141% between 2001 and 2021 — and described “dementia neurology deserts” that will leave some states with less than 10 neurologists per 10,000 people with dementia as early as 2025. The shortages extend to other specialties, clinical professionals, and direct care workers, the report authors wrote.
“Dementia healthcare is a complex maze composed of primary care providers, specialists, social services, medication management, and caregiver support,” Sam Fazio, PhD, senior director, psychosocial research and quality care, Alzheimer’s Association, said in a press release.
“As the number of individuals living with Alzheimer’s continues to grow, ensuring patients, their caregivers, and families have a clear understanding of how to navigate dementia care resources is critical to improving health outcomes,” Dr. Fazio added.
The “2024 Alzheimer’s Disease Facts and Figures” study and accompanying report “Mapping a Better Future for Dementia Care Navigation” were published online on March 20 by the Alzheimer’s Association and will appear in the May issue of Alzheimer’s & Dementia.
Significant Increase in Mortality
The number of people over 65 with AD rose slightly in 2024 to 6.9 million from 6.7 million in 2023. The number of younger-onset AD cases remained roughly the same.
States and counties in the eastern and southeastern United States have the highest percentage of people over 65 with AD, with the District of Columbia reporting 16.8% and New York, Florida, and Mississippi between 12.5% and 12.7%. Alaska has the lowest with 8.8%.
Based on an analysis of death certificate data, the number of deaths from AD increased 141% between 2000 and 2021, while deaths from heart disease — the number-one cause of death — decreased 2.1%. Among people aged 70, 61% of those with AD are expected to die before age 80 compared with 30% of those without AD.
The cost of health and long-term care for people with AD has also risen, the data suggested, with a projected total for 2024 of $360 billion, a $15 billion increase since 2023. That figure does not include unpaid caregiving by family and friends, which the report valued at nearly $350 billion.
With the prevalence of AD expected to rise — the report projected 11.2 million by 2040 and 12.7 million by 2050 — mortality, morbidity, and healthcare costs will only continue to go up. Without new treatments and advancements in care, study authors estimated the cost will reach $1 trillion in 2050.
The report also waded into the issue of workforce deficits. Between 2012 and 2022, the number of direct care workers in the United States increased from 3.2 million to 4.8 million. Study authors estimated more than 1 million additional direct care workers will be needed before 2031.
There is a shortage of clinicians as well, especially for geriatricians, specially trained family physicians, or board-certified internists who can screen for, detect, and diagnose possible dementia. The National Center for Health Workforce Analysis (NCHWA) determined shortages in that specialty began a decade ago, and the projected need for geriatricians is expected to far exceed the supply in every region of the United States by 2050.
The NCHWA also projected a shortfall of neurologists by 2025. The report listed 20 US states as “dementia neurology deserts,” meaning they’re projected to have fewer than 10 neurologists per 10,000 people with dementia in 2025.
Several factors may contribute to the scarcity of specialists. In addition to an aging population, contributors include lower pay for geriatricians and neurologists compared with other specialists, an inadequate number of clinician educators with relevant specialties on faculties of health professional schools, and limited incentives to choose these specialties.
Underestimating a ‘Serious Problem’
The report “probably underestimates” the “serious problem with dementia specialty care in the United States,” David S. Knopman, MD, professor of neurology, Mayo Clinic, Rochester, Minnesota, told this news organization.
Given the complexity of managing treatments for AD, such as the monoclonal antibody lecanemab, or those for dementia with Lewy bodies, “my sense is that very few geriatricians are likely to take an active role in dementia care,” said Dr. Knopman.
Very few neurologists have specialty training in dementia diagnosis and care, he added, and neurologists who do specialize in dementia are generally located exclusively in tertiary medical centers.
“While neurologists are more likely to be able to diagnose dementia subtypes compared to geriatricians or general internists or family physicians, non-specialty neurologists are also unlikely to have the expertise to manage lecanemab therapy or to deal with diagnosis and management of dementia subtypes,” Dr. Knopman said.
“Filling the pipeline with new trainees is going to take a long, long time,” he added.
As it stands, most dementia diagnoses are not made by specialists. The report cited a study of Medicare beneficiaries that found 85% of people living with dementia were diagnosed by providers such as primary care physicians (PCPs).
Barriers to Care
Although screening is now a reimbursable service by Medicare, PCPs experience numerous barriers to detecting cognitive impairment and diagnosing dementia. Routinely used cognitive assessments are time-consuming and labor-intensive, making them challenging to use in a busy clinical setting.
“Even if dementia is diagnosed, providers sometimes wait to disclose this information to the patient due to diagnostic uncertainty, time constraints, stigma, and fear of causing emotional distress,” the authors wrote.
A previous survey by the Alzheimer’s Association uncovered a high degree of uncertainty and discomfort among PCPs in making a dementia diagnosis. While almost a third reported referring patients to specialists, 55% said there were not enough geriatricians and other specialists in their area to meet the demand.
In tackling the theme of dementia care navigation, the report included a survey of 1204 nonphysician healthcare workers, including nurses, physician assistants, and social workers.
About 60% believed the US healthcare system isn’t effectively helping patients and families navigate the system and that training in dementia care navigation is lacking and not standardized. Respondents also said nonmedical professionals are best suited to help people with dementia and their caregivers navigate care.
Respondents identified a range of barriers that make navigating dementia care difficult for patients and families. More than three in four (77%) identified a lack of community-based resources as a barrier. And 70% called out restrictions in current payment models as a barrier, with 41% saying this was the greatest barrier.
Alternative Model
In July, the Centers for Medicare & Medicaid Services will launch a pilot model in dementia care management, the Guiding an Improved Dementia Experience. The program will test a monthly per-patient payment model as a fee-for-service replacement.
Healthcare providers who participate in the program will deliver supportive services to people living with dementia and provide access to a care navigator to help patients and caregivers access services and support.
“There is growing momentum in this country to enhance dementia care navigation,” Dr. Fazio said in the release. “Dementia care navigation programs have shown they can be a huge benefit to people living with dementia and their caregivers.”
These programs are unfortunately not widespread across the country, but the Alzheimer’s Association hopes this report “will be a catalyst for change,” Dr. Fazio added.
A separate survey of dementia caregivers found they would overwhelmingly welcome navigator support. The vast majority (97%) said they would find navigation services helpful.
Such services may also go a long way to alleviating stresses involved in dementia caregiving, a top stressor being care coordination, the report noted. Seven in 10 caregiver survey respondents (70%) reported coordinating care is stressful. More than half (53%) said navigating healthcare is difficult, and two-thirds (66%) said they have difficulty finding resources and supports.
Around-the-clock support in addition to care coordination and help understanding their care recipient’s condition are among the top services dementia caregiver respondents cited as being most helpful.
Dr. Knopman reported no relevant conflicts of interest.
A version of this article appeared on Medscape.com.
An estimated 6.9 million older adults are living with Alzheimer’s disease (AD) in the United States, and another 200,000 people under age 65 have younger-onset AD, new data showed.
The report also included sobering statistics on AD-related mortality — which increased 141% between 2001 and 2021 — and described “dementia neurology deserts” that will leave some states with less than 10 neurologists per 10,000 people with dementia as early as 2025. The shortages extend to other specialties, clinical professionals, and direct care workers, the report authors wrote.
“Dementia healthcare is a complex maze composed of primary care providers, specialists, social services, medication management, and caregiver support,” Sam Fazio, PhD, senior director, psychosocial research and quality care, Alzheimer’s Association, said in a press release.
“As the number of individuals living with Alzheimer’s continues to grow, ensuring patients, their caregivers, and families have a clear understanding of how to navigate dementia care resources is critical to improving health outcomes,” Dr. Fazio added.
The “2024 Alzheimer’s Disease Facts and Figures” study and accompanying report “Mapping a Better Future for Dementia Care Navigation” were published online on March 20 by the Alzheimer’s Association and will appear in the May issue of Alzheimer’s & Dementia.
Significant Increase in Mortality
The number of people over 65 with AD rose slightly in 2024 to 6.9 million from 6.7 million in 2023. The number of younger-onset AD cases remained roughly the same.
States and counties in the eastern and southeastern United States have the highest percentage of people over 65 with AD, with the District of Columbia reporting 16.8% and New York, Florida, and Mississippi between 12.5% and 12.7%. Alaska has the lowest with 8.8%.
Based on an analysis of death certificate data, the number of deaths from AD increased 141% between 2000 and 2021, while deaths from heart disease — the number-one cause of death — decreased 2.1%. Among people aged 70, 61% of those with AD are expected to die before age 80 compared with 30% of those without AD.
The cost of health and long-term care for people with AD has also risen, the data suggested, with a projected total for 2024 of $360 billion, a $15 billion increase since 2023. That figure does not include unpaid caregiving by family and friends, which the report valued at nearly $350 billion.
With the prevalence of AD expected to rise — the report projected 11.2 million by 2040 and 12.7 million by 2050 — mortality, morbidity, and healthcare costs will only continue to go up. Without new treatments and advancements in care, study authors estimated the cost will reach $1 trillion in 2050.
The report also waded into the issue of workforce deficits. Between 2012 and 2022, the number of direct care workers in the United States increased from 3.2 million to 4.8 million. Study authors estimated more than 1 million additional direct care workers will be needed before 2031.
There is a shortage of clinicians as well, especially for geriatricians, specially trained family physicians, or board-certified internists who can screen for, detect, and diagnose possible dementia. The National Center for Health Workforce Analysis (NCHWA) determined shortages in that specialty began a decade ago, and the projected need for geriatricians is expected to far exceed the supply in every region of the United States by 2050.
The NCHWA also projected a shortfall of neurologists by 2025. The report listed 20 US states as “dementia neurology deserts,” meaning they’re projected to have fewer than 10 neurologists per 10,000 people with dementia in 2025.
Several factors may contribute to the scarcity of specialists. In addition to an aging population, contributors include lower pay for geriatricians and neurologists compared with other specialists, an inadequate number of clinician educators with relevant specialties on faculties of health professional schools, and limited incentives to choose these specialties.
Underestimating a ‘Serious Problem’
The report “probably underestimates” the “serious problem with dementia specialty care in the United States,” David S. Knopman, MD, professor of neurology, Mayo Clinic, Rochester, Minnesota, told this news organization.
Given the complexity of managing treatments for AD, such as the monoclonal antibody lecanemab, or those for dementia with Lewy bodies, “my sense is that very few geriatricians are likely to take an active role in dementia care,” said Dr. Knopman.
Very few neurologists have specialty training in dementia diagnosis and care, he added, and neurologists who do specialize in dementia are generally located exclusively in tertiary medical centers.
“While neurologists are more likely to be able to diagnose dementia subtypes compared to geriatricians or general internists or family physicians, non-specialty neurologists are also unlikely to have the expertise to manage lecanemab therapy or to deal with diagnosis and management of dementia subtypes,” Dr. Knopman said.
“Filling the pipeline with new trainees is going to take a long, long time,” he added.
As it stands, most dementia diagnoses are not made by specialists. The report cited a study of Medicare beneficiaries that found 85% of people living with dementia were diagnosed by providers such as primary care physicians (PCPs).
Barriers to Care
Although screening is now a reimbursable service by Medicare, PCPs experience numerous barriers to detecting cognitive impairment and diagnosing dementia. Routinely used cognitive assessments are time-consuming and labor-intensive, making them challenging to use in a busy clinical setting.
“Even if dementia is diagnosed, providers sometimes wait to disclose this information to the patient due to diagnostic uncertainty, time constraints, stigma, and fear of causing emotional distress,” the authors wrote.
A previous survey by the Alzheimer’s Association uncovered a high degree of uncertainty and discomfort among PCPs in making a dementia diagnosis. While almost a third reported referring patients to specialists, 55% said there were not enough geriatricians and other specialists in their area to meet the demand.
In tackling the theme of dementia care navigation, the report included a survey of 1204 nonphysician healthcare workers, including nurses, physician assistants, and social workers.
About 60% believed the US healthcare system isn’t effectively helping patients and families navigate the system and that training in dementia care navigation is lacking and not standardized. Respondents also said nonmedical professionals are best suited to help people with dementia and their caregivers navigate care.
Respondents identified a range of barriers that make navigating dementia care difficult for patients and families. More than three in four (77%) identified a lack of community-based resources as a barrier. And 70% called out restrictions in current payment models as a barrier, with 41% saying this was the greatest barrier.
Alternative Model
In July, the Centers for Medicare & Medicaid Services will launch a pilot model in dementia care management, the Guiding an Improved Dementia Experience. The program will test a monthly per-patient payment model as a fee-for-service replacement.
Healthcare providers who participate in the program will deliver supportive services to people living with dementia and provide access to a care navigator to help patients and caregivers access services and support.
“There is growing momentum in this country to enhance dementia care navigation,” Dr. Fazio said in the release. “Dementia care navigation programs have shown they can be a huge benefit to people living with dementia and their caregivers.”
These programs are unfortunately not widespread across the country, but the Alzheimer’s Association hopes this report “will be a catalyst for change,” Dr. Fazio added.
A separate survey of dementia caregivers found they would overwhelmingly welcome navigator support. The vast majority (97%) said they would find navigation services helpful.
Such services may also go a long way to alleviating stresses involved in dementia caregiving, a top stressor being care coordination, the report noted. Seven in 10 caregiver survey respondents (70%) reported coordinating care is stressful. More than half (53%) said navigating healthcare is difficult, and two-thirds (66%) said they have difficulty finding resources and supports.
Around-the-clock support in addition to care coordination and help understanding their care recipient’s condition are among the top services dementia caregiver respondents cited as being most helpful.
Dr. Knopman reported no relevant conflicts of interest.
A version of this article appeared on Medscape.com.
Skin Test Accurately Detects Parkinson’s, Other Neurodegenerative Disorders
A simple skin biopsy test is able to detect an abnormal form of alpha-synuclein with high accuracy in individuals with neurodegenerative disorders such as Parkinson’s disease (PD).
Synucleinopathies include PD, dementia with Lewy bodies (DLB), multiple system atrophy (MSA), and pure autonomic failure (PAF).
“Each year, there are nearly 200,000 people in the U.S. who face a diagnosis of Parkinson’s disease, dementia with Lewy bodies, and related disorders,” study investigator Christopher H. Gibbons, MD, professor of neurology at Harvard Medical School in Boston, said in a press release.
He explained that patients often experience delays in diagnosis or are misdiagnosed due to the complexity of synucleinopathies.
“With a simple, minimally invasive skin biopsy test, this blinded, multicenter study demonstrated how we can more objectively identify the underlying pathology of synucleinopathies and offer better diagnostic answers and care for patients.”
The findings were published online on March 20 in JAMA.
An Urgent Priority
Affecting an estimated 2.5 million people in the United States, synucleinopathies are progressive neurodegenerative diseases with varying prognoses, so identifying a reliable diagnostic biomarker is an “urgent unmet priority,” the researchers noted.
The disorders share some symptoms such as tremors and cognitive changes, and all are characterized by P-SYN, an abnormal protein found in the cutaneous nerve fibers.
The study included 428 adults aged 40-99 years (mean age, 70 years) recruited from 30 academic and community-based neurology practices across the United States, with 277 diagnosed with PD, DLB, MSA, or PAF. It also included a control group of 120 participants with no symptoms suggestive of synucleinopathy.
Investigators used the commercially available Syn-One Test, developed in 2019 by CND Life Sciences, to analyze levels of P-SYN via 3-mm punch skin biopsies from each participant.
The test detected P-SYN in 95.5% of study participants overall, including 89 of 96 (92.7%) with PD, 54 of 55 (98.2%) with MSA, 48 of 50 (96%) with DLB, 22 of 22 (100%) with PAF, and 4 of 120 (3.3%) of the controls with no synucleinopathy.
The investigators said it is possible that some of the controls who tested positive had a subclinical form of synucleinopathy, which would explain the false positives.
Study limitations include clinical consensus diagnostic criteria without video or autopsy confirmation, a lack of genetic testing on participants (some genetic forms of PD do not have alpha-synuclein deposition), and the fact that controls were younger than those in disease groups.
“Further research is needed in unselected clinical populations to externally validate the findings and fully characterize the potential role of skin biopsy detection of P-SYN in clinical care,” the authors wrote.
Syn-One is not approved by the US Food and Drug Administration as a diagnostic test for PD but is available as a pathologic assay that determines whether a tissue sample contains phosphorylated alpha-synuclein and can be billed through Medicare.
The study was funded by the National Institutes of Health. Dr. Gibbons reported having stock options in CND Life Sciences outside the submitted work. Other disclosures are noted in the original article.
A version of this article appeared on Medscape.com.
A simple skin biopsy test is able to detect an abnormal form of alpha-synuclein with high accuracy in individuals with neurodegenerative disorders such as Parkinson’s disease (PD).
Synucleinopathies include PD, dementia with Lewy bodies (DLB), multiple system atrophy (MSA), and pure autonomic failure (PAF).
“Each year, there are nearly 200,000 people in the U.S. who face a diagnosis of Parkinson’s disease, dementia with Lewy bodies, and related disorders,” study investigator Christopher H. Gibbons, MD, professor of neurology at Harvard Medical School in Boston, said in a press release.
He explained that patients often experience delays in diagnosis or are misdiagnosed due to the complexity of synucleinopathies.
“With a simple, minimally invasive skin biopsy test, this blinded, multicenter study demonstrated how we can more objectively identify the underlying pathology of synucleinopathies and offer better diagnostic answers and care for patients.”
The findings were published online on March 20 in JAMA.
An Urgent Priority
Affecting an estimated 2.5 million people in the United States, synucleinopathies are progressive neurodegenerative diseases with varying prognoses, so identifying a reliable diagnostic biomarker is an “urgent unmet priority,” the researchers noted.
The disorders share some symptoms such as tremors and cognitive changes, and all are characterized by P-SYN, an abnormal protein found in the cutaneous nerve fibers.
The study included 428 adults aged 40-99 years (mean age, 70 years) recruited from 30 academic and community-based neurology practices across the United States, with 277 diagnosed with PD, DLB, MSA, or PAF. It also included a control group of 120 participants with no symptoms suggestive of synucleinopathy.
Investigators used the commercially available Syn-One Test, developed in 2019 by CND Life Sciences, to analyze levels of P-SYN via 3-mm punch skin biopsies from each participant.
The test detected P-SYN in 95.5% of study participants overall, including 89 of 96 (92.7%) with PD, 54 of 55 (98.2%) with MSA, 48 of 50 (96%) with DLB, 22 of 22 (100%) with PAF, and 4 of 120 (3.3%) of the controls with no synucleinopathy.
The investigators said it is possible that some of the controls who tested positive had a subclinical form of synucleinopathy, which would explain the false positives.
Study limitations include clinical consensus diagnostic criteria without video or autopsy confirmation, a lack of genetic testing on participants (some genetic forms of PD do not have alpha-synuclein deposition), and the fact that controls were younger than those in disease groups.
“Further research is needed in unselected clinical populations to externally validate the findings and fully characterize the potential role of skin biopsy detection of P-SYN in clinical care,” the authors wrote.
Syn-One is not approved by the US Food and Drug Administration as a diagnostic test for PD but is available as a pathologic assay that determines whether a tissue sample contains phosphorylated alpha-synuclein and can be billed through Medicare.
The study was funded by the National Institutes of Health. Dr. Gibbons reported having stock options in CND Life Sciences outside the submitted work. Other disclosures are noted in the original article.
A version of this article appeared on Medscape.com.
A simple skin biopsy test is able to detect an abnormal form of alpha-synuclein with high accuracy in individuals with neurodegenerative disorders such as Parkinson’s disease (PD).
Synucleinopathies include PD, dementia with Lewy bodies (DLB), multiple system atrophy (MSA), and pure autonomic failure (PAF).
“Each year, there are nearly 200,000 people in the U.S. who face a diagnosis of Parkinson’s disease, dementia with Lewy bodies, and related disorders,” study investigator Christopher H. Gibbons, MD, professor of neurology at Harvard Medical School in Boston, said in a press release.
He explained that patients often experience delays in diagnosis or are misdiagnosed due to the complexity of synucleinopathies.
“With a simple, minimally invasive skin biopsy test, this blinded, multicenter study demonstrated how we can more objectively identify the underlying pathology of synucleinopathies and offer better diagnostic answers and care for patients.”
The findings were published online on March 20 in JAMA.
An Urgent Priority
Affecting an estimated 2.5 million people in the United States, synucleinopathies are progressive neurodegenerative diseases with varying prognoses, so identifying a reliable diagnostic biomarker is an “urgent unmet priority,” the researchers noted.
The disorders share some symptoms such as tremors and cognitive changes, and all are characterized by P-SYN, an abnormal protein found in the cutaneous nerve fibers.
The study included 428 adults aged 40-99 years (mean age, 70 years) recruited from 30 academic and community-based neurology practices across the United States, with 277 diagnosed with PD, DLB, MSA, or PAF. It also included a control group of 120 participants with no symptoms suggestive of synucleinopathy.
Investigators used the commercially available Syn-One Test, developed in 2019 by CND Life Sciences, to analyze levels of P-SYN via 3-mm punch skin biopsies from each participant.
The test detected P-SYN in 95.5% of study participants overall, including 89 of 96 (92.7%) with PD, 54 of 55 (98.2%) with MSA, 48 of 50 (96%) with DLB, 22 of 22 (100%) with PAF, and 4 of 120 (3.3%) of the controls with no synucleinopathy.
The investigators said it is possible that some of the controls who tested positive had a subclinical form of synucleinopathy, which would explain the false positives.
Study limitations include clinical consensus diagnostic criteria without video or autopsy confirmation, a lack of genetic testing on participants (some genetic forms of PD do not have alpha-synuclein deposition), and the fact that controls were younger than those in disease groups.
“Further research is needed in unselected clinical populations to externally validate the findings and fully characterize the potential role of skin biopsy detection of P-SYN in clinical care,” the authors wrote.
Syn-One is not approved by the US Food and Drug Administration as a diagnostic test for PD but is available as a pathologic assay that determines whether a tissue sample contains phosphorylated alpha-synuclein and can be billed through Medicare.
The study was funded by the National Institutes of Health. Dr. Gibbons reported having stock options in CND Life Sciences outside the submitted work. Other disclosures are noted in the original article.
A version of this article appeared on Medscape.com.
Glucose Level Fluctuations Affect Cognition in T1D
TOPLINE:
Naturally occurring glucose fluctuations affect cognitive function in people with type 1 diabetes, according to a new study. It matters less whether glucose is considerably higher or lower than the patient’s usual glucose level. Rather,
METHODOLOGY:
- The investigators used continuous glucose monitoring (CGM) digital sensors and smartphone-based cognitive tests (cognitive ecological momentary assessment [EMA]) to collect repeated, high-frequency glucose and cognitive data. Glucose data were collected every 5 minutes; cognitive data were collected three times daily for 15 days as participants went about their daily lives.
- The study included 200 participants (mean [standard deviation] age, 47.5 [15.6] years; 53.5% female; 86% White; mean A1c, 7.5 mmol/mol [1.3]).
- Using CGM and EMA, the researchers obtained “intensive” longitudinal measurements of glucose as well as cognition (processing speed and sustained attention).
- Hierarchical Bayesian modeling estimated dynamic, within-person associations between glucose and cognition, and data-driven lasso regression identified identify clinical characteristics that predicted differences from person to person in cognitive vulnerability to glucose fluctuations.
TAKEAWAY:
- Cognitive performance was reduced both at low and high glucose levels, “reflecting vulnerability to glucose fluctuations.”
- Large glucose fluctuations were associated with slower as well as less accurate processing speed, although slight glucose elevations (relative to the individual’s own means) were associated with faster processing speed, regardless of the absolute level (eg, euglycemic vs hyperglycemic) of those means.
- By contrast, glucose fluctuations were unrelated to sustained attention.
- The researchers identified seven clinical characteristics that predicted individual differences in cognitive vulnerability to glucose fluctuations: Older age, time in hypoglycemia, lifetime severe hypoglycemic events, microvascular complications, glucose variability, fatigue, and larger neck circumference.
IN PRACTICE:
“Our results demonstrate that people can differ a lot from one another in how their brains are impacted by glucose,” co-senior author Laura Germine, PhD, director of the Laboratory for Brain and Cognitive Health Technology, McLean Hospital, Boston, said in a news release. “We found that minimizing glucose fluctuations in daily life is important for optimizing processing speed, and this is especially true for people who are older or have other diabetes-related health conditions.”
SOURCE:
Zoë Hawks, PhD, research investigator, McLean Hospital, Boston, was the lead and corresponding author on the study. It was published online on March 18 in Digital Medicine.
LIMITATIONS:
The researchers required 24-hour access to a smartphone with reliable Internet access, which might have biased sampling toward people of higher economic status. Moreover, the present sample was predominantly White and non-Hispanic, so findings may not be generalizable to other populations.
DISCLOSURES:
The research was supported by grants from the National Institutes of Health, the Brain and Behavior Research Foundation, and the Alzheimer’s Association. Dr. Hawks received consulting fees from Blueprint Health. The other authors’ disclosures were listed in the original paper.
A version of this article appeared on Medscape.com.
TOPLINE:
Naturally occurring glucose fluctuations affect cognitive function in people with type 1 diabetes, according to a new study. It matters less whether glucose is considerably higher or lower than the patient’s usual glucose level. Rather,
METHODOLOGY:
- The investigators used continuous glucose monitoring (CGM) digital sensors and smartphone-based cognitive tests (cognitive ecological momentary assessment [EMA]) to collect repeated, high-frequency glucose and cognitive data. Glucose data were collected every 5 minutes; cognitive data were collected three times daily for 15 days as participants went about their daily lives.
- The study included 200 participants (mean [standard deviation] age, 47.5 [15.6] years; 53.5% female; 86% White; mean A1c, 7.5 mmol/mol [1.3]).
- Using CGM and EMA, the researchers obtained “intensive” longitudinal measurements of glucose as well as cognition (processing speed and sustained attention).
- Hierarchical Bayesian modeling estimated dynamic, within-person associations between glucose and cognition, and data-driven lasso regression identified identify clinical characteristics that predicted differences from person to person in cognitive vulnerability to glucose fluctuations.
TAKEAWAY:
- Cognitive performance was reduced both at low and high glucose levels, “reflecting vulnerability to glucose fluctuations.”
- Large glucose fluctuations were associated with slower as well as less accurate processing speed, although slight glucose elevations (relative to the individual’s own means) were associated with faster processing speed, regardless of the absolute level (eg, euglycemic vs hyperglycemic) of those means.
- By contrast, glucose fluctuations were unrelated to sustained attention.
- The researchers identified seven clinical characteristics that predicted individual differences in cognitive vulnerability to glucose fluctuations: Older age, time in hypoglycemia, lifetime severe hypoglycemic events, microvascular complications, glucose variability, fatigue, and larger neck circumference.
IN PRACTICE:
“Our results demonstrate that people can differ a lot from one another in how their brains are impacted by glucose,” co-senior author Laura Germine, PhD, director of the Laboratory for Brain and Cognitive Health Technology, McLean Hospital, Boston, said in a news release. “We found that minimizing glucose fluctuations in daily life is important for optimizing processing speed, and this is especially true for people who are older or have other diabetes-related health conditions.”
SOURCE:
Zoë Hawks, PhD, research investigator, McLean Hospital, Boston, was the lead and corresponding author on the study. It was published online on March 18 in Digital Medicine.
LIMITATIONS:
The researchers required 24-hour access to a smartphone with reliable Internet access, which might have biased sampling toward people of higher economic status. Moreover, the present sample was predominantly White and non-Hispanic, so findings may not be generalizable to other populations.
DISCLOSURES:
The research was supported by grants from the National Institutes of Health, the Brain and Behavior Research Foundation, and the Alzheimer’s Association. Dr. Hawks received consulting fees from Blueprint Health. The other authors’ disclosures were listed in the original paper.
A version of this article appeared on Medscape.com.
TOPLINE:
Naturally occurring glucose fluctuations affect cognitive function in people with type 1 diabetes, according to a new study. It matters less whether glucose is considerably higher or lower than the patient’s usual glucose level. Rather,
METHODOLOGY:
- The investigators used continuous glucose monitoring (CGM) digital sensors and smartphone-based cognitive tests (cognitive ecological momentary assessment [EMA]) to collect repeated, high-frequency glucose and cognitive data. Glucose data were collected every 5 minutes; cognitive data were collected three times daily for 15 days as participants went about their daily lives.
- The study included 200 participants (mean [standard deviation] age, 47.5 [15.6] years; 53.5% female; 86% White; mean A1c, 7.5 mmol/mol [1.3]).
- Using CGM and EMA, the researchers obtained “intensive” longitudinal measurements of glucose as well as cognition (processing speed and sustained attention).
- Hierarchical Bayesian modeling estimated dynamic, within-person associations between glucose and cognition, and data-driven lasso regression identified identify clinical characteristics that predicted differences from person to person in cognitive vulnerability to glucose fluctuations.
TAKEAWAY:
- Cognitive performance was reduced both at low and high glucose levels, “reflecting vulnerability to glucose fluctuations.”
- Large glucose fluctuations were associated with slower as well as less accurate processing speed, although slight glucose elevations (relative to the individual’s own means) were associated with faster processing speed, regardless of the absolute level (eg, euglycemic vs hyperglycemic) of those means.
- By contrast, glucose fluctuations were unrelated to sustained attention.
- The researchers identified seven clinical characteristics that predicted individual differences in cognitive vulnerability to glucose fluctuations: Older age, time in hypoglycemia, lifetime severe hypoglycemic events, microvascular complications, glucose variability, fatigue, and larger neck circumference.
IN PRACTICE:
“Our results demonstrate that people can differ a lot from one another in how their brains are impacted by glucose,” co-senior author Laura Germine, PhD, director of the Laboratory for Brain and Cognitive Health Technology, McLean Hospital, Boston, said in a news release. “We found that minimizing glucose fluctuations in daily life is important for optimizing processing speed, and this is especially true for people who are older or have other diabetes-related health conditions.”
SOURCE:
Zoë Hawks, PhD, research investigator, McLean Hospital, Boston, was the lead and corresponding author on the study. It was published online on March 18 in Digital Medicine.
LIMITATIONS:
The researchers required 24-hour access to a smartphone with reliable Internet access, which might have biased sampling toward people of higher economic status. Moreover, the present sample was predominantly White and non-Hispanic, so findings may not be generalizable to other populations.
DISCLOSURES:
The research was supported by grants from the National Institutes of Health, the Brain and Behavior Research Foundation, and the Alzheimer’s Association. Dr. Hawks received consulting fees from Blueprint Health. The other authors’ disclosures were listed in the original paper.
A version of this article appeared on Medscape.com.
Disadvantaged Neighborhoods Tied to Higher Dementia Risk, Brain Aging
Living in a disadvantaged neighborhood is associated with accelerated brain aging and a higher risk for early dementia, regardless of income level or education, new research suggested.
“If you want to prevent dementia and you’re not asking someone about their neighborhood, you’re missing information that’s important to know,” lead author Aaron Reuben, PhD, postdoctoral scholar in neuropsychology and environmental health at Duke University, Durham, North Carolina, said in a news release.
The study was published online in Alzheimer’s & Dementia.
Higher Risk in Men
Few interventions exist to halt or delay the progression of Alzheimer’s disease and related dementias (ADRD), which has increasingly led to a focus on primary prevention.
Although previous research pointed to a link between socioeconomically disadvantaged neighborhoods and a greater risk for cognitive deficits, mild cognitive impairment, dementia, and poor brain health, the timeline for the emergence of that risk is unknown.
To fill in the gaps, investigators studied data on all 1.4 million New Zealand residents, dividing neighborhoods into quintiles based on level of disadvantage (assessed by the New Zealand Index of Deprivation) to see whether dementia diagnoses followed neighborhood socioeconomic gradients.
After adjusting for covariates, they found that overall, those living in disadvantaged areas were slightly more likely to develop dementia across the 20-year study period (adjusted hazard ratio [HR], 1.09; 95% CI, 1.08-1.10).
The more disadvantaged the neighborhood, the higher the dementia risk, with a 43% higher risk for ADRD among those in the highest quintile than among those in the lowest quintile (HR, 1.43; 95% CI, 1.36-1.49).
The effect was larger in men than in women and in younger vs older individuals, with the youngest age group showing 21% greater risk in women and 26% greater risk in men vs the oldest age group.
Dementia Prevention Starts Early
Researchers then turned to the Dunedin Study, a cohort of 938 New Zealanders (50% female) followed from birth to age 45 to track their psychological, social, and physiological health with brain scans, memory tests, and cognitive self-assessments.
The analysis suggested that by age 45, those living in more disadvantaged neighborhoods across adulthood had accumulated a significantly greater number of midlife risk factors for later ADRD.
They also had worse structural brain integrity, with each standard deviation increase in neighborhood disadvantage resulting in a thinner cortex, greater white matter hyperintensities volume, and older brain age.
Those living in poorer areas had lower cognitive test scores, reported more issues with everyday cognitive function, and showed a greater reduction in IQ from childhood to midlife. Analysis of brain scans also revealed mean brain ages 2.98 years older than those living in the least disadvantaged areas (P = .001).
Limitations included the study’s observational design, which could not establish causation, and the fact that the researchers did not have access to individual-level socioeconomic information for the entire population. Additionally, brain-integrity measures in the Dunedin Study were largely cross-sectional.
“If you want to truly prevent dementia, you’ve got to start early because 20 years before anyone will get a diagnosis, we’re seeing dementia’s emergence,” Dr. Reuben said. “And it could be even earlier.”
Funding for the study was provided by the National Institutes for Health; UK Medical Research Council; Health Research Council of New Zealand; Brain Research New Zealand; New Zealand Ministry of Business, Innovation, & Employment; and the Duke University and the University of North Carolina Alzheimer’s Disease Research Center. The authors declared no relevant financial relationships.
A version of this article appeared on Medscape.com.
Living in a disadvantaged neighborhood is associated with accelerated brain aging and a higher risk for early dementia, regardless of income level or education, new research suggested.
“If you want to prevent dementia and you’re not asking someone about their neighborhood, you’re missing information that’s important to know,” lead author Aaron Reuben, PhD, postdoctoral scholar in neuropsychology and environmental health at Duke University, Durham, North Carolina, said in a news release.
The study was published online in Alzheimer’s & Dementia.
Higher Risk in Men
Few interventions exist to halt or delay the progression of Alzheimer’s disease and related dementias (ADRD), which has increasingly led to a focus on primary prevention.
Although previous research pointed to a link between socioeconomically disadvantaged neighborhoods and a greater risk for cognitive deficits, mild cognitive impairment, dementia, and poor brain health, the timeline for the emergence of that risk is unknown.
To fill in the gaps, investigators studied data on all 1.4 million New Zealand residents, dividing neighborhoods into quintiles based on level of disadvantage (assessed by the New Zealand Index of Deprivation) to see whether dementia diagnoses followed neighborhood socioeconomic gradients.
After adjusting for covariates, they found that overall, those living in disadvantaged areas were slightly more likely to develop dementia across the 20-year study period (adjusted hazard ratio [HR], 1.09; 95% CI, 1.08-1.10).
The more disadvantaged the neighborhood, the higher the dementia risk, with a 43% higher risk for ADRD among those in the highest quintile than among those in the lowest quintile (HR, 1.43; 95% CI, 1.36-1.49).
The effect was larger in men than in women and in younger vs older individuals, with the youngest age group showing 21% greater risk in women and 26% greater risk in men vs the oldest age group.
Dementia Prevention Starts Early
Researchers then turned to the Dunedin Study, a cohort of 938 New Zealanders (50% female) followed from birth to age 45 to track their psychological, social, and physiological health with brain scans, memory tests, and cognitive self-assessments.
The analysis suggested that by age 45, those living in more disadvantaged neighborhoods across adulthood had accumulated a significantly greater number of midlife risk factors for later ADRD.
They also had worse structural brain integrity, with each standard deviation increase in neighborhood disadvantage resulting in a thinner cortex, greater white matter hyperintensities volume, and older brain age.
Those living in poorer areas had lower cognitive test scores, reported more issues with everyday cognitive function, and showed a greater reduction in IQ from childhood to midlife. Analysis of brain scans also revealed mean brain ages 2.98 years older than those living in the least disadvantaged areas (P = .001).
Limitations included the study’s observational design, which could not establish causation, and the fact that the researchers did not have access to individual-level socioeconomic information for the entire population. Additionally, brain-integrity measures in the Dunedin Study were largely cross-sectional.
“If you want to truly prevent dementia, you’ve got to start early because 20 years before anyone will get a diagnosis, we’re seeing dementia’s emergence,” Dr. Reuben said. “And it could be even earlier.”
Funding for the study was provided by the National Institutes for Health; UK Medical Research Council; Health Research Council of New Zealand; Brain Research New Zealand; New Zealand Ministry of Business, Innovation, & Employment; and the Duke University and the University of North Carolina Alzheimer’s Disease Research Center. The authors declared no relevant financial relationships.
A version of this article appeared on Medscape.com.
Living in a disadvantaged neighborhood is associated with accelerated brain aging and a higher risk for early dementia, regardless of income level or education, new research suggested.
“If you want to prevent dementia and you’re not asking someone about their neighborhood, you’re missing information that’s important to know,” lead author Aaron Reuben, PhD, postdoctoral scholar in neuropsychology and environmental health at Duke University, Durham, North Carolina, said in a news release.
The study was published online in Alzheimer’s & Dementia.
Higher Risk in Men
Few interventions exist to halt or delay the progression of Alzheimer’s disease and related dementias (ADRD), which has increasingly led to a focus on primary prevention.
Although previous research pointed to a link between socioeconomically disadvantaged neighborhoods and a greater risk for cognitive deficits, mild cognitive impairment, dementia, and poor brain health, the timeline for the emergence of that risk is unknown.
To fill in the gaps, investigators studied data on all 1.4 million New Zealand residents, dividing neighborhoods into quintiles based on level of disadvantage (assessed by the New Zealand Index of Deprivation) to see whether dementia diagnoses followed neighborhood socioeconomic gradients.
After adjusting for covariates, they found that overall, those living in disadvantaged areas were slightly more likely to develop dementia across the 20-year study period (adjusted hazard ratio [HR], 1.09; 95% CI, 1.08-1.10).
The more disadvantaged the neighborhood, the higher the dementia risk, with a 43% higher risk for ADRD among those in the highest quintile than among those in the lowest quintile (HR, 1.43; 95% CI, 1.36-1.49).
The effect was larger in men than in women and in younger vs older individuals, with the youngest age group showing 21% greater risk in women and 26% greater risk in men vs the oldest age group.
Dementia Prevention Starts Early
Researchers then turned to the Dunedin Study, a cohort of 938 New Zealanders (50% female) followed from birth to age 45 to track their psychological, social, and physiological health with brain scans, memory tests, and cognitive self-assessments.
The analysis suggested that by age 45, those living in more disadvantaged neighborhoods across adulthood had accumulated a significantly greater number of midlife risk factors for later ADRD.
They also had worse structural brain integrity, with each standard deviation increase in neighborhood disadvantage resulting in a thinner cortex, greater white matter hyperintensities volume, and older brain age.
Those living in poorer areas had lower cognitive test scores, reported more issues with everyday cognitive function, and showed a greater reduction in IQ from childhood to midlife. Analysis of brain scans also revealed mean brain ages 2.98 years older than those living in the least disadvantaged areas (P = .001).
Limitations included the study’s observational design, which could not establish causation, and the fact that the researchers did not have access to individual-level socioeconomic information for the entire population. Additionally, brain-integrity measures in the Dunedin Study were largely cross-sectional.
“If you want to truly prevent dementia, you’ve got to start early because 20 years before anyone will get a diagnosis, we’re seeing dementia’s emergence,” Dr. Reuben said. “And it could be even earlier.”
Funding for the study was provided by the National Institutes for Health; UK Medical Research Council; Health Research Council of New Zealand; Brain Research New Zealand; New Zealand Ministry of Business, Innovation, & Employment; and the Duke University and the University of North Carolina Alzheimer’s Disease Research Center. The authors declared no relevant financial relationships.
A version of this article appeared on Medscape.com.
FROM ALZHEIMER’S AND DEMENTIA
FDA Issues New Guidance for Early Alzheimer’s Drug Development
The agency’s draft guidance is the first update since 2018 for products aimed at the earliest stages of the disease, which the FDA defines as stages 1, 2, and 3. Such guidance — when it is made final, after public comment closes in mid-May — is considered a template that will guide discussions between the FDA and drug makers and help determine the structure of clinical trials.
It is considered the FDA’s “current thinking on the topic,” and should not be construed as “legally enforceable responsibilities,” the FDA document, which was published March 12, noted.
In a statement to this news agency, the Alzheimer’s Association said it “is fully supportive of the FDA’s revised draft guidance.”
The association is enthusiastic about the agency’s encouragement of “the use of biologically based diagnostic criteria that are grounded in a contemporary understanding of the pathophysiology and evolution” of Alzheimer’s disease, Rebecca M. Edelmayer, PhD, senior director of scientific engagement for the Alzheimer’s Association, said in the statement.
Dr. Edelmayer noted that an Alzheimer’s Association work group is “leading the process of defining and building consensus for biologically based diagnostic and staging criteria for Alzheimer’s disease.
A New POV
The FDA noted that “it is expected that biomarker evidence of disease will establish the reliable diagnosis of subjects in trials of early Alzheimer’s disease.” This is crucial when many individuals in the earliest phases of Alzheimer’s disease may have mild cognitive decline but no functional decline, the agency added.
In 2018, the FDA suggested that biomarker evidence of disease might only play a role in identifying trial participants but should not be a defining element.
In another shift away from 2018 guidance, the FDA gave more credence to surrogate endpoints as measures of a drug’s efficacy for early disease.
“Surrogate endpoints or intermediate clinical endpoints that do not directly measure clinical benefit but that are considered reasonably likely to predict clinical benefit may support an accelerated approval,” the agency noted.
The FDA added that it “has considered a reduction of the brain amyloid beta burden, as assessed by positron emission tomography, to be a surrogate endpoint that is ‘reasonably likely to predict clinical benefit,’ ” noting that this endpoint was used as a basis for accelerated approval for the monoclonal antibodies lecanemab (Leqembi) and aducanumab (Aduhelm).
“The FDA has determined there is substantial evidence that reduction of amyloid beta plaques in the brain is reasonably likely to predict important clinical benefits to patients,” said Dr. Edelmayer, adding the agency’s “determination is correct.”
However, she noted, “’reasonably likely’ is not a guarantee, and long-term, real-world data in representative populations is required to provide more conclusive evidence,” which is why the FDA requires post-approval studies for accelerated approvals.
A Faster Pathway to Approval
The agency noted that clinical outcomes should also be measured in trials of products seeking accelerated approval, “to assess early clinical changes that may potentially provide support for any changes observed on biomarkers.”
Indeed, it’s not always a slam-dunk for drugs that may show positive effects on biomarkers. The FDA is taking a closer look at donanemab for early symptomatic Alzheimer’s disease. Patients were enrolled based on PET-positive amyloid or tau, but efficacy was evaluated based on cognition and functional measures.
Earlier this month the agency postponed an approval decision and instead will convene an advisory panel meeting to assess overall safety and efficacy and the unique trial design, which allowed patients to stop treatment based on amyloid levels.
The FDA emphasized throughout its guidance document that it is trying to find a faster pathway to approval for therapies for early Alzheimer’s disease. If conventional approaches for testing therapeutics were used in early disease it might “take longer to establish a clinically meaningful treatment effect” because of the “minimal or absent cognitive and functional deficits seen in those stages of the disease,” the agency wrote.
The use of surrogate endpoints “may allow for shorter trial durations,” the FDA added.
Dr. Edelmayer applauded the agency’s efforts to shorten the process. “Finding ways to make the trials shorter and easier to conduct, without sacrificing scientific rigor or patient safety, is a very worthwhile thing to do,” she said.
The FDA noted that a key principle in developing guidance for early Alzheimer’s disease therapies is that treatment “must begin before there are overt clinical symptoms.”
“We enthusiastically support this idea,” said Dr. Edelmeyer. “Prevention of Alzheimer’s dementia is possible through changing the course, stopping the progression, and eventually interrupting the causes of the disease, most likely through a combination of lifestyle/behavior choices and pharmaceutical intervention,” she added.
A version of this article appeared on Medscape.com.
The agency’s draft guidance is the first update since 2018 for products aimed at the earliest stages of the disease, which the FDA defines as stages 1, 2, and 3. Such guidance — when it is made final, after public comment closes in mid-May — is considered a template that will guide discussions between the FDA and drug makers and help determine the structure of clinical trials.
It is considered the FDA’s “current thinking on the topic,” and should not be construed as “legally enforceable responsibilities,” the FDA document, which was published March 12, noted.
In a statement to this news agency, the Alzheimer’s Association said it “is fully supportive of the FDA’s revised draft guidance.”
The association is enthusiastic about the agency’s encouragement of “the use of biologically based diagnostic criteria that are grounded in a contemporary understanding of the pathophysiology and evolution” of Alzheimer’s disease, Rebecca M. Edelmayer, PhD, senior director of scientific engagement for the Alzheimer’s Association, said in the statement.
Dr. Edelmayer noted that an Alzheimer’s Association work group is “leading the process of defining and building consensus for biologically based diagnostic and staging criteria for Alzheimer’s disease.
A New POV
The FDA noted that “it is expected that biomarker evidence of disease will establish the reliable diagnosis of subjects in trials of early Alzheimer’s disease.” This is crucial when many individuals in the earliest phases of Alzheimer’s disease may have mild cognitive decline but no functional decline, the agency added.
In 2018, the FDA suggested that biomarker evidence of disease might only play a role in identifying trial participants but should not be a defining element.
In another shift away from 2018 guidance, the FDA gave more credence to surrogate endpoints as measures of a drug’s efficacy for early disease.
“Surrogate endpoints or intermediate clinical endpoints that do not directly measure clinical benefit but that are considered reasonably likely to predict clinical benefit may support an accelerated approval,” the agency noted.
The FDA added that it “has considered a reduction of the brain amyloid beta burden, as assessed by positron emission tomography, to be a surrogate endpoint that is ‘reasonably likely to predict clinical benefit,’ ” noting that this endpoint was used as a basis for accelerated approval for the monoclonal antibodies lecanemab (Leqembi) and aducanumab (Aduhelm).
“The FDA has determined there is substantial evidence that reduction of amyloid beta plaques in the brain is reasonably likely to predict important clinical benefits to patients,” said Dr. Edelmayer, adding the agency’s “determination is correct.”
However, she noted, “’reasonably likely’ is not a guarantee, and long-term, real-world data in representative populations is required to provide more conclusive evidence,” which is why the FDA requires post-approval studies for accelerated approvals.
A Faster Pathway to Approval
The agency noted that clinical outcomes should also be measured in trials of products seeking accelerated approval, “to assess early clinical changes that may potentially provide support for any changes observed on biomarkers.”
Indeed, it’s not always a slam-dunk for drugs that may show positive effects on biomarkers. The FDA is taking a closer look at donanemab for early symptomatic Alzheimer’s disease. Patients were enrolled based on PET-positive amyloid or tau, but efficacy was evaluated based on cognition and functional measures.
Earlier this month the agency postponed an approval decision and instead will convene an advisory panel meeting to assess overall safety and efficacy and the unique trial design, which allowed patients to stop treatment based on amyloid levels.
The FDA emphasized throughout its guidance document that it is trying to find a faster pathway to approval for therapies for early Alzheimer’s disease. If conventional approaches for testing therapeutics were used in early disease it might “take longer to establish a clinically meaningful treatment effect” because of the “minimal or absent cognitive and functional deficits seen in those stages of the disease,” the agency wrote.
The use of surrogate endpoints “may allow for shorter trial durations,” the FDA added.
Dr. Edelmayer applauded the agency’s efforts to shorten the process. “Finding ways to make the trials shorter and easier to conduct, without sacrificing scientific rigor or patient safety, is a very worthwhile thing to do,” she said.
The FDA noted that a key principle in developing guidance for early Alzheimer’s disease therapies is that treatment “must begin before there are overt clinical symptoms.”
“We enthusiastically support this idea,” said Dr. Edelmeyer. “Prevention of Alzheimer’s dementia is possible through changing the course, stopping the progression, and eventually interrupting the causes of the disease, most likely through a combination of lifestyle/behavior choices and pharmaceutical intervention,” she added.
A version of this article appeared on Medscape.com.
The agency’s draft guidance is the first update since 2018 for products aimed at the earliest stages of the disease, which the FDA defines as stages 1, 2, and 3. Such guidance — when it is made final, after public comment closes in mid-May — is considered a template that will guide discussions between the FDA and drug makers and help determine the structure of clinical trials.
It is considered the FDA’s “current thinking on the topic,” and should not be construed as “legally enforceable responsibilities,” the FDA document, which was published March 12, noted.
In a statement to this news agency, the Alzheimer’s Association said it “is fully supportive of the FDA’s revised draft guidance.”
The association is enthusiastic about the agency’s encouragement of “the use of biologically based diagnostic criteria that are grounded in a contemporary understanding of the pathophysiology and evolution” of Alzheimer’s disease, Rebecca M. Edelmayer, PhD, senior director of scientific engagement for the Alzheimer’s Association, said in the statement.
Dr. Edelmayer noted that an Alzheimer’s Association work group is “leading the process of defining and building consensus for biologically based diagnostic and staging criteria for Alzheimer’s disease.
A New POV
The FDA noted that “it is expected that biomarker evidence of disease will establish the reliable diagnosis of subjects in trials of early Alzheimer’s disease.” This is crucial when many individuals in the earliest phases of Alzheimer’s disease may have mild cognitive decline but no functional decline, the agency added.
In 2018, the FDA suggested that biomarker evidence of disease might only play a role in identifying trial participants but should not be a defining element.
In another shift away from 2018 guidance, the FDA gave more credence to surrogate endpoints as measures of a drug’s efficacy for early disease.
“Surrogate endpoints or intermediate clinical endpoints that do not directly measure clinical benefit but that are considered reasonably likely to predict clinical benefit may support an accelerated approval,” the agency noted.
The FDA added that it “has considered a reduction of the brain amyloid beta burden, as assessed by positron emission tomography, to be a surrogate endpoint that is ‘reasonably likely to predict clinical benefit,’ ” noting that this endpoint was used as a basis for accelerated approval for the monoclonal antibodies lecanemab (Leqembi) and aducanumab (Aduhelm).
“The FDA has determined there is substantial evidence that reduction of amyloid beta plaques in the brain is reasonably likely to predict important clinical benefits to patients,” said Dr. Edelmayer, adding the agency’s “determination is correct.”
However, she noted, “’reasonably likely’ is not a guarantee, and long-term, real-world data in representative populations is required to provide more conclusive evidence,” which is why the FDA requires post-approval studies for accelerated approvals.
A Faster Pathway to Approval
The agency noted that clinical outcomes should also be measured in trials of products seeking accelerated approval, “to assess early clinical changes that may potentially provide support for any changes observed on biomarkers.”
Indeed, it’s not always a slam-dunk for drugs that may show positive effects on biomarkers. The FDA is taking a closer look at donanemab for early symptomatic Alzheimer’s disease. Patients were enrolled based on PET-positive amyloid or tau, but efficacy was evaluated based on cognition and functional measures.
Earlier this month the agency postponed an approval decision and instead will convene an advisory panel meeting to assess overall safety and efficacy and the unique trial design, which allowed patients to stop treatment based on amyloid levels.
The FDA emphasized throughout its guidance document that it is trying to find a faster pathway to approval for therapies for early Alzheimer’s disease. If conventional approaches for testing therapeutics were used in early disease it might “take longer to establish a clinically meaningful treatment effect” because of the “minimal or absent cognitive and functional deficits seen in those stages of the disease,” the agency wrote.
The use of surrogate endpoints “may allow for shorter trial durations,” the FDA added.
Dr. Edelmayer applauded the agency’s efforts to shorten the process. “Finding ways to make the trials shorter and easier to conduct, without sacrificing scientific rigor or patient safety, is a very worthwhile thing to do,” she said.
The FDA noted that a key principle in developing guidance for early Alzheimer’s disease therapies is that treatment “must begin before there are overt clinical symptoms.”
“We enthusiastically support this idea,” said Dr. Edelmeyer. “Prevention of Alzheimer’s dementia is possible through changing the course, stopping the progression, and eventually interrupting the causes of the disease, most likely through a combination of lifestyle/behavior choices and pharmaceutical intervention,” she added.
A version of this article appeared on Medscape.com.
Does Abdominal Fat Location Matter for Brain Health?
TOPLINE:
METHODOLOGY:
- Obesity is a well-known risk factor for poorer cognition and dementia, but the distribution of body fat may influence the risk and underlying mechanisms in the fat-brain-cognition pathway.
- The study examined associations of several abdominal fat depots with cognitive functioning and AD-related brain volumes.
- The study sample included 204 men and women from the Israel Registry for Alzheimer’s Prevention (mean age, 59 years; 60% women) who had a high AD risk due to parental family history.
- Abdominal MRI scans assessed fat stored as subcutaneous adipose tissue (SAT) beneath the skin, visceral adipose tissue (VAT) around abdominal organs, and ectopic, a harmful condition in which lipids accumulate in lean tissues such as the liver and pancreas.
- A structural volumetric brain MRI scan was undertaken by 142 participants to assess specific regions implicated in chosen previous research.
TAKEAWAY:
- High body mass index was associated with high pancreatic fat percentage in both men and women (P < .001) and with high SAT percentage in women (P = .01) but not with VAT percentage in either sex.
- After adjustment for cardiovascular risk factors, a higher pancreatic fat percentage was linked to lower global cognition (beta, −0.33; P = .02) and executive function (beta, −0.32; P = .02) in men, and with lower hippocampal volume in women (beta, −0.25; P = .03).
- In men only, a higher SAT percentage was associated with a lower middle frontal gyrus volume (beta, −0.27; P = .03), while a higher VAT percentage was linked to higher middle frontal gyrus (beta, 0.29; P = .03) and superior frontal gyrus volumes (beta, 0.31; P = .02).
- Hepatic fat was not associated with brain volumes or cognition in either men or women.
IN PRACTICE:
“These results suggest that already in midlife, abdominal fat accumulation may have deleterious effects on brain health, especially in men,” the authors wrote.
SOURCE:
This study was led by Sapir G. Shekhtman, Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel, and published online in Obesity (Silver Spring).
LIMITATIONS:
No causal inferences could be drawn from this study due to its cross-sectional nature. It did not represent the population of middle-aged adults as a whole, but rather those at high risk of developing AD. Factors contributing to fat accumulation, such as menopausal status or treatment, inflammation, insulin resistance, daily exercise, and dietary factors, were not included in this study.
DISCLOSURES:
This work was supported by grants from the National Institutes of Health. The authors declared no conflicts of interest.
A version of this article appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Obesity is a well-known risk factor for poorer cognition and dementia, but the distribution of body fat may influence the risk and underlying mechanisms in the fat-brain-cognition pathway.
- The study examined associations of several abdominal fat depots with cognitive functioning and AD-related brain volumes.
- The study sample included 204 men and women from the Israel Registry for Alzheimer’s Prevention (mean age, 59 years; 60% women) who had a high AD risk due to parental family history.
- Abdominal MRI scans assessed fat stored as subcutaneous adipose tissue (SAT) beneath the skin, visceral adipose tissue (VAT) around abdominal organs, and ectopic, a harmful condition in which lipids accumulate in lean tissues such as the liver and pancreas.
- A structural volumetric brain MRI scan was undertaken by 142 participants to assess specific regions implicated in chosen previous research.
TAKEAWAY:
- High body mass index was associated with high pancreatic fat percentage in both men and women (P < .001) and with high SAT percentage in women (P = .01) but not with VAT percentage in either sex.
- After adjustment for cardiovascular risk factors, a higher pancreatic fat percentage was linked to lower global cognition (beta, −0.33; P = .02) and executive function (beta, −0.32; P = .02) in men, and with lower hippocampal volume in women (beta, −0.25; P = .03).
- In men only, a higher SAT percentage was associated with a lower middle frontal gyrus volume (beta, −0.27; P = .03), while a higher VAT percentage was linked to higher middle frontal gyrus (beta, 0.29; P = .03) and superior frontal gyrus volumes (beta, 0.31; P = .02).
- Hepatic fat was not associated with brain volumes or cognition in either men or women.
IN PRACTICE:
“These results suggest that already in midlife, abdominal fat accumulation may have deleterious effects on brain health, especially in men,” the authors wrote.
SOURCE:
This study was led by Sapir G. Shekhtman, Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel, and published online in Obesity (Silver Spring).
LIMITATIONS:
No causal inferences could be drawn from this study due to its cross-sectional nature. It did not represent the population of middle-aged adults as a whole, but rather those at high risk of developing AD. Factors contributing to fat accumulation, such as menopausal status or treatment, inflammation, insulin resistance, daily exercise, and dietary factors, were not included in this study.
DISCLOSURES:
This work was supported by grants from the National Institutes of Health. The authors declared no conflicts of interest.
A version of this article appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Obesity is a well-known risk factor for poorer cognition and dementia, but the distribution of body fat may influence the risk and underlying mechanisms in the fat-brain-cognition pathway.
- The study examined associations of several abdominal fat depots with cognitive functioning and AD-related brain volumes.
- The study sample included 204 men and women from the Israel Registry for Alzheimer’s Prevention (mean age, 59 years; 60% women) who had a high AD risk due to parental family history.
- Abdominal MRI scans assessed fat stored as subcutaneous adipose tissue (SAT) beneath the skin, visceral adipose tissue (VAT) around abdominal organs, and ectopic, a harmful condition in which lipids accumulate in lean tissues such as the liver and pancreas.
- A structural volumetric brain MRI scan was undertaken by 142 participants to assess specific regions implicated in chosen previous research.
TAKEAWAY:
- High body mass index was associated with high pancreatic fat percentage in both men and women (P < .001) and with high SAT percentage in women (P = .01) but not with VAT percentage in either sex.
- After adjustment for cardiovascular risk factors, a higher pancreatic fat percentage was linked to lower global cognition (beta, −0.33; P = .02) and executive function (beta, −0.32; P = .02) in men, and with lower hippocampal volume in women (beta, −0.25; P = .03).
- In men only, a higher SAT percentage was associated with a lower middle frontal gyrus volume (beta, −0.27; P = .03), while a higher VAT percentage was linked to higher middle frontal gyrus (beta, 0.29; P = .03) and superior frontal gyrus volumes (beta, 0.31; P = .02).
- Hepatic fat was not associated with brain volumes or cognition in either men or women.
IN PRACTICE:
“These results suggest that already in midlife, abdominal fat accumulation may have deleterious effects on brain health, especially in men,” the authors wrote.
SOURCE:
This study was led by Sapir G. Shekhtman, Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel, and published online in Obesity (Silver Spring).
LIMITATIONS:
No causal inferences could be drawn from this study due to its cross-sectional nature. It did not represent the population of middle-aged adults as a whole, but rather those at high risk of developing AD. Factors contributing to fat accumulation, such as menopausal status or treatment, inflammation, insulin resistance, daily exercise, and dietary factors, were not included in this study.
DISCLOSURES:
This work was supported by grants from the National Institutes of Health. The authors declared no conflicts of interest.
A version of this article appeared on Medscape.com.
Neurological Disorders Now Top Global Cause of Illness, Disability
, a new comprehensive analysis showed.
In 2021, neurological conditions were responsible for 443 million years of healthy life lost due to illness, disability, and premature death — a measurement known as disability-adjusted life years (DALY) — making them the top contributor to the global disease burden, ahead of cardiovascular diseases.
Some 3.4 billion people — 43% of the entire global population — had a neurological illness in 2021, the report noted.
“As the world’s leading cause of overall disease burden, and with case numbers rising 59% globally since 1990, nervous system conditions must be addressed through effective, culturally acceptable, and affordable prevention, treatment, rehabilitation, and long-term care strategies,” lead author Jaimie Steinmetz, PhD, from the Institute of Health Metrics and Evaluation (IHME), University of Washington, Seattle, said in a news release.
The findings, from the Global Burden of Disease, Injuries, and Risk Factors Study (GBD) 2021, “have important health service and policy implications and serve as evidence that global neurological heath loss has been under-recognized and is increasing and unevenly distributed geographically and socioeconomically,” the authors noted.
The study was published online in The Lancet: Neurology.
The Top 10
The top 10 contributors to neurological health loss in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer’s disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications from preterm birth, autistic spectrum disorders, and nervous system cancers.
Neurological consequences of COVID-19 ranked 20th out of 37 unique conditions assessed.
In 2021, there were more than 23 million global cases of COVID-19 with long-term cognitive symptoms or Guillain-Barré syndrome, accounting for 57% of all infectious neurological disease cases and contributing to 2.48 million years of healthy life lost, the study found.
The most prevalent neurological disorders were tension-type headache (about 2 billion cases) and migraine (about 1.1 billion cases), while diabetic neuropathy is the fastest-growing of all neurological conditions.
“The number of people with diabetic neuropathy has more than tripled globally since 1990, rising to 206 million in 2021. This is in line with the increase in the global prevalence of diabetes,” co-senior author Liane Ong, PhD, from IHME, said in the release.
The data showed striking differences in the burden of neurological conditions between world regions and national income levels, with over 80% of neurological deaths and health loss occurring in low- and middle-income countries.
Regions with the highest burden of neurological conditions were central and western sub-Saharan Africa, while high-income Asia Pacific and Australasia had the lowest burden.
“Nervous system health loss disproportionately impacts many of the poorest countries partly due to the higher prevalence of conditions affecting neonates and children under 5, especially birth-related complications and infections,” co-senior author Tarun Dua, MD, with the World Health Organization (WHO) brain health unit, noted in the news release.
“Improved infant survival has led to an increase in long-term disability, while limited access to treatment and rehabilitation services is contributing to the much higher proportion of deaths in these countries,” Dr. Dua said.
Prioritize Prevention
The analysis also provides estimates of the proportion of neurological conditions that are potentially preventable by eliminating known risk factors for stroke, dementia, multiple sclerosis, Parkinson’s disease, encephalitis, meningitis, and intellectual disability.
It shows that modifying 18 risk factors over a person’s lifetime — most importantly high systolic blood pressure — could prevent 84% of global DALYs from stroke. Controlling lead exposure could lower intellectual disability cases by 63% and reducing high fasting plasma glucose to normal levels could cut dementia by roughly 15%.
“Because many neurological conditions lack cures, and access to medical care is often limited, understanding modifiable risk factors and the potentially avoidable neurological condition burden is essential to help curb this global health crisis,” co-lead author Katrin Seeher, PhD, mental health specialist with WHO’s brain health unit, said in the release.
It’s important to note that nervous system conditions include infectious and vector-borne diseases and injuries as well as noncommunicable diseases and injuries, Dr. Steinmetz said, “demanding different strategies for prevention and treatment throughout life.”
“We hope that our findings can help policymakers more comprehensively understand the impact of neurological conditions on both adults and children to inform more targeted interventions in individual countries, as well as guide ongoing awareness and advocacy efforts around the world,” Dr. Steinmetz added.
In an accompanying editorial, Wolfgang Grisold, MD, president of the World Federation of Neurology, London, noted that the study builds on previous findings and expands the number of neurological conditions studied from 15 to 37.
“This important new GBD report highlights that the burden of neurological conditions is greater than previously thought,” wrote Dr. Grisold, who was not a part of the study. “In the next iteration, more attention should be given to neuromuscular diseases, the effects of cancer in the nervous system, and neuropathic pain. Comparing the disability caused by conditions with episodic occurrence versus those that cause permanent and progressive disease will remain challenging because the effects on the individuals vary substantially.”
The study was funded by the Bill and Melinda Gates Foundation. Full disclosures are included in the original article.
A version of this article appeared on Medscape.com.
, a new comprehensive analysis showed.
In 2021, neurological conditions were responsible for 443 million years of healthy life lost due to illness, disability, and premature death — a measurement known as disability-adjusted life years (DALY) — making them the top contributor to the global disease burden, ahead of cardiovascular diseases.
Some 3.4 billion people — 43% of the entire global population — had a neurological illness in 2021, the report noted.
“As the world’s leading cause of overall disease burden, and with case numbers rising 59% globally since 1990, nervous system conditions must be addressed through effective, culturally acceptable, and affordable prevention, treatment, rehabilitation, and long-term care strategies,” lead author Jaimie Steinmetz, PhD, from the Institute of Health Metrics and Evaluation (IHME), University of Washington, Seattle, said in a news release.
The findings, from the Global Burden of Disease, Injuries, and Risk Factors Study (GBD) 2021, “have important health service and policy implications and serve as evidence that global neurological heath loss has been under-recognized and is increasing and unevenly distributed geographically and socioeconomically,” the authors noted.
The study was published online in The Lancet: Neurology.
The Top 10
The top 10 contributors to neurological health loss in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer’s disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications from preterm birth, autistic spectrum disorders, and nervous system cancers.
Neurological consequences of COVID-19 ranked 20th out of 37 unique conditions assessed.
In 2021, there were more than 23 million global cases of COVID-19 with long-term cognitive symptoms or Guillain-Barré syndrome, accounting for 57% of all infectious neurological disease cases and contributing to 2.48 million years of healthy life lost, the study found.
The most prevalent neurological disorders were tension-type headache (about 2 billion cases) and migraine (about 1.1 billion cases), while diabetic neuropathy is the fastest-growing of all neurological conditions.
“The number of people with diabetic neuropathy has more than tripled globally since 1990, rising to 206 million in 2021. This is in line with the increase in the global prevalence of diabetes,” co-senior author Liane Ong, PhD, from IHME, said in the release.
The data showed striking differences in the burden of neurological conditions between world regions and national income levels, with over 80% of neurological deaths and health loss occurring in low- and middle-income countries.
Regions with the highest burden of neurological conditions were central and western sub-Saharan Africa, while high-income Asia Pacific and Australasia had the lowest burden.
“Nervous system health loss disproportionately impacts many of the poorest countries partly due to the higher prevalence of conditions affecting neonates and children under 5, especially birth-related complications and infections,” co-senior author Tarun Dua, MD, with the World Health Organization (WHO) brain health unit, noted in the news release.
“Improved infant survival has led to an increase in long-term disability, while limited access to treatment and rehabilitation services is contributing to the much higher proportion of deaths in these countries,” Dr. Dua said.
Prioritize Prevention
The analysis also provides estimates of the proportion of neurological conditions that are potentially preventable by eliminating known risk factors for stroke, dementia, multiple sclerosis, Parkinson’s disease, encephalitis, meningitis, and intellectual disability.
It shows that modifying 18 risk factors over a person’s lifetime — most importantly high systolic blood pressure — could prevent 84% of global DALYs from stroke. Controlling lead exposure could lower intellectual disability cases by 63% and reducing high fasting plasma glucose to normal levels could cut dementia by roughly 15%.
“Because many neurological conditions lack cures, and access to medical care is often limited, understanding modifiable risk factors and the potentially avoidable neurological condition burden is essential to help curb this global health crisis,” co-lead author Katrin Seeher, PhD, mental health specialist with WHO’s brain health unit, said in the release.
It’s important to note that nervous system conditions include infectious and vector-borne diseases and injuries as well as noncommunicable diseases and injuries, Dr. Steinmetz said, “demanding different strategies for prevention and treatment throughout life.”
“We hope that our findings can help policymakers more comprehensively understand the impact of neurological conditions on both adults and children to inform more targeted interventions in individual countries, as well as guide ongoing awareness and advocacy efforts around the world,” Dr. Steinmetz added.
In an accompanying editorial, Wolfgang Grisold, MD, president of the World Federation of Neurology, London, noted that the study builds on previous findings and expands the number of neurological conditions studied from 15 to 37.
“This important new GBD report highlights that the burden of neurological conditions is greater than previously thought,” wrote Dr. Grisold, who was not a part of the study. “In the next iteration, more attention should be given to neuromuscular diseases, the effects of cancer in the nervous system, and neuropathic pain. Comparing the disability caused by conditions with episodic occurrence versus those that cause permanent and progressive disease will remain challenging because the effects on the individuals vary substantially.”
The study was funded by the Bill and Melinda Gates Foundation. Full disclosures are included in the original article.
A version of this article appeared on Medscape.com.
, a new comprehensive analysis showed.
In 2021, neurological conditions were responsible for 443 million years of healthy life lost due to illness, disability, and premature death — a measurement known as disability-adjusted life years (DALY) — making them the top contributor to the global disease burden, ahead of cardiovascular diseases.
Some 3.4 billion people — 43% of the entire global population — had a neurological illness in 2021, the report noted.
“As the world’s leading cause of overall disease burden, and with case numbers rising 59% globally since 1990, nervous system conditions must be addressed through effective, culturally acceptable, and affordable prevention, treatment, rehabilitation, and long-term care strategies,” lead author Jaimie Steinmetz, PhD, from the Institute of Health Metrics and Evaluation (IHME), University of Washington, Seattle, said in a news release.
The findings, from the Global Burden of Disease, Injuries, and Risk Factors Study (GBD) 2021, “have important health service and policy implications and serve as evidence that global neurological heath loss has been under-recognized and is increasing and unevenly distributed geographically and socioeconomically,” the authors noted.
The study was published online in The Lancet: Neurology.
The Top 10
The top 10 contributors to neurological health loss in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer’s disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications from preterm birth, autistic spectrum disorders, and nervous system cancers.
Neurological consequences of COVID-19 ranked 20th out of 37 unique conditions assessed.
In 2021, there were more than 23 million global cases of COVID-19 with long-term cognitive symptoms or Guillain-Barré syndrome, accounting for 57% of all infectious neurological disease cases and contributing to 2.48 million years of healthy life lost, the study found.
The most prevalent neurological disorders were tension-type headache (about 2 billion cases) and migraine (about 1.1 billion cases), while diabetic neuropathy is the fastest-growing of all neurological conditions.
“The number of people with diabetic neuropathy has more than tripled globally since 1990, rising to 206 million in 2021. This is in line with the increase in the global prevalence of diabetes,” co-senior author Liane Ong, PhD, from IHME, said in the release.
The data showed striking differences in the burden of neurological conditions between world regions and national income levels, with over 80% of neurological deaths and health loss occurring in low- and middle-income countries.
Regions with the highest burden of neurological conditions were central and western sub-Saharan Africa, while high-income Asia Pacific and Australasia had the lowest burden.
“Nervous system health loss disproportionately impacts many of the poorest countries partly due to the higher prevalence of conditions affecting neonates and children under 5, especially birth-related complications and infections,” co-senior author Tarun Dua, MD, with the World Health Organization (WHO) brain health unit, noted in the news release.
“Improved infant survival has led to an increase in long-term disability, while limited access to treatment and rehabilitation services is contributing to the much higher proportion of deaths in these countries,” Dr. Dua said.
Prioritize Prevention
The analysis also provides estimates of the proportion of neurological conditions that are potentially preventable by eliminating known risk factors for stroke, dementia, multiple sclerosis, Parkinson’s disease, encephalitis, meningitis, and intellectual disability.
It shows that modifying 18 risk factors over a person’s lifetime — most importantly high systolic blood pressure — could prevent 84% of global DALYs from stroke. Controlling lead exposure could lower intellectual disability cases by 63% and reducing high fasting plasma glucose to normal levels could cut dementia by roughly 15%.
“Because many neurological conditions lack cures, and access to medical care is often limited, understanding modifiable risk factors and the potentially avoidable neurological condition burden is essential to help curb this global health crisis,” co-lead author Katrin Seeher, PhD, mental health specialist with WHO’s brain health unit, said in the release.
It’s important to note that nervous system conditions include infectious and vector-borne diseases and injuries as well as noncommunicable diseases and injuries, Dr. Steinmetz said, “demanding different strategies for prevention and treatment throughout life.”
“We hope that our findings can help policymakers more comprehensively understand the impact of neurological conditions on both adults and children to inform more targeted interventions in individual countries, as well as guide ongoing awareness and advocacy efforts around the world,” Dr. Steinmetz added.
In an accompanying editorial, Wolfgang Grisold, MD, president of the World Federation of Neurology, London, noted that the study builds on previous findings and expands the number of neurological conditions studied from 15 to 37.
“This important new GBD report highlights that the burden of neurological conditions is greater than previously thought,” wrote Dr. Grisold, who was not a part of the study. “In the next iteration, more attention should be given to neuromuscular diseases, the effects of cancer in the nervous system, and neuropathic pain. Comparing the disability caused by conditions with episodic occurrence versus those that cause permanent and progressive disease will remain challenging because the effects on the individuals vary substantially.”
The study was funded by the Bill and Melinda Gates Foundation. Full disclosures are included in the original article.
A version of this article appeared on Medscape.com.
FROM THE LANCET NEUROLOGY
Essential Tremor Tied to a Threefold Increased Risk for Dementia
, new research showed.
In a prospective, longitudinal study, incidence of dementia was nearly 20% among older adults with ET. However, the rates were lower than those in adults with Parkinson’s disease.
The study is “the most complete exposition of the longitudinal trajectory of cognitive impairment in an ET cohort,” said the authors, led by Elan D. Louis, MD, MSc, from University of Texas Southwestern Medical Center in Dallas, Texas.
The findings were released ahead of the study’s scheduled presentation at the annual meeting of the American Academy of Neurology.
Mild Cognitive Impairment Prevalence Nearly Double
For the study, 222 adults with ET with an average age of 79 years at baseline underwent detailed cognitive assessments and were followed for an average of 5 years.
At baseline, 168 people had normal cognitive skills, 35 had mild cognitive impairment (MCI), and 19 had dementia. During the follow-up, 59 individuals developed MCI and 41 developed dementia.
During the follow-up, the cumulative prevalence of dementia was 18.5%, and the average annual conversion rate of MCI to dementia was 12.2% — nearly threefold higher than rates in the general population and roughly one-half the magnitude of those reported for adults with Parkinson’s disease.
The cumulative prevalence of MCI (26.6%) was nearly double that of the general population but less than that in patients with Parkinson’s disease.
“Our data indicate that the prevalence of and conversion rates to dementia in ET fall between those associated with the natural course of aging and the more pronounced rates observed in individuals with Parkinson’s disease,” the researchers wrote in their conference abstract.
Far From Trivial
Reached for comment, Shaheen Lakhan, MD, a neurologist and researcher based in Miami, Florida, said, “The days of viewing ET as just a ‘nuisance tremor’ are over. This study shatters the notion that essential tremor is a trivial condition.”
“Moving forward, the research agenda must further elucidate the link between ET and dementia and develop neuroprotective strategies. But this study represents a seismic shift in how we understand essential tremor,” Dr. Lakhan said.
“The benign label no longer applies given the cognitive risks ET patients face. Our clinical practice and communication with patients must adapt accordingly,” he added.
The study was supported by the National Institutes of Health. Drs. Louis and Lakhan had no relevant disclosures.
A version of this article appeared on Medscape.com.
, new research showed.
In a prospective, longitudinal study, incidence of dementia was nearly 20% among older adults with ET. However, the rates were lower than those in adults with Parkinson’s disease.
The study is “the most complete exposition of the longitudinal trajectory of cognitive impairment in an ET cohort,” said the authors, led by Elan D. Louis, MD, MSc, from University of Texas Southwestern Medical Center in Dallas, Texas.
The findings were released ahead of the study’s scheduled presentation at the annual meeting of the American Academy of Neurology.
Mild Cognitive Impairment Prevalence Nearly Double
For the study, 222 adults with ET with an average age of 79 years at baseline underwent detailed cognitive assessments and were followed for an average of 5 years.
At baseline, 168 people had normal cognitive skills, 35 had mild cognitive impairment (MCI), and 19 had dementia. During the follow-up, 59 individuals developed MCI and 41 developed dementia.
During the follow-up, the cumulative prevalence of dementia was 18.5%, and the average annual conversion rate of MCI to dementia was 12.2% — nearly threefold higher than rates in the general population and roughly one-half the magnitude of those reported for adults with Parkinson’s disease.
The cumulative prevalence of MCI (26.6%) was nearly double that of the general population but less than that in patients with Parkinson’s disease.
“Our data indicate that the prevalence of and conversion rates to dementia in ET fall between those associated with the natural course of aging and the more pronounced rates observed in individuals with Parkinson’s disease,” the researchers wrote in their conference abstract.
Far From Trivial
Reached for comment, Shaheen Lakhan, MD, a neurologist and researcher based in Miami, Florida, said, “The days of viewing ET as just a ‘nuisance tremor’ are over. This study shatters the notion that essential tremor is a trivial condition.”
“Moving forward, the research agenda must further elucidate the link between ET and dementia and develop neuroprotective strategies. But this study represents a seismic shift in how we understand essential tremor,” Dr. Lakhan said.
“The benign label no longer applies given the cognitive risks ET patients face. Our clinical practice and communication with patients must adapt accordingly,” he added.
The study was supported by the National Institutes of Health. Drs. Louis and Lakhan had no relevant disclosures.
A version of this article appeared on Medscape.com.
, new research showed.
In a prospective, longitudinal study, incidence of dementia was nearly 20% among older adults with ET. However, the rates were lower than those in adults with Parkinson’s disease.
The study is “the most complete exposition of the longitudinal trajectory of cognitive impairment in an ET cohort,” said the authors, led by Elan D. Louis, MD, MSc, from University of Texas Southwestern Medical Center in Dallas, Texas.
The findings were released ahead of the study’s scheduled presentation at the annual meeting of the American Academy of Neurology.
Mild Cognitive Impairment Prevalence Nearly Double
For the study, 222 adults with ET with an average age of 79 years at baseline underwent detailed cognitive assessments and were followed for an average of 5 years.
At baseline, 168 people had normal cognitive skills, 35 had mild cognitive impairment (MCI), and 19 had dementia. During the follow-up, 59 individuals developed MCI and 41 developed dementia.
During the follow-up, the cumulative prevalence of dementia was 18.5%, and the average annual conversion rate of MCI to dementia was 12.2% — nearly threefold higher than rates in the general population and roughly one-half the magnitude of those reported for adults with Parkinson’s disease.
The cumulative prevalence of MCI (26.6%) was nearly double that of the general population but less than that in patients with Parkinson’s disease.
“Our data indicate that the prevalence of and conversion rates to dementia in ET fall between those associated with the natural course of aging and the more pronounced rates observed in individuals with Parkinson’s disease,” the researchers wrote in their conference abstract.
Far From Trivial
Reached for comment, Shaheen Lakhan, MD, a neurologist and researcher based in Miami, Florida, said, “The days of viewing ET as just a ‘nuisance tremor’ are over. This study shatters the notion that essential tremor is a trivial condition.”
“Moving forward, the research agenda must further elucidate the link between ET and dementia and develop neuroprotective strategies. But this study represents a seismic shift in how we understand essential tremor,” Dr. Lakhan said.
“The benign label no longer applies given the cognitive risks ET patients face. Our clinical practice and communication with patients must adapt accordingly,” he added.
The study was supported by the National Institutes of Health. Drs. Louis and Lakhan had no relevant disclosures.
A version of this article appeared on Medscape.com.
FROM AAN 2024