Alzheimer's & Cognition

Eastern and southeastern areas of the United States have the highest rates of Alzheimer’s disease (AD), new research shows.

Investigators at Rush University in Chicago found AD prevalence was highest in Maryland, New York, Mississippi, and Florida. At the county level, Miami-Dade in Florida, Baltimore city, and Bronx County in New York were among the U.S. counties with the highest prevalence of the disease.

Such geographical variations may be caused by the unique make-up of regional populations, study investigator Kumar Rajan, PhD, professor of medicine and director of Rush Institute for Healthy Aging, Rush University Medical Center, Chicago, said in an interview.

Dr. Rajan presented the research at the Alzheimer’s Association International Conference.
 

High-impact research

An estimated 6.7 million Americans are living with AD, a figure that’s expected to double by 2050. Estimating the prevalence of Alzheimer’s across states’ counties can provide a better understanding of region-specific disease burden and have policy implications for resource allocation, Dr. Rajan noted.

To determine the state- and county-specific prevalence of AD, the researchers applied AD data from the Chicago Health and Aging Project, a population-based study that’s about 60% African American, to county- and state-level data from the National Center for Health Statistics.

“We used estimates in our study in Chicago, which began in the 1990s and has approximately 10,800 people, and projected those estimates to county-level populations to see what the variations look like,” said Dr. Rajan.

Of 3,142 counties in 50 states, the East and Southeastern regions of the United States had the highest AD prevalence. For states, the highest rates were in Maryland (12.9%), New York (12.7%), Mississippi (12.5%), and Florida (12.5%).

California and Illinois were also among the top 10 states with the highest prevalence of Alzheimer’s.

California had the highest number of residents, with 719,000 (95% confidence interval, 665,000-774,400), followed by Florida with 579,000 (95% CI, 539,900 to 620,000), and Texas with 459,000 (95% CI, 422,700 to 496,000).

The three counties with the highest prevalence, all with 16.6%, were Miami-Dade County, Baltimore city, and Bronx County.

One county in the top 10 for AD prevalence was El Paso, Tex., which Dr. Rajan found “a bit surprising,” as Texas was not among the top four states with the highest prevalence.

In addition to older age, what’s likely driving elevated AD prevalence in these areas is the substantially larger proportion of minority populations who are at higher risk for AD, possibly due to health disparities, said Dr. Rajan.

Determining local-level estimates of AD should have “a very high impact” on public health programs aimed at AD prevention, detection, and treatment, he said. In addition, as more AD drugs are approved, there will likely be county-level and even state-level implications for Medicare coverage.

In addition, these new findings could help physicians treating or caring for minority populations “understand the landscape of what the disease looks like,” said Dr. Rajan.

A limitation of the study was that it was based on data from a single study, he noted.

The next step is to expand this research. Dr. Rajan and others are establishing the Regional and Ethnic Variations in Alzheimer’s and Cognitive Health Consortium, with the goal of gaining a better understanding of AD prevalence across six U.S. regions.
 

Optimal resource distribution

In a comment, Percy Griffin, PhD, director of scientific engagement, Alzheimer’s Association, said the research provides useful information about AD prevalence at the local level.

“We need to understand how specific demographics and characteristics can help explain some of the high prevalence in certain areas.”

Compared with White Americans, Dr. Griffin noted that Black Americans are twice as likely to have AD, and older Hispanic Americans are 1.5 times as likely.

This new data will help pinpoint areas of high risk and high need so that funding, staffing, and other resources for those with AD and other dementias can be optimally distributed, he said.

“It gives us that kind of geographic specificity in terms of the prevalence so we can dig deeper and better allocate resources on a county level,” he added.

The Alzheimer’s Association “is fully committed to working with local agencies and being in the communities to assist them in their efforts to intervene in this disease.”

The study also highlights the need for more research to determine what factors other than age and race – such as potential environmental factors – might affect regional AD prevalence, he said.

The study received funding from the National Institutes of Health. Dr. Rajan and Dr. Griffin reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Eastern and southeastern areas of the United States have the highest rates of Alzheimer’s disease (AD), new research shows.

Investigators at Rush University in Chicago found AD prevalence was highest in Maryland, New York, Mississippi, and Florida. At the county level, Miami-Dade in Florida, Baltimore city, and Bronx County in New York were among the U.S. counties with the highest prevalence of the disease.

Such geographical variations may be caused by the unique make-up of regional populations, study investigator Kumar Rajan, PhD, professor of medicine and director of Rush Institute for Healthy Aging, Rush University Medical Center, Chicago, said in an interview.

Dr. Rajan presented the research at the Alzheimer’s Association International Conference.
 

High-impact research

An estimated 6.7 million Americans are living with AD, a figure that’s expected to double by 2050. Estimating the prevalence of Alzheimer’s across states’ counties can provide a better understanding of region-specific disease burden and have policy implications for resource allocation, Dr. Rajan noted.

To determine the state- and county-specific prevalence of AD, the researchers applied AD data from the Chicago Health and Aging Project, a population-based study that’s about 60% African American, to county- and state-level data from the National Center for Health Statistics.

“We used estimates in our study in Chicago, which began in the 1990s and has approximately 10,800 people, and projected those estimates to county-level populations to see what the variations look like,” said Dr. Rajan.

Of 3,142 counties in 50 states, the East and Southeastern regions of the United States had the highest AD prevalence. For states, the highest rates were in Maryland (12.9%), New York (12.7%), Mississippi (12.5%), and Florida (12.5%).

California and Illinois were also among the top 10 states with the highest prevalence of Alzheimer’s.

California had the highest number of residents, with 719,000 (95% confidence interval, 665,000-774,400), followed by Florida with 579,000 (95% CI, 539,900 to 620,000), and Texas with 459,000 (95% CI, 422,700 to 496,000).

The three counties with the highest prevalence, all with 16.6%, were Miami-Dade County, Baltimore city, and Bronx County.

One county in the top 10 for AD prevalence was El Paso, Tex., which Dr. Rajan found “a bit surprising,” as Texas was not among the top four states with the highest prevalence.

In addition to older age, what’s likely driving elevated AD prevalence in these areas is the substantially larger proportion of minority populations who are at higher risk for AD, possibly due to health disparities, said Dr. Rajan.

Determining local-level estimates of AD should have “a very high impact” on public health programs aimed at AD prevention, detection, and treatment, he said. In addition, as more AD drugs are approved, there will likely be county-level and even state-level implications for Medicare coverage.

In addition, these new findings could help physicians treating or caring for minority populations “understand the landscape of what the disease looks like,” said Dr. Rajan.

A limitation of the study was that it was based on data from a single study, he noted.

The next step is to expand this research. Dr. Rajan and others are establishing the Regional and Ethnic Variations in Alzheimer’s and Cognitive Health Consortium, with the goal of gaining a better understanding of AD prevalence across six U.S. regions.
 

Optimal resource distribution

In a comment, Percy Griffin, PhD, director of scientific engagement, Alzheimer’s Association, said the research provides useful information about AD prevalence at the local level.

“We need to understand how specific demographics and characteristics can help explain some of the high prevalence in certain areas.”

Compared with White Americans, Dr. Griffin noted that Black Americans are twice as likely to have AD, and older Hispanic Americans are 1.5 times as likely.

This new data will help pinpoint areas of high risk and high need so that funding, staffing, and other resources for those with AD and other dementias can be optimally distributed, he said.

“It gives us that kind of geographic specificity in terms of the prevalence so we can dig deeper and better allocate resources on a county level,” he added.

The Alzheimer’s Association “is fully committed to working with local agencies and being in the communities to assist them in their efforts to intervene in this disease.”

The study also highlights the need for more research to determine what factors other than age and race – such as potential environmental factors – might affect regional AD prevalence, he said.

The study received funding from the National Institutes of Health. Dr. Rajan and Dr. Griffin reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Eastern and southeastern areas of the United States have the highest rates of Alzheimer’s disease (AD), new research shows.

Investigators at Rush University in Chicago found AD prevalence was highest in Maryland, New York, Mississippi, and Florida. At the county level, Miami-Dade in Florida, Baltimore city, and Bronx County in New York were among the U.S. counties with the highest prevalence of the disease.

Such geographical variations may be caused by the unique make-up of regional populations, study investigator Kumar Rajan, PhD, professor of medicine and director of Rush Institute for Healthy Aging, Rush University Medical Center, Chicago, said in an interview.

Dr. Rajan presented the research at the Alzheimer’s Association International Conference.
 

High-impact research

An estimated 6.7 million Americans are living with AD, a figure that’s expected to double by 2050. Estimating the prevalence of Alzheimer’s across states’ counties can provide a better understanding of region-specific disease burden and have policy implications for resource allocation, Dr. Rajan noted.

To determine the state- and county-specific prevalence of AD, the researchers applied AD data from the Chicago Health and Aging Project, a population-based study that’s about 60% African American, to county- and state-level data from the National Center for Health Statistics.

“We used estimates in our study in Chicago, which began in the 1990s and has approximately 10,800 people, and projected those estimates to county-level populations to see what the variations look like,” said Dr. Rajan.

Of 3,142 counties in 50 states, the East and Southeastern regions of the United States had the highest AD prevalence. For states, the highest rates were in Maryland (12.9%), New York (12.7%), Mississippi (12.5%), and Florida (12.5%).

California and Illinois were also among the top 10 states with the highest prevalence of Alzheimer’s.

California had the highest number of residents, with 719,000 (95% confidence interval, 665,000-774,400), followed by Florida with 579,000 (95% CI, 539,900 to 620,000), and Texas with 459,000 (95% CI, 422,700 to 496,000).

The three counties with the highest prevalence, all with 16.6%, were Miami-Dade County, Baltimore city, and Bronx County.

One county in the top 10 for AD prevalence was El Paso, Tex., which Dr. Rajan found “a bit surprising,” as Texas was not among the top four states with the highest prevalence.

In addition to older age, what’s likely driving elevated AD prevalence in these areas is the substantially larger proportion of minority populations who are at higher risk for AD, possibly due to health disparities, said Dr. Rajan.

Determining local-level estimates of AD should have “a very high impact” on public health programs aimed at AD prevention, detection, and treatment, he said. In addition, as more AD drugs are approved, there will likely be county-level and even state-level implications for Medicare coverage.

In addition, these new findings could help physicians treating or caring for minority populations “understand the landscape of what the disease looks like,” said Dr. Rajan.

A limitation of the study was that it was based on data from a single study, he noted.

The next step is to expand this research. Dr. Rajan and others are establishing the Regional and Ethnic Variations in Alzheimer’s and Cognitive Health Consortium, with the goal of gaining a better understanding of AD prevalence across six U.S. regions.
 

Optimal resource distribution

In a comment, Percy Griffin, PhD, director of scientific engagement, Alzheimer’s Association, said the research provides useful information about AD prevalence at the local level.

“We need to understand how specific demographics and characteristics can help explain some of the high prevalence in certain areas.”

Compared with White Americans, Dr. Griffin noted that Black Americans are twice as likely to have AD, and older Hispanic Americans are 1.5 times as likely.

This new data will help pinpoint areas of high risk and high need so that funding, staffing, and other resources for those with AD and other dementias can be optimally distributed, he said.

“It gives us that kind of geographic specificity in terms of the prevalence so we can dig deeper and better allocate resources on a county level,” he added.

The Alzheimer’s Association “is fully committed to working with local agencies and being in the communities to assist them in their efforts to intervene in this disease.”

The study also highlights the need for more research to determine what factors other than age and race – such as potential environmental factors – might affect regional AD prevalence, he said.

The study received funding from the National Institutes of Health. Dr. Rajan and Dr. Griffin reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The history and findings in this case are suggestive of late-onset familial AD (onset after age 65 years).

AD is a common neurodegenerative disease associated with progressive impairment of behavioral and cognitive functions, including memory, comprehension, language, attention, reasoning, and judgment. In 2020, 5.8 million Americans were living with AD. By 2050, this number is projected to increase to 13.9 million people, or almost 3.3% of the US population. Globally, 152 million people are projected to have AD and other dementias by 2050. The worldwide increase in incidence and prevalence of AD is at least partially explained by an aging population and increased life expectancy. 

The cause of AD remains unclear, but there is substantial evidence that AD is a highly heritable disorder. Familial AD is characterized by having more than one member in more than one generation with AD. The autosomal-dominant form of AD is linked to mutations in three genes: AAP on chromosome 21, PSEN1 on chromosome 14, and PSEN2 on chromosome 1. APP mutations may cause increased generation and aggregation of beta-amyloid peptide, whereas PSEN1 and PSEN2 mutations result in aggregation of beta-amyloid by interfering with the processing of gamma-secretase.

APOE is another genetic marker that increases the risk for AD. Isoform e4 of the APOE gene (located on chromosome 19) has been associated with more sporadic and familial forms of AD that present after age 65 years. Approximately 50% of individuals carrying one APOEe4 develop AD, and 90% of individuals who have two alleles develop AD. Variants in the gene for the sortilin receptor, SORT1, have also been found in familial and sporadic forms of AD.

The cognitive and behavioral impairment associated with AD significantly affects a patient's social and occupational functioning. Insidiously progressive memory loss is a characteristic symptoms seen in patients presenting with AD. As the disease advances over the course of several years, other areas of cognition are impaired. Patients may develop language disorders (eg, anomic aphasia or anomia) and impairment in visuospatial skills and executive functions. A slow progression of behavioral changes may also occur in individuals with AD.

Clinical criteria for the diagnosis of AD (eg, insidious onset of cognitive impairment, clear history of worsening symptoms) have been developed and are often used to diagnose patients. In addition, biomarker evidence may help to increase the diagnostic certainty. Several cerebrospinal fluid and blood biomarkers have shown excellent diagnostic ability by identifying tau pathology and cerebral amyloid-beta for AD.

Neuroimaging is becoming increasingly important for identifying the underlying causes of cognitive impairment. Currently, MRI is considered the preferred neuroimaging modality for AD because it allows for accurate measurement of the three-dimensional volume of brain structures, particularly the size of the hippocampus and related regions. CT can be used when MRI is not available or is contraindicated, such as in a patient with a pacemaker. PET is another noninvasive method for depicting tau pathology deposition and distribution in patients with cognitive impairment. In 2020, US Food and Drug Administration approved the first tau PET tracer, ¹⁸F-flortaucipir, which marked a significant achievement to improve AD diagnosis. 

At present, the only therapies available for AD are symptomatic therapies. Cholinesterase inhibitors and a partial N-methyl-D-aspartate antagonist are the standard medical treatments for AD. Antiamyloid therapies are also available for patients with mild cognitive impairment or mild dementia. These include aducanumab, a first-in-class amyloid-beta–directed antibody that was approved in 2021, and lecanemab, another amyloid-beta–directed antibody that was approved in 2023. Both aducanumab and lecanemab are recommended for the treatment of patients with mild cognitive impairment or mild dementia stage of disease, the population in which the safety and efficacy of these newer agents were demonstrated in clinical trials. 

Secondary symptoms of AD, such as depression, agitation, aggression, hallucinations, delusions, and/or sleep disorders, can be treated with psychotropic agents. Behavioral interventions including patient-centered approaches and caregiver training can also be helpful for managing the cognitive and behavioral manifestations of AD, often in combination with pharmacologic interventions (eg, anxiolytics for anxiety and agitation, neuroleptics for delusions or hallucinations, and antidepressants or mood stabilizers for mood disorders). Regular physical activity and exercise may also play a role in delaying AD progression and possibly conferring a protective effect on brain health. 

Jasvinder Chawla, MD, Professor of Neurology, Loyola University Medical Center, Maywood; Director, Clinical Neurophysiology Lab, Department of Neurology, Hines VA Hospital, Hines, IL.

Jasvinder Chawla, MD, has disclosed no relevant financial relationships.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.
 

The history and findings in this case are suggestive of late-onset familial AD (onset after age 65 years).

AD is a common neurodegenerative disease associated with progressive impairment of behavioral and cognitive functions, including memory, comprehension, language, attention, reasoning, and judgment. In 2020, 5.8 million Americans were living with AD. By 2050, this number is projected to increase to 13.9 million people, or almost 3.3% of the US population. Globally, 152 million people are projected to have AD and other dementias by 2050. The worldwide increase in incidence and prevalence of AD is at least partially explained by an aging population and increased life expectancy. 

The cause of AD remains unclear, but there is substantial evidence that AD is a highly heritable disorder. Familial AD is characterized by having more than one member in more than one generation with AD. The autosomal-dominant form of AD is linked to mutations in three genes: AAP on chromosome 21, PSEN1 on chromosome 14, and PSEN2 on chromosome 1. APP mutations may cause increased generation and aggregation of beta-amyloid peptide, whereas PSEN1 and PSEN2 mutations result in aggregation of beta-amyloid by interfering with the processing of gamma-secretase.

APOE is another genetic marker that increases the risk for AD. Isoform e4 of the APOE gene (located on chromosome 19) has been associated with more sporadic and familial forms of AD that present after age 65 years. Approximately 50% of individuals carrying one APOEe4 develop AD, and 90% of individuals who have two alleles develop AD. Variants in the gene for the sortilin receptor, SORT1, have also been found in familial and sporadic forms of AD.

The cognitive and behavioral impairment associated with AD significantly affects a patient's social and occupational functioning. Insidiously progressive memory loss is a characteristic symptoms seen in patients presenting with AD. As the disease advances over the course of several years, other areas of cognition are impaired. Patients may develop language disorders (eg, anomic aphasia or anomia) and impairment in visuospatial skills and executive functions. A slow progression of behavioral changes may also occur in individuals with AD.

Clinical criteria for the diagnosis of AD (eg, insidious onset of cognitive impairment, clear history of worsening symptoms) have been developed and are often used to diagnose patients. In addition, biomarker evidence may help to increase the diagnostic certainty. Several cerebrospinal fluid and blood biomarkers have shown excellent diagnostic ability by identifying tau pathology and cerebral amyloid-beta for AD.

Neuroimaging is becoming increasingly important for identifying the underlying causes of cognitive impairment. Currently, MRI is considered the preferred neuroimaging modality for AD because it allows for accurate measurement of the three-dimensional volume of brain structures, particularly the size of the hippocampus and related regions. CT can be used when MRI is not available or is contraindicated, such as in a patient with a pacemaker. PET is another noninvasive method for depicting tau pathology deposition and distribution in patients with cognitive impairment. In 2020, US Food and Drug Administration approved the first tau PET tracer, ¹⁸F-flortaucipir, which marked a significant achievement to improve AD diagnosis. 

At present, the only therapies available for AD are symptomatic therapies. Cholinesterase inhibitors and a partial N-methyl-D-aspartate antagonist are the standard medical treatments for AD. Antiamyloid therapies are also available for patients with mild cognitive impairment or mild dementia. These include aducanumab, a first-in-class amyloid-beta–directed antibody that was approved in 2021, and lecanemab, another amyloid-beta–directed antibody that was approved in 2023. Both aducanumab and lecanemab are recommended for the treatment of patients with mild cognitive impairment or mild dementia stage of disease, the population in which the safety and efficacy of these newer agents were demonstrated in clinical trials. 

Secondary symptoms of AD, such as depression, agitation, aggression, hallucinations, delusions, and/or sleep disorders, can be treated with psychotropic agents. Behavioral interventions including patient-centered approaches and caregiver training can also be helpful for managing the cognitive and behavioral manifestations of AD, often in combination with pharmacologic interventions (eg, anxiolytics for anxiety and agitation, neuroleptics for delusions or hallucinations, and antidepressants or mood stabilizers for mood disorders). Regular physical activity and exercise may also play a role in delaying AD progression and possibly conferring a protective effect on brain health. 

Jasvinder Chawla, MD, Professor of Neurology, Loyola University Medical Center, Maywood; Director, Clinical Neurophysiology Lab, Department of Neurology, Hines VA Hospital, Hines, IL.

Jasvinder Chawla, MD, has disclosed no relevant financial relationships.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.
 

The history and findings in this case are suggestive of late-onset familial AD (onset after age 65 years).

AD is a common neurodegenerative disease associated with progressive impairment of behavioral and cognitive functions, including memory, comprehension, language, attention, reasoning, and judgment. In 2020, 5.8 million Americans were living with AD. By 2050, this number is projected to increase to 13.9 million people, or almost 3.3% of the US population. Globally, 152 million people are projected to have AD and other dementias by 2050. The worldwide increase in incidence and prevalence of AD is at least partially explained by an aging population and increased life expectancy. 

The cause of AD remains unclear, but there is substantial evidence that AD is a highly heritable disorder. Familial AD is characterized by having more than one member in more than one generation with AD. The autosomal-dominant form of AD is linked to mutations in three genes: AAP on chromosome 21, PSEN1 on chromosome 14, and PSEN2 on chromosome 1. APP mutations may cause increased generation and aggregation of beta-amyloid peptide, whereas PSEN1 and PSEN2 mutations result in aggregation of beta-amyloid by interfering with the processing of gamma-secretase.

APOE is another genetic marker that increases the risk for AD. Isoform e4 of the APOE gene (located on chromosome 19) has been associated with more sporadic and familial forms of AD that present after age 65 years. Approximately 50% of individuals carrying one APOEe4 develop AD, and 90% of individuals who have two alleles develop AD. Variants in the gene for the sortilin receptor, SORT1, have also been found in familial and sporadic forms of AD.

The cognitive and behavioral impairment associated with AD significantly affects a patient's social and occupational functioning. Insidiously progressive memory loss is a characteristic symptoms seen in patients presenting with AD. As the disease advances over the course of several years, other areas of cognition are impaired. Patients may develop language disorders (eg, anomic aphasia or anomia) and impairment in visuospatial skills and executive functions. A slow progression of behavioral changes may also occur in individuals with AD.

Clinical criteria for the diagnosis of AD (eg, insidious onset of cognitive impairment, clear history of worsening symptoms) have been developed and are often used to diagnose patients. In addition, biomarker evidence may help to increase the diagnostic certainty. Several cerebrospinal fluid and blood biomarkers have shown excellent diagnostic ability by identifying tau pathology and cerebral amyloid-beta for AD.

Neuroimaging is becoming increasingly important for identifying the underlying causes of cognitive impairment. Currently, MRI is considered the preferred neuroimaging modality for AD because it allows for accurate measurement of the three-dimensional volume of brain structures, particularly the size of the hippocampus and related regions. CT can be used when MRI is not available or is contraindicated, such as in a patient with a pacemaker. PET is another noninvasive method for depicting tau pathology deposition and distribution in patients with cognitive impairment. In 2020, US Food and Drug Administration approved the first tau PET tracer, ¹⁸F-flortaucipir, which marked a significant achievement to improve AD diagnosis. 

At present, the only therapies available for AD are symptomatic therapies. Cholinesterase inhibitors and a partial N-methyl-D-aspartate antagonist are the standard medical treatments for AD. Antiamyloid therapies are also available for patients with mild cognitive impairment or mild dementia. These include aducanumab, a first-in-class amyloid-beta–directed antibody that was approved in 2021, and lecanemab, another amyloid-beta–directed antibody that was approved in 2023. Both aducanumab and lecanemab are recommended for the treatment of patients with mild cognitive impairment or mild dementia stage of disease, the population in which the safety and efficacy of these newer agents were demonstrated in clinical trials. 

Secondary symptoms of AD, such as depression, agitation, aggression, hallucinations, delusions, and/or sleep disorders, can be treated with psychotropic agents. Behavioral interventions including patient-centered approaches and caregiver training can also be helpful for managing the cognitive and behavioral manifestations of AD, often in combination with pharmacologic interventions (eg, anxiolytics for anxiety and agitation, neuroleptics for delusions or hallucinations, and antidepressants or mood stabilizers for mood disorders). Regular physical activity and exercise may also play a role in delaying AD progression and possibly conferring a protective effect on brain health. 

Jasvinder Chawla, MD, Professor of Neurology, Loyola University Medical Center, Maywood; Director, Clinical Neurophysiology Lab, Department of Neurology, Hines VA Hospital, Hines, IL.

Jasvinder Chawla, MD, has disclosed no relevant financial relationships.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.
 

Brain disorders, including mental illness, neurologic conditions, and stroke, account for more than 15% of all health loss worldwide – more than either cardiovascular disease or cancer – at huge cost to health care systems and society, an analysis of data from the most recent Global Burden of Disease (GBD) study shows.

“The burden of brain conditions will increase as populations continue to grow and age,” said study presenter Shayla Smith, MPH, an epidemiologist at the Institute for Health Metrics and Evaluation, the University of Washington, Seattle, in a press release.

“By 2050, more than 50 million people will be aged 65-79,” she explained, adding that the COVID-19 pandemic “has also influenced the prevalence of mental disorders globally, as people were forced to isolate and social networks broke down.”

Other factors related to brain disorders, she noted, include education level, obesity, and smoking.

“There’s still research to be done on what is the most effective way to maintain brain health, but some literature suggests a healthy brain can be achieved through a healthy lifestyle of managing conditions such as high blood pressure and diabetes, limiting alcohol consumption and smoking, prioritizing sleep, eating healthy, and staying physically and mentally active,” said Ms. Smith.

The findings were presented at the annual meeting of the Congress of the European Academy of Neurology.
 

An ‘ambitious exercise’

Coinvestigator Xaviera Steele, also from the IHME, told press conference attendees that the institute was established at the University of Washington in 2007 with the aim of “standardizing the measurement of health outcomes around the world and for all health conditions.”

A central part of that is the GBD study, “which is a very ambitious exercise in descriptive epidemiology in an effort to systematically quantify health loss” due to disease, injury, and risk factors over time, stratified by country, region, age, and sex. In addition, researchers are mapping and projecting trends over the next century and are estimating disease expenditure by country, by type of expense, and by condition “to derive a health care access and quality score for each health system in the world,” Ms. Steele said.

They are also estimating exposure to risk factors, how those risk factors contribute to health burden, and associated health outcomes by race and ethnicity to reflect the “disparities that we know are very prevalent in countries such as the United States.” From that work, Ms. Steele said that brain health and related conditions “do emerge as one of the more pressing challenges of the 21st century.”
 

Increase in dementia, mental health conditions

The data, which were gathered from 200,000 sources by the IHME, indicate that the number of individuals aged 65 years or older will increase by 350% by 2100. Ms. Steele underlined that “policy action will be needed to help families, who will struggle to provide high-quality care for their loved ones with dementia at a reasonable cost.”

The IHME calculates that in Europe health care spending on Alzheimer’s disease will increase by 226% between 2015 and 2040.

Turning to other conditions, Ms. Steele showed that since 1990, the number of individuals living with anxiety in the European region has increased by 14%, while the number living with depressive disorders has gone up by 13%.

Worldwide, the figures are even starker. Depression is estimated to affect 300 million people across the globe, which represents a 71% increase since 1990. The number of strokes increased by 95% over the same period.

Nevertheless, the “impact of brain conditions such as stroke has decreased since the 1990s due to improved treatments available,” Ms. Smith noted in the press release.

To estimate the toll caused by brain conditions, including neurologic disorders, mental disorders, cerebrovascular disease, brain cancer, brain injuries, and select infectious conditions, the researchers calculated disability-adjusted life years (DALYs).

This, Ms. Smith explained in her presentation, “captures the morbidity and mortality associated with brain conditions” and is adjusted for patient location, age, and sex.

The investigators found that, globally, brain conditions accounted for more than 15% of all health loss in 2021, at 406 DALYs – more than the 206 million DALYs that were associated with cancer, and the 402 million that were linked to cardiovascular disease.

This health loss is associated with a $1.22 trillion loss in income for people living with health disorders worldwide and accounts for $1.14 trillion in direct health care costs.

The burden of mental disorders, neurologic conditions, and stroke is expected to increase dramatically between now and 2050, said Ms. Smith, who noted that health loss linked to brain conditions is higher in younger patients. This will create “new challenges for health systems, employers, patients, and families,” she said in the press release.

“Our goal is to see an improved prevention and treatment landscape for other brain conditions and reverse the growing health loss that we are currently forecasting.”
 

Worrying increase in stroke

Jurgita Valaikiene, MD, PhD, center of neurology, clinic of neurology and neurosurgery, Vilnius (Lithuania) University Faculty of Medicine, who chaired the session, was taken aback by the findings, particularly by the worldwide increase in stroke cases.

“I work in stroke,” she said, and “we spend a lot of time on the diagnosis of stroke” and its prevention. “We try to be faster, to catch asymptomatic stenosis in the neck or head, and to apply the best medical treatment to avoid a stroke. But despite that, the numbers are increasing. I understand the population is getting older ... but still it’s a huge number.”

Dr. Valaikiene pointed out that stroke is not necessarily a condition of aging, insofar as increasing age “is not related directly to stenosis in the neck. “For example, we can have healthier vessels in older age and unhealthy vessels, with high-grade stenosis, in someone aged 30 or 40 years.”

“There are a lot of risk factors, such as smoking, physical activity, and so on. It depends on the individual,” she added.

The study was funded by the Institute for Health Metrics and Evaluation at the University of Washington. The authors have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Brain disorders, including mental illness, neurologic conditions, and stroke, account for more than 15% of all health loss worldwide – more than either cardiovascular disease or cancer – at huge cost to health care systems and society, an analysis of data from the most recent Global Burden of Disease (GBD) study shows.

“The burden of brain conditions will increase as populations continue to grow and age,” said study presenter Shayla Smith, MPH, an epidemiologist at the Institute for Health Metrics and Evaluation, the University of Washington, Seattle, in a press release.

“By 2050, more than 50 million people will be aged 65-79,” she explained, adding that the COVID-19 pandemic “has also influenced the prevalence of mental disorders globally, as people were forced to isolate and social networks broke down.”

Other factors related to brain disorders, she noted, include education level, obesity, and smoking.

“There’s still research to be done on what is the most effective way to maintain brain health, but some literature suggests a healthy brain can be achieved through a healthy lifestyle of managing conditions such as high blood pressure and diabetes, limiting alcohol consumption and smoking, prioritizing sleep, eating healthy, and staying physically and mentally active,” said Ms. Smith.

The findings were presented at the annual meeting of the Congress of the European Academy of Neurology.
 

An ‘ambitious exercise’

Coinvestigator Xaviera Steele, also from the IHME, told press conference attendees that the institute was established at the University of Washington in 2007 with the aim of “standardizing the measurement of health outcomes around the world and for all health conditions.”

A central part of that is the GBD study, “which is a very ambitious exercise in descriptive epidemiology in an effort to systematically quantify health loss” due to disease, injury, and risk factors over time, stratified by country, region, age, and sex. In addition, researchers are mapping and projecting trends over the next century and are estimating disease expenditure by country, by type of expense, and by condition “to derive a health care access and quality score for each health system in the world,” Ms. Steele said.

They are also estimating exposure to risk factors, how those risk factors contribute to health burden, and associated health outcomes by race and ethnicity to reflect the “disparities that we know are very prevalent in countries such as the United States.” From that work, Ms. Steele said that brain health and related conditions “do emerge as one of the more pressing challenges of the 21st century.”
 

Increase in dementia, mental health conditions

The data, which were gathered from 200,000 sources by the IHME, indicate that the number of individuals aged 65 years or older will increase by 350% by 2100. Ms. Steele underlined that “policy action will be needed to help families, who will struggle to provide high-quality care for their loved ones with dementia at a reasonable cost.”

The IHME calculates that in Europe health care spending on Alzheimer’s disease will increase by 226% between 2015 and 2040.

Turning to other conditions, Ms. Steele showed that since 1990, the number of individuals living with anxiety in the European region has increased by 14%, while the number living with depressive disorders has gone up by 13%.

Worldwide, the figures are even starker. Depression is estimated to affect 300 million people across the globe, which represents a 71% increase since 1990. The number of strokes increased by 95% over the same period.

Nevertheless, the “impact of brain conditions such as stroke has decreased since the 1990s due to improved treatments available,” Ms. Smith noted in the press release.

To estimate the toll caused by brain conditions, including neurologic disorders, mental disorders, cerebrovascular disease, brain cancer, brain injuries, and select infectious conditions, the researchers calculated disability-adjusted life years (DALYs).

This, Ms. Smith explained in her presentation, “captures the morbidity and mortality associated with brain conditions” and is adjusted for patient location, age, and sex.

The investigators found that, globally, brain conditions accounted for more than 15% of all health loss in 2021, at 406 DALYs – more than the 206 million DALYs that were associated with cancer, and the 402 million that were linked to cardiovascular disease.

This health loss is associated with a $1.22 trillion loss in income for people living with health disorders worldwide and accounts for $1.14 trillion in direct health care costs.

The burden of mental disorders, neurologic conditions, and stroke is expected to increase dramatically between now and 2050, said Ms. Smith, who noted that health loss linked to brain conditions is higher in younger patients. This will create “new challenges for health systems, employers, patients, and families,” she said in the press release.

“Our goal is to see an improved prevention and treatment landscape for other brain conditions and reverse the growing health loss that we are currently forecasting.”
 

Worrying increase in stroke

Jurgita Valaikiene, MD, PhD, center of neurology, clinic of neurology and neurosurgery, Vilnius (Lithuania) University Faculty of Medicine, who chaired the session, was taken aback by the findings, particularly by the worldwide increase in stroke cases.

“I work in stroke,” she said, and “we spend a lot of time on the diagnosis of stroke” and its prevention. “We try to be faster, to catch asymptomatic stenosis in the neck or head, and to apply the best medical treatment to avoid a stroke. But despite that, the numbers are increasing. I understand the population is getting older ... but still it’s a huge number.”

Dr. Valaikiene pointed out that stroke is not necessarily a condition of aging, insofar as increasing age “is not related directly to stenosis in the neck. “For example, we can have healthier vessels in older age and unhealthy vessels, with high-grade stenosis, in someone aged 30 or 40 years.”

“There are a lot of risk factors, such as smoking, physical activity, and so on. It depends on the individual,” she added.

The study was funded by the Institute for Health Metrics and Evaluation at the University of Washington. The authors have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Brain disorders, including mental illness, neurologic conditions, and stroke, account for more than 15% of all health loss worldwide – more than either cardiovascular disease or cancer – at huge cost to health care systems and society, an analysis of data from the most recent Global Burden of Disease (GBD) study shows.

“The burden of brain conditions will increase as populations continue to grow and age,” said study presenter Shayla Smith, MPH, an epidemiologist at the Institute for Health Metrics and Evaluation, the University of Washington, Seattle, in a press release.

“By 2050, more than 50 million people will be aged 65-79,” she explained, adding that the COVID-19 pandemic “has also influenced the prevalence of mental disorders globally, as people were forced to isolate and social networks broke down.”

Other factors related to brain disorders, she noted, include education level, obesity, and smoking.

“There’s still research to be done on what is the most effective way to maintain brain health, but some literature suggests a healthy brain can be achieved through a healthy lifestyle of managing conditions such as high blood pressure and diabetes, limiting alcohol consumption and smoking, prioritizing sleep, eating healthy, and staying physically and mentally active,” said Ms. Smith.

The findings were presented at the annual meeting of the Congress of the European Academy of Neurology.
 

An ‘ambitious exercise’

Coinvestigator Xaviera Steele, also from the IHME, told press conference attendees that the institute was established at the University of Washington in 2007 with the aim of “standardizing the measurement of health outcomes around the world and for all health conditions.”

A central part of that is the GBD study, “which is a very ambitious exercise in descriptive epidemiology in an effort to systematically quantify health loss” due to disease, injury, and risk factors over time, stratified by country, region, age, and sex. In addition, researchers are mapping and projecting trends over the next century and are estimating disease expenditure by country, by type of expense, and by condition “to derive a health care access and quality score for each health system in the world,” Ms. Steele said.

They are also estimating exposure to risk factors, how those risk factors contribute to health burden, and associated health outcomes by race and ethnicity to reflect the “disparities that we know are very prevalent in countries such as the United States.” From that work, Ms. Steele said that brain health and related conditions “do emerge as one of the more pressing challenges of the 21st century.”
 

Increase in dementia, mental health conditions

The data, which were gathered from 200,000 sources by the IHME, indicate that the number of individuals aged 65 years or older will increase by 350% by 2100. Ms. Steele underlined that “policy action will be needed to help families, who will struggle to provide high-quality care for their loved ones with dementia at a reasonable cost.”

The IHME calculates that in Europe health care spending on Alzheimer’s disease will increase by 226% between 2015 and 2040.

Turning to other conditions, Ms. Steele showed that since 1990, the number of individuals living with anxiety in the European region has increased by 14%, while the number living with depressive disorders has gone up by 13%.

Worldwide, the figures are even starker. Depression is estimated to affect 300 million people across the globe, which represents a 71% increase since 1990. The number of strokes increased by 95% over the same period.

Nevertheless, the “impact of brain conditions such as stroke has decreased since the 1990s due to improved treatments available,” Ms. Smith noted in the press release.

To estimate the toll caused by brain conditions, including neurologic disorders, mental disorders, cerebrovascular disease, brain cancer, brain injuries, and select infectious conditions, the researchers calculated disability-adjusted life years (DALYs).

This, Ms. Smith explained in her presentation, “captures the morbidity and mortality associated with brain conditions” and is adjusted for patient location, age, and sex.

The investigators found that, globally, brain conditions accounted for more than 15% of all health loss in 2021, at 406 DALYs – more than the 206 million DALYs that were associated with cancer, and the 402 million that were linked to cardiovascular disease.

This health loss is associated with a $1.22 trillion loss in income for people living with health disorders worldwide and accounts for $1.14 trillion in direct health care costs.

The burden of mental disorders, neurologic conditions, and stroke is expected to increase dramatically between now and 2050, said Ms. Smith, who noted that health loss linked to brain conditions is higher in younger patients. This will create “new challenges for health systems, employers, patients, and families,” she said in the press release.

“Our goal is to see an improved prevention and treatment landscape for other brain conditions and reverse the growing health loss that we are currently forecasting.”
 

Worrying increase in stroke

Jurgita Valaikiene, MD, PhD, center of neurology, clinic of neurology and neurosurgery, Vilnius (Lithuania) University Faculty of Medicine, who chaired the session, was taken aback by the findings, particularly by the worldwide increase in stroke cases.

“I work in stroke,” she said, and “we spend a lot of time on the diagnosis of stroke” and its prevention. “We try to be faster, to catch asymptomatic stenosis in the neck or head, and to apply the best medical treatment to avoid a stroke. But despite that, the numbers are increasing. I understand the population is getting older ... but still it’s a huge number.”

Dr. Valaikiene pointed out that stroke is not necessarily a condition of aging, insofar as increasing age “is not related directly to stenosis in the neck. “For example, we can have healthier vessels in older age and unhealthy vessels, with high-grade stenosis, in someone aged 30 or 40 years.”

“There are a lot of risk factors, such as smoking, physical activity, and so on. It depends on the individual,” she added.

The study was funded by the Institute for Health Metrics and Evaluation at the University of Washington. The authors have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Like many stressful chronic conditions, hearing loss appears to foster fatigue, according to an analysis of National Health and Nutrition Examination Study data published in JAMA Otolaryngology – Head & Neck Surgery.

Researchers at Johns Hopkins University, Baltimore, examined NHANES data from 2015 to 2016 and 2017 to 2018, including findings on more than 3,000 participants aged 40 and older. Based on the audiometry subset of NHANES data, hearing loss was associated with a higher frequency of fatigue – even after adjustment for demographics, comorbidities, and lifestyle variables such as smoking, alcohol, and body mass index, in a nationally representative sample of adults in middle and older age.

“We wanted to get away from small clinical data and take a look at the population level to see if hearing loss was related to fatigue and, further perhaps, to cognitive decline,” said coauthor Nicholas S. Reed, AuD, PhD, an assistant professor of epidemiology at Johns Hopkins University, Baltimore, in an interview. “We found people with hearing loss had twice the risk of reporting fatigue nearly every day versus those not reporting fatigue.” This cross-sectional study provides needed population-based evidence from a nationally representative sample, according to Dr. Reed and associates, who have been researching the possible connection between age-related hearing loss, physical activity levels, and cognitive decline.
 

Study details

The 3,031 age-eligible participants had a mean age of 58 years; 48% were male, and 10% were Black. Some hearing loss was reported by 24%.

They responded to the following question: “Over the last 2 weeks, how often have you been bothered by feeling tired or having little energy?” Response categories were “not at all,” “several days,” “more than half the days,” and “nearly every day.” Those with hearing loss were more likely to report fatigue for more than half the days (relative risk ratio, 2.16; 95% confidence interval, 1.27-3.67) and nearly every day (RRR, 2.05; 95% CI, 1.16-3.65), compared with not having fatigue. Additional adjustment for comorbidities and depressive symptoms showed similar results.

Hearing loss was defined as > 25 decibels hearing level (dB HL) versus normal hearing of ≤ 25 dB HL, and continuously by every 10 dB HL poorer. Each 10-dB HL of audiometric hearing loss was associated with a higher likelihood of reporting fatigue nearly every day (RRR, 1.24; 95% CI,1.04-1.47), but not for more than half the days.

The association tended to be stronger in younger, non-Hispanic White, and female participants, but statistical testing did not support differential associations by age, sex, race, or ethnicity.

While some might intuitively expect hearing loss to cause noticeably more fatigue in middle-aged people who may be straining to hear during hours in the daily workplace or at home, Dr. Reed said older people probably feel more hearing-related fatigue owing to age and comorbidities. “And higher physical activity levels of middle-aged adults can be protective.”

Dr. Reed advised primary care physicians to be sure to ask about fatigue and hearing status during wellness exams and take appropriate steps to diagnose and correct hearing problems. “Make sure hearing is part of the health equation because hearing loss can be part of the culprit. And it’s very possible that hearing loss is also contributing to cognitive decline.”

Dr. Reed’s group will soon release data on a clinical trial on hearing loss and cognitive decline.

The authors called for studies incorporating fatigue assessments in order to clarify how hearing loss might contribute to physical and mental fatigue and how it could be associated with downstream outcomes such as fatigue-related physical impairment. Dr. Reed reported grants from the National Institute on Aging during the conduct of the study and stock compensation from the Neosensory Advisory Board outside of the submitted work. Several coauthors reported academic or government research funding as well as fees and honoraria from various private-sector companies.

Like many stressful chronic conditions, hearing loss appears to foster fatigue, according to an analysis of National Health and Nutrition Examination Study data published in JAMA Otolaryngology – Head & Neck Surgery.

Researchers at Johns Hopkins University, Baltimore, examined NHANES data from 2015 to 2016 and 2017 to 2018, including findings on more than 3,000 participants aged 40 and older. Based on the audiometry subset of NHANES data, hearing loss was associated with a higher frequency of fatigue – even after adjustment for demographics, comorbidities, and lifestyle variables such as smoking, alcohol, and body mass index, in a nationally representative sample of adults in middle and older age.

“We wanted to get away from small clinical data and take a look at the population level to see if hearing loss was related to fatigue and, further perhaps, to cognitive decline,” said coauthor Nicholas S. Reed, AuD, PhD, an assistant professor of epidemiology at Johns Hopkins University, Baltimore, in an interview. “We found people with hearing loss had twice the risk of reporting fatigue nearly every day versus those not reporting fatigue.” This cross-sectional study provides needed population-based evidence from a nationally representative sample, according to Dr. Reed and associates, who have been researching the possible connection between age-related hearing loss, physical activity levels, and cognitive decline.
 

Study details

The 3,031 age-eligible participants had a mean age of 58 years; 48% were male, and 10% were Black. Some hearing loss was reported by 24%.

They responded to the following question: “Over the last 2 weeks, how often have you been bothered by feeling tired or having little energy?” Response categories were “not at all,” “several days,” “more than half the days,” and “nearly every day.” Those with hearing loss were more likely to report fatigue for more than half the days (relative risk ratio, 2.16; 95% confidence interval, 1.27-3.67) and nearly every day (RRR, 2.05; 95% CI, 1.16-3.65), compared with not having fatigue. Additional adjustment for comorbidities and depressive symptoms showed similar results.

Hearing loss was defined as > 25 decibels hearing level (dB HL) versus normal hearing of ≤ 25 dB HL, and continuously by every 10 dB HL poorer. Each 10-dB HL of audiometric hearing loss was associated with a higher likelihood of reporting fatigue nearly every day (RRR, 1.24; 95% CI,1.04-1.47), but not for more than half the days.

The association tended to be stronger in younger, non-Hispanic White, and female participants, but statistical testing did not support differential associations by age, sex, race, or ethnicity.

While some might intuitively expect hearing loss to cause noticeably more fatigue in middle-aged people who may be straining to hear during hours in the daily workplace or at home, Dr. Reed said older people probably feel more hearing-related fatigue owing to age and comorbidities. “And higher physical activity levels of middle-aged adults can be protective.”

Dr. Reed advised primary care physicians to be sure to ask about fatigue and hearing status during wellness exams and take appropriate steps to diagnose and correct hearing problems. “Make sure hearing is part of the health equation because hearing loss can be part of the culprit. And it’s very possible that hearing loss is also contributing to cognitive decline.”

Dr. Reed’s group will soon release data on a clinical trial on hearing loss and cognitive decline.

The authors called for studies incorporating fatigue assessments in order to clarify how hearing loss might contribute to physical and mental fatigue and how it could be associated with downstream outcomes such as fatigue-related physical impairment. Dr. Reed reported grants from the National Institute on Aging during the conduct of the study and stock compensation from the Neosensory Advisory Board outside of the submitted work. Several coauthors reported academic or government research funding as well as fees and honoraria from various private-sector companies.

Like many stressful chronic conditions, hearing loss appears to foster fatigue, according to an analysis of National Health and Nutrition Examination Study data published in JAMA Otolaryngology – Head & Neck Surgery.

Researchers at Johns Hopkins University, Baltimore, examined NHANES data from 2015 to 2016 and 2017 to 2018, including findings on more than 3,000 participants aged 40 and older. Based on the audiometry subset of NHANES data, hearing loss was associated with a higher frequency of fatigue – even after adjustment for demographics, comorbidities, and lifestyle variables such as smoking, alcohol, and body mass index, in a nationally representative sample of adults in middle and older age.

“We wanted to get away from small clinical data and take a look at the population level to see if hearing loss was related to fatigue and, further perhaps, to cognitive decline,” said coauthor Nicholas S. Reed, AuD, PhD, an assistant professor of epidemiology at Johns Hopkins University, Baltimore, in an interview. “We found people with hearing loss had twice the risk of reporting fatigue nearly every day versus those not reporting fatigue.” This cross-sectional study provides needed population-based evidence from a nationally representative sample, according to Dr. Reed and associates, who have been researching the possible connection between age-related hearing loss, physical activity levels, and cognitive decline.
 

Study details

The 3,031 age-eligible participants had a mean age of 58 years; 48% were male, and 10% were Black. Some hearing loss was reported by 24%.

They responded to the following question: “Over the last 2 weeks, how often have you been bothered by feeling tired or having little energy?” Response categories were “not at all,” “several days,” “more than half the days,” and “nearly every day.” Those with hearing loss were more likely to report fatigue for more than half the days (relative risk ratio, 2.16; 95% confidence interval, 1.27-3.67) and nearly every day (RRR, 2.05; 95% CI, 1.16-3.65), compared with not having fatigue. Additional adjustment for comorbidities and depressive symptoms showed similar results.

Hearing loss was defined as > 25 decibels hearing level (dB HL) versus normal hearing of ≤ 25 dB HL, and continuously by every 10 dB HL poorer. Each 10-dB HL of audiometric hearing loss was associated with a higher likelihood of reporting fatigue nearly every day (RRR, 1.24; 95% CI,1.04-1.47), but not for more than half the days.

The association tended to be stronger in younger, non-Hispanic White, and female participants, but statistical testing did not support differential associations by age, sex, race, or ethnicity.

While some might intuitively expect hearing loss to cause noticeably more fatigue in middle-aged people who may be straining to hear during hours in the daily workplace or at home, Dr. Reed said older people probably feel more hearing-related fatigue owing to age and comorbidities. “And higher physical activity levels of middle-aged adults can be protective.”

Dr. Reed advised primary care physicians to be sure to ask about fatigue and hearing status during wellness exams and take appropriate steps to diagnose and correct hearing problems. “Make sure hearing is part of the health equation because hearing loss can be part of the culprit. And it’s very possible that hearing loss is also contributing to cognitive decline.”

Dr. Reed’s group will soon release data on a clinical trial on hearing loss and cognitive decline.

The authors called for studies incorporating fatigue assessments in order to clarify how hearing loss might contribute to physical and mental fatigue and how it could be associated with downstream outcomes such as fatigue-related physical impairment. Dr. Reed reported grants from the National Institute on Aging during the conduct of the study and stock compensation from the Neosensory Advisory Board outside of the submitted work. Several coauthors reported academic or government research funding as well as fees and honoraria from various private-sector companies.

Mr. Jones has Alzheimer’s disease, recently diagnosed.

His wife is a retired hospice nurse, who’s seen plenty of patients and families deal with the illness over the years.

She came in recently, just herself, to go over his treatment options and what can be reasonably expected with them. So we went through the usual suspects, new and old.

I intermittently stopped to ask if she had any questions. At one such break she suddenly said:

“I’d rather he die now than be treated with any of these.”

I tried to address her safety concerns with the different medications, but that wasn’t the issue. Her real, and understandable, point is that none of them are cures. They don’t even stop the disease. Realistically, all we’re doing is slowing things down for maybe a year at most.

Families are different, and no one can really know how they’ll react in this situation until it happens.

Some will want me to do a full-court press, because another year of time is more family gatherings and independence, maybe a grandchild’s birth or wedding, or just being able to keep someone at home longer before starting to look into the cost of memory care.

Others, like Mrs. Jones, don’t see a point. The disease is incurable. Why bother to prolong it when the end is the same? Is it worth adding another year of medications, adult diapers, and the occasional 911 call if they wander off?

That’s a valid view, too. She wasn’t advocating a cause, such as euthanasia, but she did have legitimate concerns.

For all the marketing hype over Leqembi today or Cognex (remember that?) in 1989, the issue is the same. We have new and shinier toys, but still no cures. Whether it’s worth it to prolong life (or suffering) is a glass half-full or half-empty question that only patients and their families can answer.

It ain’t easy.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

Mr. Jones has Alzheimer’s disease, recently diagnosed.

His wife is a retired hospice nurse, who’s seen plenty of patients and families deal with the illness over the years.

She came in recently, just herself, to go over his treatment options and what can be reasonably expected with them. So we went through the usual suspects, new and old.

I intermittently stopped to ask if she had any questions. At one such break she suddenly said:

“I’d rather he die now than be treated with any of these.”

I tried to address her safety concerns with the different medications, but that wasn’t the issue. Her real, and understandable, point is that none of them are cures. They don’t even stop the disease. Realistically, all we’re doing is slowing things down for maybe a year at most.

Families are different, and no one can really know how they’ll react in this situation until it happens.

Some will want me to do a full-court press, because another year of time is more family gatherings and independence, maybe a grandchild’s birth or wedding, or just being able to keep someone at home longer before starting to look into the cost of memory care.

Others, like Mrs. Jones, don’t see a point. The disease is incurable. Why bother to prolong it when the end is the same? Is it worth adding another year of medications, adult diapers, and the occasional 911 call if they wander off?

That’s a valid view, too. She wasn’t advocating a cause, such as euthanasia, but she did have legitimate concerns.

For all the marketing hype over Leqembi today or Cognex (remember that?) in 1989, the issue is the same. We have new and shinier toys, but still no cures. Whether it’s worth it to prolong life (or suffering) is a glass half-full or half-empty question that only patients and their families can answer.

It ain’t easy.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

Mr. Jones has Alzheimer’s disease, recently diagnosed.

His wife is a retired hospice nurse, who’s seen plenty of patients and families deal with the illness over the years.

She came in recently, just herself, to go over his treatment options and what can be reasonably expected with them. So we went through the usual suspects, new and old.

I intermittently stopped to ask if she had any questions. At one such break she suddenly said:

“I’d rather he die now than be treated with any of these.”

I tried to address her safety concerns with the different medications, but that wasn’t the issue. Her real, and understandable, point is that none of them are cures. They don’t even stop the disease. Realistically, all we’re doing is slowing things down for maybe a year at most.

Families are different, and no one can really know how they’ll react in this situation until it happens.

Some will want me to do a full-court press, because another year of time is more family gatherings and independence, maybe a grandchild’s birth or wedding, or just being able to keep someone at home longer before starting to look into the cost of memory care.

Others, like Mrs. Jones, don’t see a point. The disease is incurable. Why bother to prolong it when the end is the same? Is it worth adding another year of medications, adult diapers, and the occasional 911 call if they wander off?

That’s a valid view, too. She wasn’t advocating a cause, such as euthanasia, but she did have legitimate concerns.

For all the marketing hype over Leqembi today or Cognex (remember that?) in 1989, the issue is the same. We have new and shinier toys, but still no cures. Whether it’s worth it to prolong life (or suffering) is a glass half-full or half-empty question that only patients and their families can answer.

It ain’t easy.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

Topline

A new study provides early evidence of sex differences in rapid effects of stress systems on the cognitive control of negative emotions.

Methodology

• The study included 80 healthy participants, mean age 24 years.
• Half the subjects immersed their nondominant hand (including the wrist) in ice water for up to 3 minutes; the other half, which served as the control group, immersed their hand in warm water for 3 minutes.
• Participants were asked to deliberately downregulate emotional responses to high-intensity negative pictures.
• Participants regularly provided saliva samples to check cortisol levels and were monitored for cardiovascular activity.
• Researchers assessed pupil dilation, which along with subject ratings of their affective state served as emotion regulation (ER) outcome measures.

Takeaway

• In men, stress rapidly improved the ability to downregulate emotional arousal via distraction that was fully mediated by cortisol.
• In women, sympathetic nervous system (SNS) reactivity was linked to decreased regulatory performances.
• Direct stress effects on ER were smaller than expected.

In practice

The study contributes to a “better understanding of the neuroendocrinological mechanisms of stress effects on ER that may help to develop adequate preventive and curative interventions of stress- and emotion-related disorders,” the researchers write.

Source

The study was conducted by Katja Langer, Valerie Jentsch, and Oliver Wolf from the Department of Cognitive Psychology, Ruhr University Bochum (Germany). It was published in the May 2023 issue of Psychoneuroendocrinology.

Limitations

The results have some inconsistencies. The ER paradigm is somewhat artificial and not fully comparable with emotional trigger and regulatory requirements in everyday life. The study did not directly assess levels of catecholamines such as adrenaline and noradrenaline.

Disclosures

The study received support from the German Research Foundation (DFG). The authors have no reported conflicts of interest.

A version of this article originally appeared on Medscape.com.

Topline

A new study provides early evidence of sex differences in rapid effects of stress systems on the cognitive control of negative emotions.

Methodology

• The study included 80 healthy participants, mean age 24 years.
• Half the subjects immersed their nondominant hand (including the wrist) in ice water for up to 3 minutes; the other half, which served as the control group, immersed their hand in warm water for 3 minutes.
• Participants were asked to deliberately downregulate emotional responses to high-intensity negative pictures.
• Participants regularly provided saliva samples to check cortisol levels and were monitored for cardiovascular activity.
• Researchers assessed pupil dilation, which along with subject ratings of their affective state served as emotion regulation (ER) outcome measures.

Takeaway

• In men, stress rapidly improved the ability to downregulate emotional arousal via distraction that was fully mediated by cortisol.
• In women, sympathetic nervous system (SNS) reactivity was linked to decreased regulatory performances.
• Direct stress effects on ER were smaller than expected.

In practice

The study contributes to a “better understanding of the neuroendocrinological mechanisms of stress effects on ER that may help to develop adequate preventive and curative interventions of stress- and emotion-related disorders,” the researchers write.

Source

The study was conducted by Katja Langer, Valerie Jentsch, and Oliver Wolf from the Department of Cognitive Psychology, Ruhr University Bochum (Germany). It was published in the May 2023 issue of Psychoneuroendocrinology.

Limitations

The results have some inconsistencies. The ER paradigm is somewhat artificial and not fully comparable with emotional trigger and regulatory requirements in everyday life. The study did not directly assess levels of catecholamines such as adrenaline and noradrenaline.

Disclosures

The study received support from the German Research Foundation (DFG). The authors have no reported conflicts of interest.

A version of this article originally appeared on Medscape.com.

Topline

A new study provides early evidence of sex differences in rapid effects of stress systems on the cognitive control of negative emotions.

Methodology

• The study included 80 healthy participants, mean age 24 years.
• Half the subjects immersed their nondominant hand (including the wrist) in ice water for up to 3 minutes; the other half, which served as the control group, immersed their hand in warm water for 3 minutes.
• Participants were asked to deliberately downregulate emotional responses to high-intensity negative pictures.
• Participants regularly provided saliva samples to check cortisol levels and were monitored for cardiovascular activity.
• Researchers assessed pupil dilation, which along with subject ratings of their affective state served as emotion regulation (ER) outcome measures.

Takeaway

• In men, stress rapidly improved the ability to downregulate emotional arousal via distraction that was fully mediated by cortisol.
• In women, sympathetic nervous system (SNS) reactivity was linked to decreased regulatory performances.
• Direct stress effects on ER were smaller than expected.

In practice

The study contributes to a “better understanding of the neuroendocrinological mechanisms of stress effects on ER that may help to develop adequate preventive and curative interventions of stress- and emotion-related disorders,” the researchers write.

Source

The study was conducted by Katja Langer, Valerie Jentsch, and Oliver Wolf from the Department of Cognitive Psychology, Ruhr University Bochum (Germany). It was published in the May 2023 issue of Psychoneuroendocrinology.

Limitations

The results have some inconsistencies. The ER paradigm is somewhat artificial and not fully comparable with emotional trigger and regulatory requirements in everyday life. The study did not directly assess levels of catecholamines such as adrenaline and noradrenaline.

Disclosures

The study received support from the German Research Foundation (DFG). The authors have no reported conflicts of interest.

A version of this article originally appeared on Medscape.com.

A new European consensus statement offers expert guidance on which biomarkers to use for patients presenting with cognitive complaints.

Led by Giovanni B. Frisoni, MD, laboratory of neuroimaging of aging, University of Geneva, and director of the memory clinic at Geneva University Hospital, the multidisciplinary task force set out to define a patient-centered diagnostic workflow for the rational and cost-effective use of biomarkers in memory clinics.

The new algorithm is part of a consensus statement presented at the Congress of the European Academy of Neurology 2023. An interim update was published in June in Alzheimer’s and Dementia.
 

Which biomarker?

Many biomarkers can aid diagnosis, said Dr. Frisoni; the challenge is choosing which biomarker to use for an individual patient.

A literature-based search, he said, yields a number of recommendations, but the vast majority of these are either disease based or biomarker based. The task force notes that “in vivo biomarkers enable early etiological diagnosis of neurocognitive disorders. While they have good analytical validity, their clinical validity and utility are uncertain.”

“When you have a patient in front of you, you don’ t know whether they have Alzheimer’s disease,” Dr. Frisoni said.

“You have a differential diagnosis to make, and you have a number of biomarkers – a number of weapons in your armamentarium – you have to choose. You can’t use all of them – we would like to, but we cannot.”

He added that trying to determine from the literature which biomarker is most appropriate given individual clinical conditions and all of the potential combinations is impossible.

“You will not find evidence of the comparative diagnostic value and the added diagnostic value” of one test vs, another, he noted.

“Is CSF [cerebrospinal fluid] better than amyloid PET in a particular clinical situation? What do I gain in terms of positive and negative predictive value in all the possible clinical conditions that I encounter in my clinical practice?”

Dr. Frisoni said the reality is that clinicians in memory clinics end up using biomarkers that are “based on clinical opportunities.”

For instance, “if you have a proficient nuclear medic, you use PET a lot.” In contrast, “if you have a proficient laboratory medic,” CSF markers will be favored – a situation that he said is “not ideal” and has resulted in large discrepancies in diagnostic approaches across Europe.
 

Harmonizing clinical practice

In a bid to harmonize clinical practice, 22 European experts from 11 European scientific societies and the executive director of Alzheimer Europe set out to develop a multidisciplinary consensus algorithm for the biomarker-based diagnosis of neurocognitive disorders in general, rather than specific neurocognitive disorders.

They used the Delphi method, in which a systematic literature review of the literature was followed by the drafting of a series of clinical statements by an executive board. These were then presented to the expert panel. If a majority consensus was reached on a given statement, it was considered closed. Questions for which there was no consensus were revised and presented to the panel again. The process was repeated until a consensus was reached.

A total of 56 statements underwent six rounds of discussion. A final online meeting led to the development of a diagnostic algorithm for patients who attend memory clinics for cognitive complaints.

The algorithm features three potential assessment waves. Wave 1 defines 11 clinical profiles that are based on the results of clinical and neuropsychological assessments, blood exams, brain imaging, and, in specific cases, electroencephalography. Wave 2 defines first-line biomarkers based on Wave 1 clinical profiles, and Wave 3 defines the second-line biomarker based on Wave 2 biomarker results.

When a patient’s clinical profile suggests Alzheimer’s disease and, in undefined cases, cerebrospinal fluid biomarkers are used first line. When CSF is inconclusive, 18-fluorodeoxyglucose positron emission tomography (FDG-PET) is used second line.

When the clinical profile suggests frontotemporal lobar degeneration or motor tauopathies, FDG-PET is first line and CSF biomarkers second line in atypical metabolic patter cases. When the clinical profile suggests Lewy body disease, dopamine transporter SPECT is first line and cardia I23I-metaiodobenzylguanidine scintigraphy is second line.

Dr. Frisoni noted that the panel strongly recommends performing biomarker tests for patients younger than 70. For those aged 70-85 years, biomarker testing is only recommended for patients with specific clinical features. For patients older than 85, biomarker testing is recommended only in “exceptional circumstances.”

Dr. Frisoni noted that the consensus document has a number of limitations.

“First of all, we could not capture all the theoretical possible combinations” of potential diagnosis and relevant biomarker tests. “There are so many that it’s virtually impossible.”

He also noted that the agreement among the panel for the use of some markers was “relatively low” at “barely 50%,” while for others, the agreement was approximately 70%.

The consensus document also does not explicitly address patients with “mixed pathologies,” which are common. In addition, it does not include emerging biomarkers, such as neurofilament light polypeptide levels, an indicator of axonal compromise.

“Last, but not least,” Dr. Frisoni said, the consensus document requires validation.

“This is a paper and pencil exercise. We, as self-appointed experts, can recommend ... whatever we want, but we must check whether what we write is applicable, feasible.”

In other words, it must be determined whether the “real patient journey” fits with the “ideal patient journey” set out in the consensus document.

This kind of validation, Dr. Frisoni said, is “usually not done for this type of exercise,” but “we want to do it in this case.”
 

Pros and cons

Bogdan Draganski, MD, consultant in neurology at the department of clinical neurosciences and director of the neuroimaging research laboratory, University Hospital of Lausanne (Switzerland), who cochaired the session, told this news organization that he was “swaying between two extremes” when considering the usefulness of the consensus document.

On one hand, the “reductionist approach” of breaking down a “complex issue into an algorithm” via the Delphi method risks introducing subjective bias.

He said machine learning and artificial intelligence could answer some of the questions posed by clinicians and, by extension, the statements included in the Delphi process by assessing the available data in a more objective manner.

On the other hand, Dr. Draganski said that reducing the options available to clinicians when making a differential diagnosis into the current algorithm is, pragmatically speaking, a “good approach.”

From this standpoint, the danger of using machine learning to answer clinical questions is that it “doesn’t take the responsibility” for the final decision, which means “we’re closing the loop of subjective decision-making for an individual doctor.”

He also applauded the idea of trying to provide more uniform patient assessment across Europe, although he believes “we have a long way to go” before it can deliver on the promise of personalized medicine.

Like Dr. Frisoni, Dr. Draganski noted the fact that patients with potential neurocognitive disorders often have multiple pathologies, which can include cardiovascular problems, depression, and cancer and that that could affect the choice of diagnostic biomarkers.

The second issue, he said, concerns implementation of the consensus document, which is a political decision that centers around “how politicians will define ‘uniformity’ and equal access to technological or nontechnological platforms.”

Achieving uniformity will require a pan-regional collaboration, he noted.

The task force was supported by unrestricted grants from F. Hoffmann-La Roche, Biogen International GmbH, Eisai Europe Limited, Life Molecular Imaging GmbH, and OM Pharma Suisse SA. The authors have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A new European consensus statement offers expert guidance on which biomarkers to use for patients presenting with cognitive complaints.

Led by Giovanni B. Frisoni, MD, laboratory of neuroimaging of aging, University of Geneva, and director of the memory clinic at Geneva University Hospital, the multidisciplinary task force set out to define a patient-centered diagnostic workflow for the rational and cost-effective use of biomarkers in memory clinics.

The new algorithm is part of a consensus statement presented at the Congress of the European Academy of Neurology 2023. An interim update was published in June in Alzheimer’s and Dementia.
 

Which biomarker?

Many biomarkers can aid diagnosis, said Dr. Frisoni; the challenge is choosing which biomarker to use for an individual patient.

A literature-based search, he said, yields a number of recommendations, but the vast majority of these are either disease based or biomarker based. The task force notes that “in vivo biomarkers enable early etiological diagnosis of neurocognitive disorders. While they have good analytical validity, their clinical validity and utility are uncertain.”

“When you have a patient in front of you, you don’ t know whether they have Alzheimer’s disease,” Dr. Frisoni said.

“You have a differential diagnosis to make, and you have a number of biomarkers – a number of weapons in your armamentarium – you have to choose. You can’t use all of them – we would like to, but we cannot.”

He added that trying to determine from the literature which biomarker is most appropriate given individual clinical conditions and all of the potential combinations is impossible.

“You will not find evidence of the comparative diagnostic value and the added diagnostic value” of one test vs, another, he noted.

“Is CSF [cerebrospinal fluid] better than amyloid PET in a particular clinical situation? What do I gain in terms of positive and negative predictive value in all the possible clinical conditions that I encounter in my clinical practice?”

Dr. Frisoni said the reality is that clinicians in memory clinics end up using biomarkers that are “based on clinical opportunities.”

For instance, “if you have a proficient nuclear medic, you use PET a lot.” In contrast, “if you have a proficient laboratory medic,” CSF markers will be favored – a situation that he said is “not ideal” and has resulted in large discrepancies in diagnostic approaches across Europe.
 

Harmonizing clinical practice

In a bid to harmonize clinical practice, 22 European experts from 11 European scientific societies and the executive director of Alzheimer Europe set out to develop a multidisciplinary consensus algorithm for the biomarker-based diagnosis of neurocognitive disorders in general, rather than specific neurocognitive disorders.

They used the Delphi method, in which a systematic literature review of the literature was followed by the drafting of a series of clinical statements by an executive board. These were then presented to the expert panel. If a majority consensus was reached on a given statement, it was considered closed. Questions for which there was no consensus were revised and presented to the panel again. The process was repeated until a consensus was reached.

A total of 56 statements underwent six rounds of discussion. A final online meeting led to the development of a diagnostic algorithm for patients who attend memory clinics for cognitive complaints.

The algorithm features three potential assessment waves. Wave 1 defines 11 clinical profiles that are based on the results of clinical and neuropsychological assessments, blood exams, brain imaging, and, in specific cases, electroencephalography. Wave 2 defines first-line biomarkers based on Wave 1 clinical profiles, and Wave 3 defines the second-line biomarker based on Wave 2 biomarker results.

When a patient’s clinical profile suggests Alzheimer’s disease and, in undefined cases, cerebrospinal fluid biomarkers are used first line. When CSF is inconclusive, 18-fluorodeoxyglucose positron emission tomography (FDG-PET) is used second line.

When the clinical profile suggests frontotemporal lobar degeneration or motor tauopathies, FDG-PET is first line and CSF biomarkers second line in atypical metabolic patter cases. When the clinical profile suggests Lewy body disease, dopamine transporter SPECT is first line and cardia I23I-metaiodobenzylguanidine scintigraphy is second line.

Dr. Frisoni noted that the panel strongly recommends performing biomarker tests for patients younger than 70. For those aged 70-85 years, biomarker testing is only recommended for patients with specific clinical features. For patients older than 85, biomarker testing is recommended only in “exceptional circumstances.”

Dr. Frisoni noted that the consensus document has a number of limitations.

“First of all, we could not capture all the theoretical possible combinations” of potential diagnosis and relevant biomarker tests. “There are so many that it’s virtually impossible.”

He also noted that the agreement among the panel for the use of some markers was “relatively low” at “barely 50%,” while for others, the agreement was approximately 70%.

The consensus document also does not explicitly address patients with “mixed pathologies,” which are common. In addition, it does not include emerging biomarkers, such as neurofilament light polypeptide levels, an indicator of axonal compromise.

“Last, but not least,” Dr. Frisoni said, the consensus document requires validation.

“This is a paper and pencil exercise. We, as self-appointed experts, can recommend ... whatever we want, but we must check whether what we write is applicable, feasible.”

In other words, it must be determined whether the “real patient journey” fits with the “ideal patient journey” set out in the consensus document.

This kind of validation, Dr. Frisoni said, is “usually not done for this type of exercise,” but “we want to do it in this case.”
 

Pros and cons

Bogdan Draganski, MD, consultant in neurology at the department of clinical neurosciences and director of the neuroimaging research laboratory, University Hospital of Lausanne (Switzerland), who cochaired the session, told this news organization that he was “swaying between two extremes” when considering the usefulness of the consensus document.

On one hand, the “reductionist approach” of breaking down a “complex issue into an algorithm” via the Delphi method risks introducing subjective bias.

He said machine learning and artificial intelligence could answer some of the questions posed by clinicians and, by extension, the statements included in the Delphi process by assessing the available data in a more objective manner.

On the other hand, Dr. Draganski said that reducing the options available to clinicians when making a differential diagnosis into the current algorithm is, pragmatically speaking, a “good approach.”

From this standpoint, the danger of using machine learning to answer clinical questions is that it “doesn’t take the responsibility” for the final decision, which means “we’re closing the loop of subjective decision-making for an individual doctor.”

He also applauded the idea of trying to provide more uniform patient assessment across Europe, although he believes “we have a long way to go” before it can deliver on the promise of personalized medicine.

Like Dr. Frisoni, Dr. Draganski noted the fact that patients with potential neurocognitive disorders often have multiple pathologies, which can include cardiovascular problems, depression, and cancer and that that could affect the choice of diagnostic biomarkers.

The second issue, he said, concerns implementation of the consensus document, which is a political decision that centers around “how politicians will define ‘uniformity’ and equal access to technological or nontechnological platforms.”

Achieving uniformity will require a pan-regional collaboration, he noted.

The task force was supported by unrestricted grants from F. Hoffmann-La Roche, Biogen International GmbH, Eisai Europe Limited, Life Molecular Imaging GmbH, and OM Pharma Suisse SA. The authors have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A new European consensus statement offers expert guidance on which biomarkers to use for patients presenting with cognitive complaints.

Led by Giovanni B. Frisoni, MD, laboratory of neuroimaging of aging, University of Geneva, and director of the memory clinic at Geneva University Hospital, the multidisciplinary task force set out to define a patient-centered diagnostic workflow for the rational and cost-effective use of biomarkers in memory clinics.

The new algorithm is part of a consensus statement presented at the Congress of the European Academy of Neurology 2023. An interim update was published in June in Alzheimer’s and Dementia.
 

Which biomarker?

Many biomarkers can aid diagnosis, said Dr. Frisoni; the challenge is choosing which biomarker to use for an individual patient.

A literature-based search, he said, yields a number of recommendations, but the vast majority of these are either disease based or biomarker based. The task force notes that “in vivo biomarkers enable early etiological diagnosis of neurocognitive disorders. While they have good analytical validity, their clinical validity and utility are uncertain.”

“When you have a patient in front of you, you don’ t know whether they have Alzheimer’s disease,” Dr. Frisoni said.

“You have a differential diagnosis to make, and you have a number of biomarkers – a number of weapons in your armamentarium – you have to choose. You can’t use all of them – we would like to, but we cannot.”

He added that trying to determine from the literature which biomarker is most appropriate given individual clinical conditions and all of the potential combinations is impossible.

“You will not find evidence of the comparative diagnostic value and the added diagnostic value” of one test vs, another, he noted.

“Is CSF [cerebrospinal fluid] better than amyloid PET in a particular clinical situation? What do I gain in terms of positive and negative predictive value in all the possible clinical conditions that I encounter in my clinical practice?”

Dr. Frisoni said the reality is that clinicians in memory clinics end up using biomarkers that are “based on clinical opportunities.”

For instance, “if you have a proficient nuclear medic, you use PET a lot.” In contrast, “if you have a proficient laboratory medic,” CSF markers will be favored – a situation that he said is “not ideal” and has resulted in large discrepancies in diagnostic approaches across Europe.
 

Harmonizing clinical practice

In a bid to harmonize clinical practice, 22 European experts from 11 European scientific societies and the executive director of Alzheimer Europe set out to develop a multidisciplinary consensus algorithm for the biomarker-based diagnosis of neurocognitive disorders in general, rather than specific neurocognitive disorders.

They used the Delphi method, in which a systematic literature review of the literature was followed by the drafting of a series of clinical statements by an executive board. These were then presented to the expert panel. If a majority consensus was reached on a given statement, it was considered closed. Questions for which there was no consensus were revised and presented to the panel again. The process was repeated until a consensus was reached.

A total of 56 statements underwent six rounds of discussion. A final online meeting led to the development of a diagnostic algorithm for patients who attend memory clinics for cognitive complaints.

The algorithm features three potential assessment waves. Wave 1 defines 11 clinical profiles that are based on the results of clinical and neuropsychological assessments, blood exams, brain imaging, and, in specific cases, electroencephalography. Wave 2 defines first-line biomarkers based on Wave 1 clinical profiles, and Wave 3 defines the second-line biomarker based on Wave 2 biomarker results.

When a patient’s clinical profile suggests Alzheimer’s disease and, in undefined cases, cerebrospinal fluid biomarkers are used first line. When CSF is inconclusive, 18-fluorodeoxyglucose positron emission tomography (FDG-PET) is used second line.

When the clinical profile suggests frontotemporal lobar degeneration or motor tauopathies, FDG-PET is first line and CSF biomarkers second line in atypical metabolic patter cases. When the clinical profile suggests Lewy body disease, dopamine transporter SPECT is first line and cardia I23I-metaiodobenzylguanidine scintigraphy is second line.

Dr. Frisoni noted that the panel strongly recommends performing biomarker tests for patients younger than 70. For those aged 70-85 years, biomarker testing is only recommended for patients with specific clinical features. For patients older than 85, biomarker testing is recommended only in “exceptional circumstances.”

Dr. Frisoni noted that the consensus document has a number of limitations.

“First of all, we could not capture all the theoretical possible combinations” of potential diagnosis and relevant biomarker tests. “There are so many that it’s virtually impossible.”

He also noted that the agreement among the panel for the use of some markers was “relatively low” at “barely 50%,” while for others, the agreement was approximately 70%.

The consensus document also does not explicitly address patients with “mixed pathologies,” which are common. In addition, it does not include emerging biomarkers, such as neurofilament light polypeptide levels, an indicator of axonal compromise.

“Last, but not least,” Dr. Frisoni said, the consensus document requires validation.

“This is a paper and pencil exercise. We, as self-appointed experts, can recommend ... whatever we want, but we must check whether what we write is applicable, feasible.”

In other words, it must be determined whether the “real patient journey” fits with the “ideal patient journey” set out in the consensus document.

This kind of validation, Dr. Frisoni said, is “usually not done for this type of exercise,” but “we want to do it in this case.”
 

Pros and cons

Bogdan Draganski, MD, consultant in neurology at the department of clinical neurosciences and director of the neuroimaging research laboratory, University Hospital of Lausanne (Switzerland), who cochaired the session, told this news organization that he was “swaying between two extremes” when considering the usefulness of the consensus document.

On one hand, the “reductionist approach” of breaking down a “complex issue into an algorithm” via the Delphi method risks introducing subjective bias.

He said machine learning and artificial intelligence could answer some of the questions posed by clinicians and, by extension, the statements included in the Delphi process by assessing the available data in a more objective manner.

On the other hand, Dr. Draganski said that reducing the options available to clinicians when making a differential diagnosis into the current algorithm is, pragmatically speaking, a “good approach.”

From this standpoint, the danger of using machine learning to answer clinical questions is that it “doesn’t take the responsibility” for the final decision, which means “we’re closing the loop of subjective decision-making for an individual doctor.”

He also applauded the idea of trying to provide more uniform patient assessment across Europe, although he believes “we have a long way to go” before it can deliver on the promise of personalized medicine.

Like Dr. Frisoni, Dr. Draganski noted the fact that patients with potential neurocognitive disorders often have multiple pathologies, which can include cardiovascular problems, depression, and cancer and that that could affect the choice of diagnostic biomarkers.

The second issue, he said, concerns implementation of the consensus document, which is a political decision that centers around “how politicians will define ‘uniformity’ and equal access to technological or nontechnological platforms.”

Achieving uniformity will require a pan-regional collaboration, he noted.

The task force was supported by unrestricted grants from F. Hoffmann-La Roche, Biogen International GmbH, Eisai Europe Limited, Life Molecular Imaging GmbH, and OM Pharma Suisse SA. The authors have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Kate Whitley was petrified of COVID-19 from the beginning of the pandemic because she has Hashimoto disease, an autoimmune disorder that she knew put her at high risk for complications.

She was right to be worried. Two months after contracting the infection in September 2022, the 42-year-old Nashville resident was diagnosed with long COVID. For Ms. Whitley, the resulting brain fog has been the most challenging factor. She is the owner of a successful paper goods store, and she can’t remember basic aspects of her job. She can’t tolerate loud noises and gets so distracted that she has trouble remembering what she was doing.

Ms. Whitley doesn’t like the term “brain fog” because it doesn’t begin to describe the dramatic disruption to her life over the past 7 months.

“I just can’t think anymore,” she said. “It makes you realize that you’re nothing without your brain. Sometimes I feel like a shell of my former self.”

Brain fog is among the most common symptoms of long COVID, and also one of the most poorly understood. A reported 46% of those diagnosed with long COVID complain of brain fog or a loss of memory. Many clinicians agree that the term is vague and often doesn’t truly represent the condition. That, in turn, makes it harder for doctors to diagnose and treat it. There are no standard tests for it, nor are there guidelines for symptom management or treatment.

“There’s a lot of imprecision in the term because it might mean different things to different patients,” said James C. Jackson, PsyD, a neuropsychiatrist at Vanderbilt University, Nashville, Tenn., and author of a new book, “Clearing the Fog: From Surviving to Thriving With Long COVID – A Practical Guide.”

Dr. Jackson, who began treating Ms. Whitley in February 2023, said that it makes more sense to call brain fog a brain impairment or an acquired brain injury (ABI) because it doesn’t occur gradually. COVID damages the brain and causes injury. For those with long COVID who were previously in the intensive care unit and may have undergone ventilation, hypoxic brain injury may result from the lack of oxygen to the brain.

Even among those with milder cases of acute COVID, there’s some evidence that persistent neuroinflammation in the brain caused by an activated immune system may also cause damage.

In both cases, the results can be debilitating. Ms. Whitley also has dysautonomia – a disorder of the autonomic nervous system that can cause dizziness, sweating, and headaches along with fatigue and heart palpitations.

She said that she’s so forgetful that when she sees people socially, she’s nervous of what she’ll say. “I feel like I’m constantly sticking my foot in my mouth because I can’t remember details of other people’s lives,” she said.

Although brain disorders such as Alzheimer’s disease and other forms of dementia are marked by a slow decline, ABI occurs more suddenly and may include a loss of executive function and attention.

“With a brain injury, you’re doing fine, and then some event happens (in this case COVID), and immediately after that, your cognitive function is different,” said Dr. Jackson.

Additionally, ABI is an actual diagnosis, whereas brain fog is not.

“With a brain injury, there’s a treatment pathway for cognitive rehabilitation,” said Dr. Jackson.

Treatments may include speech, cognitive, and occupational therapy as well as meeting with a neuropsychiatrist for treatment of the mental and behavioral disorders that may result. Dr. Jackson said that while many patients aren’t functioning cognitively or physically at 100%, they can make enough strides that they don’t have to give up things such as driving and, in some cases, their jobs.

Other experts agree that long COVID may damage the brain. An April 2022 study published in the journal Nature found strong evidence that SARS-CoV-2 infection may cause brain-related abnormalities, for example, a reduction in gray matter in certain parts of the brain, including the prefrontal cortex, hypothalamus, and amygdala.

Additionally, white matter, which is found deeper in the brain and is responsible for the exchange of information between different parts of the brain, may also be at risk of damage as a result of the virus, according to a November 2022 study published in the journal SN Comprehensive Clinical Medicine.

Calling it a “fog” makes it easier for clinicians and the general public to dismiss its severity, said Tyler Reed Bell, PhD, a researcher who specializes in viruses that cause brain injury. He is a fellow in the department of psychiatry at the University of California, San Diego. Brain fog can make driving and returning to work especially dangerous. Because of difficulty focusing, patients are much more likely to make mistakes that cause accidents.

“The COVID virus is very invasive to the brain,” Dr. Bell said.

Others contend this may be a rush to judgment. Karla L. Thompson, PhD, lead neuropsychologist at the University of North Carolina at Chapel Hill’s COVID Recovery Clinic, agrees that in more serious cases of COVID that cause a lack of oxygen to the brain, it’s reasonable to call it a brain injury. But brain fog can also be associated with other long COVID symptoms, not just damage to the brain.

Chronic fatigue and poor sleep are both commonly reported symptoms of long COVID that negatively affect brain function, she said. Sleep disturbances, cardiac problems, dysautonomia, and emotional distress could also affect the way the brain functions post COVID. Finding the right treatment requires identifying all the factors contributing to cognitive impairment.

Part of the problem in treating long COVID brain fog is that diagnostic technology is not sensitive enough to detect inflammation that could be causing damage.

Grace McComsey, MD, who leads the long COVID RECOVER study at University Hospitals Health System in Cleveland, said her team is working on identifying biomarkers that could detect brain inflammation in a way similar to the manner researchers have identified biomarkers to help diagnose chronic fatigue syndrome. Additionally, a new study published last month in JAMA for the first time clearly defined 12 symptoms of long COVID, and brain fog was listed among them. All of this contributes to the development of clear diagnostic criteria.

“It will make a big difference once we have some consistency among clinicians in diagnosing the condition,” said Dr. McComsey.

Ms. Whitley is thankful for the treatment that she’s received thus far. She’s seeing a cognitive rehabilitation therapist, who assesses her memory, cognition, and attention span and gives her tools to break up simple tasks, such as driving, so that they don’t feel overwhelming. She’s back behind the wheel and back to work.

But perhaps most importantly, Ms. Whitley joined a support group, led by Dr. Jackson, that includes other people experiencing the same symptoms she is. When she was at her darkest, they understood.

“Talking to other survivors has been the only solace in all this,” Ms. Whitley said. “Together, we grieve all that’s been lost.”

A version of this article first appeared on Medscape.com.

Kate Whitley was petrified of COVID-19 from the beginning of the pandemic because she has Hashimoto disease, an autoimmune disorder that she knew put her at high risk for complications.

She was right to be worried. Two months after contracting the infection in September 2022, the 42-year-old Nashville resident was diagnosed with long COVID. For Ms. Whitley, the resulting brain fog has been the most challenging factor. She is the owner of a successful paper goods store, and she can’t remember basic aspects of her job. She can’t tolerate loud noises and gets so distracted that she has trouble remembering what she was doing.

Ms. Whitley doesn’t like the term “brain fog” because it doesn’t begin to describe the dramatic disruption to her life over the past 7 months.

“I just can’t think anymore,” she said. “It makes you realize that you’re nothing without your brain. Sometimes I feel like a shell of my former self.”

Brain fog is among the most common symptoms of long COVID, and also one of the most poorly understood. A reported 46% of those diagnosed with long COVID complain of brain fog or a loss of memory. Many clinicians agree that the term is vague and often doesn’t truly represent the condition. That, in turn, makes it harder for doctors to diagnose and treat it. There are no standard tests for it, nor are there guidelines for symptom management or treatment.

“There’s a lot of imprecision in the term because it might mean different things to different patients,” said James C. Jackson, PsyD, a neuropsychiatrist at Vanderbilt University, Nashville, Tenn., and author of a new book, “Clearing the Fog: From Surviving to Thriving With Long COVID – A Practical Guide.”

Dr. Jackson, who began treating Ms. Whitley in February 2023, said that it makes more sense to call brain fog a brain impairment or an acquired brain injury (ABI) because it doesn’t occur gradually. COVID damages the brain and causes injury. For those with long COVID who were previously in the intensive care unit and may have undergone ventilation, hypoxic brain injury may result from the lack of oxygen to the brain.

Even among those with milder cases of acute COVID, there’s some evidence that persistent neuroinflammation in the brain caused by an activated immune system may also cause damage.

In both cases, the results can be debilitating. Ms. Whitley also has dysautonomia – a disorder of the autonomic nervous system that can cause dizziness, sweating, and headaches along with fatigue and heart palpitations.

She said that she’s so forgetful that when she sees people socially, she’s nervous of what she’ll say. “I feel like I’m constantly sticking my foot in my mouth because I can’t remember details of other people’s lives,” she said.

Although brain disorders such as Alzheimer’s disease and other forms of dementia are marked by a slow decline, ABI occurs more suddenly and may include a loss of executive function and attention.

“With a brain injury, you’re doing fine, and then some event happens (in this case COVID), and immediately after that, your cognitive function is different,” said Dr. Jackson.

Additionally, ABI is an actual diagnosis, whereas brain fog is not.

“With a brain injury, there’s a treatment pathway for cognitive rehabilitation,” said Dr. Jackson.

Treatments may include speech, cognitive, and occupational therapy as well as meeting with a neuropsychiatrist for treatment of the mental and behavioral disorders that may result. Dr. Jackson said that while many patients aren’t functioning cognitively or physically at 100%, they can make enough strides that they don’t have to give up things such as driving and, in some cases, their jobs.

Other experts agree that long COVID may damage the brain. An April 2022 study published in the journal Nature found strong evidence that SARS-CoV-2 infection may cause brain-related abnormalities, for example, a reduction in gray matter in certain parts of the brain, including the prefrontal cortex, hypothalamus, and amygdala.

Additionally, white matter, which is found deeper in the brain and is responsible for the exchange of information between different parts of the brain, may also be at risk of damage as a result of the virus, according to a November 2022 study published in the journal SN Comprehensive Clinical Medicine.

Calling it a “fog” makes it easier for clinicians and the general public to dismiss its severity, said Tyler Reed Bell, PhD, a researcher who specializes in viruses that cause brain injury. He is a fellow in the department of psychiatry at the University of California, San Diego. Brain fog can make driving and returning to work especially dangerous. Because of difficulty focusing, patients are much more likely to make mistakes that cause accidents.

“The COVID virus is very invasive to the brain,” Dr. Bell said.

Others contend this may be a rush to judgment. Karla L. Thompson, PhD, lead neuropsychologist at the University of North Carolina at Chapel Hill’s COVID Recovery Clinic, agrees that in more serious cases of COVID that cause a lack of oxygen to the brain, it’s reasonable to call it a brain injury. But brain fog can also be associated with other long COVID symptoms, not just damage to the brain.

Chronic fatigue and poor sleep are both commonly reported symptoms of long COVID that negatively affect brain function, she said. Sleep disturbances, cardiac problems, dysautonomia, and emotional distress could also affect the way the brain functions post COVID. Finding the right treatment requires identifying all the factors contributing to cognitive impairment.

Part of the problem in treating long COVID brain fog is that diagnostic technology is not sensitive enough to detect inflammation that could be causing damage.

Grace McComsey, MD, who leads the long COVID RECOVER study at University Hospitals Health System in Cleveland, said her team is working on identifying biomarkers that could detect brain inflammation in a way similar to the manner researchers have identified biomarkers to help diagnose chronic fatigue syndrome. Additionally, a new study published last month in JAMA for the first time clearly defined 12 symptoms of long COVID, and brain fog was listed among them. All of this contributes to the development of clear diagnostic criteria.

“It will make a big difference once we have some consistency among clinicians in diagnosing the condition,” said Dr. McComsey.

Ms. Whitley is thankful for the treatment that she’s received thus far. She’s seeing a cognitive rehabilitation therapist, who assesses her memory, cognition, and attention span and gives her tools to break up simple tasks, such as driving, so that they don’t feel overwhelming. She’s back behind the wheel and back to work.

But perhaps most importantly, Ms. Whitley joined a support group, led by Dr. Jackson, that includes other people experiencing the same symptoms she is. When she was at her darkest, they understood.

“Talking to other survivors has been the only solace in all this,” Ms. Whitley said. “Together, we grieve all that’s been lost.”

A version of this article first appeared on Medscape.com.

Kate Whitley was petrified of COVID-19 from the beginning of the pandemic because she has Hashimoto disease, an autoimmune disorder that she knew put her at high risk for complications.

She was right to be worried. Two months after contracting the infection in September 2022, the 42-year-old Nashville resident was diagnosed with long COVID. For Ms. Whitley, the resulting brain fog has been the most challenging factor. She is the owner of a successful paper goods store, and she can’t remember basic aspects of her job. She can’t tolerate loud noises and gets so distracted that she has trouble remembering what she was doing.

Ms. Whitley doesn’t like the term “brain fog” because it doesn’t begin to describe the dramatic disruption to her life over the past 7 months.

“I just can’t think anymore,” she said. “It makes you realize that you’re nothing without your brain. Sometimes I feel like a shell of my former self.”

Brain fog is among the most common symptoms of long COVID, and also one of the most poorly understood. A reported 46% of those diagnosed with long COVID complain of brain fog or a loss of memory. Many clinicians agree that the term is vague and often doesn’t truly represent the condition. That, in turn, makes it harder for doctors to diagnose and treat it. There are no standard tests for it, nor are there guidelines for symptom management or treatment.

“There’s a lot of imprecision in the term because it might mean different things to different patients,” said James C. Jackson, PsyD, a neuropsychiatrist at Vanderbilt University, Nashville, Tenn., and author of a new book, “Clearing the Fog: From Surviving to Thriving With Long COVID – A Practical Guide.”

Dr. Jackson, who began treating Ms. Whitley in February 2023, said that it makes more sense to call brain fog a brain impairment or an acquired brain injury (ABI) because it doesn’t occur gradually. COVID damages the brain and causes injury. For those with long COVID who were previously in the intensive care unit and may have undergone ventilation, hypoxic brain injury may result from the lack of oxygen to the brain.

Even among those with milder cases of acute COVID, there’s some evidence that persistent neuroinflammation in the brain caused by an activated immune system may also cause damage.

In both cases, the results can be debilitating. Ms. Whitley also has dysautonomia – a disorder of the autonomic nervous system that can cause dizziness, sweating, and headaches along with fatigue and heart palpitations.

She said that she’s so forgetful that when she sees people socially, she’s nervous of what she’ll say. “I feel like I’m constantly sticking my foot in my mouth because I can’t remember details of other people’s lives,” she said.

Although brain disorders such as Alzheimer’s disease and other forms of dementia are marked by a slow decline, ABI occurs more suddenly and may include a loss of executive function and attention.

“With a brain injury, you’re doing fine, and then some event happens (in this case COVID), and immediately after that, your cognitive function is different,” said Dr. Jackson.

Additionally, ABI is an actual diagnosis, whereas brain fog is not.

“With a brain injury, there’s a treatment pathway for cognitive rehabilitation,” said Dr. Jackson.

Treatments may include speech, cognitive, and occupational therapy as well as meeting with a neuropsychiatrist for treatment of the mental and behavioral disorders that may result. Dr. Jackson said that while many patients aren’t functioning cognitively or physically at 100%, they can make enough strides that they don’t have to give up things such as driving and, in some cases, their jobs.

Other experts agree that long COVID may damage the brain. An April 2022 study published in the journal Nature found strong evidence that SARS-CoV-2 infection may cause brain-related abnormalities, for example, a reduction in gray matter in certain parts of the brain, including the prefrontal cortex, hypothalamus, and amygdala.

Additionally, white matter, which is found deeper in the brain and is responsible for the exchange of information between different parts of the brain, may also be at risk of damage as a result of the virus, according to a November 2022 study published in the journal SN Comprehensive Clinical Medicine.

Calling it a “fog” makes it easier for clinicians and the general public to dismiss its severity, said Tyler Reed Bell, PhD, a researcher who specializes in viruses that cause brain injury. He is a fellow in the department of psychiatry at the University of California, San Diego. Brain fog can make driving and returning to work especially dangerous. Because of difficulty focusing, patients are much more likely to make mistakes that cause accidents.

“The COVID virus is very invasive to the brain,” Dr. Bell said.

Others contend this may be a rush to judgment. Karla L. Thompson, PhD, lead neuropsychologist at the University of North Carolina at Chapel Hill’s COVID Recovery Clinic, agrees that in more serious cases of COVID that cause a lack of oxygen to the brain, it’s reasonable to call it a brain injury. But brain fog can also be associated with other long COVID symptoms, not just damage to the brain.

Chronic fatigue and poor sleep are both commonly reported symptoms of long COVID that negatively affect brain function, she said. Sleep disturbances, cardiac problems, dysautonomia, and emotional distress could also affect the way the brain functions post COVID. Finding the right treatment requires identifying all the factors contributing to cognitive impairment.

Part of the problem in treating long COVID brain fog is that diagnostic technology is not sensitive enough to detect inflammation that could be causing damage.

Grace McComsey, MD, who leads the long COVID RECOVER study at University Hospitals Health System in Cleveland, said her team is working on identifying biomarkers that could detect brain inflammation in a way similar to the manner researchers have identified biomarkers to help diagnose chronic fatigue syndrome. Additionally, a new study published last month in JAMA for the first time clearly defined 12 symptoms of long COVID, and brain fog was listed among them. All of this contributes to the development of clear diagnostic criteria.

“It will make a big difference once we have some consistency among clinicians in diagnosing the condition,” said Dr. McComsey.

Ms. Whitley is thankful for the treatment that she’s received thus far. She’s seeing a cognitive rehabilitation therapist, who assesses her memory, cognition, and attention span and gives her tools to break up simple tasks, such as driving, so that they don’t feel overwhelming. She’s back behind the wheel and back to work.

But perhaps most importantly, Ms. Whitley joined a support group, led by Dr. Jackson, that includes other people experiencing the same symptoms she is. When she was at her darkest, they understood.

“Talking to other survivors has been the only solace in all this,” Ms. Whitley said. “Together, we grieve all that’s been lost.”

A version of this article first appeared on Medscape.com.

Lean muscle mass may offer protection against the development of Alzheimer’s disease (AD), new research suggests.

Investigators analyzed data on more than 450,000 participants in the UK Biobank as well as two independent samples of more than 320,000 individuals with and without AD, and more than 260,000 individuals participating in a separate genes and intelligence study.

They estimated lean muscle and fat tissue in the arms and legs and found, in adjusted analyses, over 500 genetic variants associated with lean mass.

On average, higher genetically lean mass was associated with a “modest but statistically robust” reduction in AD risk and with superior performance on cognitive tasks.

“Using human genetic data, we found evidence for a protective effect of lean mass on risk of Alzheimer’s disease,” study investigators Iyas Daghlas, MD, a resident in the department of neurology, University of California, San Francisco, said in an interview.

Although “clinical intervention studies are needed to confirm this effect, this study supports current recommendations to maintain a healthy lifestyle to prevent dementia,” he said.

The study was published online in BMJ Medicine.
 

Naturally randomized research

Several measures of body composition have been investigated for their potential association with AD. Lean mass – a “proxy for muscle mass, defined as the difference between total mass and fat mass” – has been shown to be reduced in patients with AD compared with controls, the researchers noted.

“Previous research studies have tested the relationship of body mass index with Alzheimer’s disease and did not find evidence for a causal effect,” Dr. Daghlas said. “We wondered whether BMI was an insufficiently granular measure and hypothesized that disaggregating body mass into lean mass and fat mass could reveal novel associations with disease.”

Most studies have used case-control designs, which might be biased by “residual confounding or reverse causality.” Naturally randomized data “may be used as an alternative to conventional observational studies to investigate causal relations between risk factors and diseases,” the researchers wrote.

In particular, the Mendelian randomization (MR) paradigm randomly allocates germline genetic variants and uses them as proxies for a specific risk factor.

MR “is a technique that permits researchers to investigate cause-and-effect relationships using human genetic data,” Dr. Daghlas explained. “In effect, we’re studying the results of a naturally randomized experiment whereby some individuals are genetically allocated to carry more lean mass.” 

The current study used MR to investigate the effect of genetically proxied lean mass on the risk of AD and the “related phenotype” of cognitive performance.
 

Genetic proxy

As genetic proxies for lean mass, the researchers chose single nucleotide polymorphisms (genetic variants) that were associated, in a genome-wide association study (GWAS), with appendicular lean mass.

Appendicular lean mass “more accurately reflects the effects of lean mass than whole body lean mass, which includes smooth and cardiac muscle,” the authors explained.

This GWAS used phenotypic and genetic data from 450,243 participants in the UK Biobank cohort (mean age 57 years). All participants were of European ancestry.

The researchers adjusted for age, sex, and genetic ancestry. They measured appendicular lean mass using bioimpedance – an electric current that flows at different rates through the body, depending on its composition.

In addition to the UK Biobank participants, the researchers drew on an independent sample of 21,982 people with AD; a control group of 41,944 people without AD; a replication sample of 7,329 people with and 252,879 people without AD to validate the findings; and 269,867 people taking part in a genome-wide study of cognitive performance.

The researchers identified 584 variants that met criteria for use as genetic proxies for lean mass. None were located within the APOE gene region. In the aggregate, these variants explained 10.3% of the variance in appendicular lean mass.

Each standard deviation increase in genetically proxied lean mass was associated with a 12% reduction in AD risk (odds ratio [OR], 0.88; 95% confidence interval [CI], 0.82-0.95; P < .001). This finding was replicated in the independent consortium (OR, 0.91; 95% CI, 0.83-0.99; P = .02).

The findings remained “consistent” in sensitivity analyses.
 

A modifiable risk factor?

Higher appendicular lean mass was associated with higher levels of cognitive performance, with each SD increase in lean mass associated with an SD increase in cognitive performance (OR, 0.09; 95% CI, 0.06-0.11; P = .001).

“Adjusting for potential mediation through performance did not reduce the association between appendicular lean mass and risk of AD,” the authors wrote.

They obtained similar results using genetically proxied trunk and whole-body lean mass, after adjusting for fat mass.

The authors noted several limitations. The bioimpedance measures “only predict, but do not directly measure, lean mass.” Moreover, the approach didn’t examine whether a “critical window of risk factor timing” exists, during which lean mass might play a role in influencing AD risk and after which “interventions would no longer be effective.” Nor could the study determine whether increasing lean mass could reverse AD pathology in patients with preclinical disease or mild cognitive impairment.

Nevertheless, the findings suggest “that lean mass might be a possible modifiable protective factor for Alzheimer’s disease,” the authors wrote. “The mechanisms underlying this finding, as well as the clinical and public health implications, warrant further investigation.”
 

Novel strategies

In a comment, Iva Miljkovic, MD, PhD, associate professor, department of epidemiology, University of Pittsburgh, said the investigators used “very rigorous methodology.”

The finding suggesting that lean mass is associated with better cognitive function is “important, as cognitive impairment can become stable rather than progress to a pathological state; and, in some cases, can even be reversed.”

In those cases, “identifying the underlying cause – e.g., low lean mass – can significantly improve cognitive function,” said Dr. Miljkovic, senior author of a study showing muscle fat as a risk factor for cognitive decline.

More research will enable us to “expand our understanding” of the mechanisms involved and determine whether interventions aimed at preventing muscle loss and/or increasing muscle fat may have a beneficial effect on cognitive function,” she said. “This might lead to novel strategies to prevent AD.”

Dr. Daghlas is supported by the British Heart Foundation Centre of Research Excellence at Imperial College, London, and is employed part-time by Novo Nordisk. Dr. Miljkovic reports no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Lean muscle mass may offer protection against the development of Alzheimer’s disease (AD), new research suggests.

Investigators analyzed data on more than 450,000 participants in the UK Biobank as well as two independent samples of more than 320,000 individuals with and without AD, and more than 260,000 individuals participating in a separate genes and intelligence study.

They estimated lean muscle and fat tissue in the arms and legs and found, in adjusted analyses, over 500 genetic variants associated with lean mass.

On average, higher genetically lean mass was associated with a “modest but statistically robust” reduction in AD risk and with superior performance on cognitive tasks.

“Using human genetic data, we found evidence for a protective effect of lean mass on risk of Alzheimer’s disease,” study investigators Iyas Daghlas, MD, a resident in the department of neurology, University of California, San Francisco, said in an interview.

Although “clinical intervention studies are needed to confirm this effect, this study supports current recommendations to maintain a healthy lifestyle to prevent dementia,” he said.

The study was published online in BMJ Medicine.
 

Naturally randomized research

Several measures of body composition have been investigated for their potential association with AD. Lean mass – a “proxy for muscle mass, defined as the difference between total mass and fat mass” – has been shown to be reduced in patients with AD compared with controls, the researchers noted.

“Previous research studies have tested the relationship of body mass index with Alzheimer’s disease and did not find evidence for a causal effect,” Dr. Daghlas said. “We wondered whether BMI was an insufficiently granular measure and hypothesized that disaggregating body mass into lean mass and fat mass could reveal novel associations with disease.”

Most studies have used case-control designs, which might be biased by “residual confounding or reverse causality.” Naturally randomized data “may be used as an alternative to conventional observational studies to investigate causal relations between risk factors and diseases,” the researchers wrote.

In particular, the Mendelian randomization (MR) paradigm randomly allocates germline genetic variants and uses them as proxies for a specific risk factor.

MR “is a technique that permits researchers to investigate cause-and-effect relationships using human genetic data,” Dr. Daghlas explained. “In effect, we’re studying the results of a naturally randomized experiment whereby some individuals are genetically allocated to carry more lean mass.” 

The current study used MR to investigate the effect of genetically proxied lean mass on the risk of AD and the “related phenotype” of cognitive performance.
 

Genetic proxy

As genetic proxies for lean mass, the researchers chose single nucleotide polymorphisms (genetic variants) that were associated, in a genome-wide association study (GWAS), with appendicular lean mass.

Appendicular lean mass “more accurately reflects the effects of lean mass than whole body lean mass, which includes smooth and cardiac muscle,” the authors explained.

This GWAS used phenotypic and genetic data from 450,243 participants in the UK Biobank cohort (mean age 57 years). All participants were of European ancestry.

The researchers adjusted for age, sex, and genetic ancestry. They measured appendicular lean mass using bioimpedance – an electric current that flows at different rates through the body, depending on its composition.

In addition to the UK Biobank participants, the researchers drew on an independent sample of 21,982 people with AD; a control group of 41,944 people without AD; a replication sample of 7,329 people with and 252,879 people without AD to validate the findings; and 269,867 people taking part in a genome-wide study of cognitive performance.

The researchers identified 584 variants that met criteria for use as genetic proxies for lean mass. None were located within the APOE gene region. In the aggregate, these variants explained 10.3% of the variance in appendicular lean mass.

Each standard deviation increase in genetically proxied lean mass was associated with a 12% reduction in AD risk (odds ratio [OR], 0.88; 95% confidence interval [CI], 0.82-0.95; P < .001). This finding was replicated in the independent consortium (OR, 0.91; 95% CI, 0.83-0.99; P = .02).

The findings remained “consistent” in sensitivity analyses.
 

A modifiable risk factor?

Higher appendicular lean mass was associated with higher levels of cognitive performance, with each SD increase in lean mass associated with an SD increase in cognitive performance (OR, 0.09; 95% CI, 0.06-0.11; P = .001).

“Adjusting for potential mediation through performance did not reduce the association between appendicular lean mass and risk of AD,” the authors wrote.

They obtained similar results using genetically proxied trunk and whole-body lean mass, after adjusting for fat mass.

The authors noted several limitations. The bioimpedance measures “only predict, but do not directly measure, lean mass.” Moreover, the approach didn’t examine whether a “critical window of risk factor timing” exists, during which lean mass might play a role in influencing AD risk and after which “interventions would no longer be effective.” Nor could the study determine whether increasing lean mass could reverse AD pathology in patients with preclinical disease or mild cognitive impairment.

Nevertheless, the findings suggest “that lean mass might be a possible modifiable protective factor for Alzheimer’s disease,” the authors wrote. “The mechanisms underlying this finding, as well as the clinical and public health implications, warrant further investigation.”
 

Novel strategies

In a comment, Iva Miljkovic, MD, PhD, associate professor, department of epidemiology, University of Pittsburgh, said the investigators used “very rigorous methodology.”

The finding suggesting that lean mass is associated with better cognitive function is “important, as cognitive impairment can become stable rather than progress to a pathological state; and, in some cases, can even be reversed.”

In those cases, “identifying the underlying cause – e.g., low lean mass – can significantly improve cognitive function,” said Dr. Miljkovic, senior author of a study showing muscle fat as a risk factor for cognitive decline.

More research will enable us to “expand our understanding” of the mechanisms involved and determine whether interventions aimed at preventing muscle loss and/or increasing muscle fat may have a beneficial effect on cognitive function,” she said. “This might lead to novel strategies to prevent AD.”

Dr. Daghlas is supported by the British Heart Foundation Centre of Research Excellence at Imperial College, London, and is employed part-time by Novo Nordisk. Dr. Miljkovic reports no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Lean muscle mass may offer protection against the development of Alzheimer’s disease (AD), new research suggests.

Investigators analyzed data on more than 450,000 participants in the UK Biobank as well as two independent samples of more than 320,000 individuals with and without AD, and more than 260,000 individuals participating in a separate genes and intelligence study.

They estimated lean muscle and fat tissue in the arms and legs and found, in adjusted analyses, over 500 genetic variants associated with lean mass.

On average, higher genetically lean mass was associated with a “modest but statistically robust” reduction in AD risk and with superior performance on cognitive tasks.

“Using human genetic data, we found evidence for a protective effect of lean mass on risk of Alzheimer’s disease,” study investigators Iyas Daghlas, MD, a resident in the department of neurology, University of California, San Francisco, said in an interview.

Although “clinical intervention studies are needed to confirm this effect, this study supports current recommendations to maintain a healthy lifestyle to prevent dementia,” he said.

The study was published online in BMJ Medicine.
 

Naturally randomized research

Several measures of body composition have been investigated for their potential association with AD. Lean mass – a “proxy for muscle mass, defined as the difference between total mass and fat mass” – has been shown to be reduced in patients with AD compared with controls, the researchers noted.

“Previous research studies have tested the relationship of body mass index with Alzheimer’s disease and did not find evidence for a causal effect,” Dr. Daghlas said. “We wondered whether BMI was an insufficiently granular measure and hypothesized that disaggregating body mass into lean mass and fat mass could reveal novel associations with disease.”

Most studies have used case-control designs, which might be biased by “residual confounding or reverse causality.” Naturally randomized data “may be used as an alternative to conventional observational studies to investigate causal relations between risk factors and diseases,” the researchers wrote.

In particular, the Mendelian randomization (MR) paradigm randomly allocates germline genetic variants and uses them as proxies for a specific risk factor.

MR “is a technique that permits researchers to investigate cause-and-effect relationships using human genetic data,” Dr. Daghlas explained. “In effect, we’re studying the results of a naturally randomized experiment whereby some individuals are genetically allocated to carry more lean mass.” 

The current study used MR to investigate the effect of genetically proxied lean mass on the risk of AD and the “related phenotype” of cognitive performance.
 

Genetic proxy

As genetic proxies for lean mass, the researchers chose single nucleotide polymorphisms (genetic variants) that were associated, in a genome-wide association study (GWAS), with appendicular lean mass.

Appendicular lean mass “more accurately reflects the effects of lean mass than whole body lean mass, which includes smooth and cardiac muscle,” the authors explained.

This GWAS used phenotypic and genetic data from 450,243 participants in the UK Biobank cohort (mean age 57 years). All participants were of European ancestry.

The researchers adjusted for age, sex, and genetic ancestry. They measured appendicular lean mass using bioimpedance – an electric current that flows at different rates through the body, depending on its composition.

In addition to the UK Biobank participants, the researchers drew on an independent sample of 21,982 people with AD; a control group of 41,944 people without AD; a replication sample of 7,329 people with and 252,879 people without AD to validate the findings; and 269,867 people taking part in a genome-wide study of cognitive performance.

The researchers identified 584 variants that met criteria for use as genetic proxies for lean mass. None were located within the APOE gene region. In the aggregate, these variants explained 10.3% of the variance in appendicular lean mass.

Each standard deviation increase in genetically proxied lean mass was associated with a 12% reduction in AD risk (odds ratio [OR], 0.88; 95% confidence interval [CI], 0.82-0.95; P < .001). This finding was replicated in the independent consortium (OR, 0.91; 95% CI, 0.83-0.99; P = .02).

The findings remained “consistent” in sensitivity analyses.
 

A modifiable risk factor?

Higher appendicular lean mass was associated with higher levels of cognitive performance, with each SD increase in lean mass associated with an SD increase in cognitive performance (OR, 0.09; 95% CI, 0.06-0.11; P = .001).

“Adjusting for potential mediation through performance did not reduce the association between appendicular lean mass and risk of AD,” the authors wrote.

They obtained similar results using genetically proxied trunk and whole-body lean mass, after adjusting for fat mass.

The authors noted several limitations. The bioimpedance measures “only predict, but do not directly measure, lean mass.” Moreover, the approach didn’t examine whether a “critical window of risk factor timing” exists, during which lean mass might play a role in influencing AD risk and after which “interventions would no longer be effective.” Nor could the study determine whether increasing lean mass could reverse AD pathology in patients with preclinical disease or mild cognitive impairment.

Nevertheless, the findings suggest “that lean mass might be a possible modifiable protective factor for Alzheimer’s disease,” the authors wrote. “The mechanisms underlying this finding, as well as the clinical and public health implications, warrant further investigation.”
 

Novel strategies

In a comment, Iva Miljkovic, MD, PhD, associate professor, department of epidemiology, University of Pittsburgh, said the investigators used “very rigorous methodology.”

The finding suggesting that lean mass is associated with better cognitive function is “important, as cognitive impairment can become stable rather than progress to a pathological state; and, in some cases, can even be reversed.”

In those cases, “identifying the underlying cause – e.g., low lean mass – can significantly improve cognitive function,” said Dr. Miljkovic, senior author of a study showing muscle fat as a risk factor for cognitive decline.

More research will enable us to “expand our understanding” of the mechanisms involved and determine whether interventions aimed at preventing muscle loss and/or increasing muscle fat may have a beneficial effect on cognitive function,” she said. “This might lead to novel strategies to prevent AD.”

Dr. Daghlas is supported by the British Heart Foundation Centre of Research Excellence at Imperial College, London, and is employed part-time by Novo Nordisk. Dr. Miljkovic reports no relevant financial relationships.

A version of this article first appeared on Medscape.com.