MDedge Neurology

A proinflammatory diet, as measured by the dietary inflammatory index (DII), is associated with increased risk of all-cause dementia, although not Alzheimer’s disease, according to a new analysis of longitudinal data from the Framingham Heart Study Offspring Cohort.

The lack of an association with Alzheimer’s disease was a surprise because amyloid-beta prompts microglia and astrocytes to release markers of systemic inflammation, according to Debora Melo van Lent, PhD, who is a postdoctoral fellow at the University of Texas Health San Antonio – Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases. “We expected to see a relationship between higher DII scores and an increased risk for incident Alzheimer’s disease,” said Dr. Melo van Lent, who presented the findings at the 2021 Alzheimer’s Association International Conference.

Dr. Melo van Lent added that the most likely explanation is that the study was underpowered to produce a positive association, and the team is conducting further study in a larger population.
 

A modifiable risk factor

The study is the first to look at all-cause dementia and Alzheimer’s disease dementia and their association with DII, Dr. Melo van Lent said.

“As diet is a modifiable risk factor, we can actually do something about it. If we take a closer look at five components of the DII which are most anti-inflammatory, these components are present in green leafy vegetables, vegetables, fruit, soy, whole grains, and green and black tea. Most of these components are included in the Mediterranean diet. When we look at the three most proinflammatory components, they are present in high caloric products; such as butter or margarine, pastries and sweets, fried snacks, and red or processed meat. These components are present in ‘Western diets,’ which are discouraged,” said Dr. Melo van Lent.

The researchers analyzed data from 1,486 participants who were free of dementia, stroke, or other neurologic diseases at baseline. They analyzed DII scores both in a continuous range and divided into quartiles, using the first quartile as a reference.

The mean age of participants was 69 years, and 53% were women. During follow-up, 11.3% developed AD dementia, and 14.8% developed non-AD dementia.

In the continuous model, DII was associated with increased risk of all-cause dementia after adjusting for age, sex, APOE E4 status, body mass index, smoking, physical activity index score, total energy intake, lipid-lowering medications, and total cholesterol to HDL cholesterol ratio (hazard ratio, 1.18; P =.001). In the quartile analysis, after adjustments, compared with quartile 1, there was an increased risk of all-cause dementia for those in quartile 3 (HR, 1.69; P =.020) and quartile 4 (HR, 1.84; P =.013).

In the continuous analysis, after adjustments, there was an association between DII score and Alzheimer’s dementia (HR, 1.15; P =.020). In the quartile analysis, no associations were significant, though there was a trend of quartile 4 versus quartile 1 (HR, 1.65; P =.077).

The researchers found no significant interactions between higher DII scores and sex, the APOE E4 allele, or physical activity with respect to all-cause dementia or Alzheimer’s dementia.
 

Intertwined variables

The results were interesting, but cause and effect relationships can be difficult to tease out from such a study, according to Claire Sexton, DPhil, director of scientific programs and outreach at the Alzheimer’s Association, who was asked to comment on the study. Dr. Sexton noted that individuals who eat well are more likely to have energy to exercise, which could in turn help them to sleep better, and all of those factors could be involved in reducing dementia risk. “They’re all kind of intertwined. So in this study, they were taking into account physical activity, but they can’t take into account every single variable. It’s important for them to be followed up by randomized control trials.”

Dr. Sexton also referenced the U.S. Pointer study being conducted by the Alzheimer’s Association, which is examining various interventions related to diet, physical activity, and cognitive stimulation. “Whether intervening and improving people’s health behaviors then goes on to reduce their risk for dementia is a key question. We still need more results from studies to be reporting out before we get definitive answers,” she said.

The study was funded by the ASPEN Rhoads Research Foundation. Dr. Melo van Lent and Dr. Sexton have no relevant financial disclosures.

A proinflammatory diet, as measured by the dietary inflammatory index (DII), is associated with increased risk of all-cause dementia, although not Alzheimer’s disease, according to a new analysis of longitudinal data from the Framingham Heart Study Offspring Cohort.

The lack of an association with Alzheimer’s disease was a surprise because amyloid-beta prompts microglia and astrocytes to release markers of systemic inflammation, according to Debora Melo van Lent, PhD, who is a postdoctoral fellow at the University of Texas Health San Antonio – Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases. “We expected to see a relationship between higher DII scores and an increased risk for incident Alzheimer’s disease,” said Dr. Melo van Lent, who presented the findings at the 2021 Alzheimer’s Association International Conference.

Dr. Melo van Lent added that the most likely explanation is that the study was underpowered to produce a positive association, and the team is conducting further study in a larger population.
 

A modifiable risk factor

The study is the first to look at all-cause dementia and Alzheimer’s disease dementia and their association with DII, Dr. Melo van Lent said.

“As diet is a modifiable risk factor, we can actually do something about it. If we take a closer look at five components of the DII which are most anti-inflammatory, these components are present in green leafy vegetables, vegetables, fruit, soy, whole grains, and green and black tea. Most of these components are included in the Mediterranean diet. When we look at the three most proinflammatory components, they are present in high caloric products; such as butter or margarine, pastries and sweets, fried snacks, and red or processed meat. These components are present in ‘Western diets,’ which are discouraged,” said Dr. Melo van Lent.

The researchers analyzed data from 1,486 participants who were free of dementia, stroke, or other neurologic diseases at baseline. They analyzed DII scores both in a continuous range and divided into quartiles, using the first quartile as a reference.

The mean age of participants was 69 years, and 53% were women. During follow-up, 11.3% developed AD dementia, and 14.8% developed non-AD dementia.

In the continuous model, DII was associated with increased risk of all-cause dementia after adjusting for age, sex, APOE E4 status, body mass index, smoking, physical activity index score, total energy intake, lipid-lowering medications, and total cholesterol to HDL cholesterol ratio (hazard ratio, 1.18; P =.001). In the quartile analysis, after adjustments, compared with quartile 1, there was an increased risk of all-cause dementia for those in quartile 3 (HR, 1.69; P =.020) and quartile 4 (HR, 1.84; P =.013).

In the continuous analysis, after adjustments, there was an association between DII score and Alzheimer’s dementia (HR, 1.15; P =.020). In the quartile analysis, no associations were significant, though there was a trend of quartile 4 versus quartile 1 (HR, 1.65; P =.077).

The researchers found no significant interactions between higher DII scores and sex, the APOE E4 allele, or physical activity with respect to all-cause dementia or Alzheimer’s dementia.
 

Intertwined variables

The results were interesting, but cause and effect relationships can be difficult to tease out from such a study, according to Claire Sexton, DPhil, director of scientific programs and outreach at the Alzheimer’s Association, who was asked to comment on the study. Dr. Sexton noted that individuals who eat well are more likely to have energy to exercise, which could in turn help them to sleep better, and all of those factors could be involved in reducing dementia risk. “They’re all kind of intertwined. So in this study, they were taking into account physical activity, but they can’t take into account every single variable. It’s important for them to be followed up by randomized control trials.”

Dr. Sexton also referenced the U.S. Pointer study being conducted by the Alzheimer’s Association, which is examining various interventions related to diet, physical activity, and cognitive stimulation. “Whether intervening and improving people’s health behaviors then goes on to reduce their risk for dementia is a key question. We still need more results from studies to be reporting out before we get definitive answers,” she said.

The study was funded by the ASPEN Rhoads Research Foundation. Dr. Melo van Lent and Dr. Sexton have no relevant financial disclosures.

A proinflammatory diet, as measured by the dietary inflammatory index (DII), is associated with increased risk of all-cause dementia, although not Alzheimer’s disease, according to a new analysis of longitudinal data from the Framingham Heart Study Offspring Cohort.

The lack of an association with Alzheimer’s disease was a surprise because amyloid-beta prompts microglia and astrocytes to release markers of systemic inflammation, according to Debora Melo van Lent, PhD, who is a postdoctoral fellow at the University of Texas Health San Antonio – Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases. “We expected to see a relationship between higher DII scores and an increased risk for incident Alzheimer’s disease,” said Dr. Melo van Lent, who presented the findings at the 2021 Alzheimer’s Association International Conference.

Dr. Melo van Lent added that the most likely explanation is that the study was underpowered to produce a positive association, and the team is conducting further study in a larger population.
 

A modifiable risk factor

The study is the first to look at all-cause dementia and Alzheimer’s disease dementia and their association with DII, Dr. Melo van Lent said.

“As diet is a modifiable risk factor, we can actually do something about it. If we take a closer look at five components of the DII which are most anti-inflammatory, these components are present in green leafy vegetables, vegetables, fruit, soy, whole grains, and green and black tea. Most of these components are included in the Mediterranean diet. When we look at the three most proinflammatory components, they are present in high caloric products; such as butter or margarine, pastries and sweets, fried snacks, and red or processed meat. These components are present in ‘Western diets,’ which are discouraged,” said Dr. Melo van Lent.

The researchers analyzed data from 1,486 participants who were free of dementia, stroke, or other neurologic diseases at baseline. They analyzed DII scores both in a continuous range and divided into quartiles, using the first quartile as a reference.

The mean age of participants was 69 years, and 53% were women. During follow-up, 11.3% developed AD dementia, and 14.8% developed non-AD dementia.

In the continuous model, DII was associated with increased risk of all-cause dementia after adjusting for age, sex, APOE E4 status, body mass index, smoking, physical activity index score, total energy intake, lipid-lowering medications, and total cholesterol to HDL cholesterol ratio (hazard ratio, 1.18; P =.001). In the quartile analysis, after adjustments, compared with quartile 1, there was an increased risk of all-cause dementia for those in quartile 3 (HR, 1.69; P =.020) and quartile 4 (HR, 1.84; P =.013).

In the continuous analysis, after adjustments, there was an association between DII score and Alzheimer’s dementia (HR, 1.15; P =.020). In the quartile analysis, no associations were significant, though there was a trend of quartile 4 versus quartile 1 (HR, 1.65; P =.077).

The researchers found no significant interactions between higher DII scores and sex, the APOE E4 allele, or physical activity with respect to all-cause dementia or Alzheimer’s dementia.
 

Intertwined variables

The results were interesting, but cause and effect relationships can be difficult to tease out from such a study, according to Claire Sexton, DPhil, director of scientific programs and outreach at the Alzheimer’s Association, who was asked to comment on the study. Dr. Sexton noted that individuals who eat well are more likely to have energy to exercise, which could in turn help them to sleep better, and all of those factors could be involved in reducing dementia risk. “They’re all kind of intertwined. So in this study, they were taking into account physical activity, but they can’t take into account every single variable. It’s important for them to be followed up by randomized control trials.”

Dr. Sexton also referenced the U.S. Pointer study being conducted by the Alzheimer’s Association, which is examining various interventions related to diet, physical activity, and cognitive stimulation. “Whether intervening and improving people’s health behaviors then goes on to reduce their risk for dementia is a key question. We still need more results from studies to be reporting out before we get definitive answers,” she said.

The study was funded by the ASPEN Rhoads Research Foundation. Dr. Melo van Lent and Dr. Sexton have no relevant financial disclosures.

The global prevalence of young-onset dementia is significantly higher than previously thought. Results of a large meta-analysis show that currently 3.9 million individuals are living with young-onset dementia. Among these patients, symptoms of the disease start before age 65.

Recent global young-onset dementia estimates have ranged from 42.3 to 54.0 per 100,000 population, the researchers noted. However, the new study, which included 74 global studies with 2.7 million participants, shows that the global age-standardized prevalence of young-onset dementia is 119.00 per 100,000 among individuals aged 30-64 years; there was little difference in prevalence between men and women. On the basis of the latest population estimates, these new prevalence data imply that there are approximately 175,000 persons with young-onset dementia in the United States.

Although the new global estimate of young-onset dementia is higher than previously thought, “it is still probably an underestimation owing to lack of high-quality data. This should raise awareness for policy makers and health care professionals to organize more and better care for this subgroup of individuals with dementia,” wrote the investigators, with first author Stevie Hendriks, MSc, Maastricht (the Netherlands) University, and the Young-Onset Dementia Epidemiology Study Group.

The study was published online July 19, 2021, in JAMA Neurology.
 

‘Essential’ data

Young-onset dementia is exceedingly rare in those aged 30-63 years (1.1 per 100,000) but is more prevalent at age 60-64 years (77.4 per 100,000). “Our findings fit the general observation that prevalence of dementia increases exponentially from 60 years of age onward,” they wrote.

The prevalence of young-onset dementia was similar in men and women, lower in the United States than in Europe, highest in upper- to middle-income countries, and highest for Alzheimer’s disease, followed by vascular dementia and frontotemporal dementia.

Monitoring the prevalence of young-onset dementia is “essential” to adequately plan and organize health services, the investigators noted.

To ensure more accurate prevalence estimates in the future, “efforts should be made to conduct more cohort studies and to standardize procedures and reporting of prevalence studies. In addition, more data are needed from low-income countries as well as studies that include younger age ranges,” they said.
 

New insights

In an accompanying editorial, David S. Knopman, MD, department of neurology, Mayo Clinic, Rochester, Minn., noted that the study provides new insights into an “underappreciated problem.”.

Young-onset dementia is a “particularly disheartening diagnosis because it affects individuals in their prime years, in the midst of their careers, and while raising families,” Dr. Knopman wrote.

“Most dementia care is geared for older patients, and as a consequence, services are rarely available to address the needs of someone diagnosed with dementia in their 50s who has dependent children at home and a spouse who must continue working. Understanding the prevalence and incidence of young-onset dementia is a first step in addressing this challenge,” Dr. Knopman wrote.

He noted that the authors of this analysis have “done a service to the dementia community by collecting and analyzing the dozens of individual studies of young-onset dementia.

“The product, a rationally derived estimate of dementia prevalence across the population aged 30-64 years, provides a basis for initiating more efforts to improve methods for timely diagnosis and to address the unique needs of patients with young-onset dementia,” Dr. Knopman concluded.

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

The global prevalence of young-onset dementia is significantly higher than previously thought. Results of a large meta-analysis show that currently 3.9 million individuals are living with young-onset dementia. Among these patients, symptoms of the disease start before age 65.

Recent global young-onset dementia estimates have ranged from 42.3 to 54.0 per 100,000 population, the researchers noted. However, the new study, which included 74 global studies with 2.7 million participants, shows that the global age-standardized prevalence of young-onset dementia is 119.00 per 100,000 among individuals aged 30-64 years; there was little difference in prevalence between men and women. On the basis of the latest population estimates, these new prevalence data imply that there are approximately 175,000 persons with young-onset dementia in the United States.

Although the new global estimate of young-onset dementia is higher than previously thought, “it is still probably an underestimation owing to lack of high-quality data. This should raise awareness for policy makers and health care professionals to organize more and better care for this subgroup of individuals with dementia,” wrote the investigators, with first author Stevie Hendriks, MSc, Maastricht (the Netherlands) University, and the Young-Onset Dementia Epidemiology Study Group.

The study was published online July 19, 2021, in JAMA Neurology.
 

‘Essential’ data

Young-onset dementia is exceedingly rare in those aged 30-63 years (1.1 per 100,000) but is more prevalent at age 60-64 years (77.4 per 100,000). “Our findings fit the general observation that prevalence of dementia increases exponentially from 60 years of age onward,” they wrote.

The prevalence of young-onset dementia was similar in men and women, lower in the United States than in Europe, highest in upper- to middle-income countries, and highest for Alzheimer’s disease, followed by vascular dementia and frontotemporal dementia.

Monitoring the prevalence of young-onset dementia is “essential” to adequately plan and organize health services, the investigators noted.

To ensure more accurate prevalence estimates in the future, “efforts should be made to conduct more cohort studies and to standardize procedures and reporting of prevalence studies. In addition, more data are needed from low-income countries as well as studies that include younger age ranges,” they said.
 

New insights

In an accompanying editorial, David S. Knopman, MD, department of neurology, Mayo Clinic, Rochester, Minn., noted that the study provides new insights into an “underappreciated problem.”.

Young-onset dementia is a “particularly disheartening diagnosis because it affects individuals in their prime years, in the midst of their careers, and while raising families,” Dr. Knopman wrote.

“Most dementia care is geared for older patients, and as a consequence, services are rarely available to address the needs of someone diagnosed with dementia in their 50s who has dependent children at home and a spouse who must continue working. Understanding the prevalence and incidence of young-onset dementia is a first step in addressing this challenge,” Dr. Knopman wrote.

He noted that the authors of this analysis have “done a service to the dementia community by collecting and analyzing the dozens of individual studies of young-onset dementia.

“The product, a rationally derived estimate of dementia prevalence across the population aged 30-64 years, provides a basis for initiating more efforts to improve methods for timely diagnosis and to address the unique needs of patients with young-onset dementia,” Dr. Knopman concluded.

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

The global prevalence of young-onset dementia is significantly higher than previously thought. Results of a large meta-analysis show that currently 3.9 million individuals are living with young-onset dementia. Among these patients, symptoms of the disease start before age 65.

Recent global young-onset dementia estimates have ranged from 42.3 to 54.0 per 100,000 population, the researchers noted. However, the new study, which included 74 global studies with 2.7 million participants, shows that the global age-standardized prevalence of young-onset dementia is 119.00 per 100,000 among individuals aged 30-64 years; there was little difference in prevalence between men and women. On the basis of the latest population estimates, these new prevalence data imply that there are approximately 175,000 persons with young-onset dementia in the United States.

Although the new global estimate of young-onset dementia is higher than previously thought, “it is still probably an underestimation owing to lack of high-quality data. This should raise awareness for policy makers and health care professionals to organize more and better care for this subgroup of individuals with dementia,” wrote the investigators, with first author Stevie Hendriks, MSc, Maastricht (the Netherlands) University, and the Young-Onset Dementia Epidemiology Study Group.

The study was published online July 19, 2021, in JAMA Neurology.
 

‘Essential’ data

Young-onset dementia is exceedingly rare in those aged 30-63 years (1.1 per 100,000) but is more prevalent at age 60-64 years (77.4 per 100,000). “Our findings fit the general observation that prevalence of dementia increases exponentially from 60 years of age onward,” they wrote.

The prevalence of young-onset dementia was similar in men and women, lower in the United States than in Europe, highest in upper- to middle-income countries, and highest for Alzheimer’s disease, followed by vascular dementia and frontotemporal dementia.

Monitoring the prevalence of young-onset dementia is “essential” to adequately plan and organize health services, the investigators noted.

To ensure more accurate prevalence estimates in the future, “efforts should be made to conduct more cohort studies and to standardize procedures and reporting of prevalence studies. In addition, more data are needed from low-income countries as well as studies that include younger age ranges,” they said.
 

New insights

In an accompanying editorial, David S. Knopman, MD, department of neurology, Mayo Clinic, Rochester, Minn., noted that the study provides new insights into an “underappreciated problem.”.

Young-onset dementia is a “particularly disheartening diagnosis because it affects individuals in their prime years, in the midst of their careers, and while raising families,” Dr. Knopman wrote.

“Most dementia care is geared for older patients, and as a consequence, services are rarely available to address the needs of someone diagnosed with dementia in their 50s who has dependent children at home and a spouse who must continue working. Understanding the prevalence and incidence of young-onset dementia is a first step in addressing this challenge,” Dr. Knopman wrote.

He noted that the authors of this analysis have “done a service to the dementia community by collecting and analyzing the dozens of individual studies of young-onset dementia.

“The product, a rationally derived estimate of dementia prevalence across the population aged 30-64 years, provides a basis for initiating more efforts to improve methods for timely diagnosis and to address the unique needs of patients with young-onset dementia,” Dr. Knopman concluded.

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

About one-third of U.S. adults struggled with medical debt during the pandemic, according to data from a Commonwealth Fund survey released July 16.

Despite the passage of four major relief bills in 2020 and 2021 and federal efforts to offset pandemic- and job-related coverage loss, many people continued to face financial challenges, especially those with a low income and those who are Black or Latino.

The survey, which included responses from 5,450 adults, revealed that 10% of adults aged 19-64 were uninsured during the first half of 2021, a rate lower than what was recorded in 2020 and 2019 in both federal and private surveys. However, uninsured rates were highest among those with low income, those younger than 50 years old, and Black and Latino adults.

For most adults who lost employee health insurance, the coverage gap was relatively brief, with 54% saying their coverage gap lasted 3-4 months. Only 16% of adults said coverage gaps lasted a year or longer.

“The good news is that this survey is suggesting that the coverage losses during the pandemic may have been offset by federal efforts to help people get and maintain health insurance coverage,” lead author Sara Collins, PhD, Commonwealth Fund vice president for health care coverage, access, and tracking, said in an interview.

“The bad news is that a third of Americans continue to struggle with medical bills and medical debt, even among those who have health insurance coverage,” Dr. Collins added.

Indeed, the survey found that about one-third of insured adults reported a medical bill problem or that they were paying off medical debt, as did approximately half of those who were uninsured. Medical debt caused 35% of respondents to use up most or all of their savings to pay it off.

Meanwhile, 27% of adults said medical bills left them unable to pay for necessities such as food, heat, or rent. What surprised Dr. Collins was that 43% of adults said they received a lower credit rating as a result of their medical debt, and 35% said they had taken on more credit card debt to pay off these bills.

“The fact that it’s bleeding over into people’s financial security in terms of their credit scores, I think is something that really needs to be looked at by policymakers,” Dr. Collins said.

When analyzed by race/ethnicity, the researchers found that 55% of Black adults and 44% of Latino/Hispanic adults reported medical bills and debt problems, compared with 32% of White adults. In addition, 47% of those living below the poverty line also reported problems with medical bills.

According to the survey, 45% of respondents were directly affected by the pandemic in at least one of three ways – testing positive or getting sick from COVID-19, losing income, or losing employer coverage – with Black and Latinx adults and those with lower incomes at greater risk.

George Abraham, MD, president of the American College of Physicians, said the Commonwealth Fund’s findings were not surprising because it has always been known that underrepresented populations struggle for access to care because of socioeconomic factors. He said these populations were more vulnerable in terms of more severe infections and disease burden during the pandemic.

“[This study] validates what primary care physicians have been saying all along in regard to our patients’ access to care and their ability to cover health care costs,” said Dr. Abraham, who was not involved with the study. “This will hopefully be an eye-opener and wake-up call that reiterates that we still do not have equitable access to care and vulnerable populations are disproportionately affected.”

He believes that, although people are insured, many of them may contend with medical debt when they fall ill because they can’t afford the premiums.

“Even though they may have been registered for health coverage, they may not have active coverage at the time of illness simply because they weren’t able to make their last premium payments because they’ve been down, because they lost their job, or whatever else,” Dr. Abraham explained. “On paper, they appear to have health care coverage. But in reality, clearly, that coverage does not match their needs or it’s not affordable.”

For Dr. Abraham, the study emphasizes the need to continue support for health care reform, including pricing it so that insurance is available for those with fewer socioeconomic resources.

Yalda Jabbarpour, MD, medical director of the Robert Graham Center for Policy Studies, Washington, said high-deductible health plans need to be “reined in” because they can lead to greater debt, particularly among vulnerable populations.

“Hopefully this will encourage policymakers to look more closely at the problem of medical debt as a contributing factor to financial instability,” Dr. Jabbarpour said. “Federal relief is important, so is expanding access to comprehensive, affordable health care coverage.”

Dr. Collins said there should also be a way to raise awareness of the health care marketplace and coverage options so that people have an easier time getting insured.

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

About one-third of U.S. adults struggled with medical debt during the pandemic, according to data from a Commonwealth Fund survey released July 16.

Despite the passage of four major relief bills in 2020 and 2021 and federal efforts to offset pandemic- and job-related coverage loss, many people continued to face financial challenges, especially those with a low income and those who are Black or Latino.

The survey, which included responses from 5,450 adults, revealed that 10% of adults aged 19-64 were uninsured during the first half of 2021, a rate lower than what was recorded in 2020 and 2019 in both federal and private surveys. However, uninsured rates were highest among those with low income, those younger than 50 years old, and Black and Latino adults.

For most adults who lost employee health insurance, the coverage gap was relatively brief, with 54% saying their coverage gap lasted 3-4 months. Only 16% of adults said coverage gaps lasted a year or longer.

“The good news is that this survey is suggesting that the coverage losses during the pandemic may have been offset by federal efforts to help people get and maintain health insurance coverage,” lead author Sara Collins, PhD, Commonwealth Fund vice president for health care coverage, access, and tracking, said in an interview.

“The bad news is that a third of Americans continue to struggle with medical bills and medical debt, even among those who have health insurance coverage,” Dr. Collins added.

Indeed, the survey found that about one-third of insured adults reported a medical bill problem or that they were paying off medical debt, as did approximately half of those who were uninsured. Medical debt caused 35% of respondents to use up most or all of their savings to pay it off.

Meanwhile, 27% of adults said medical bills left them unable to pay for necessities such as food, heat, or rent. What surprised Dr. Collins was that 43% of adults said they received a lower credit rating as a result of their medical debt, and 35% said they had taken on more credit card debt to pay off these bills.

“The fact that it’s bleeding over into people’s financial security in terms of their credit scores, I think is something that really needs to be looked at by policymakers,” Dr. Collins said.

When analyzed by race/ethnicity, the researchers found that 55% of Black adults and 44% of Latino/Hispanic adults reported medical bills and debt problems, compared with 32% of White adults. In addition, 47% of those living below the poverty line also reported problems with medical bills.

According to the survey, 45% of respondents were directly affected by the pandemic in at least one of three ways – testing positive or getting sick from COVID-19, losing income, or losing employer coverage – with Black and Latinx adults and those with lower incomes at greater risk.

George Abraham, MD, president of the American College of Physicians, said the Commonwealth Fund’s findings were not surprising because it has always been known that underrepresented populations struggle for access to care because of socioeconomic factors. He said these populations were more vulnerable in terms of more severe infections and disease burden during the pandemic.

“[This study] validates what primary care physicians have been saying all along in regard to our patients’ access to care and their ability to cover health care costs,” said Dr. Abraham, who was not involved with the study. “This will hopefully be an eye-opener and wake-up call that reiterates that we still do not have equitable access to care and vulnerable populations are disproportionately affected.”

He believes that, although people are insured, many of them may contend with medical debt when they fall ill because they can’t afford the premiums.

“Even though they may have been registered for health coverage, they may not have active coverage at the time of illness simply because they weren’t able to make their last premium payments because they’ve been down, because they lost their job, or whatever else,” Dr. Abraham explained. “On paper, they appear to have health care coverage. But in reality, clearly, that coverage does not match their needs or it’s not affordable.”

For Dr. Abraham, the study emphasizes the need to continue support for health care reform, including pricing it so that insurance is available for those with fewer socioeconomic resources.

Yalda Jabbarpour, MD, medical director of the Robert Graham Center for Policy Studies, Washington, said high-deductible health plans need to be “reined in” because they can lead to greater debt, particularly among vulnerable populations.

“Hopefully this will encourage policymakers to look more closely at the problem of medical debt as a contributing factor to financial instability,” Dr. Jabbarpour said. “Federal relief is important, so is expanding access to comprehensive, affordable health care coverage.”

Dr. Collins said there should also be a way to raise awareness of the health care marketplace and coverage options so that people have an easier time getting insured.

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

About one-third of U.S. adults struggled with medical debt during the pandemic, according to data from a Commonwealth Fund survey released July 16.

Despite the passage of four major relief bills in 2020 and 2021 and federal efforts to offset pandemic- and job-related coverage loss, many people continued to face financial challenges, especially those with a low income and those who are Black or Latino.

The survey, which included responses from 5,450 adults, revealed that 10% of adults aged 19-64 were uninsured during the first half of 2021, a rate lower than what was recorded in 2020 and 2019 in both federal and private surveys. However, uninsured rates were highest among those with low income, those younger than 50 years old, and Black and Latino adults.

For most adults who lost employee health insurance, the coverage gap was relatively brief, with 54% saying their coverage gap lasted 3-4 months. Only 16% of adults said coverage gaps lasted a year or longer.

“The good news is that this survey is suggesting that the coverage losses during the pandemic may have been offset by federal efforts to help people get and maintain health insurance coverage,” lead author Sara Collins, PhD, Commonwealth Fund vice president for health care coverage, access, and tracking, said in an interview.

“The bad news is that a third of Americans continue to struggle with medical bills and medical debt, even among those who have health insurance coverage,” Dr. Collins added.

Indeed, the survey found that about one-third of insured adults reported a medical bill problem or that they were paying off medical debt, as did approximately half of those who were uninsured. Medical debt caused 35% of respondents to use up most or all of their savings to pay it off.

Meanwhile, 27% of adults said medical bills left them unable to pay for necessities such as food, heat, or rent. What surprised Dr. Collins was that 43% of adults said they received a lower credit rating as a result of their medical debt, and 35% said they had taken on more credit card debt to pay off these bills.

“The fact that it’s bleeding over into people’s financial security in terms of their credit scores, I think is something that really needs to be looked at by policymakers,” Dr. Collins said.

When analyzed by race/ethnicity, the researchers found that 55% of Black adults and 44% of Latino/Hispanic adults reported medical bills and debt problems, compared with 32% of White adults. In addition, 47% of those living below the poverty line also reported problems with medical bills.

According to the survey, 45% of respondents were directly affected by the pandemic in at least one of three ways – testing positive or getting sick from COVID-19, losing income, or losing employer coverage – with Black and Latinx adults and those with lower incomes at greater risk.

George Abraham, MD, president of the American College of Physicians, said the Commonwealth Fund’s findings were not surprising because it has always been known that underrepresented populations struggle for access to care because of socioeconomic factors. He said these populations were more vulnerable in terms of more severe infections and disease burden during the pandemic.

“[This study] validates what primary care physicians have been saying all along in regard to our patients’ access to care and their ability to cover health care costs,” said Dr. Abraham, who was not involved with the study. “This will hopefully be an eye-opener and wake-up call that reiterates that we still do not have equitable access to care and vulnerable populations are disproportionately affected.”

He believes that, although people are insured, many of them may contend with medical debt when they fall ill because they can’t afford the premiums.

“Even though they may have been registered for health coverage, they may not have active coverage at the time of illness simply because they weren’t able to make their last premium payments because they’ve been down, because they lost their job, or whatever else,” Dr. Abraham explained. “On paper, they appear to have health care coverage. But in reality, clearly, that coverage does not match their needs or it’s not affordable.”

For Dr. Abraham, the study emphasizes the need to continue support for health care reform, including pricing it so that insurance is available for those with fewer socioeconomic resources.

Yalda Jabbarpour, MD, medical director of the Robert Graham Center for Policy Studies, Washington, said high-deductible health plans need to be “reined in” because they can lead to greater debt, particularly among vulnerable populations.

“Hopefully this will encourage policymakers to look more closely at the problem of medical debt as a contributing factor to financial instability,” Dr. Jabbarpour said. “Federal relief is important, so is expanding access to comprehensive, affordable health care coverage.”

Dr. Collins said there should also be a way to raise awareness of the health care marketplace and coverage options so that people have an easier time getting insured.

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

Plasma biomarkers such as amyloid-beta 40 and 42, phosphorylated tau 181 and 217, and neurofilament light hold great promise for diagnosing and determining a prognosis for Alzheimer’s disease. Such tests are likely to be widely available in the near future.

But work remains to be done to translate findings from academic studies to the more general population. A key consideration is that plasma levels of these biomarkers could be affected by other conditions, which could in turn skew test results, according to Michelle Mielke, PhD, who spoke on the topic at the 2021 Alzheimer’s Association International Conference.

“The markers, which we’ve published on as well, look really promising. But they have primarily been looked at in more specialty clinics or memory clinics, and have not been examined in the general community. The goal of this presentation was really just to take a look at this in the community, in older individuals that have multiple comorbidities, and to understand what factors might affect the levels of these markers. Because as we do go forward and develop cut points, we are going to have to consider these aspects,” said Dr. Mielke in an interview. She is a professor of epidemiology and neurology at the Mayo Clinic in Rochester, Minn.
 

Case in point

To illustrate the point, Dr. Mielke presented data from her group, which analyzed P-tau 181 and P-tau 217 data from 1,329 Mayo clinic patients. Of that total, 1,161 were cognitively unimpaired (CU), 153 had mild cognitive impairment (MCI), and 15 had dementia. The median age was 67, 55% were male, and 26% had the APOE e4 allele.

After adjustment for age and sex, there were statistically significantly elevated levels of both biomarkers among patients who had tested positive for amyloid and patients who had had a stroke or myocardial infarction, and in the presence of chronic kidney disease (CKD). There also was a trend towards an increase of biomarker levels with increasing body mass index. The differences remained even after the analysis was restricted to individuals who were amyloid negative.

The researchers then looked more closely at the impact of CKD, stroke, and MI on P-tau cut points and the ability to predict abnormal amyloid positron emission tomography (PET) scans. They defined an abnormal range as 1.96 standard deviation units beyond the mean among amyloid-negative individuals who are cognitively impaired. They excluded subjects with those risk factors and then established new cut points in the absence of the factors. The approach led to a significant change for the cutoff of P-tau 181 values, from 1.57 pg/mL or greater for individuals without stroke, MI, or CKD, and 1.75 pg/mL or greater for individuals with one such factor. There was little difference in the cutoff value for P-tau 217, from 0.25 pg/mL to 0.26 pg/mL.

Among people without a history of stroke, MI, or CKD, a P-tau 181 cutoff of 1.57 pg/mL or greater had an area under the receiving operating characteristic (AUROC) value of 0.717 (95% confidence interval, 0.691-0.744), compared with an AUROC of 0.687 (95% CI, 0.662-0.712) at a cutoff of 1.75 pg/mL or greater among people with those conditions. For P-tau 217, the values were 0.737 pg/mL (95% CI, 0.712-0.762) and 0.724 pg/mL (95% CI, 0.699-0.748), respectively.

“The sensitivity was better when they excluded those individuals with these conditions. Specificity was slightly, but not significantly, lower,” said Dr. Mielke during her talk.
 

Other considerations

Dr. Mielke added that it will be important to account for these and other factors when applying biomarkers in community settings, but they should also be considered in the context of health care disparities. Stroke, MI, and CKD are more common in African Americans, for example, suggesting that there could be racial differences in biomarker levels, though she said the difference in biomarker levels would be more likely attributable to the underlying comorbidities than race per se. “As shown, these factors can affect the consideration of an accuracy of cut points for clinical use. So I think future discussions will be needed as to how best to determine the cut points, and how to base them off of (different) populations,” said Dr. Mielke.

These sorts of refinements are important, according to Christopher Weber, PhD, who was asked for comment. “We have learned the importance of an early and accurate diagnosis. The blood test is a biomarker that does detect the hallmarks of Alzheimer’s disease sometimes up to decades before symptoms even appear,” said Dr. Weber, who is director of Global Science Initiatives at the Alzheimer’s Association.

But “there’s a lot more that we need to learn regarding when exactly to use them, who they’re appropriate for. And I think validation is the key to these blood biomarkers,” Dr. Weber added.

Dr. Mielke has been a consultant with the Brain Protection Company and Biogen. Dr. Weber has no relevant financial disclosures.

Plasma biomarkers such as amyloid-beta 40 and 42, phosphorylated tau 181 and 217, and neurofilament light hold great promise for diagnosing and determining a prognosis for Alzheimer’s disease. Such tests are likely to be widely available in the near future.

But work remains to be done to translate findings from academic studies to the more general population. A key consideration is that plasma levels of these biomarkers could be affected by other conditions, which could in turn skew test results, according to Michelle Mielke, PhD, who spoke on the topic at the 2021 Alzheimer’s Association International Conference.

“The markers, which we’ve published on as well, look really promising. But they have primarily been looked at in more specialty clinics or memory clinics, and have not been examined in the general community. The goal of this presentation was really just to take a look at this in the community, in older individuals that have multiple comorbidities, and to understand what factors might affect the levels of these markers. Because as we do go forward and develop cut points, we are going to have to consider these aspects,” said Dr. Mielke in an interview. She is a professor of epidemiology and neurology at the Mayo Clinic in Rochester, Minn.
 

Case in point

To illustrate the point, Dr. Mielke presented data from her group, which analyzed P-tau 181 and P-tau 217 data from 1,329 Mayo clinic patients. Of that total, 1,161 were cognitively unimpaired (CU), 153 had mild cognitive impairment (MCI), and 15 had dementia. The median age was 67, 55% were male, and 26% had the APOE e4 allele.

After adjustment for age and sex, there were statistically significantly elevated levels of both biomarkers among patients who had tested positive for amyloid and patients who had had a stroke or myocardial infarction, and in the presence of chronic kidney disease (CKD). There also was a trend towards an increase of biomarker levels with increasing body mass index. The differences remained even after the analysis was restricted to individuals who were amyloid negative.

The researchers then looked more closely at the impact of CKD, stroke, and MI on P-tau cut points and the ability to predict abnormal amyloid positron emission tomography (PET) scans. They defined an abnormal range as 1.96 standard deviation units beyond the mean among amyloid-negative individuals who are cognitively impaired. They excluded subjects with those risk factors and then established new cut points in the absence of the factors. The approach led to a significant change for the cutoff of P-tau 181 values, from 1.57 pg/mL or greater for individuals without stroke, MI, or CKD, and 1.75 pg/mL or greater for individuals with one such factor. There was little difference in the cutoff value for P-tau 217, from 0.25 pg/mL to 0.26 pg/mL.

Among people without a history of stroke, MI, or CKD, a P-tau 181 cutoff of 1.57 pg/mL or greater had an area under the receiving operating characteristic (AUROC) value of 0.717 (95% confidence interval, 0.691-0.744), compared with an AUROC of 0.687 (95% CI, 0.662-0.712) at a cutoff of 1.75 pg/mL or greater among people with those conditions. For P-tau 217, the values were 0.737 pg/mL (95% CI, 0.712-0.762) and 0.724 pg/mL (95% CI, 0.699-0.748), respectively.

“The sensitivity was better when they excluded those individuals with these conditions. Specificity was slightly, but not significantly, lower,” said Dr. Mielke during her talk.
 

Other considerations

Dr. Mielke added that it will be important to account for these and other factors when applying biomarkers in community settings, but they should also be considered in the context of health care disparities. Stroke, MI, and CKD are more common in African Americans, for example, suggesting that there could be racial differences in biomarker levels, though she said the difference in biomarker levels would be more likely attributable to the underlying comorbidities than race per se. “As shown, these factors can affect the consideration of an accuracy of cut points for clinical use. So I think future discussions will be needed as to how best to determine the cut points, and how to base them off of (different) populations,” said Dr. Mielke.

These sorts of refinements are important, according to Christopher Weber, PhD, who was asked for comment. “We have learned the importance of an early and accurate diagnosis. The blood test is a biomarker that does detect the hallmarks of Alzheimer’s disease sometimes up to decades before symptoms even appear,” said Dr. Weber, who is director of Global Science Initiatives at the Alzheimer’s Association.

But “there’s a lot more that we need to learn regarding when exactly to use them, who they’re appropriate for. And I think validation is the key to these blood biomarkers,” Dr. Weber added.

Dr. Mielke has been a consultant with the Brain Protection Company and Biogen. Dr. Weber has no relevant financial disclosures.

Plasma biomarkers such as amyloid-beta 40 and 42, phosphorylated tau 181 and 217, and neurofilament light hold great promise for diagnosing and determining a prognosis for Alzheimer’s disease. Such tests are likely to be widely available in the near future.

But work remains to be done to translate findings from academic studies to the more general population. A key consideration is that plasma levels of these biomarkers could be affected by other conditions, which could in turn skew test results, according to Michelle Mielke, PhD, who spoke on the topic at the 2021 Alzheimer’s Association International Conference.

“The markers, which we’ve published on as well, look really promising. But they have primarily been looked at in more specialty clinics or memory clinics, and have not been examined in the general community. The goal of this presentation was really just to take a look at this in the community, in older individuals that have multiple comorbidities, and to understand what factors might affect the levels of these markers. Because as we do go forward and develop cut points, we are going to have to consider these aspects,” said Dr. Mielke in an interview. She is a professor of epidemiology and neurology at the Mayo Clinic in Rochester, Minn.
 

Case in point

To illustrate the point, Dr. Mielke presented data from her group, which analyzed P-tau 181 and P-tau 217 data from 1,329 Mayo clinic patients. Of that total, 1,161 were cognitively unimpaired (CU), 153 had mild cognitive impairment (MCI), and 15 had dementia. The median age was 67, 55% were male, and 26% had the APOE e4 allele.

After adjustment for age and sex, there were statistically significantly elevated levels of both biomarkers among patients who had tested positive for amyloid and patients who had had a stroke or myocardial infarction, and in the presence of chronic kidney disease (CKD). There also was a trend towards an increase of biomarker levels with increasing body mass index. The differences remained even after the analysis was restricted to individuals who were amyloid negative.

The researchers then looked more closely at the impact of CKD, stroke, and MI on P-tau cut points and the ability to predict abnormal amyloid positron emission tomography (PET) scans. They defined an abnormal range as 1.96 standard deviation units beyond the mean among amyloid-negative individuals who are cognitively impaired. They excluded subjects with those risk factors and then established new cut points in the absence of the factors. The approach led to a significant change for the cutoff of P-tau 181 values, from 1.57 pg/mL or greater for individuals without stroke, MI, or CKD, and 1.75 pg/mL or greater for individuals with one such factor. There was little difference in the cutoff value for P-tau 217, from 0.25 pg/mL to 0.26 pg/mL.

Among people without a history of stroke, MI, or CKD, a P-tau 181 cutoff of 1.57 pg/mL or greater had an area under the receiving operating characteristic (AUROC) value of 0.717 (95% confidence interval, 0.691-0.744), compared with an AUROC of 0.687 (95% CI, 0.662-0.712) at a cutoff of 1.75 pg/mL or greater among people with those conditions. For P-tau 217, the values were 0.737 pg/mL (95% CI, 0.712-0.762) and 0.724 pg/mL (95% CI, 0.699-0.748), respectively.

“The sensitivity was better when they excluded those individuals with these conditions. Specificity was slightly, but not significantly, lower,” said Dr. Mielke during her talk.
 

Other considerations

Dr. Mielke added that it will be important to account for these and other factors when applying biomarkers in community settings, but they should also be considered in the context of health care disparities. Stroke, MI, and CKD are more common in African Americans, for example, suggesting that there could be racial differences in biomarker levels, though she said the difference in biomarker levels would be more likely attributable to the underlying comorbidities than race per se. “As shown, these factors can affect the consideration of an accuracy of cut points for clinical use. So I think future discussions will be needed as to how best to determine the cut points, and how to base them off of (different) populations,” said Dr. Mielke.

These sorts of refinements are important, according to Christopher Weber, PhD, who was asked for comment. “We have learned the importance of an early and accurate diagnosis. The blood test is a biomarker that does detect the hallmarks of Alzheimer’s disease sometimes up to decades before symptoms even appear,” said Dr. Weber, who is director of Global Science Initiatives at the Alzheimer’s Association.

But “there’s a lot more that we need to learn regarding when exactly to use them, who they’re appropriate for. And I think validation is the key to these blood biomarkers,” Dr. Weber added.

Dr. Mielke has been a consultant with the Brain Protection Company and Biogen. Dr. Weber has no relevant financial disclosures.

A dietary supplement that mimics the effects of the high-fat, low-carbohydrate ketogenic diet is well tolerated and appears to reduce seizures in children and adults with treatment-resistant epilepsy, early research suggests. However, at least one expert has concerns.

In an open-label feasibility study, researchers assessed a liquid supplement known as K.Vita (Vitaflo International), which contains both decanoic acid and octanoic acid.

Although the study was small, the findings are promising, said coinvestigator Matthew Walker, MD, PhD, University College London Institute of Neurology, department of clinical and experimental epilepsy.

“The dietary supplement was reasonably well tolerated and while we weren’t specifically looking for efficacy here, we did see some patients had quite dramatic results in terms of reduced seizures,” Dr. Walker said.

Unlike the ketogenic diet, this dietary supplement is “very easy” to follow, involves only minor dietary modifications, and doesn’t require the intervention of a dietitian, he added.

The findings were published online July 23, 2021, in Brain Communications.
 

Key ingredients

In the ketogenic diet, the body uses body fat as its primary fuel source. The switch from carbohydrates to fat for body fuel results in built-up ketones.

Previous research shows the ketogenic diet is effective in reducing seizures in some patients with epilepsy. However, many patients find it difficult to tolerate, especially for extended periods. Dr. Walker also noted that ketones may have other long-term side effects, including osteoporosis.

He added that his team was keen to learn what elements of the ketogenic diet affect seizures. “Interestingly, we found that one of the fats used in the ketogenic diet, decanoic acid, has quite marked antiseizure effects,” Dr. Walker said.

Previous research has shown that decanoic acid, a medium-chain triglyceride–derived fatty acid, can cross the blood-brain barrier and decrease excitatory neurotransmission and network excitability in vitro.

Dr. Walker noted that ketones are necessary in order to reduce seizures.

“Rather than have a very high-fat, low-carbohydrate diet that causes ketones, we thought ‘why don’t we use a diet in which we just use mainly this fat, this decanoic acid, and avoid ketosis,’ ” he said.

The researchers then went to work developing the K.Vita dietary supplement, which mainly contains decanoic acid but also another fat, octanoic acid.
 

Assessing feasibility

The feasibility study included 61 patients (59% female) who began taking the supplement. Of these, 35 were children (aged 3-18 years) and 26 were adults. The children had Dravet syndrome or another genetically driven form of epilepsy, while most of the adults had a focal epilepsy.

All participants had failed multiple antiseizure medications – a median of 3 for children and 10 for adults who completed the trial. Of the 61 original participants, 20 (19 children and 1 adult) had tried the ketogenic diet but had stopped it for various reasons, including noncompliance and lack of efficacy.

The liquid supplement was introduced gradually. The amount administered was based on weight in the children and was a standard amount in adults, with the target being 240 mL.

Participants consumed the supplement in equal servings taken at regular intervals as part of a meal or snack. They could take it alone or mix it with yogurt or another food.

Patients with feeding tubes took the supplement immediately before or after or mixed into an enteral feed, with a water flush afterward.

Researchers provided patients and caregivers with guidance on excluding highly refined sugary foods and beverages. Starchy foods such as bread, pasta, rice, and potatoes were not restricted.

The study consisted of three visits: baseline, 5 weeks, and 12 weeks, in addition to regular phone and email contact. Participants were also asked to keep a seizure diary.
 

Highly acceptable to patients

Overall, the study withdrawal rate was 33%. After a protocol change involving a slower introduction of the supplement, there were fewer withdrawals, Dr. Walker reported. He noted that the proportion of participants who completed the study (41 of 61) is “much better than with most studies of adults following the ketogenic diet.”

The most frequently reported gastrointestinal symptoms with the supplement were bloating and constipation, but these were predominantly mild and tended to decrease over time. This, said Dr. Walker, contrasts to the ketogenic diet where side effects tend to persist.

There was no significant change in body weight or body mass index. “We did not see weight gain as a problem at all,” Dr. Walker said.

Of 15 caregivers and 19 adults who returned an acceptability questionnaire, 84% agreed or strongly agreed the supplement had a good flavor (strawberry); 88% liked the appearance and color; 77% liked the texture and consistency; and 88% agreed or strongly agreed it was easy to take.

About one-third of adults and two-thirds of caregivers said they believed the supplement reduced seizures.
 

50% seizure reduction

Only three children and one adult became ketotic. This is typically classified as a beta-hydroxybutyrate (BHB) greater than 1 mmol/L (10.4 mg/dL). The BHB levels detected were markedly lower than those observed in individuals following a ketogenic diet, the investigators note.

Of the 41 participants, 19 completed the diaries. There were also data from physician recordings, so researchers were able to retrieve seizure frequencies for 32 of the 41 (78%). Of these 32 patients, 14 (44%) had a 50% or greater reduction in seizures. Overall, children and adults “responded similarly,” Dr. Walker said.

He acknowledged the study numbers are small and emphasized that larger studies are needed to determine efficacy. He also hopes for a future randomized controlled trial comparing K.Vita with another supplement that contains different types of fats.

Interestingly, the product has already “passed” the regulatory approval process in the United Kingdom, so it can be labeled as a medicinal food and should be available for use at the beginning of 2022, Dr. Walker said.
 

Study concerns

Asked to comment on the findings, Daniel Goldenholz, MD, PhD, instructor in the department of neurology, Beth Israel Deaconess Medical Center, Boston, said the supplement may be helpful, but he has concerns about the study.

Many patients with epilepsy are “desperate” for therapies that will help treat their seizures, said Dr. Goldenholz, who was not involved with the research. “If there’s a dietary therapy that has the potential for being helpful, I’m loving that. I need that. My patients are begging for something that works.” It is “really exciting” that researchers are working on that goal, Dr. Goldenholz added.

However, he noted that it is too soon to start talking to patients about this new product. He also pointed out that a significant fraction of the study participants dropped out, many because they couldn’t tolerate the supplement. In addition, others didn’t produce a seizure diary.

Dr. Goldenholz and colleagues have published several studies showing that patients with no intervention at all can sometimes show a reduction in seizures compared with their baseline results.

“We found sizable 50% reductions attributable entirely to the natural fluctuations in seizure rates, rather than any therapy at all, he said.

Dr. Goldenholz added that he hopes to see future studies on this topic, and on similar therapies “with sufficient data and more reliable metrics for efficacy.”

The study was funded by Vitaflo International. Dr. Walker reports having received grants from Vitaflo International and personal fees from UCB Pharma, Eisai, and Sage. In addition, along with colleagues, he has a patent (Nutritional product) pending.

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

A dietary supplement that mimics the effects of the high-fat, low-carbohydrate ketogenic diet is well tolerated and appears to reduce seizures in children and adults with treatment-resistant epilepsy, early research suggests. However, at least one expert has concerns.

In an open-label feasibility study, researchers assessed a liquid supplement known as K.Vita (Vitaflo International), which contains both decanoic acid and octanoic acid.

Although the study was small, the findings are promising, said coinvestigator Matthew Walker, MD, PhD, University College London Institute of Neurology, department of clinical and experimental epilepsy.

“The dietary supplement was reasonably well tolerated and while we weren’t specifically looking for efficacy here, we did see some patients had quite dramatic results in terms of reduced seizures,” Dr. Walker said.

Unlike the ketogenic diet, this dietary supplement is “very easy” to follow, involves only minor dietary modifications, and doesn’t require the intervention of a dietitian, he added.

The findings were published online July 23, 2021, in Brain Communications.
 

Key ingredients

In the ketogenic diet, the body uses body fat as its primary fuel source. The switch from carbohydrates to fat for body fuel results in built-up ketones.

Previous research shows the ketogenic diet is effective in reducing seizures in some patients with epilepsy. However, many patients find it difficult to tolerate, especially for extended periods. Dr. Walker also noted that ketones may have other long-term side effects, including osteoporosis.

He added that his team was keen to learn what elements of the ketogenic diet affect seizures. “Interestingly, we found that one of the fats used in the ketogenic diet, decanoic acid, has quite marked antiseizure effects,” Dr. Walker said.

Previous research has shown that decanoic acid, a medium-chain triglyceride–derived fatty acid, can cross the blood-brain barrier and decrease excitatory neurotransmission and network excitability in vitro.

Dr. Walker noted that ketones are necessary in order to reduce seizures.

“Rather than have a very high-fat, low-carbohydrate diet that causes ketones, we thought ‘why don’t we use a diet in which we just use mainly this fat, this decanoic acid, and avoid ketosis,’ ” he said.

The researchers then went to work developing the K.Vita dietary supplement, which mainly contains decanoic acid but also another fat, octanoic acid.
 

Assessing feasibility

The feasibility study included 61 patients (59% female) who began taking the supplement. Of these, 35 were children (aged 3-18 years) and 26 were adults. The children had Dravet syndrome or another genetically driven form of epilepsy, while most of the adults had a focal epilepsy.

All participants had failed multiple antiseizure medications – a median of 3 for children and 10 for adults who completed the trial. Of the 61 original participants, 20 (19 children and 1 adult) had tried the ketogenic diet but had stopped it for various reasons, including noncompliance and lack of efficacy.

The liquid supplement was introduced gradually. The amount administered was based on weight in the children and was a standard amount in adults, with the target being 240 mL.

Participants consumed the supplement in equal servings taken at regular intervals as part of a meal or snack. They could take it alone or mix it with yogurt or another food.

Patients with feeding tubes took the supplement immediately before or after or mixed into an enteral feed, with a water flush afterward.

Researchers provided patients and caregivers with guidance on excluding highly refined sugary foods and beverages. Starchy foods such as bread, pasta, rice, and potatoes were not restricted.

The study consisted of three visits: baseline, 5 weeks, and 12 weeks, in addition to regular phone and email contact. Participants were also asked to keep a seizure diary.
 

Highly acceptable to patients

Overall, the study withdrawal rate was 33%. After a protocol change involving a slower introduction of the supplement, there were fewer withdrawals, Dr. Walker reported. He noted that the proportion of participants who completed the study (41 of 61) is “much better than with most studies of adults following the ketogenic diet.”

The most frequently reported gastrointestinal symptoms with the supplement were bloating and constipation, but these were predominantly mild and tended to decrease over time. This, said Dr. Walker, contrasts to the ketogenic diet where side effects tend to persist.

There was no significant change in body weight or body mass index. “We did not see weight gain as a problem at all,” Dr. Walker said.

Of 15 caregivers and 19 adults who returned an acceptability questionnaire, 84% agreed or strongly agreed the supplement had a good flavor (strawberry); 88% liked the appearance and color; 77% liked the texture and consistency; and 88% agreed or strongly agreed it was easy to take.

About one-third of adults and two-thirds of caregivers said they believed the supplement reduced seizures.
 

50% seizure reduction

Only three children and one adult became ketotic. This is typically classified as a beta-hydroxybutyrate (BHB) greater than 1 mmol/L (10.4 mg/dL). The BHB levels detected were markedly lower than those observed in individuals following a ketogenic diet, the investigators note.

Of the 41 participants, 19 completed the diaries. There were also data from physician recordings, so researchers were able to retrieve seizure frequencies for 32 of the 41 (78%). Of these 32 patients, 14 (44%) had a 50% or greater reduction in seizures. Overall, children and adults “responded similarly,” Dr. Walker said.

He acknowledged the study numbers are small and emphasized that larger studies are needed to determine efficacy. He also hopes for a future randomized controlled trial comparing K.Vita with another supplement that contains different types of fats.

Interestingly, the product has already “passed” the regulatory approval process in the United Kingdom, so it can be labeled as a medicinal food and should be available for use at the beginning of 2022, Dr. Walker said.
 

Study concerns

Asked to comment on the findings, Daniel Goldenholz, MD, PhD, instructor in the department of neurology, Beth Israel Deaconess Medical Center, Boston, said the supplement may be helpful, but he has concerns about the study.

Many patients with epilepsy are “desperate” for therapies that will help treat their seizures, said Dr. Goldenholz, who was not involved with the research. “If there’s a dietary therapy that has the potential for being helpful, I’m loving that. I need that. My patients are begging for something that works.” It is “really exciting” that researchers are working on that goal, Dr. Goldenholz added.

However, he noted that it is too soon to start talking to patients about this new product. He also pointed out that a significant fraction of the study participants dropped out, many because they couldn’t tolerate the supplement. In addition, others didn’t produce a seizure diary.

Dr. Goldenholz and colleagues have published several studies showing that patients with no intervention at all can sometimes show a reduction in seizures compared with their baseline results.

“We found sizable 50% reductions attributable entirely to the natural fluctuations in seizure rates, rather than any therapy at all, he said.

Dr. Goldenholz added that he hopes to see future studies on this topic, and on similar therapies “with sufficient data and more reliable metrics for efficacy.”

The study was funded by Vitaflo International. Dr. Walker reports having received grants from Vitaflo International and personal fees from UCB Pharma, Eisai, and Sage. In addition, along with colleagues, he has a patent (Nutritional product) pending.

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

A dietary supplement that mimics the effects of the high-fat, low-carbohydrate ketogenic diet is well tolerated and appears to reduce seizures in children and adults with treatment-resistant epilepsy, early research suggests. However, at least one expert has concerns.

In an open-label feasibility study, researchers assessed a liquid supplement known as K.Vita (Vitaflo International), which contains both decanoic acid and octanoic acid.

Although the study was small, the findings are promising, said coinvestigator Matthew Walker, MD, PhD, University College London Institute of Neurology, department of clinical and experimental epilepsy.

“The dietary supplement was reasonably well tolerated and while we weren’t specifically looking for efficacy here, we did see some patients had quite dramatic results in terms of reduced seizures,” Dr. Walker said.

Unlike the ketogenic diet, this dietary supplement is “very easy” to follow, involves only minor dietary modifications, and doesn’t require the intervention of a dietitian, he added.

The findings were published online July 23, 2021, in Brain Communications.
 

Key ingredients

In the ketogenic diet, the body uses body fat as its primary fuel source. The switch from carbohydrates to fat for body fuel results in built-up ketones.

Previous research shows the ketogenic diet is effective in reducing seizures in some patients with epilepsy. However, many patients find it difficult to tolerate, especially for extended periods. Dr. Walker also noted that ketones may have other long-term side effects, including osteoporosis.

He added that his team was keen to learn what elements of the ketogenic diet affect seizures. “Interestingly, we found that one of the fats used in the ketogenic diet, decanoic acid, has quite marked antiseizure effects,” Dr. Walker said.

Previous research has shown that decanoic acid, a medium-chain triglyceride–derived fatty acid, can cross the blood-brain barrier and decrease excitatory neurotransmission and network excitability in vitro.

Dr. Walker noted that ketones are necessary in order to reduce seizures.

“Rather than have a very high-fat, low-carbohydrate diet that causes ketones, we thought ‘why don’t we use a diet in which we just use mainly this fat, this decanoic acid, and avoid ketosis,’ ” he said.

The researchers then went to work developing the K.Vita dietary supplement, which mainly contains decanoic acid but also another fat, octanoic acid.
 

Assessing feasibility

The feasibility study included 61 patients (59% female) who began taking the supplement. Of these, 35 were children (aged 3-18 years) and 26 were adults. The children had Dravet syndrome or another genetically driven form of epilepsy, while most of the adults had a focal epilepsy.

All participants had failed multiple antiseizure medications – a median of 3 for children and 10 for adults who completed the trial. Of the 61 original participants, 20 (19 children and 1 adult) had tried the ketogenic diet but had stopped it for various reasons, including noncompliance and lack of efficacy.

The liquid supplement was introduced gradually. The amount administered was based on weight in the children and was a standard amount in adults, with the target being 240 mL.

Participants consumed the supplement in equal servings taken at regular intervals as part of a meal or snack. They could take it alone or mix it with yogurt or another food.

Patients with feeding tubes took the supplement immediately before or after or mixed into an enteral feed, with a water flush afterward.

Researchers provided patients and caregivers with guidance on excluding highly refined sugary foods and beverages. Starchy foods such as bread, pasta, rice, and potatoes were not restricted.

The study consisted of three visits: baseline, 5 weeks, and 12 weeks, in addition to regular phone and email contact. Participants were also asked to keep a seizure diary.
 

Highly acceptable to patients

Overall, the study withdrawal rate was 33%. After a protocol change involving a slower introduction of the supplement, there were fewer withdrawals, Dr. Walker reported. He noted that the proportion of participants who completed the study (41 of 61) is “much better than with most studies of adults following the ketogenic diet.”

The most frequently reported gastrointestinal symptoms with the supplement were bloating and constipation, but these were predominantly mild and tended to decrease over time. This, said Dr. Walker, contrasts to the ketogenic diet where side effects tend to persist.

There was no significant change in body weight or body mass index. “We did not see weight gain as a problem at all,” Dr. Walker said.

Of 15 caregivers and 19 adults who returned an acceptability questionnaire, 84% agreed or strongly agreed the supplement had a good flavor (strawberry); 88% liked the appearance and color; 77% liked the texture and consistency; and 88% agreed or strongly agreed it was easy to take.

About one-third of adults and two-thirds of caregivers said they believed the supplement reduced seizures.
 

50% seizure reduction

Only three children and one adult became ketotic. This is typically classified as a beta-hydroxybutyrate (BHB) greater than 1 mmol/L (10.4 mg/dL). The BHB levels detected were markedly lower than those observed in individuals following a ketogenic diet, the investigators note.

Of the 41 participants, 19 completed the diaries. There were also data from physician recordings, so researchers were able to retrieve seizure frequencies for 32 of the 41 (78%). Of these 32 patients, 14 (44%) had a 50% or greater reduction in seizures. Overall, children and adults “responded similarly,” Dr. Walker said.

He acknowledged the study numbers are small and emphasized that larger studies are needed to determine efficacy. He also hopes for a future randomized controlled trial comparing K.Vita with another supplement that contains different types of fats.

Interestingly, the product has already “passed” the regulatory approval process in the United Kingdom, so it can be labeled as a medicinal food and should be available for use at the beginning of 2022, Dr. Walker said.
 

Study concerns

Asked to comment on the findings, Daniel Goldenholz, MD, PhD, instructor in the department of neurology, Beth Israel Deaconess Medical Center, Boston, said the supplement may be helpful, but he has concerns about the study.

Many patients with epilepsy are “desperate” for therapies that will help treat their seizures, said Dr. Goldenholz, who was not involved with the research. “If there’s a dietary therapy that has the potential for being helpful, I’m loving that. I need that. My patients are begging for something that works.” It is “really exciting” that researchers are working on that goal, Dr. Goldenholz added.

However, he noted that it is too soon to start talking to patients about this new product. He also pointed out that a significant fraction of the study participants dropped out, many because they couldn’t tolerate the supplement. In addition, others didn’t produce a seizure diary.

Dr. Goldenholz and colleagues have published several studies showing that patients with no intervention at all can sometimes show a reduction in seizures compared with their baseline results.

“We found sizable 50% reductions attributable entirely to the natural fluctuations in seizure rates, rather than any therapy at all, he said.

Dr. Goldenholz added that he hopes to see future studies on this topic, and on similar therapies “with sufficient data and more reliable metrics for efficacy.”

The study was funded by Vitaflo International. Dr. Walker reports having received grants from Vitaflo International and personal fees from UCB Pharma, Eisai, and Sage. In addition, along with colleagues, he has a patent (Nutritional product) pending.

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

Researchers have identified clusters of blood-based metabolites, molecules produced by cells during metabolism, that appear to predict subsequent dementia risk in new findings that may provide a prevention target.

Investigators found one of the clusters includes small high-density lipoprotein (HDL) metabolites associated with vascular dementia, while another cluster involves ketone bodies and citrate that are primarily associated with Alzheimer’s disease.

Ketone bodies, or ketones, are three related compounds – acetone, acetoacetic acid, and beta-hydroxybutyric acid (BHB) – produced by the liver during fat metabolism. Citrate is a salt or ester of citric acid.

Weight loss before dementia explained?

For the study, investigators included 125,000 patients from the UK Biobank, which includes 51,031 who were over age 60 at baseline. Of these, 1,188 developed dementia during a follow-up of about 10 years; 553 were diagnosed with Alzheimer’s disease and 298 with vascular dementia.

Researchers used a platform that covers 249 metabolic measures, including small molecules, fatty acids, and lipoprotein lipids.

They estimated risk associated with these metabolites, adjusting for age, sex, body mass index, technical variables, ethnicity, smoking, alcohol, education, metabolic and neuropsychiatric medication, and APOE4 genotypes.

Of the 249 metabolites, 47 (19%) were associated with dementia risk in those over age 60, after adjustment.

The investigators examined effect estimates for associations of metabolites with both Alzheimer’s disease and vascular dementia over age 60 versus hippocampal volume under age 60. They found a “very strong, very significant” association for Alzheimer’s disease, and a “marginally significant” association for vascular dementia, said Dr. van Duijn.

This would be expected, as there is a much stronger correlation between hippocampal and Alzheimer’s disease versus vascular dementia, she added.

“We not only see that the metabolites predict dementia, but also early pathology. This makes these findings rather interesting for targeting prevention,” she said. An analysis of total brain volume showed “very strong, very similar, very significant associations” for both Alzheimer’s disease and vascular dementia,” added Dr. van Duijn.

The researchers found a major shift in various metabolites involved in energy metabolism in the 10-year period before the diagnosis of Alzheimer’s disease. These changes include low levels of branched-chain amino acids and omega-3 fatty acids and high levels of glucose, citrate, acetone, beta-hydroxybutyrate, and acetate. “This finding is in line with that in APOE models that show reduced energy metabolism over age in the brain,” said Dr. van Duijn.

She added that high levels of some of these metabolites are associated with low body weight before dementia onset, which may explain the weight loss seen in patients before developing the disease. “Our hypothesis is that the liver is burning the fat reserves of the patients in order to provide the brain with fuel,” she explained.
 

Diet a prevention target?

The results also showed ketone bodies increase with age, which may represent the aging brain’s “compensation mechanism” to deal with an energy shortage, said Dr. van Duijn. “Supplementation of ketone bodies, branched-chain amino and omega-3 fatty acids may help support brain function.”

The fact that ketone bodies were positively associated with the risk of dementia is “a very important finding,” she said.

Following this and other presentations, session cochair Rima Kaddurah-Daouk, PhD, professor in psychiatry and behavioral sciences, Institute for Brain Sciences, Duke University, Durham, N.C., noted the research is “an important part of trying to decipher some of the mysteries in Alzheimer’s disease.”

The research contributes to the understanding of how nutrition and diet could influence metabolism and then the brain and is “opening the horizon” for thinking about “strategies for therapeutic interventions,” she said.

The study received funding support from the National Institute on Aging. The investigators have reported no relevant financial relationships.

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

Researchers have identified clusters of blood-based metabolites, molecules produced by cells during metabolism, that appear to predict subsequent dementia risk in new findings that may provide a prevention target.

Investigators found one of the clusters includes small high-density lipoprotein (HDL) metabolites associated with vascular dementia, while another cluster involves ketone bodies and citrate that are primarily associated with Alzheimer’s disease.

Ketone bodies, or ketones, are three related compounds – acetone, acetoacetic acid, and beta-hydroxybutyric acid (BHB) – produced by the liver during fat metabolism. Citrate is a salt or ester of citric acid.

Weight loss before dementia explained?

For the study, investigators included 125,000 patients from the UK Biobank, which includes 51,031 who were over age 60 at baseline. Of these, 1,188 developed dementia during a follow-up of about 10 years; 553 were diagnosed with Alzheimer’s disease and 298 with vascular dementia.

Researchers used a platform that covers 249 metabolic measures, including small molecules, fatty acids, and lipoprotein lipids.

They estimated risk associated with these metabolites, adjusting for age, sex, body mass index, technical variables, ethnicity, smoking, alcohol, education, metabolic and neuropsychiatric medication, and APOE4 genotypes.

Of the 249 metabolites, 47 (19%) were associated with dementia risk in those over age 60, after adjustment.

The investigators examined effect estimates for associations of metabolites with both Alzheimer’s disease and vascular dementia over age 60 versus hippocampal volume under age 60. They found a “very strong, very significant” association for Alzheimer’s disease, and a “marginally significant” association for vascular dementia, said Dr. van Duijn.

This would be expected, as there is a much stronger correlation between hippocampal and Alzheimer’s disease versus vascular dementia, she added.

“We not only see that the metabolites predict dementia, but also early pathology. This makes these findings rather interesting for targeting prevention,” she said. An analysis of total brain volume showed “very strong, very similar, very significant associations” for both Alzheimer’s disease and vascular dementia,” added Dr. van Duijn.

The researchers found a major shift in various metabolites involved in energy metabolism in the 10-year period before the diagnosis of Alzheimer’s disease. These changes include low levels of branched-chain amino acids and omega-3 fatty acids and high levels of glucose, citrate, acetone, beta-hydroxybutyrate, and acetate. “This finding is in line with that in APOE models that show reduced energy metabolism over age in the brain,” said Dr. van Duijn.

She added that high levels of some of these metabolites are associated with low body weight before dementia onset, which may explain the weight loss seen in patients before developing the disease. “Our hypothesis is that the liver is burning the fat reserves of the patients in order to provide the brain with fuel,” she explained.
 

Diet a prevention target?

The results also showed ketone bodies increase with age, which may represent the aging brain’s “compensation mechanism” to deal with an energy shortage, said Dr. van Duijn. “Supplementation of ketone bodies, branched-chain amino and omega-3 fatty acids may help support brain function.”

The fact that ketone bodies were positively associated with the risk of dementia is “a very important finding,” she said.

Following this and other presentations, session cochair Rima Kaddurah-Daouk, PhD, professor in psychiatry and behavioral sciences, Institute for Brain Sciences, Duke University, Durham, N.C., noted the research is “an important part of trying to decipher some of the mysteries in Alzheimer’s disease.”

The research contributes to the understanding of how nutrition and diet could influence metabolism and then the brain and is “opening the horizon” for thinking about “strategies for therapeutic interventions,” she said.

The study received funding support from the National Institute on Aging. The investigators have reported no relevant financial relationships.

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

Researchers have identified clusters of blood-based metabolites, molecules produced by cells during metabolism, that appear to predict subsequent dementia risk in new findings that may provide a prevention target.

Investigators found one of the clusters includes small high-density lipoprotein (HDL) metabolites associated with vascular dementia, while another cluster involves ketone bodies and citrate that are primarily associated with Alzheimer’s disease.

Ketone bodies, or ketones, are three related compounds – acetone, acetoacetic acid, and beta-hydroxybutyric acid (BHB) – produced by the liver during fat metabolism. Citrate is a salt or ester of citric acid.

Weight loss before dementia explained?

For the study, investigators included 125,000 patients from the UK Biobank, which includes 51,031 who were over age 60 at baseline. Of these, 1,188 developed dementia during a follow-up of about 10 years; 553 were diagnosed with Alzheimer’s disease and 298 with vascular dementia.

Researchers used a platform that covers 249 metabolic measures, including small molecules, fatty acids, and lipoprotein lipids.

They estimated risk associated with these metabolites, adjusting for age, sex, body mass index, technical variables, ethnicity, smoking, alcohol, education, metabolic and neuropsychiatric medication, and APOE4 genotypes.

Of the 249 metabolites, 47 (19%) were associated with dementia risk in those over age 60, after adjustment.

The investigators examined effect estimates for associations of metabolites with both Alzheimer’s disease and vascular dementia over age 60 versus hippocampal volume under age 60. They found a “very strong, very significant” association for Alzheimer’s disease, and a “marginally significant” association for vascular dementia, said Dr. van Duijn.

This would be expected, as there is a much stronger correlation between hippocampal and Alzheimer’s disease versus vascular dementia, she added.

“We not only see that the metabolites predict dementia, but also early pathology. This makes these findings rather interesting for targeting prevention,” she said. An analysis of total brain volume showed “very strong, very similar, very significant associations” for both Alzheimer’s disease and vascular dementia,” added Dr. van Duijn.

The researchers found a major shift in various metabolites involved in energy metabolism in the 10-year period before the diagnosis of Alzheimer’s disease. These changes include low levels of branched-chain amino acids and omega-3 fatty acids and high levels of glucose, citrate, acetone, beta-hydroxybutyrate, and acetate. “This finding is in line with that in APOE models that show reduced energy metabolism over age in the brain,” said Dr. van Duijn.

She added that high levels of some of these metabolites are associated with low body weight before dementia onset, which may explain the weight loss seen in patients before developing the disease. “Our hypothesis is that the liver is burning the fat reserves of the patients in order to provide the brain with fuel,” she explained.
 

Diet a prevention target?

The results also showed ketone bodies increase with age, which may represent the aging brain’s “compensation mechanism” to deal with an energy shortage, said Dr. van Duijn. “Supplementation of ketone bodies, branched-chain amino and omega-3 fatty acids may help support brain function.”

The fact that ketone bodies were positively associated with the risk of dementia is “a very important finding,” she said.

Following this and other presentations, session cochair Rima Kaddurah-Daouk, PhD, professor in psychiatry and behavioral sciences, Institute for Brain Sciences, Duke University, Durham, N.C., noted the research is “an important part of trying to decipher some of the mysteries in Alzheimer’s disease.”

The research contributes to the understanding of how nutrition and diet could influence metabolism and then the brain and is “opening the horizon” for thinking about “strategies for therapeutic interventions,” she said.

The study received funding support from the National Institute on Aging. The investigators have reported no relevant financial relationships.

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

Around the world, cases of dementia are projected to hit 153 million in 2050, up from around 57 million in 2019, new global prevalence data show. “These extreme increases are due largely to demographic trends, including population growth and aging,” said study investigator Emma Nichols, MPH, a researcher at the Institute for Health Metrics and Evaluation at the University of Washington in Seattle.

“Our estimates of expected increases can and should inform policy and planning efforts that will be needed to address the needs of the growing number of individuals with dementia in the future,” Ms. Nichols said.

The latest global prevalence data were reported at the 2021 Alzheimer’s Association International Conference.

“The numbers are staggering: Nearly 153 million cases of dementia are predicted worldwide by the year 2050. To put that in context, that number is equal to approximately half of the U.S. population in 2020,” Heather M. Snyder, PhD, vice president of medical and scientific relations for the Alzheimer’s Association, said in a statement.
 

Prevalence by country

To more accurately forecast global dementia prevalence and produce country-level estimates, the investigators leveraged data from 1999 to 2019 from the Global Burden of Disease study, a comprehensive set of estimates of worldwide health trends.

These data suggest global dementia cases will increase from 57.4 million (50.4 to 65.1) in 2019 to 152.8 million (130.8 to 175.9) in 2050.

Regions that will experience the worst of the increase are eastern Sub-Saharan Africa, North Africa, and the Middle East.

The researchers also factored into the forecasts expected trends in obesity, diabetes, smoking, and educational attainment.

Increases in better education around the world are projected to decrease dementia prevalence by 6.2 million cases worldwide by 2050. However, anticipated trends in smoking, high body mass index, and diabetes will offset this gain, increasing global dementia cases by 6.8 million cases.

“A reversal of these expected trends in cardiovascular risks would be necessary to alter the anticipated trends,” Ms. Nichols said. “Interventions targeted at modifiable risk factors for dementia represent a viable strategy to help address the anticipated trends in dementia burden,” she added.
 

Need for effective prevention, treatment

Commenting on the research, Rebecca M. Edelmayer, PhD, senior director of scientific engagement at the Alzheimer’s Association, said the global increase in dementia cases is something the association has been following for many years. “We know that if we do not find effective treatments that are going to stop, slow, or prevent Alzheimer’s disease, this number will continue to grow and it will continue to impact people globally,” Dr. Edelmayer said.

She noted that although there are some positive trends, including the fact that increased education may drive down dementia risk, other factors, such as smoking, high body mass index, and high blood sugar level, are predicted to increase in prevalence.

“Some of these factors are actually counterbalancing each other, and in the end, if we don’t continue to develop culturally tailored interventions or even risk reduction strategies for individuals across the globe, we will continue to see those numbers rise overall,” Dr. Edelmayer said.

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

Around the world, cases of dementia are projected to hit 153 million in 2050, up from around 57 million in 2019, new global prevalence data show. “These extreme increases are due largely to demographic trends, including population growth and aging,” said study investigator Emma Nichols, MPH, a researcher at the Institute for Health Metrics and Evaluation at the University of Washington in Seattle.

“Our estimates of expected increases can and should inform policy and planning efforts that will be needed to address the needs of the growing number of individuals with dementia in the future,” Ms. Nichols said.

The latest global prevalence data were reported at the 2021 Alzheimer’s Association International Conference.

“The numbers are staggering: Nearly 153 million cases of dementia are predicted worldwide by the year 2050. To put that in context, that number is equal to approximately half of the U.S. population in 2020,” Heather M. Snyder, PhD, vice president of medical and scientific relations for the Alzheimer’s Association, said in a statement.
 

Prevalence by country

To more accurately forecast global dementia prevalence and produce country-level estimates, the investigators leveraged data from 1999 to 2019 from the Global Burden of Disease study, a comprehensive set of estimates of worldwide health trends.

These data suggest global dementia cases will increase from 57.4 million (50.4 to 65.1) in 2019 to 152.8 million (130.8 to 175.9) in 2050.

Regions that will experience the worst of the increase are eastern Sub-Saharan Africa, North Africa, and the Middle East.

The researchers also factored into the forecasts expected trends in obesity, diabetes, smoking, and educational attainment.

Increases in better education around the world are projected to decrease dementia prevalence by 6.2 million cases worldwide by 2050. However, anticipated trends in smoking, high body mass index, and diabetes will offset this gain, increasing global dementia cases by 6.8 million cases.

“A reversal of these expected trends in cardiovascular risks would be necessary to alter the anticipated trends,” Ms. Nichols said. “Interventions targeted at modifiable risk factors for dementia represent a viable strategy to help address the anticipated trends in dementia burden,” she added.
 

Need for effective prevention, treatment

Commenting on the research, Rebecca M. Edelmayer, PhD, senior director of scientific engagement at the Alzheimer’s Association, said the global increase in dementia cases is something the association has been following for many years. “We know that if we do not find effective treatments that are going to stop, slow, or prevent Alzheimer’s disease, this number will continue to grow and it will continue to impact people globally,” Dr. Edelmayer said.

She noted that although there are some positive trends, including the fact that increased education may drive down dementia risk, other factors, such as smoking, high body mass index, and high blood sugar level, are predicted to increase in prevalence.

“Some of these factors are actually counterbalancing each other, and in the end, if we don’t continue to develop culturally tailored interventions or even risk reduction strategies for individuals across the globe, we will continue to see those numbers rise overall,” Dr. Edelmayer said.

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

Around the world, cases of dementia are projected to hit 153 million in 2050, up from around 57 million in 2019, new global prevalence data show. “These extreme increases are due largely to demographic trends, including population growth and aging,” said study investigator Emma Nichols, MPH, a researcher at the Institute for Health Metrics and Evaluation at the University of Washington in Seattle.

“Our estimates of expected increases can and should inform policy and planning efforts that will be needed to address the needs of the growing number of individuals with dementia in the future,” Ms. Nichols said.

The latest global prevalence data were reported at the 2021 Alzheimer’s Association International Conference.

“The numbers are staggering: Nearly 153 million cases of dementia are predicted worldwide by the year 2050. To put that in context, that number is equal to approximately half of the U.S. population in 2020,” Heather M. Snyder, PhD, vice president of medical and scientific relations for the Alzheimer’s Association, said in a statement.
 

Prevalence by country

To more accurately forecast global dementia prevalence and produce country-level estimates, the investigators leveraged data from 1999 to 2019 from the Global Burden of Disease study, a comprehensive set of estimates of worldwide health trends.

These data suggest global dementia cases will increase from 57.4 million (50.4 to 65.1) in 2019 to 152.8 million (130.8 to 175.9) in 2050.

Regions that will experience the worst of the increase are eastern Sub-Saharan Africa, North Africa, and the Middle East.

The researchers also factored into the forecasts expected trends in obesity, diabetes, smoking, and educational attainment.

Increases in better education around the world are projected to decrease dementia prevalence by 6.2 million cases worldwide by 2050. However, anticipated trends in smoking, high body mass index, and diabetes will offset this gain, increasing global dementia cases by 6.8 million cases.

“A reversal of these expected trends in cardiovascular risks would be necessary to alter the anticipated trends,” Ms. Nichols said. “Interventions targeted at modifiable risk factors for dementia represent a viable strategy to help address the anticipated trends in dementia burden,” she added.
 

Need for effective prevention, treatment

Commenting on the research, Rebecca M. Edelmayer, PhD, senior director of scientific engagement at the Alzheimer’s Association, said the global increase in dementia cases is something the association has been following for many years. “We know that if we do not find effective treatments that are going to stop, slow, or prevent Alzheimer’s disease, this number will continue to grow and it will continue to impact people globally,” Dr. Edelmayer said.

She noted that although there are some positive trends, including the fact that increased education may drive down dementia risk, other factors, such as smoking, high body mass index, and high blood sugar level, are predicted to increase in prevalence.

“Some of these factors are actually counterbalancing each other, and in the end, if we don’t continue to develop culturally tailored interventions or even risk reduction strategies for individuals across the globe, we will continue to see those numbers rise overall,” Dr. Edelmayer said.

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

With COVID, the fun never ends

Welcome to America’s favorite pandemic-themed game show! Let’s play Covidiot Proof! And now, here’s your host, the lovely and talented Anthony Grouchy!

sabelskaya/iStock/Getty Images Plus

Tony: Hello everyone! Our first category today is America or [blank], and the first clue is for you, Don. This country requires “individuals to use a health pass to patronize indoor establishments such as restaurants, bars, nightclubs and cinemas.”

Don: Freedom-loving Americans would never stand for that, Tony, so I’m going to say Greece.

Tony: That’s correct, Don. One hundred points for you. Okay Joe, here’s your clue: In this country, some people wear disguises to get a COVID vaccination so their friends and families won’t find out.

Joe: Sounds like communism to me, Tony. I’ll say Cuba.

Tony: Sorry Joe, that’s incorrect. Don?

Don: The friends and families sound like freedom-loving Americans, so it must be America.

Tony: It is America. Missouri, to be exact. And now, one last question for both of you to win the game. True or false? Did the pastor of a church in Tennessee say that mask-wearers would be kicked out of the building because “I am not playing these Democrat games up in this church”?

Joe: That’s fake news, Tony. It’s gotta be false.

Tony: Incorrect! It’s absolutely true. That means today’s winner is … Joe? Yes, I’m being told that Tennessee goes to Joe.

Don: That’s bulls#&@! I won this thing! I’ll see you in court!
 

More money, more life

Does it seem to you that the wealthy live forever, while the less financially comfortable live shorter lives? If you answered, yes, it turns out that you’re right.

utah778/Thinkstock

Researchers analyzed the effect of net worth at midlife with mortality. To take out genetic differences among the sample of 5,400 adults aged 46 years, the investigators also studied a subset of 2,490 twin and sibling pairs.

“The within-family association provides strong evidence that an association between wealth accumulation and life expectancy exists, because comparing siblings within the same family to each other controls for all of the life experience and biology that they share,” said coauthor Eric Finegood of Northwestern University, Chicago.

But what if one sibling has a history of cancer, heart disease, or other health conditions? The cost of treatment and employment limitations could affect someone’s ability to stack their wealth, right? Absolutely. The researchers took that into account and looked at only healthy individuals and found the same results. More money, longer life.

We have the policies and programs in place for heart health, diabetes prevention, and smoking cessation, as they are seen as major threats to public health. So why not do the same for financial security? A low bank account may just be more harmful.
 

Holding the ‘health care and wellness’ gun

Cigarettes are not good for us. We know this.

seanika/ThinkStock

It’s, therefore, not surprising to learn that a business has requested for a U.K. ban on the sale of cigarettes by 2030. However, when that someone turns out to be the CEO of Philip Morris International, tobacco company and maker of Marlboro cigarettes, things get a little confusing.

Banning cigarettes, according to Jacek Olczak, would reduce confusion among consumers, many of whom feel that the alternatives are worse for their health. His company can “see the world without cigarettes ... and actually, the sooner it happens, the better it is for everyone.” A truly noble sentiment from the CEO of a large tobacco company. Nothing nefarious going on here.

Philip Morris International is actually leaning hard into nonsmoking means of tobacco consumption, even going so far as to brand itself a “health care and wellness company” on a mission to “unsmoke the world.” And if those aren’t egregious business euphemisms, we don’t know what is.

Of course, for all the completely believable and sincere rhetoric, the fact is that Marlboros are still on the shelves. Philip Morris is still making and advertising them. If their concern was genuine, why wouldn’t they just stop manufacturing them now?

So, we ask ourselves if this a selfless act of kindness or is it an unscrupulous corporate act to get a leg up on their competitors? We’ll leave it up to the readers to decide.

Okay, we lied, it’s the second one.
 

Autopsy of the living dead

Imagine the absolute terror you’d feel if you opened your eyes to bright, blinding white lights only to see a bone saw 3 inches from your forehead and getting closer by the second. Horrifying for you, certainly, but think about the poor pathologist behind the saw who probably thought a zombie apocalypse was coming. This was close to being a reality for a 29-year-old prisoner at the Asturias Central Penitentiary in Spain.

Gonzalo Montoya Jiménez was discovered in his cell unresponsive. Three physicians examined him and found he was showing signs of death, such as cyanosis and rigor mortis. Mr. Jiménez was processed like any other body and was sent, in a body bag, to a hospital mortuary, where he spent time in a freezer for body preservation. Just before he was due for his autopsy, he began showing signs of life.

It’s not completely clear why this happened to poor Mr. Jiménez, but it was reported that he wasn’t feeling well the day before and that he has epilepsy. Hospital officials suggested he may have been cataleptic, possibly because he had trouble adhering to his medication schedule.

Mr. Jiménez was moved to another hospital under armed guard after coming back to life and regained consciousness after a day or so. Talk about cheating death.
 

With COVID, the fun never ends

Welcome to America’s favorite pandemic-themed game show! Let’s play Covidiot Proof! And now, here’s your host, the lovely and talented Anthony Grouchy!

sabelskaya/iStock/Getty Images Plus

Tony: Hello everyone! Our first category today is America or [blank], and the first clue is for you, Don. This country requires “individuals to use a health pass to patronize indoor establishments such as restaurants, bars, nightclubs and cinemas.”

Don: Freedom-loving Americans would never stand for that, Tony, so I’m going to say Greece.

Tony: That’s correct, Don. One hundred points for you. Okay Joe, here’s your clue: In this country, some people wear disguises to get a COVID vaccination so their friends and families won’t find out.

Joe: Sounds like communism to me, Tony. I’ll say Cuba.

Tony: Sorry Joe, that’s incorrect. Don?

Don: The friends and families sound like freedom-loving Americans, so it must be America.

Tony: It is America. Missouri, to be exact. And now, one last question for both of you to win the game. True or false? Did the pastor of a church in Tennessee say that mask-wearers would be kicked out of the building because “I am not playing these Democrat games up in this church”?

Joe: That’s fake news, Tony. It’s gotta be false.

Tony: Incorrect! It’s absolutely true. That means today’s winner is … Joe? Yes, I’m being told that Tennessee goes to Joe.

Don: That’s bulls#&@! I won this thing! I’ll see you in court!
 

More money, more life

Does it seem to you that the wealthy live forever, while the less financially comfortable live shorter lives? If you answered, yes, it turns out that you’re right.

utah778/Thinkstock

Researchers analyzed the effect of net worth at midlife with mortality. To take out genetic differences among the sample of 5,400 adults aged 46 years, the investigators also studied a subset of 2,490 twin and sibling pairs.

“The within-family association provides strong evidence that an association between wealth accumulation and life expectancy exists, because comparing siblings within the same family to each other controls for all of the life experience and biology that they share,” said coauthor Eric Finegood of Northwestern University, Chicago.

But what if one sibling has a history of cancer, heart disease, or other health conditions? The cost of treatment and employment limitations could affect someone’s ability to stack their wealth, right? Absolutely. The researchers took that into account and looked at only healthy individuals and found the same results. More money, longer life.

We have the policies and programs in place for heart health, diabetes prevention, and smoking cessation, as they are seen as major threats to public health. So why not do the same for financial security? A low bank account may just be more harmful.
 

Holding the ‘health care and wellness’ gun

Cigarettes are not good for us. We know this.

seanika/ThinkStock

It’s, therefore, not surprising to learn that a business has requested for a U.K. ban on the sale of cigarettes by 2030. However, when that someone turns out to be the CEO of Philip Morris International, tobacco company and maker of Marlboro cigarettes, things get a little confusing.

Banning cigarettes, according to Jacek Olczak, would reduce confusion among consumers, many of whom feel that the alternatives are worse for their health. His company can “see the world without cigarettes ... and actually, the sooner it happens, the better it is for everyone.” A truly noble sentiment from the CEO of a large tobacco company. Nothing nefarious going on here.

Philip Morris International is actually leaning hard into nonsmoking means of tobacco consumption, even going so far as to brand itself a “health care and wellness company” on a mission to “unsmoke the world.” And if those aren’t egregious business euphemisms, we don’t know what is.

Of course, for all the completely believable and sincere rhetoric, the fact is that Marlboros are still on the shelves. Philip Morris is still making and advertising them. If their concern was genuine, why wouldn’t they just stop manufacturing them now?

So, we ask ourselves if this a selfless act of kindness or is it an unscrupulous corporate act to get a leg up on their competitors? We’ll leave it up to the readers to decide.

Okay, we lied, it’s the second one.
 

Autopsy of the living dead

Imagine the absolute terror you’d feel if you opened your eyes to bright, blinding white lights only to see a bone saw 3 inches from your forehead and getting closer by the second. Horrifying for you, certainly, but think about the poor pathologist behind the saw who probably thought a zombie apocalypse was coming. This was close to being a reality for a 29-year-old prisoner at the Asturias Central Penitentiary in Spain.

Gonzalo Montoya Jiménez was discovered in his cell unresponsive. Three physicians examined him and found he was showing signs of death, such as cyanosis and rigor mortis. Mr. Jiménez was processed like any other body and was sent, in a body bag, to a hospital mortuary, where he spent time in a freezer for body preservation. Just before he was due for his autopsy, he began showing signs of life.

It’s not completely clear why this happened to poor Mr. Jiménez, but it was reported that he wasn’t feeling well the day before and that he has epilepsy. Hospital officials suggested he may have been cataleptic, possibly because he had trouble adhering to his medication schedule.

Mr. Jiménez was moved to another hospital under armed guard after coming back to life and regained consciousness after a day or so. Talk about cheating death.
 

With COVID, the fun never ends

Welcome to America’s favorite pandemic-themed game show! Let’s play Covidiot Proof! And now, here’s your host, the lovely and talented Anthony Grouchy!

sabelskaya/iStock/Getty Images Plus

Tony: Hello everyone! Our first category today is America or [blank], and the first clue is for you, Don. This country requires “individuals to use a health pass to patronize indoor establishments such as restaurants, bars, nightclubs and cinemas.”

Don: Freedom-loving Americans would never stand for that, Tony, so I’m going to say Greece.

Tony: That’s correct, Don. One hundred points for you. Okay Joe, here’s your clue: In this country, some people wear disguises to get a COVID vaccination so their friends and families won’t find out.

Joe: Sounds like communism to me, Tony. I’ll say Cuba.

Tony: Sorry Joe, that’s incorrect. Don?

Don: The friends and families sound like freedom-loving Americans, so it must be America.

Tony: It is America. Missouri, to be exact. And now, one last question for both of you to win the game. True or false? Did the pastor of a church in Tennessee say that mask-wearers would be kicked out of the building because “I am not playing these Democrat games up in this church”?

Joe: That’s fake news, Tony. It’s gotta be false.

Tony: Incorrect! It’s absolutely true. That means today’s winner is … Joe? Yes, I’m being told that Tennessee goes to Joe.

Don: That’s bulls#&@! I won this thing! I’ll see you in court!
 

More money, more life

Does it seem to you that the wealthy live forever, while the less financially comfortable live shorter lives? If you answered, yes, it turns out that you’re right.

utah778/Thinkstock

Researchers analyzed the effect of net worth at midlife with mortality. To take out genetic differences among the sample of 5,400 adults aged 46 years, the investigators also studied a subset of 2,490 twin and sibling pairs.

“The within-family association provides strong evidence that an association between wealth accumulation and life expectancy exists, because comparing siblings within the same family to each other controls for all of the life experience and biology that they share,” said coauthor Eric Finegood of Northwestern University, Chicago.

But what if one sibling has a history of cancer, heart disease, or other health conditions? The cost of treatment and employment limitations could affect someone’s ability to stack their wealth, right? Absolutely. The researchers took that into account and looked at only healthy individuals and found the same results. More money, longer life.

We have the policies and programs in place for heart health, diabetes prevention, and smoking cessation, as they are seen as major threats to public health. So why not do the same for financial security? A low bank account may just be more harmful.
 

Holding the ‘health care and wellness’ gun

Cigarettes are not good for us. We know this.

seanika/ThinkStock

It’s, therefore, not surprising to learn that a business has requested for a U.K. ban on the sale of cigarettes by 2030. However, when that someone turns out to be the CEO of Philip Morris International, tobacco company and maker of Marlboro cigarettes, things get a little confusing.

Banning cigarettes, according to Jacek Olczak, would reduce confusion among consumers, many of whom feel that the alternatives are worse for their health. His company can “see the world without cigarettes ... and actually, the sooner it happens, the better it is for everyone.” A truly noble sentiment from the CEO of a large tobacco company. Nothing nefarious going on here.

Philip Morris International is actually leaning hard into nonsmoking means of tobacco consumption, even going so far as to brand itself a “health care and wellness company” on a mission to “unsmoke the world.” And if those aren’t egregious business euphemisms, we don’t know what is.

Of course, for all the completely believable and sincere rhetoric, the fact is that Marlboros are still on the shelves. Philip Morris is still making and advertising them. If their concern was genuine, why wouldn’t they just stop manufacturing them now?

So, we ask ourselves if this a selfless act of kindness or is it an unscrupulous corporate act to get a leg up on their competitors? We’ll leave it up to the readers to decide.

Okay, we lied, it’s the second one.
 

Autopsy of the living dead

Imagine the absolute terror you’d feel if you opened your eyes to bright, blinding white lights only to see a bone saw 3 inches from your forehead and getting closer by the second. Horrifying for you, certainly, but think about the poor pathologist behind the saw who probably thought a zombie apocalypse was coming. This was close to being a reality for a 29-year-old prisoner at the Asturias Central Penitentiary in Spain.

Gonzalo Montoya Jiménez was discovered in his cell unresponsive. Three physicians examined him and found he was showing signs of death, such as cyanosis and rigor mortis. Mr. Jiménez was processed like any other body and was sent, in a body bag, to a hospital mortuary, where he spent time in a freezer for body preservation. Just before he was due for his autopsy, he began showing signs of life.

It’s not completely clear why this happened to poor Mr. Jiménez, but it was reported that he wasn’t feeling well the day before and that he has epilepsy. Hospital officials suggested he may have been cataleptic, possibly because he had trouble adhering to his medication schedule.

Mr. Jiménez was moved to another hospital under armed guard after coming back to life and regained consciousness after a day or so. Talk about cheating death.
 

Drinking six or more cups of coffee per day is associated with smaller brain volume and a 53% increased risk for dementia compared with light coffee consumption (1-2 cups per day), according to the results of a large study.

amenic181/Getty Images

“With coffee intake, moderation is the key, and especially high levels of consumption may have adverse long-term effects on the brain,” said study investigator Elina Hypponen, PhD, professor of nutritional and genetic epidemiology and director of the Australian Center for Precision Health at the University of South Australia.

“These new data are concerning, and there is a need to conduct further carefully controlled studies to clarify the effects of coffee on the brain.”

The study was published online June 24 in Nutritional Neuroscience.
 

Potent stimulant

Coffee is a potent nervous system stimulant and is among the most popular nonalcoholic beverages. Some previous research suggests it benefits the brain, but the investigators noted that other research shows a negative or U-shaped relationship.

To investigate, the researchers examined data from the U.K. Biobank, a long-term prospective epidemiologic study of more than 500,000 participants aged 37-73 years who were recruited in 22 assessment centers in the United Kingdom between March 2006 and October 2010.

During the baseline assessment, information was gathered using touchscreen questionnaires, verbal interviews, and physical examinations that involved collection of blood, urine, and saliva samples. An imaging substudy was incorporated in 2014, the goal of which was to conduct brain, heart, and body MRI imaging for 100,000 participants.

The investigators conducted analyses on disease outcomes for 398,646 participants for whom information on habitual coffee consumption was available. Brain volume analyses were conducted in 17,702 participants for whom valid brain imaging data were available.

Participants reported coffee intake in cups per day. Researchers grouped coffee consumption into seven categories: nondrinkers, decaffeinated coffee drinkers, and caffeinated coffee drinkers who consumed less than 1 cup/d, 1-2 cups/d, 3-4 cups/d, 5-6 cups/d, and more than 6 cups/d.

The reference category was those who consumed 1-2 cups/d, rather than those who abstained from coffee, because persons who abstain are more likely to be at suboptimal health.

“Comparing the health of coffee drinkers to the health of those choosing to abstain from coffee will typically lead to an impression of a health benefit, even if there would not be one,” said Dr. Hypponen.

The researchers obtained total and regional brain volumes from the MRI imaging substudy starting 4-6 years after baseline assessment. They accessed information on incident dementia and stroke using primary care data, hospital admission electronic health records, national death registers, and self-reported medical conditions.

Covariates included socioeconomic, health, and other factors, such as smoking, alcohol and tea consumption, physical activity, stressful life events, and body mass index.

The investigators found that there was a linear inverse association between coffee consumption and total brain volume (fully adjusted beta per cup, –1.42; 95% confidence interval, –1.89 to –0.94), with consistent patterns for gray matter, white matter, and hippocampal volumes.

There was no evidence to support an association with white matter hyperintensity (WMH) volume (beta –0.01; 95% CI, –0.07 to 0.05).
 

Higher consumption, higher risk

The analysis also revealed a nonlinear association between coffee consumption and the odds of dementia (P nonlinearity = .0001), with slightly higher odds seen with non–coffee drinkers and decaffeinated-coffee drinkers and more notable increases for participants in the highest categories of coffee consumption compared with light coffee drinkers.

After adjustment for all covariates, the odds ratio of dementia among persons in the category of coffee intake was 1.53 (95% CI, 1.28-1.83). After full adjustments, the association with heavy coffee consumption and stroke was not significant, although “we can’t exclude a weak effect,” said Dr. Hypponen.

“For the highest coffee consumption group, the data support an association which may be anywhere from 0% to 37% higher odds of stroke after full adjustment,” she added.

People at risk for hypertension may develop “unpleasant sensations” and stop drinking coffee before a serious adverse event occurs, said Dr. Hypponen. In a previous study, she and her colleagues showed that those who have genetically higher blood pressure tend to drink less coffee than their counterparts without the condition.

“This type of effect might be expected to naturally limit the adverse effects of coffee on the risk of stroke,” said Dr. Hypponen.

The odds remained elevated for participants drinking more than 6 cups/d after the researchers accounted for sleep quality. There were no differences in risk between men and women or by age.

An examination of the consumption of tea, which often contains caffeine, did not show an association with brain volume or the odds of dementia or stroke.

“We don’t know whether the difference between associations seen for coffee and tea intake reflects the difference in related caffeine intake or some other explanation, such as dehydration or effects operating through blood cholesterol,” said Dr. Hypponen.

Although reverse causation is possible, there’s no reason to believe that it is relevant to the study results. Genetic evidence suggests a causal role of higher coffee intake on risk for Alzheimer’s disease. In addition, results of a clinical trial support the association between higher caffeine intake and smaller gray matter volume, said Dr. Hypponen.

The mechanisms linking coffee consumption to brain volumes and dementia are not well established. However, Dr. Hypponen noted that caffeine has been used to induce apoptosis in cancer studies using glial cells.

“Furthermore, adenosine receptors, which mediate many of the effects of caffeine in the brain, have been suggested to influence the release of growth factors, which in turn can have an influence on astrocyte proliferation and angiogenesis in the brain,” she said.

Some types of coffee contain cafestol, which increases blood cholesterol and can have adverse effects though related mechanisms, said Dr. Hypponen.

The mechanism may also involve dehydration, which may have a harmful effect on the brain. The study suggested a correlation between dehydration and high coffee intake. “Of course, if this is the case, it is good news, as then we can do something about it simply by drinking some water every time we have a cup of coffee,” she said.
 

Misleading conclusions

Coffee contains antioxidants, and although previous studies have suggested it might be beneficial, this hypothesis is “too simplistic,” said Dr. Hypponen. “While coffee is not going to be all ‘bad’ either, there are a lot of controversies and suggestions about beneficial effects of coffee which may not be true, or at least do not reflect the full story.”

If the drinking of coffee is at least partly determined by an individual’s health status, then that would often lead to misleading conclusions in observational studies, said Dr. Hypponen.

“When one uses as a comparison people who already have poor health and who do not drink coffee because of that, coffee intake will by default appear beneficial simply because there are more people with disease among those choosing abstinence,” she said.

Before now, there was “very little evidence about the association between coffee intake and brain morphology,” and the studies that were conducted were relatively small, said Dr. Hypponen.

One of these smaller studies included a group of women aged 13-30 years. It found that coffee consumption was not associated with total brain volumes, but the findings suggested a U-shaped association with hippocampal volume; higher values were seen both for nondrinkers and the groups with higher consumption.

A small study of elderly patients with diabetes showed no evidence of an association with white matter volume, but there was a possible age-dependent association with gray matter volume.

The largest of the earlier studies had results that were very similar to those of the current study, suggesting that increasing coffee intake is associated with smaller hippocampal volumes, said Dr. Hypponen.

One of the study’s limitations included the fact that full dietary information was available only for a subsample and that factors such as dehydration were measured at baseline rather than at the time of brain MRI.

Another possible study limitation was the use of self-reported data and the fact that lifestyle changes may have occurred between baseline and MRI or covariate measurement.

In addition, the study is subject to a healthy-volunteer bias, and its implications are restricted to White British persons. The association needs to be studied in other ethnic populations, the authors noted.
 

A reason to cut back?

Commenting on the findings, Walter Willett, MD, DrPH, professor of epidemiology and nutrition, Harvard T. H. Chan School of Public Health, Boston, said the study is large and quite well done.

“It does raise questions about an increase in risk of dementia with six or more cups of coffee per day,” said Dr. Willett. “At the same time, it provides reassurance about lack of adverse effects of coffee for those consuming three or four cups per day, and little increase in risk, if any, with five cups per day.”

It’s not entirely clear whether the increase in risk with six or more cups of coffee per day represents a “true effect” of coffee, inasmuch as the study did not seem to adjust fully for dietary factors, high consumption of alcohol, or past smoking, said Dr. Willett.

The findings don’t suggest that coffee lovers should give up their Java. “But six or more cups per day is a lot, and those who drink that much might consider cutting back a bit while research continues,” said Dr. Willett.

The study was supported by the National Health and Medical Research Council.

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

Drinking six or more cups of coffee per day is associated with smaller brain volume and a 53% increased risk for dementia compared with light coffee consumption (1-2 cups per day), according to the results of a large study.

amenic181/Getty Images

“With coffee intake, moderation is the key, and especially high levels of consumption may have adverse long-term effects on the brain,” said study investigator Elina Hypponen, PhD, professor of nutritional and genetic epidemiology and director of the Australian Center for Precision Health at the University of South Australia.

“These new data are concerning, and there is a need to conduct further carefully controlled studies to clarify the effects of coffee on the brain.”

The study was published online June 24 in Nutritional Neuroscience.
 

Potent stimulant

Coffee is a potent nervous system stimulant and is among the most popular nonalcoholic beverages. Some previous research suggests it benefits the brain, but the investigators noted that other research shows a negative or U-shaped relationship.

To investigate, the researchers examined data from the U.K. Biobank, a long-term prospective epidemiologic study of more than 500,000 participants aged 37-73 years who were recruited in 22 assessment centers in the United Kingdom between March 2006 and October 2010.

During the baseline assessment, information was gathered using touchscreen questionnaires, verbal interviews, and physical examinations that involved collection of blood, urine, and saliva samples. An imaging substudy was incorporated in 2014, the goal of which was to conduct brain, heart, and body MRI imaging for 100,000 participants.

The investigators conducted analyses on disease outcomes for 398,646 participants for whom information on habitual coffee consumption was available. Brain volume analyses were conducted in 17,702 participants for whom valid brain imaging data were available.

Participants reported coffee intake in cups per day. Researchers grouped coffee consumption into seven categories: nondrinkers, decaffeinated coffee drinkers, and caffeinated coffee drinkers who consumed less than 1 cup/d, 1-2 cups/d, 3-4 cups/d, 5-6 cups/d, and more than 6 cups/d.

The reference category was those who consumed 1-2 cups/d, rather than those who abstained from coffee, because persons who abstain are more likely to be at suboptimal health.

“Comparing the health of coffee drinkers to the health of those choosing to abstain from coffee will typically lead to an impression of a health benefit, even if there would not be one,” said Dr. Hypponen.

The researchers obtained total and regional brain volumes from the MRI imaging substudy starting 4-6 years after baseline assessment. They accessed information on incident dementia and stroke using primary care data, hospital admission electronic health records, national death registers, and self-reported medical conditions.

Covariates included socioeconomic, health, and other factors, such as smoking, alcohol and tea consumption, physical activity, stressful life events, and body mass index.

The investigators found that there was a linear inverse association between coffee consumption and total brain volume (fully adjusted beta per cup, –1.42; 95% confidence interval, –1.89 to –0.94), with consistent patterns for gray matter, white matter, and hippocampal volumes.

There was no evidence to support an association with white matter hyperintensity (WMH) volume (beta –0.01; 95% CI, –0.07 to 0.05).
 

Higher consumption, higher risk

The analysis also revealed a nonlinear association between coffee consumption and the odds of dementia (P nonlinearity = .0001), with slightly higher odds seen with non–coffee drinkers and decaffeinated-coffee drinkers and more notable increases for participants in the highest categories of coffee consumption compared with light coffee drinkers.

After adjustment for all covariates, the odds ratio of dementia among persons in the category of coffee intake was 1.53 (95% CI, 1.28-1.83). After full adjustments, the association with heavy coffee consumption and stroke was not significant, although “we can’t exclude a weak effect,” said Dr. Hypponen.

“For the highest coffee consumption group, the data support an association which may be anywhere from 0% to 37% higher odds of stroke after full adjustment,” she added.

People at risk for hypertension may develop “unpleasant sensations” and stop drinking coffee before a serious adverse event occurs, said Dr. Hypponen. In a previous study, she and her colleagues showed that those who have genetically higher blood pressure tend to drink less coffee than their counterparts without the condition.

“This type of effect might be expected to naturally limit the adverse effects of coffee on the risk of stroke,” said Dr. Hypponen.

The odds remained elevated for participants drinking more than 6 cups/d after the researchers accounted for sleep quality. There were no differences in risk between men and women or by age.

An examination of the consumption of tea, which often contains caffeine, did not show an association with brain volume or the odds of dementia or stroke.

“We don’t know whether the difference between associations seen for coffee and tea intake reflects the difference in related caffeine intake or some other explanation, such as dehydration or effects operating through blood cholesterol,” said Dr. Hypponen.

Although reverse causation is possible, there’s no reason to believe that it is relevant to the study results. Genetic evidence suggests a causal role of higher coffee intake on risk for Alzheimer’s disease. In addition, results of a clinical trial support the association between higher caffeine intake and smaller gray matter volume, said Dr. Hypponen.

The mechanisms linking coffee consumption to brain volumes and dementia are not well established. However, Dr. Hypponen noted that caffeine has been used to induce apoptosis in cancer studies using glial cells.

“Furthermore, adenosine receptors, which mediate many of the effects of caffeine in the brain, have been suggested to influence the release of growth factors, which in turn can have an influence on astrocyte proliferation and angiogenesis in the brain,” she said.

Some types of coffee contain cafestol, which increases blood cholesterol and can have adverse effects though related mechanisms, said Dr. Hypponen.

The mechanism may also involve dehydration, which may have a harmful effect on the brain. The study suggested a correlation between dehydration and high coffee intake. “Of course, if this is the case, it is good news, as then we can do something about it simply by drinking some water every time we have a cup of coffee,” she said.
 

Misleading conclusions

Coffee contains antioxidants, and although previous studies have suggested it might be beneficial, this hypothesis is “too simplistic,” said Dr. Hypponen. “While coffee is not going to be all ‘bad’ either, there are a lot of controversies and suggestions about beneficial effects of coffee which may not be true, or at least do not reflect the full story.”

If the drinking of coffee is at least partly determined by an individual’s health status, then that would often lead to misleading conclusions in observational studies, said Dr. Hypponen.

“When one uses as a comparison people who already have poor health and who do not drink coffee because of that, coffee intake will by default appear beneficial simply because there are more people with disease among those choosing abstinence,” she said.

Before now, there was “very little evidence about the association between coffee intake and brain morphology,” and the studies that were conducted were relatively small, said Dr. Hypponen.

One of these smaller studies included a group of women aged 13-30 years. It found that coffee consumption was not associated with total brain volumes, but the findings suggested a U-shaped association with hippocampal volume; higher values were seen both for nondrinkers and the groups with higher consumption.

A small study of elderly patients with diabetes showed no evidence of an association with white matter volume, but there was a possible age-dependent association with gray matter volume.

The largest of the earlier studies had results that were very similar to those of the current study, suggesting that increasing coffee intake is associated with smaller hippocampal volumes, said Dr. Hypponen.

One of the study’s limitations included the fact that full dietary information was available only for a subsample and that factors such as dehydration were measured at baseline rather than at the time of brain MRI.

Another possible study limitation was the use of self-reported data and the fact that lifestyle changes may have occurred between baseline and MRI or covariate measurement.

In addition, the study is subject to a healthy-volunteer bias, and its implications are restricted to White British persons. The association needs to be studied in other ethnic populations, the authors noted.
 

A reason to cut back?

Commenting on the findings, Walter Willett, MD, DrPH, professor of epidemiology and nutrition, Harvard T. H. Chan School of Public Health, Boston, said the study is large and quite well done.

“It does raise questions about an increase in risk of dementia with six or more cups of coffee per day,” said Dr. Willett. “At the same time, it provides reassurance about lack of adverse effects of coffee for those consuming three or four cups per day, and little increase in risk, if any, with five cups per day.”

It’s not entirely clear whether the increase in risk with six or more cups of coffee per day represents a “true effect” of coffee, inasmuch as the study did not seem to adjust fully for dietary factors, high consumption of alcohol, or past smoking, said Dr. Willett.

The findings don’t suggest that coffee lovers should give up their Java. “But six or more cups per day is a lot, and those who drink that much might consider cutting back a bit while research continues,” said Dr. Willett.

The study was supported by the National Health and Medical Research Council.

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

Drinking six or more cups of coffee per day is associated with smaller brain volume and a 53% increased risk for dementia compared with light coffee consumption (1-2 cups per day), according to the results of a large study.

amenic181/Getty Images

“With coffee intake, moderation is the key, and especially high levels of consumption may have adverse long-term effects on the brain,” said study investigator Elina Hypponen, PhD, professor of nutritional and genetic epidemiology and director of the Australian Center for Precision Health at the University of South Australia.

“These new data are concerning, and there is a need to conduct further carefully controlled studies to clarify the effects of coffee on the brain.”

The study was published online June 24 in Nutritional Neuroscience.
 

Potent stimulant

Coffee is a potent nervous system stimulant and is among the most popular nonalcoholic beverages. Some previous research suggests it benefits the brain, but the investigators noted that other research shows a negative or U-shaped relationship.

To investigate, the researchers examined data from the U.K. Biobank, a long-term prospective epidemiologic study of more than 500,000 participants aged 37-73 years who were recruited in 22 assessment centers in the United Kingdom between March 2006 and October 2010.

During the baseline assessment, information was gathered using touchscreen questionnaires, verbal interviews, and physical examinations that involved collection of blood, urine, and saliva samples. An imaging substudy was incorporated in 2014, the goal of which was to conduct brain, heart, and body MRI imaging for 100,000 participants.

The investigators conducted analyses on disease outcomes for 398,646 participants for whom information on habitual coffee consumption was available. Brain volume analyses were conducted in 17,702 participants for whom valid brain imaging data were available.

Participants reported coffee intake in cups per day. Researchers grouped coffee consumption into seven categories: nondrinkers, decaffeinated coffee drinkers, and caffeinated coffee drinkers who consumed less than 1 cup/d, 1-2 cups/d, 3-4 cups/d, 5-6 cups/d, and more than 6 cups/d.

The reference category was those who consumed 1-2 cups/d, rather than those who abstained from coffee, because persons who abstain are more likely to be at suboptimal health.

“Comparing the health of coffee drinkers to the health of those choosing to abstain from coffee will typically lead to an impression of a health benefit, even if there would not be one,” said Dr. Hypponen.

The researchers obtained total and regional brain volumes from the MRI imaging substudy starting 4-6 years after baseline assessment. They accessed information on incident dementia and stroke using primary care data, hospital admission electronic health records, national death registers, and self-reported medical conditions.

Covariates included socioeconomic, health, and other factors, such as smoking, alcohol and tea consumption, physical activity, stressful life events, and body mass index.

The investigators found that there was a linear inverse association between coffee consumption and total brain volume (fully adjusted beta per cup, –1.42; 95% confidence interval, –1.89 to –0.94), with consistent patterns for gray matter, white matter, and hippocampal volumes.

There was no evidence to support an association with white matter hyperintensity (WMH) volume (beta –0.01; 95% CI, –0.07 to 0.05).
 

Higher consumption, higher risk

The analysis also revealed a nonlinear association between coffee consumption and the odds of dementia (P nonlinearity = .0001), with slightly higher odds seen with non–coffee drinkers and decaffeinated-coffee drinkers and more notable increases for participants in the highest categories of coffee consumption compared with light coffee drinkers.

After adjustment for all covariates, the odds ratio of dementia among persons in the category of coffee intake was 1.53 (95% CI, 1.28-1.83). After full adjustments, the association with heavy coffee consumption and stroke was not significant, although “we can’t exclude a weak effect,” said Dr. Hypponen.

“For the highest coffee consumption group, the data support an association which may be anywhere from 0% to 37% higher odds of stroke after full adjustment,” she added.

People at risk for hypertension may develop “unpleasant sensations” and stop drinking coffee before a serious adverse event occurs, said Dr. Hypponen. In a previous study, she and her colleagues showed that those who have genetically higher blood pressure tend to drink less coffee than their counterparts without the condition.

“This type of effect might be expected to naturally limit the adverse effects of coffee on the risk of stroke,” said Dr. Hypponen.

The odds remained elevated for participants drinking more than 6 cups/d after the researchers accounted for sleep quality. There were no differences in risk between men and women or by age.

An examination of the consumption of tea, which often contains caffeine, did not show an association with brain volume or the odds of dementia or stroke.

“We don’t know whether the difference between associations seen for coffee and tea intake reflects the difference in related caffeine intake or some other explanation, such as dehydration or effects operating through blood cholesterol,” said Dr. Hypponen.

Although reverse causation is possible, there’s no reason to believe that it is relevant to the study results. Genetic evidence suggests a causal role of higher coffee intake on risk for Alzheimer’s disease. In addition, results of a clinical trial support the association between higher caffeine intake and smaller gray matter volume, said Dr. Hypponen.

The mechanisms linking coffee consumption to brain volumes and dementia are not well established. However, Dr. Hypponen noted that caffeine has been used to induce apoptosis in cancer studies using glial cells.

“Furthermore, adenosine receptors, which mediate many of the effects of caffeine in the brain, have been suggested to influence the release of growth factors, which in turn can have an influence on astrocyte proliferation and angiogenesis in the brain,” she said.

Some types of coffee contain cafestol, which increases blood cholesterol and can have adverse effects though related mechanisms, said Dr. Hypponen.

The mechanism may also involve dehydration, which may have a harmful effect on the brain. The study suggested a correlation between dehydration and high coffee intake. “Of course, if this is the case, it is good news, as then we can do something about it simply by drinking some water every time we have a cup of coffee,” she said.
 

Misleading conclusions

Coffee contains antioxidants, and although previous studies have suggested it might be beneficial, this hypothesis is “too simplistic,” said Dr. Hypponen. “While coffee is not going to be all ‘bad’ either, there are a lot of controversies and suggestions about beneficial effects of coffee which may not be true, or at least do not reflect the full story.”

If the drinking of coffee is at least partly determined by an individual’s health status, then that would often lead to misleading conclusions in observational studies, said Dr. Hypponen.

“When one uses as a comparison people who already have poor health and who do not drink coffee because of that, coffee intake will by default appear beneficial simply because there are more people with disease among those choosing abstinence,” she said.

Before now, there was “very little evidence about the association between coffee intake and brain morphology,” and the studies that were conducted were relatively small, said Dr. Hypponen.

One of these smaller studies included a group of women aged 13-30 years. It found that coffee consumption was not associated with total brain volumes, but the findings suggested a U-shaped association with hippocampal volume; higher values were seen both for nondrinkers and the groups with higher consumption.

A small study of elderly patients with diabetes showed no evidence of an association with white matter volume, but there was a possible age-dependent association with gray matter volume.

The largest of the earlier studies had results that were very similar to those of the current study, suggesting that increasing coffee intake is associated with smaller hippocampal volumes, said Dr. Hypponen.

One of the study’s limitations included the fact that full dietary information was available only for a subsample and that factors such as dehydration were measured at baseline rather than at the time of brain MRI.

Another possible study limitation was the use of self-reported data and the fact that lifestyle changes may have occurred between baseline and MRI or covariate measurement.

In addition, the study is subject to a healthy-volunteer bias, and its implications are restricted to White British persons. The association needs to be studied in other ethnic populations, the authors noted.
 

A reason to cut back?

Commenting on the findings, Walter Willett, MD, DrPH, professor of epidemiology and nutrition, Harvard T. H. Chan School of Public Health, Boston, said the study is large and quite well done.

“It does raise questions about an increase in risk of dementia with six or more cups of coffee per day,” said Dr. Willett. “At the same time, it provides reassurance about lack of adverse effects of coffee for those consuming three or four cups per day, and little increase in risk, if any, with five cups per day.”

It’s not entirely clear whether the increase in risk with six or more cups of coffee per day represents a “true effect” of coffee, inasmuch as the study did not seem to adjust fully for dietary factors, high consumption of alcohol, or past smoking, said Dr. Willett.

The findings don’t suggest that coffee lovers should give up their Java. “But six or more cups per day is a lot, and those who drink that much might consider cutting back a bit while research continues,” said Dr. Willett.

The study was supported by the National Health and Medical Research Council.

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

Remote cognitive tests often rival in-person tests with respect to reliability. That is the message behind numerous publications in recent years, and the COVID-19 pandemic has accelerated that trend.

“The publications have just skyrocketed since 2018, but I think there are still some additional tests that we need to validate using this medium of assessment. Also, I think we need to kind of put on our thinking caps as a field and think outside the box. What novel tests can we develop that will capitalize upon the telehealth environment – interactive tests that are monitoring [the individuals’] performance in real time and giving the examiner feedback, things like that,” said Munro Cullum, PhD, in an interview. Dr. Cullum spoke on the topic at the 2021 Alzheimer’s Association International Conference.

Still, challenges remain, especially factors in the home environment that can adversely affect testing. “Some of our tests are a question-answer, pencil-paper sort of tests that can be well suited to a telemedicine environment, [but] other tests don’t translate as well. So we still have a ways to go to kind of get our test to the next generation when being administered during this type of assessment. But a lot of the verbal tests work extremely well,” said Dr. Cullum, who is a professor of psychiatry at the University of Texas Southwestern Medical Center, Dallas.
 

Preliminary evidence of equivalence

Some years ago, Dr. Cullum was interested in getting a better understanding of what existing tests could best be performed remotely, and what populations could most benefit from remote assessments. Existing studies were generally supportive of remote testing, but varied significantly in their methodology and design. He went on to publish a study in 2014 showing equivalency of existing tests in the in-person and remote environment, and that helped pave the way for a wave of more recent studies that seem to confirm equivalence of in-person methods.

“If you look at the literature overall, there is a nice, growing body of evidence suggesting support for a host of neuropsychological test instruments. For the most part, almost all have shown good reliability across test conditions,” Dr. Cullum said during the talk.

He said that he is often asked if different test norms will be required for remote tests, but that doesn’t seem to be a concern. “It looks like the regular old neuropsych test norms should serve as well in this remote assessment environment. Although as within hospital testing of patients, conservative use of norms is always an order. They are interpretive guidelines,” he added.

One concern is potential threats to validity within the home environment. He posted an image of a woman at home, taking a remote cognitive test. The desk she sat at overlooked a wooded scene, and had a sewing machine on it. A small dog lay in her lap. “So assessing the home environment, ensuring that it is as close to a clinical standard setting as possible, is certainly advised,” said Dr. Cullum.

Although much progress has been made in studying existing tests in a telemedicine environment, many commonly used tests still haven’t been studied. The risk of intrusions and distractions, and even connectivity issues, can be limiting factors. Some tests may be ineligible for remote use due to copyright issues that might prevent required materials from being displayed online. For those reasons and others, not all individuals are suited for a remote test.

Finally, remote tests should be viewed with healthy skepticism. “In doing clinical evaluations this way, we have to be extra careful to not mis- or overinterpret the findings in case there were any distractions or glitches in the examination that came up during the test,” said Dr. Cullum.
 

Looking toward the future

Moving forward, Dr. Cullum called for more research to design new tests to exploit the telehealth format. “I think this is a really important opportunity for new test development in neuropsychology with increasing incorporation of computerized measures and integration with more cognitive neuroscience and clinical neuropsychology principles.”

He also suggested that remote testing could be combined with neuroimaging, neuromodulation, and even portable magnetoencephalography. “These opportunities for research can enhance compliance, enhance large-scale studies to allow for the inclusion of brief cognitive outcome metrics that might not have other otherwise been [possible],” said Dr. Cullum.

During the question-and-answer session, someone asked if the momentum towards telehealth will continue once the COVID-19 pandemic recedes. “We believe telehealth is here to stay, or at least I do,” said session moderator Allison Lindauer, PhD, who was asked to comment. Dr. Lindauer is an associate professor at the Layton Aging and Alzheimer’s Disease Center in Portland, Ore.

Dr. Lindauer has also conducted studies on telehealth-delivered assessments and also found encouraging results. “Work like this says, we have confidence in our work, we can believe that what we’re assessing and what we’re doing – if we did it face to face, we would get similar results,” Dr. Lindauer said in an interview.

Plenty of challenges remain, and the most important is widely available broadband internet, said Dr. Lindauer. “We need a huge push to get broadband everywhere. Granted, you’re going to have people that don’t want to use the computer, or they’re nervous about doing it online. But in my experience, most people with enough coaching can do it and are fine with it.”

Dr. Cullum and Dr. Lindauer have no relevant financial disclosures.

Remote cognitive tests often rival in-person tests with respect to reliability. That is the message behind numerous publications in recent years, and the COVID-19 pandemic has accelerated that trend.

“The publications have just skyrocketed since 2018, but I think there are still some additional tests that we need to validate using this medium of assessment. Also, I think we need to kind of put on our thinking caps as a field and think outside the box. What novel tests can we develop that will capitalize upon the telehealth environment – interactive tests that are monitoring [the individuals’] performance in real time and giving the examiner feedback, things like that,” said Munro Cullum, PhD, in an interview. Dr. Cullum spoke on the topic at the 2021 Alzheimer’s Association International Conference.

Still, challenges remain, especially factors in the home environment that can adversely affect testing. “Some of our tests are a question-answer, pencil-paper sort of tests that can be well suited to a telemedicine environment, [but] other tests don’t translate as well. So we still have a ways to go to kind of get our test to the next generation when being administered during this type of assessment. But a lot of the verbal tests work extremely well,” said Dr. Cullum, who is a professor of psychiatry at the University of Texas Southwestern Medical Center, Dallas.
 

Preliminary evidence of equivalence

Some years ago, Dr. Cullum was interested in getting a better understanding of what existing tests could best be performed remotely, and what populations could most benefit from remote assessments. Existing studies were generally supportive of remote testing, but varied significantly in their methodology and design. He went on to publish a study in 2014 showing equivalency of existing tests in the in-person and remote environment, and that helped pave the way for a wave of more recent studies that seem to confirm equivalence of in-person methods.

“If you look at the literature overall, there is a nice, growing body of evidence suggesting support for a host of neuropsychological test instruments. For the most part, almost all have shown good reliability across test conditions,” Dr. Cullum said during the talk.

He said that he is often asked if different test norms will be required for remote tests, but that doesn’t seem to be a concern. “It looks like the regular old neuropsych test norms should serve as well in this remote assessment environment. Although as within hospital testing of patients, conservative use of norms is always an order. They are interpretive guidelines,” he added.

One concern is potential threats to validity within the home environment. He posted an image of a woman at home, taking a remote cognitive test. The desk she sat at overlooked a wooded scene, and had a sewing machine on it. A small dog lay in her lap. “So assessing the home environment, ensuring that it is as close to a clinical standard setting as possible, is certainly advised,” said Dr. Cullum.

Although much progress has been made in studying existing tests in a telemedicine environment, many commonly used tests still haven’t been studied. The risk of intrusions and distractions, and even connectivity issues, can be limiting factors. Some tests may be ineligible for remote use due to copyright issues that might prevent required materials from being displayed online. For those reasons and others, not all individuals are suited for a remote test.

Finally, remote tests should be viewed with healthy skepticism. “In doing clinical evaluations this way, we have to be extra careful to not mis- or overinterpret the findings in case there were any distractions or glitches in the examination that came up during the test,” said Dr. Cullum.
 

Looking toward the future

Moving forward, Dr. Cullum called for more research to design new tests to exploit the telehealth format. “I think this is a really important opportunity for new test development in neuropsychology with increasing incorporation of computerized measures and integration with more cognitive neuroscience and clinical neuropsychology principles.”

He also suggested that remote testing could be combined with neuroimaging, neuromodulation, and even portable magnetoencephalography. “These opportunities for research can enhance compliance, enhance large-scale studies to allow for the inclusion of brief cognitive outcome metrics that might not have other otherwise been [possible],” said Dr. Cullum.

During the question-and-answer session, someone asked if the momentum towards telehealth will continue once the COVID-19 pandemic recedes. “We believe telehealth is here to stay, or at least I do,” said session moderator Allison Lindauer, PhD, who was asked to comment. Dr. Lindauer is an associate professor at the Layton Aging and Alzheimer’s Disease Center in Portland, Ore.

Dr. Lindauer has also conducted studies on telehealth-delivered assessments and also found encouraging results. “Work like this says, we have confidence in our work, we can believe that what we’re assessing and what we’re doing – if we did it face to face, we would get similar results,” Dr. Lindauer said in an interview.

Plenty of challenges remain, and the most important is widely available broadband internet, said Dr. Lindauer. “We need a huge push to get broadband everywhere. Granted, you’re going to have people that don’t want to use the computer, or they’re nervous about doing it online. But in my experience, most people with enough coaching can do it and are fine with it.”

Dr. Cullum and Dr. Lindauer have no relevant financial disclosures.

Remote cognitive tests often rival in-person tests with respect to reliability. That is the message behind numerous publications in recent years, and the COVID-19 pandemic has accelerated that trend.

“The publications have just skyrocketed since 2018, but I think there are still some additional tests that we need to validate using this medium of assessment. Also, I think we need to kind of put on our thinking caps as a field and think outside the box. What novel tests can we develop that will capitalize upon the telehealth environment – interactive tests that are monitoring [the individuals’] performance in real time and giving the examiner feedback, things like that,” said Munro Cullum, PhD, in an interview. Dr. Cullum spoke on the topic at the 2021 Alzheimer’s Association International Conference.

Still, challenges remain, especially factors in the home environment that can adversely affect testing. “Some of our tests are a question-answer, pencil-paper sort of tests that can be well suited to a telemedicine environment, [but] other tests don’t translate as well. So we still have a ways to go to kind of get our test to the next generation when being administered during this type of assessment. But a lot of the verbal tests work extremely well,” said Dr. Cullum, who is a professor of psychiatry at the University of Texas Southwestern Medical Center, Dallas.
 

Preliminary evidence of equivalence

Some years ago, Dr. Cullum was interested in getting a better understanding of what existing tests could best be performed remotely, and what populations could most benefit from remote assessments. Existing studies were generally supportive of remote testing, but varied significantly in their methodology and design. He went on to publish a study in 2014 showing equivalency of existing tests in the in-person and remote environment, and that helped pave the way for a wave of more recent studies that seem to confirm equivalence of in-person methods.

“If you look at the literature overall, there is a nice, growing body of evidence suggesting support for a host of neuropsychological test instruments. For the most part, almost all have shown good reliability across test conditions,” Dr. Cullum said during the talk.

He said that he is often asked if different test norms will be required for remote tests, but that doesn’t seem to be a concern. “It looks like the regular old neuropsych test norms should serve as well in this remote assessment environment. Although as within hospital testing of patients, conservative use of norms is always an order. They are interpretive guidelines,” he added.

One concern is potential threats to validity within the home environment. He posted an image of a woman at home, taking a remote cognitive test. The desk she sat at overlooked a wooded scene, and had a sewing machine on it. A small dog lay in her lap. “So assessing the home environment, ensuring that it is as close to a clinical standard setting as possible, is certainly advised,” said Dr. Cullum.

Although much progress has been made in studying existing tests in a telemedicine environment, many commonly used tests still haven’t been studied. The risk of intrusions and distractions, and even connectivity issues, can be limiting factors. Some tests may be ineligible for remote use due to copyright issues that might prevent required materials from being displayed online. For those reasons and others, not all individuals are suited for a remote test.

Finally, remote tests should be viewed with healthy skepticism. “In doing clinical evaluations this way, we have to be extra careful to not mis- or overinterpret the findings in case there were any distractions or glitches in the examination that came up during the test,” said Dr. Cullum.
 

Looking toward the future

Moving forward, Dr. Cullum called for more research to design new tests to exploit the telehealth format. “I think this is a really important opportunity for new test development in neuropsychology with increasing incorporation of computerized measures and integration with more cognitive neuroscience and clinical neuropsychology principles.”

He also suggested that remote testing could be combined with neuroimaging, neuromodulation, and even portable magnetoencephalography. “These opportunities for research can enhance compliance, enhance large-scale studies to allow for the inclusion of brief cognitive outcome metrics that might not have other otherwise been [possible],” said Dr. Cullum.

During the question-and-answer session, someone asked if the momentum towards telehealth will continue once the COVID-19 pandemic recedes. “We believe telehealth is here to stay, or at least I do,” said session moderator Allison Lindauer, PhD, who was asked to comment. Dr. Lindauer is an associate professor at the Layton Aging and Alzheimer’s Disease Center in Portland, Ore.

Dr. Lindauer has also conducted studies on telehealth-delivered assessments and also found encouraging results. “Work like this says, we have confidence in our work, we can believe that what we’re assessing and what we’re doing – if we did it face to face, we would get similar results,” Dr. Lindauer said in an interview.

Plenty of challenges remain, and the most important is widely available broadband internet, said Dr. Lindauer. “We need a huge push to get broadband everywhere. Granted, you’re going to have people that don’t want to use the computer, or they’re nervous about doing it online. But in my experience, most people with enough coaching can do it and are fine with it.”

Dr. Cullum and Dr. Lindauer have no relevant financial disclosures.