Neurology Reviews

TOPLINE:

Oncologists show significant variability in prescribing systemic cancer therapies in the last 30 days of life. Patients treated by oncologists in the top quartile for end-of-life prescribing behavior were almost four and a half times more likely to receive end-of-life therapy than those treated by these specialists in the bottom quartile.

METHODOLOGY:

• Researchers analyzed data from the Surveillance, Epidemiology, and End Results (SEER)-Medicare database, focusing on patients who died of cancer between 2012 and 2017.
• A total of 17,609 patients with breast, lung, colorectal, or prostate cancer were included, treated by 960 oncologists across 388 practices.
• Patients were required to have had at least one systemic cancer therapy claim in the last 180 days of life, with the treating oncologist identified on the basis of the therapy claim closest to the time of death.
• The study used multilevel models to estimate oncologists’ rates of providing cancer therapy in the last 30 days of life, adjusting for patient characteristics and practice variation.
• Functional status was assessed on the basis of paid claims for durable medical equipment in the last 60 months of life, with scores categorized as 0, 1, ≥ 2, or unknown.

TAKEAWAY:

• Oncologists in the 95th percentile for high end-of-life prescribing behavior had a 45% adjusted rate of treating patients in the last 30 days of life, compared with 17% among those in the 5th percentile.
• Patients treated by high end-of-life prescribing oncologists had over four times higher odds of receiving systemic therapy in the last 30 days of life (odds ratio [OR], 4.42; 95% CI, 4.00-4.89).
• Higher end-of-life prescribing oncologists also had a higher proportion of patients hospitalized in the last 30 days of life than low prescribers (58% vs 51.9%).
• No significant association was found between oncologist prescribing behavior and patient race or ethnicity, except for Black patients who had lower odds of receiving treatment (OR, 0.77; P < .001).

IN PRACTICE:

“Given calls to rein in overutilization of end-of-life six to eight cancer therapies, our findings highlight an underappreciated area for further research: How treatment discontinuation before death is shaped by oncologists’ unique treatment propensities. Elucidating the reasons for this remarkable variability in oncologist treatment behavior could inform efforts to reduce end-of-life cancer treatment overutilization,” wrote the authors of the study.

SOURCE:

The study was led by Login S. George, PhD, Institute for Health, Health Care Policy and Aging Research, Rutgers University in New Brunswick, New Jersey. It was published online in Cancer.

LIMITATIONS:

The study’s reliance on SEER-Medicare data may limit the generalizability of the findings to patients with Medicare Advantage, private insurance, or Medicaid, as well as younger patients. The lack of data on patient preferences and other health characteristics could confound the results. The study focused on systemic therapies and may not be generalizable to other treatments such as clinical trial drugs, oral therapies, surgery, or radiation. The data from 2012 to 2017 may not reflect more recent trends in cancer treatment.

DISCLOSURES:

The study was supported by grants from the National Cancer Institute and the Rutgers Cancer Institute of New Jersey. George disclosed receiving grants from these organizations. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Oncologists show significant variability in prescribing systemic cancer therapies in the last 30 days of life. Patients treated by oncologists in the top quartile for end-of-life prescribing behavior were almost four and a half times more likely to receive end-of-life therapy than those treated by these specialists in the bottom quartile.

METHODOLOGY:

• Researchers analyzed data from the Surveillance, Epidemiology, and End Results (SEER)-Medicare database, focusing on patients who died of cancer between 2012 and 2017.
• A total of 17,609 patients with breast, lung, colorectal, or prostate cancer were included, treated by 960 oncologists across 388 practices.
• Patients were required to have had at least one systemic cancer therapy claim in the last 180 days of life, with the treating oncologist identified on the basis of the therapy claim closest to the time of death.
• The study used multilevel models to estimate oncologists’ rates of providing cancer therapy in the last 30 days of life, adjusting for patient characteristics and practice variation.
• Functional status was assessed on the basis of paid claims for durable medical equipment in the last 60 months of life, with scores categorized as 0, 1, ≥ 2, or unknown.

TAKEAWAY:

• Oncologists in the 95th percentile for high end-of-life prescribing behavior had a 45% adjusted rate of treating patients in the last 30 days of life, compared with 17% among those in the 5th percentile.
• Patients treated by high end-of-life prescribing oncologists had over four times higher odds of receiving systemic therapy in the last 30 days of life (odds ratio [OR], 4.42; 95% CI, 4.00-4.89).
• Higher end-of-life prescribing oncologists also had a higher proportion of patients hospitalized in the last 30 days of life than low prescribers (58% vs 51.9%).
• No significant association was found between oncologist prescribing behavior and patient race or ethnicity, except for Black patients who had lower odds of receiving treatment (OR, 0.77; P < .001).

IN PRACTICE:

“Given calls to rein in overutilization of end-of-life six to eight cancer therapies, our findings highlight an underappreciated area for further research: How treatment discontinuation before death is shaped by oncologists’ unique treatment propensities. Elucidating the reasons for this remarkable variability in oncologist treatment behavior could inform efforts to reduce end-of-life cancer treatment overutilization,” wrote the authors of the study.

SOURCE:

The study was led by Login S. George, PhD, Institute for Health, Health Care Policy and Aging Research, Rutgers University in New Brunswick, New Jersey. It was published online in Cancer.

LIMITATIONS:

The study’s reliance on SEER-Medicare data may limit the generalizability of the findings to patients with Medicare Advantage, private insurance, or Medicaid, as well as younger patients. The lack of data on patient preferences and other health characteristics could confound the results. The study focused on systemic therapies and may not be generalizable to other treatments such as clinical trial drugs, oral therapies, surgery, or radiation. The data from 2012 to 2017 may not reflect more recent trends in cancer treatment.

DISCLOSURES:

The study was supported by grants from the National Cancer Institute and the Rutgers Cancer Institute of New Jersey. George disclosed receiving grants from these organizations. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Oncologists show significant variability in prescribing systemic cancer therapies in the last 30 days of life. Patients treated by oncologists in the top quartile for end-of-life prescribing behavior were almost four and a half times more likely to receive end-of-life therapy than those treated by these specialists in the bottom quartile.

METHODOLOGY:

• Researchers analyzed data from the Surveillance, Epidemiology, and End Results (SEER)-Medicare database, focusing on patients who died of cancer between 2012 and 2017.
• A total of 17,609 patients with breast, lung, colorectal, or prostate cancer were included, treated by 960 oncologists across 388 practices.
• Patients were required to have had at least one systemic cancer therapy claim in the last 180 days of life, with the treating oncologist identified on the basis of the therapy claim closest to the time of death.
• The study used multilevel models to estimate oncologists’ rates of providing cancer therapy in the last 30 days of life, adjusting for patient characteristics and practice variation.
• Functional status was assessed on the basis of paid claims for durable medical equipment in the last 60 months of life, with scores categorized as 0, 1, ≥ 2, or unknown.

TAKEAWAY:

• Oncologists in the 95th percentile for high end-of-life prescribing behavior had a 45% adjusted rate of treating patients in the last 30 days of life, compared with 17% among those in the 5th percentile.
• Patients treated by high end-of-life prescribing oncologists had over four times higher odds of receiving systemic therapy in the last 30 days of life (odds ratio [OR], 4.42; 95% CI, 4.00-4.89).
• Higher end-of-life prescribing oncologists also had a higher proportion of patients hospitalized in the last 30 days of life than low prescribers (58% vs 51.9%).
• No significant association was found between oncologist prescribing behavior and patient race or ethnicity, except for Black patients who had lower odds of receiving treatment (OR, 0.77; P < .001).

IN PRACTICE:

“Given calls to rein in overutilization of end-of-life six to eight cancer therapies, our findings highlight an underappreciated area for further research: How treatment discontinuation before death is shaped by oncologists’ unique treatment propensities. Elucidating the reasons for this remarkable variability in oncologist treatment behavior could inform efforts to reduce end-of-life cancer treatment overutilization,” wrote the authors of the study.

SOURCE:

The study was led by Login S. George, PhD, Institute for Health, Health Care Policy and Aging Research, Rutgers University in New Brunswick, New Jersey. It was published online in Cancer.

LIMITATIONS:

The study’s reliance on SEER-Medicare data may limit the generalizability of the findings to patients with Medicare Advantage, private insurance, or Medicaid, as well as younger patients. The lack of data on patient preferences and other health characteristics could confound the results. The study focused on systemic therapies and may not be generalizable to other treatments such as clinical trial drugs, oral therapies, surgery, or radiation. The data from 2012 to 2017 may not reflect more recent trends in cancer treatment.

DISCLOSURES:

The study was supported by grants from the National Cancer Institute and the Rutgers Cancer Institute of New Jersey. George disclosed receiving grants from these organizations. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

An ancient virus that infected our ancestors tens of millions of years ago may be helping to fuel cancer today, according to a fascinating new study in Science Advances. Targeting these viral remnants still lingering in our DNA could lead to more effective cancer treatment with fewer side effects, the researchers said.

The study “gives a better understanding of how gene regulation can be impacted by these ancient retroviral sequences,” said Dixie Mager, PhD, scientist emeritus at the Terry Fox Laboratory at the British Columbia Cancer Research Institute, Vancouver, British Columbia, Canada. (Mager was not involved in the study.)

Long thought to be “junk” DNA with no biologic function, “endogenous retroviruses,” which have mutated over time and lost their ability to create the virus, are now known to regulate genes — allowing some genes to turn on and off. Research in recent years suggests they may play a role in diseases like cancer.

But scientists weren’t exactly sure what that role was, said senior study author Edward Chuong, PhD, a genome biologist at the University of Colorado Boulder.

Most studies have looked at whether endogenous retroviruses code for proteins that influence cancer. But these ancient viral strands usually don’t code for proteins at all.

Dr. Chuong took a different approach. Inspired by scientists who’ve studied how viral remnants regulate positive processes (immunity, brain development, or placenta development), he and his team explored whether some might regulate genes that, once activated, help cancer thrive.

Borrowing from epigenomic analysis data (data on molecules that alter gene expression) for 21 cancers mapped by the Cancer Genome Atlas, the researchers identified 19 virus-derived DNA sequences that bind to regulatory proteins more in cancer cells than in healthy cells. All of these could potentially act as gene regulators that promote cancer.

The researchers homed in on one sequence, called LTR10, because it showed especially high activity in several cancers, including lung and colorectal cancer. This DNA segment comes from a virus that entered our ancestors’ genome 30 million years ago, and it’s activated in a third of colorectal cancers.

Using the gene editing technology clustered regularly interspaced short palindromic repeats (CRISPR), Dr. Chuong’s team silenced LTR10 in colorectal cancer cells, altering the gene sequence so it couldn’t bind to regulatory proteins. Doing so dampened the activity of nearby cancer-promoting genes.

“They still behaved like cancer cells,” Dr. Chuong said. But “it made the cancer cells more susceptible to radiation. That would imply that the presence of that viral ‘switch’ actually helped those cancer cells survive radiation therapy.”

Previously, two studies had found that viral regulators play a role in promoting two types of cancer: Leukemia and prostate cancer. The new study shows these two cases weren’t flukes. All 21 cancers they looked at had at least one of those 19 viral elements, presumably working as cancer enhancers.

The study also identified what activates LTR10 to make it promote cancer. The culprit is a regulator protein called mitogen-activated protein (MAP) kinase, which is overactivated in about 40% of all human cancers.

Some cancer drugs — MAP kinase inhibitors — already target MAP kinase, and they’re often the first ones prescribed when a patient is diagnosed with cancer, Dr. Chuong said. As with many cancer treatments, doctors don’t know why they work, just that they do.

“By understanding the mechanisms in the cell, we might be able to make them work better or further optimize their treatment,” he said.

“MAP kinase inhibitors are really like a sledgehammer to the cell,” Dr. Chuong said — meaning they affect many cellular processes, not just those related to cancer.

“If we’re able to say that these viral switches are what’s important, then that could potentially help us develop a more targeted therapy that uses something like CRISPR to silence these viral elements,” he said. Or it could help providers choose a MAP kinase inhibitor from among the dozens available best suited to treat an individual patient and avoid side effects.  

Still, whether the findings translate to real cancer patients remains to be seen. “It’s very, very hard to go the final step of showing in a patient that these actually make a difference in the cancer,” Dr. Mager said.

More lab research, human trials, and at least a few years will be needed before this discovery could help treat cancer. “Directly targeting these elements as a therapy would be at least 5 years out,” Dr. Chuong said, “partly because that application would rely on CRISPR epigenome editing technology that is still being developed for clinical use.”
 

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

An ancient virus that infected our ancestors tens of millions of years ago may be helping to fuel cancer today, according to a fascinating new study in Science Advances. Targeting these viral remnants still lingering in our DNA could lead to more effective cancer treatment with fewer side effects, the researchers said.

The study “gives a better understanding of how gene regulation can be impacted by these ancient retroviral sequences,” said Dixie Mager, PhD, scientist emeritus at the Terry Fox Laboratory at the British Columbia Cancer Research Institute, Vancouver, British Columbia, Canada. (Mager was not involved in the study.)

Long thought to be “junk” DNA with no biologic function, “endogenous retroviruses,” which have mutated over time and lost their ability to create the virus, are now known to regulate genes — allowing some genes to turn on and off. Research in recent years suggests they may play a role in diseases like cancer.

But scientists weren’t exactly sure what that role was, said senior study author Edward Chuong, PhD, a genome biologist at the University of Colorado Boulder.

Most studies have looked at whether endogenous retroviruses code for proteins that influence cancer. But these ancient viral strands usually don’t code for proteins at all.

Dr. Chuong took a different approach. Inspired by scientists who’ve studied how viral remnants regulate positive processes (immunity, brain development, or placenta development), he and his team explored whether some might regulate genes that, once activated, help cancer thrive.

Borrowing from epigenomic analysis data (data on molecules that alter gene expression) for 21 cancers mapped by the Cancer Genome Atlas, the researchers identified 19 virus-derived DNA sequences that bind to regulatory proteins more in cancer cells than in healthy cells. All of these could potentially act as gene regulators that promote cancer.

The researchers homed in on one sequence, called LTR10, because it showed especially high activity in several cancers, including lung and colorectal cancer. This DNA segment comes from a virus that entered our ancestors’ genome 30 million years ago, and it’s activated in a third of colorectal cancers.

Using the gene editing technology clustered regularly interspaced short palindromic repeats (CRISPR), Dr. Chuong’s team silenced LTR10 in colorectal cancer cells, altering the gene sequence so it couldn’t bind to regulatory proteins. Doing so dampened the activity of nearby cancer-promoting genes.

“They still behaved like cancer cells,” Dr. Chuong said. But “it made the cancer cells more susceptible to radiation. That would imply that the presence of that viral ‘switch’ actually helped those cancer cells survive radiation therapy.”

Previously, two studies had found that viral regulators play a role in promoting two types of cancer: Leukemia and prostate cancer. The new study shows these two cases weren’t flukes. All 21 cancers they looked at had at least one of those 19 viral elements, presumably working as cancer enhancers.

The study also identified what activates LTR10 to make it promote cancer. The culprit is a regulator protein called mitogen-activated protein (MAP) kinase, which is overactivated in about 40% of all human cancers.

Some cancer drugs — MAP kinase inhibitors — already target MAP kinase, and they’re often the first ones prescribed when a patient is diagnosed with cancer, Dr. Chuong said. As with many cancer treatments, doctors don’t know why they work, just that they do.

“By understanding the mechanisms in the cell, we might be able to make them work better or further optimize their treatment,” he said.

“MAP kinase inhibitors are really like a sledgehammer to the cell,” Dr. Chuong said — meaning they affect many cellular processes, not just those related to cancer.

“If we’re able to say that these viral switches are what’s important, then that could potentially help us develop a more targeted therapy that uses something like CRISPR to silence these viral elements,” he said. Or it could help providers choose a MAP kinase inhibitor from among the dozens available best suited to treat an individual patient and avoid side effects.  

Still, whether the findings translate to real cancer patients remains to be seen. “It’s very, very hard to go the final step of showing in a patient that these actually make a difference in the cancer,” Dr. Mager said.

More lab research, human trials, and at least a few years will be needed before this discovery could help treat cancer. “Directly targeting these elements as a therapy would be at least 5 years out,” Dr. Chuong said, “partly because that application would rely on CRISPR epigenome editing technology that is still being developed for clinical use.”
 

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

An ancient virus that infected our ancestors tens of millions of years ago may be helping to fuel cancer today, according to a fascinating new study in Science Advances. Targeting these viral remnants still lingering in our DNA could lead to more effective cancer treatment with fewer side effects, the researchers said.

The study “gives a better understanding of how gene regulation can be impacted by these ancient retroviral sequences,” said Dixie Mager, PhD, scientist emeritus at the Terry Fox Laboratory at the British Columbia Cancer Research Institute, Vancouver, British Columbia, Canada. (Mager was not involved in the study.)

Long thought to be “junk” DNA with no biologic function, “endogenous retroviruses,” which have mutated over time and lost their ability to create the virus, are now known to regulate genes — allowing some genes to turn on and off. Research in recent years suggests they may play a role in diseases like cancer.

But scientists weren’t exactly sure what that role was, said senior study author Edward Chuong, PhD, a genome biologist at the University of Colorado Boulder.

Most studies have looked at whether endogenous retroviruses code for proteins that influence cancer. But these ancient viral strands usually don’t code for proteins at all.

Dr. Chuong took a different approach. Inspired by scientists who’ve studied how viral remnants regulate positive processes (immunity, brain development, or placenta development), he and his team explored whether some might regulate genes that, once activated, help cancer thrive.

Borrowing from epigenomic analysis data (data on molecules that alter gene expression) for 21 cancers mapped by the Cancer Genome Atlas, the researchers identified 19 virus-derived DNA sequences that bind to regulatory proteins more in cancer cells than in healthy cells. All of these could potentially act as gene regulators that promote cancer.

The researchers homed in on one sequence, called LTR10, because it showed especially high activity in several cancers, including lung and colorectal cancer. This DNA segment comes from a virus that entered our ancestors’ genome 30 million years ago, and it’s activated in a third of colorectal cancers.

Using the gene editing technology clustered regularly interspaced short palindromic repeats (CRISPR), Dr. Chuong’s team silenced LTR10 in colorectal cancer cells, altering the gene sequence so it couldn’t bind to regulatory proteins. Doing so dampened the activity of nearby cancer-promoting genes.

“They still behaved like cancer cells,” Dr. Chuong said. But “it made the cancer cells more susceptible to radiation. That would imply that the presence of that viral ‘switch’ actually helped those cancer cells survive radiation therapy.”

Previously, two studies had found that viral regulators play a role in promoting two types of cancer: Leukemia and prostate cancer. The new study shows these two cases weren’t flukes. All 21 cancers they looked at had at least one of those 19 viral elements, presumably working as cancer enhancers.

The study also identified what activates LTR10 to make it promote cancer. The culprit is a regulator protein called mitogen-activated protein (MAP) kinase, which is overactivated in about 40% of all human cancers.

Some cancer drugs — MAP kinase inhibitors — already target MAP kinase, and they’re often the first ones prescribed when a patient is diagnosed with cancer, Dr. Chuong said. As with many cancer treatments, doctors don’t know why they work, just that they do.

“By understanding the mechanisms in the cell, we might be able to make them work better or further optimize their treatment,” he said.

“MAP kinase inhibitors are really like a sledgehammer to the cell,” Dr. Chuong said — meaning they affect many cellular processes, not just those related to cancer.

“If we’re able to say that these viral switches are what’s important, then that could potentially help us develop a more targeted therapy that uses something like CRISPR to silence these viral elements,” he said. Or it could help providers choose a MAP kinase inhibitor from among the dozens available best suited to treat an individual patient and avoid side effects.  

Still, whether the findings translate to real cancer patients remains to be seen. “It’s very, very hard to go the final step of showing in a patient that these actually make a difference in the cancer,” Dr. Mager said.

More lab research, human trials, and at least a few years will be needed before this discovery could help treat cancer. “Directly targeting these elements as a therapy would be at least 5 years out,” Dr. Chuong said, “partly because that application would rely on CRISPR epigenome editing technology that is still being developed for clinical use.”
 

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

PHILADELPHIA – Drinking more than three cups of coffee a day is linked to more rapid cognitive decline over time, results from a large study suggest.

Investigators examined the impact of different amounts of coffee and tea on fluid intelligence — a measure of cognitive functions including abstract reasoning, pattern recognition, and logical thinking.

“It’s the old adage that too much of anything isn’t good. It’s all about balance, so moderate coffee consumption is okay but too much is probably not recommended,” said study investigator Kelsey R. Sewell, PhD, Advent Health Research Institute, Orlando, Florida. 

The findings of the study were presented at the 2024 Alzheimer’s Association International Conference (AAIC).
 

One of the World’s Most Widely Consumed Beverages

Coffee is one of the most widely consumed beverages around the world. The beans contain a range of bioactive compounds, including caffeine, chlorogenic acid, and small amounts of vitamins and minerals.

Consistent evidence from observational and epidemiologic studies indicates that intake of both coffee and tea has beneficial effects on stroke, heart failure, cancers, diabetes, and Parkinson’s disease.  

Several studies also suggest that coffee may reduce the risk for Alzheimer’s disease, said Dr. Sewell. However, there are limited longitudinal data on associations between coffee and tea intake and cognitive decline, particularly in distinct cognitive domains.

Dr. Sewell’s group previously published a study of cognitively unimpaired older adults that found greater coffee consumption was associated with slower cognitive decline and slower accumulation of brain beta-amyloid.

Their current study extends some of the prior findings and investigates the relationship between both coffee and tea intake and cognitive decline over time in a larger sample of older adults.

This new study included 8451 mostly female (60%) and White (97%) cognitively unimpaired adults older than 60 (mean age, 67.8 years) in the UK Biobank, a large-scale research resource containing in-depth, deidentified genetic and health information from half a million UK participants. Study subjects had a mean body mass index (BMI) of 26, and about 26% were apolipoprotein epsilon 4 (APOE e4) gene carriers.

Researchers divided coffee and tea consumption into tertiles: high, moderate, and no consumption.

For daily coffee consumption, 18% reported drinking four or more cups (high consumption), 58% reported drinking one to three cups (moderate consumption), and 25% reported that they never drink coffee. For daily tea consumption, 47% reported drinking four or more cups (high consumption), 38% reported drinking one to three cups (moderate consumption), and 15% reported that they never drink tea.

The study assessed cognitive function at baseline and at least two additional patient visits. 

Researchers used linear mixed models to assess the relationships between coffee and tea intake and cognitive outcomes. The models adjusted for age, sex, Townsend deprivation index (reflecting socioeconomic status), ethnicity, APOE e4 status, and BMI.
 

Steeper Decline 

Compared with high coffee consumption (four or more cups daily), people who never consumed coffee (beta, 0.06; standard error [SE], 0.02; P = .005) and those with moderate consumption (beta, 0.07; SE, 0.02; P = < .001) had slower decline in fluid intelligence after an average of 8.83 years of follow-up.

“We can see that those with high coffee consumption showed the steepest decline in fluid intelligence across the follow up, compared to those with moderate coffee consumption and those never consuming coffee,” said Dr. Sewell, referring to illustrative graphs.

At the same time, “our data suggest that across this time period, moderate coffee consumption can serve as some kind of protective factor against cognitive decline,” she added.

For tea, there was a somewhat different pattern. People who never drank tea had a greater decline in fluid intelligence, compared with those who had moderate consumption (beta, 0.06; SE, 0.02; P = .0090) or high consumption (beta, 0.06; SE, 0.02; P = .003).

Because this is an observational study, “we still need randomized controlled trials to better understand the neuroprotective mechanism of coffee and tea compounds,” said Dr. Sewell.

Responding later to a query from a meeting delegate about how moderate coffee drinking could be protective, Dr. Sewell said there are probably “different levels of mechanisms,” including at the molecular level (possibly involving amyloid toxicity) and the behavioral level (possibly involving sleep patterns).

Dr. Sewell said that she hopes this line of investigation will lead to new avenues of research in preventive strategies for Alzheimer’s disease. 

“We hope that coffee and tea intake could contribute to the development of a safe and inexpensive strategy for delaying the onset and reducing the incidence for Alzheimer’s disease.”

A limitation of the study is possible recall bias, because coffee and tea consumption were self-reported. However, this may not be much of an issue because coffee and tea consumption “is usually quite a habitual behavior,” said Dr. Sewell.

The study also had no data on midlife coffee or tea consumption and did not compare the effect of different preparation methods or types of coffee and tea — for example, green tea versus black tea. 

When asked if the study controlled for smoking, Dr. Sewell said it didn’t but added that it would be interesting to explore its impact on cognition.

Dr. Sewell reported no relevant conflicts of interest.

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

PHILADELPHIA – Drinking more than three cups of coffee a day is linked to more rapid cognitive decline over time, results from a large study suggest.

Investigators examined the impact of different amounts of coffee and tea on fluid intelligence — a measure of cognitive functions including abstract reasoning, pattern recognition, and logical thinking.

“It’s the old adage that too much of anything isn’t good. It’s all about balance, so moderate coffee consumption is okay but too much is probably not recommended,” said study investigator Kelsey R. Sewell, PhD, Advent Health Research Institute, Orlando, Florida. 

The findings of the study were presented at the 2024 Alzheimer’s Association International Conference (AAIC).
 

One of the World’s Most Widely Consumed Beverages

Coffee is one of the most widely consumed beverages around the world. The beans contain a range of bioactive compounds, including caffeine, chlorogenic acid, and small amounts of vitamins and minerals.

Consistent evidence from observational and epidemiologic studies indicates that intake of both coffee and tea has beneficial effects on stroke, heart failure, cancers, diabetes, and Parkinson’s disease.  

Several studies also suggest that coffee may reduce the risk for Alzheimer’s disease, said Dr. Sewell. However, there are limited longitudinal data on associations between coffee and tea intake and cognitive decline, particularly in distinct cognitive domains.

Dr. Sewell’s group previously published a study of cognitively unimpaired older adults that found greater coffee consumption was associated with slower cognitive decline and slower accumulation of brain beta-amyloid.

Their current study extends some of the prior findings and investigates the relationship between both coffee and tea intake and cognitive decline over time in a larger sample of older adults.

This new study included 8451 mostly female (60%) and White (97%) cognitively unimpaired adults older than 60 (mean age, 67.8 years) in the UK Biobank, a large-scale research resource containing in-depth, deidentified genetic and health information from half a million UK participants. Study subjects had a mean body mass index (BMI) of 26, and about 26% were apolipoprotein epsilon 4 (APOE e4) gene carriers.

Researchers divided coffee and tea consumption into tertiles: high, moderate, and no consumption.

For daily coffee consumption, 18% reported drinking four or more cups (high consumption), 58% reported drinking one to three cups (moderate consumption), and 25% reported that they never drink coffee. For daily tea consumption, 47% reported drinking four or more cups (high consumption), 38% reported drinking one to three cups (moderate consumption), and 15% reported that they never drink tea.

The study assessed cognitive function at baseline and at least two additional patient visits. 

Researchers used linear mixed models to assess the relationships between coffee and tea intake and cognitive outcomes. The models adjusted for age, sex, Townsend deprivation index (reflecting socioeconomic status), ethnicity, APOE e4 status, and BMI.
 

Steeper Decline 

Compared with high coffee consumption (four or more cups daily), people who never consumed coffee (beta, 0.06; standard error [SE], 0.02; P = .005) and those with moderate consumption (beta, 0.07; SE, 0.02; P = < .001) had slower decline in fluid intelligence after an average of 8.83 years of follow-up.

“We can see that those with high coffee consumption showed the steepest decline in fluid intelligence across the follow up, compared to those with moderate coffee consumption and those never consuming coffee,” said Dr. Sewell, referring to illustrative graphs.

At the same time, “our data suggest that across this time period, moderate coffee consumption can serve as some kind of protective factor against cognitive decline,” she added.

For tea, there was a somewhat different pattern. People who never drank tea had a greater decline in fluid intelligence, compared with those who had moderate consumption (beta, 0.06; SE, 0.02; P = .0090) or high consumption (beta, 0.06; SE, 0.02; P = .003).

Because this is an observational study, “we still need randomized controlled trials to better understand the neuroprotective mechanism of coffee and tea compounds,” said Dr. Sewell.

Responding later to a query from a meeting delegate about how moderate coffee drinking could be protective, Dr. Sewell said there are probably “different levels of mechanisms,” including at the molecular level (possibly involving amyloid toxicity) and the behavioral level (possibly involving sleep patterns).

Dr. Sewell said that she hopes this line of investigation will lead to new avenues of research in preventive strategies for Alzheimer’s disease. 

“We hope that coffee and tea intake could contribute to the development of a safe and inexpensive strategy for delaying the onset and reducing the incidence for Alzheimer’s disease.”

A limitation of the study is possible recall bias, because coffee and tea consumption were self-reported. However, this may not be much of an issue because coffee and tea consumption “is usually quite a habitual behavior,” said Dr. Sewell.

The study also had no data on midlife coffee or tea consumption and did not compare the effect of different preparation methods or types of coffee and tea — for example, green tea versus black tea. 

When asked if the study controlled for smoking, Dr. Sewell said it didn’t but added that it would be interesting to explore its impact on cognition.

Dr. Sewell reported no relevant conflicts of interest.

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

PHILADELPHIA – Drinking more than three cups of coffee a day is linked to more rapid cognitive decline over time, results from a large study suggest.

Investigators examined the impact of different amounts of coffee and tea on fluid intelligence — a measure of cognitive functions including abstract reasoning, pattern recognition, and logical thinking.

“It’s the old adage that too much of anything isn’t good. It’s all about balance, so moderate coffee consumption is okay but too much is probably not recommended,” said study investigator Kelsey R. Sewell, PhD, Advent Health Research Institute, Orlando, Florida. 

The findings of the study were presented at the 2024 Alzheimer’s Association International Conference (AAIC).
 

One of the World’s Most Widely Consumed Beverages

Coffee is one of the most widely consumed beverages around the world. The beans contain a range of bioactive compounds, including caffeine, chlorogenic acid, and small amounts of vitamins and minerals.

Consistent evidence from observational and epidemiologic studies indicates that intake of both coffee and tea has beneficial effects on stroke, heart failure, cancers, diabetes, and Parkinson’s disease.  

Several studies also suggest that coffee may reduce the risk for Alzheimer’s disease, said Dr. Sewell. However, there are limited longitudinal data on associations between coffee and tea intake and cognitive decline, particularly in distinct cognitive domains.

Dr. Sewell’s group previously published a study of cognitively unimpaired older adults that found greater coffee consumption was associated with slower cognitive decline and slower accumulation of brain beta-amyloid.

Their current study extends some of the prior findings and investigates the relationship between both coffee and tea intake and cognitive decline over time in a larger sample of older adults.

This new study included 8451 mostly female (60%) and White (97%) cognitively unimpaired adults older than 60 (mean age, 67.8 years) in the UK Biobank, a large-scale research resource containing in-depth, deidentified genetic and health information from half a million UK participants. Study subjects had a mean body mass index (BMI) of 26, and about 26% were apolipoprotein epsilon 4 (APOE e4) gene carriers.

Researchers divided coffee and tea consumption into tertiles: high, moderate, and no consumption.

For daily coffee consumption, 18% reported drinking four or more cups (high consumption), 58% reported drinking one to three cups (moderate consumption), and 25% reported that they never drink coffee. For daily tea consumption, 47% reported drinking four or more cups (high consumption), 38% reported drinking one to three cups (moderate consumption), and 15% reported that they never drink tea.

The study assessed cognitive function at baseline and at least two additional patient visits. 

Researchers used linear mixed models to assess the relationships between coffee and tea intake and cognitive outcomes. The models adjusted for age, sex, Townsend deprivation index (reflecting socioeconomic status), ethnicity, APOE e4 status, and BMI.
 

Steeper Decline 

Compared with high coffee consumption (four or more cups daily), people who never consumed coffee (beta, 0.06; standard error [SE], 0.02; P = .005) and those with moderate consumption (beta, 0.07; SE, 0.02; P = < .001) had slower decline in fluid intelligence after an average of 8.83 years of follow-up.

“We can see that those with high coffee consumption showed the steepest decline in fluid intelligence across the follow up, compared to those with moderate coffee consumption and those never consuming coffee,” said Dr. Sewell, referring to illustrative graphs.

At the same time, “our data suggest that across this time period, moderate coffee consumption can serve as some kind of protective factor against cognitive decline,” she added.

For tea, there was a somewhat different pattern. People who never drank tea had a greater decline in fluid intelligence, compared with those who had moderate consumption (beta, 0.06; SE, 0.02; P = .0090) or high consumption (beta, 0.06; SE, 0.02; P = .003).

Because this is an observational study, “we still need randomized controlled trials to better understand the neuroprotective mechanism of coffee and tea compounds,” said Dr. Sewell.

Responding later to a query from a meeting delegate about how moderate coffee drinking could be protective, Dr. Sewell said there are probably “different levels of mechanisms,” including at the molecular level (possibly involving amyloid toxicity) and the behavioral level (possibly involving sleep patterns).

Dr. Sewell said that she hopes this line of investigation will lead to new avenues of research in preventive strategies for Alzheimer’s disease. 

“We hope that coffee and tea intake could contribute to the development of a safe and inexpensive strategy for delaying the onset and reducing the incidence for Alzheimer’s disease.”

A limitation of the study is possible recall bias, because coffee and tea consumption were self-reported. However, this may not be much of an issue because coffee and tea consumption “is usually quite a habitual behavior,” said Dr. Sewell.

The study also had no data on midlife coffee or tea consumption and did not compare the effect of different preparation methods or types of coffee and tea — for example, green tea versus black tea. 

When asked if the study controlled for smoking, Dr. Sewell said it didn’t but added that it would be interesting to explore its impact on cognition.

Dr. Sewell reported no relevant conflicts of interest.

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

This transcript has been edited for clarity. 

Hi. I’m Art Caplan. I’m at the Division of Medical Ethics at New York University Grossman School of Medicine in New York City. 

There are many things screwy with our healthcare system. Many of you [reading] this are dealing with bureaucracy, paperwork, all sorts of constraints, restraints, and requirements that sometimes make the practice of medicine, or even nursing, difficult.

I don’t think I’ve seen anything screwier, from a moral point of view, than the system we have that allows for preauthorization by third-party payers, or insurers, in order to give care to patients. It’s pretty clear that a third-party payer has a conflict of interest. It’s simple: They don’t want to spend money.

Their goal as profit-making companies is to reduce what it is that they’re going to authorize. That clearly is driving how the preauthorization process works. We’re not getting a neutral review by third parties of the appropriateness of treatment recommendations or somebody saying, this is the standard of care and this is what ought to happen.

We’re letting the people who have the pocketbooks and the wallets have prior approval of what the doctor thinks is correct. That is really not the way to practice medicine. 

We now have more evidence about what really is going on. A doctor was recently interviewed by ProPublica and said that she had worked for Cigna as a reviewer. Basically, the message she got from that insurer was to speed it up, go fast, and basically “deny, deny, deny” when she got requests. Those are her words, not mine.

We get a peek under the tent of how this works, and Dr. Day is basically saying she had to leave because she just didn’t feel that it was evidence-driven. It was driven by concerns about who’s going to lose money or make money.

If you want to check to see whether something is appropriate, the question becomes, who ought to do prior review? 

Who does it now? Sometimes doctors. Sometimes nurses who aren’t in the specialty where the request is coming in for preapproval. I’ve even seen situations where some companies use nurses in other countries, such as the Philippines, to do preapproval. They send them information, like a clip, to use to deny things that basically is boilerplate language, whatever the request is.

Looming up now, some insurers are starting to think, well, maybe artificial intelligence could do it. Just review the written request, trigger certain responses on the part of the artificial intelligence — it can deny the claims just as well as a human — and maybe it’s even cheaper to set up that system for the insurer.

This is ethically nuts. We need to have a system where doctors’ judgments drive what patients get. You listen to doctors, as I do, about preapproval access and they say patients sometimes give up trying to get what they think is needed. Continuity of care is interrupted if they have to keep making requests all the time.

There are adverse events when the thing that the doctor thought was most appropriate isn’t approved and something else is used that is less safe or less efficacious. It isn’t in patient interest to have the person with the wallet saying, this is what we think you need, and then having unqualified people or even automated intelligence with no accountability and no transparency get involved in preauthorization.

This system costs us money because middlemen are doing all this work. It basically becomes one of the huge scandals, in my view, of our health system, that doctors don’t ultimately decide what the patient needs. A preauthorizing third party or robot, without transparency, without accountability, and behind closed doors second-guesses what’s going on.

I’m Art Caplan at the Division of Medical Ethics at the New York University Grossman School of Medicine.

Arthur L. Caplan, Director, Division of Medical Ethics, New York University Langone Medical Center, New York, New York, has disclosed the following relevant financial relationships: Served as a director, officer, partner, employee, advisor, consultant, or trustee for Johnson & Johnson’s Panel for Compassionate Drug Use (unpaid position). Serves as a contributing author and advisor for Medscape.

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

This transcript has been edited for clarity. 

Hi. I’m Art Caplan. I’m at the Division of Medical Ethics at New York University Grossman School of Medicine in New York City. 

There are many things screwy with our healthcare system. Many of you [reading] this are dealing with bureaucracy, paperwork, all sorts of constraints, restraints, and requirements that sometimes make the practice of medicine, or even nursing, difficult.

I don’t think I’ve seen anything screwier, from a moral point of view, than the system we have that allows for preauthorization by third-party payers, or insurers, in order to give care to patients. It’s pretty clear that a third-party payer has a conflict of interest. It’s simple: They don’t want to spend money.

Their goal as profit-making companies is to reduce what it is that they’re going to authorize. That clearly is driving how the preauthorization process works. We’re not getting a neutral review by third parties of the appropriateness of treatment recommendations or somebody saying, this is the standard of care and this is what ought to happen.

We’re letting the people who have the pocketbooks and the wallets have prior approval of what the doctor thinks is correct. That is really not the way to practice medicine. 

We now have more evidence about what really is going on. A doctor was recently interviewed by ProPublica and said that she had worked for Cigna as a reviewer. Basically, the message she got from that insurer was to speed it up, go fast, and basically “deny, deny, deny” when she got requests. Those are her words, not mine.

We get a peek under the tent of how this works, and Dr. Day is basically saying she had to leave because she just didn’t feel that it was evidence-driven. It was driven by concerns about who’s going to lose money or make money.

If you want to check to see whether something is appropriate, the question becomes, who ought to do prior review? 

Who does it now? Sometimes doctors. Sometimes nurses who aren’t in the specialty where the request is coming in for preapproval. I’ve even seen situations where some companies use nurses in other countries, such as the Philippines, to do preapproval. They send them information, like a clip, to use to deny things that basically is boilerplate language, whatever the request is.

Looming up now, some insurers are starting to think, well, maybe artificial intelligence could do it. Just review the written request, trigger certain responses on the part of the artificial intelligence — it can deny the claims just as well as a human — and maybe it’s even cheaper to set up that system for the insurer.

This is ethically nuts. We need to have a system where doctors’ judgments drive what patients get. You listen to doctors, as I do, about preapproval access and they say patients sometimes give up trying to get what they think is needed. Continuity of care is interrupted if they have to keep making requests all the time.

There are adverse events when the thing that the doctor thought was most appropriate isn’t approved and something else is used that is less safe or less efficacious. It isn’t in patient interest to have the person with the wallet saying, this is what we think you need, and then having unqualified people or even automated intelligence with no accountability and no transparency get involved in preauthorization.

This system costs us money because middlemen are doing all this work. It basically becomes one of the huge scandals, in my view, of our health system, that doctors don’t ultimately decide what the patient needs. A preauthorizing third party or robot, without transparency, without accountability, and behind closed doors second-guesses what’s going on.

I’m Art Caplan at the Division of Medical Ethics at the New York University Grossman School of Medicine.

Arthur L. Caplan, Director, Division of Medical Ethics, New York University Langone Medical Center, New York, New York, has disclosed the following relevant financial relationships: Served as a director, officer, partner, employee, advisor, consultant, or trustee for Johnson & Johnson’s Panel for Compassionate Drug Use (unpaid position). Serves as a contributing author and advisor for Medscape.

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

This transcript has been edited for clarity. 

Hi. I’m Art Caplan. I’m at the Division of Medical Ethics at New York University Grossman School of Medicine in New York City. 

There are many things screwy with our healthcare system. Many of you [reading] this are dealing with bureaucracy, paperwork, all sorts of constraints, restraints, and requirements that sometimes make the practice of medicine, or even nursing, difficult.

I don’t think I’ve seen anything screwier, from a moral point of view, than the system we have that allows for preauthorization by third-party payers, or insurers, in order to give care to patients. It’s pretty clear that a third-party payer has a conflict of interest. It’s simple: They don’t want to spend money.

Their goal as profit-making companies is to reduce what it is that they’re going to authorize. That clearly is driving how the preauthorization process works. We’re not getting a neutral review by third parties of the appropriateness of treatment recommendations or somebody saying, this is the standard of care and this is what ought to happen.

We’re letting the people who have the pocketbooks and the wallets have prior approval of what the doctor thinks is correct. That is really not the way to practice medicine. 

We now have more evidence about what really is going on. A doctor was recently interviewed by ProPublica and said that she had worked for Cigna as a reviewer. Basically, the message she got from that insurer was to speed it up, go fast, and basically “deny, deny, deny” when she got requests. Those are her words, not mine.

We get a peek under the tent of how this works, and Dr. Day is basically saying she had to leave because she just didn’t feel that it was evidence-driven. It was driven by concerns about who’s going to lose money or make money.

If you want to check to see whether something is appropriate, the question becomes, who ought to do prior review? 

Who does it now? Sometimes doctors. Sometimes nurses who aren’t in the specialty where the request is coming in for preapproval. I’ve even seen situations where some companies use nurses in other countries, such as the Philippines, to do preapproval. They send them information, like a clip, to use to deny things that basically is boilerplate language, whatever the request is.

Looming up now, some insurers are starting to think, well, maybe artificial intelligence could do it. Just review the written request, trigger certain responses on the part of the artificial intelligence — it can deny the claims just as well as a human — and maybe it’s even cheaper to set up that system for the insurer.

This is ethically nuts. We need to have a system where doctors’ judgments drive what patients get. You listen to doctors, as I do, about preapproval access and they say patients sometimes give up trying to get what they think is needed. Continuity of care is interrupted if they have to keep making requests all the time.

There are adverse events when the thing that the doctor thought was most appropriate isn’t approved and something else is used that is less safe or less efficacious. It isn’t in patient interest to have the person with the wallet saying, this is what we think you need, and then having unqualified people or even automated intelligence with no accountability and no transparency get involved in preauthorization.

This system costs us money because middlemen are doing all this work. It basically becomes one of the huge scandals, in my view, of our health system, that doctors don’t ultimately decide what the patient needs. A preauthorizing third party or robot, without transparency, without accountability, and behind closed doors second-guesses what’s going on.

I’m Art Caplan at the Division of Medical Ethics at the New York University Grossman School of Medicine.

Arthur L. Caplan, Director, Division of Medical Ethics, New York University Langone Medical Center, New York, New York, has disclosed the following relevant financial relationships: Served as a director, officer, partner, employee, advisor, consultant, or trustee for Johnson & Johnson’s Panel for Compassionate Drug Use (unpaid position). Serves as a contributing author and advisor for Medscape.

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

PHILADELPHIA – Nearly half of dementia cases worldwide could theoretically be prevented or delayed by eliminating 14 modifiable risk factors during an individual’s lifetime, a report from the Lancet Commission on dementia prevention, intervention, and care.

The report adds two new modifiable risk factors for dementia — high cholesterol and vision loss — to the 12 risk factors identified in the 2020 Lancet Commission report, which were linked to about 40% of all dementia cases. 

The original Lancet Commission report, published in 2017, identified nine modifiable risk factors that were estimated to be responsible for one third of dementia cases. 

“Our new report reveals that there is much more that can and should be done to reduce the risk of dementia. It’s never too early or too late to act, with opportunities to make an impact at any stage of life,” lead author Gill Livingston, MD, from University College London in England, said in a statement. 

The 57-page report was published online in The Lancet Neurology (to coincide with its presentation at the 2024 Alzheimer’s Association International Conference (AAIC).
 

‘Compelling’ New Evidence 

The 12 risk factors cited in the 2020 report are lower levels of education, hearing loss, hypertension, smoking, obesity, depression, physical inactivity, diabetes, excessive alcohol consumption, traumatic brain injury (TBI), air pollution, and social isolation. 

According to the authors of the current report, there is “new compelling evidence” that untreated vision loss and elevated low-density lipoprotein (LDL) cholesterol are also risk factors for dementia.

These two added risk factors are associated with 9% of all dementia cases — with an estimated 7% of cases caused by high LDL cholesterol from about age 40 years, and 2% of cases caused by untreated vision loss in later life, the authors said.

Out of all 14 risk factors, those tied to the greatest proportion of dementia in the global population are hearing impairment and high LDL cholesterol (7% each), along with less education in early life, and social isolation in later life (5% each), the report estimates. 

The new report also outlines 13 recommendations aimed at individuals and governments to help guard against dementia. They include preventing and treating hearing loss, vision loss, and depression; being cognitively active throughout life; using head protection in contact sports; reducing vascular risk factors (high cholesterol, diabetes, obesity, hypertension); improving air quality; and providing supportive community environments to increase social contact. 

Tara Spires-Jones, PhD, president of the British Neuroscience Association, emphasized that, while this research doesn’t directly link specific factors to dementia, it supports evidence that a healthy lifestyle — encompassing education, social activities, exercise, cognitive engagement, and avoiding head injuries and harmful factors for heart and lung health — can enhance brain resilience and prevent dementia.

In an interview, Heather M. Snyder, PhD, senior vice president of medical and scientific relations, Alzheimer’s Association, said: “Our brains are complex and what happens throughout our lives may increase or decrease our risk for dementia as we age. Protecting brain health as we age requires a comprehensive approach that includes discussions on diet, exercise, heart health, hearing, and vision.”

Also weighing in on the new report, Shaheen Lakhan, MD, PhD, neurologist and researcher based in Miami, Florida, said the addition of high cholesterol is “particularly noteworthy as it reinforces the intricate connection between vascular health and brain health — a link we’ve long suspected but can now target more effectively.”

As for vision loss, “it’s not just a matter of seeing clearly; it’s a matter of thinking clearly. Untreated vision loss can lead to social isolation, reduced physical activity, and cognitive decline,” said Dr. Lakhan. 
 

Dementia Is Not Inevitable

In his view, “the potential to prevent or delay nearly half of dementia cases by addressing these risk factors is nothing short of revolutionary. It shifts our perspective from viewing dementia as an inevitable part of aging to seeing it as a condition we can actively work to prevent,” Dr. Lakhan added.

He said the report’s emphasis on health equity is also important. 

“Dementia risk factors disproportionately affect socioeconomically disadvantaged groups and low- and middle-income countries. Addressing these disparities isn’t just a matter of fairness in the fight against dementia, equality in prevention is as important as equality in treatment,” Dr. Lakhan commented.

While the report offers hope, it also presents a challenge, he said. 

Implementing the recommended preventive measures requires a “coordinated effort from individuals, healthcare systems, and policymakers. The potential benefits, both in terms of quality of life and economic savings, make this effort not just worthwhile but imperative. Preventing dementia is not just a medical imperative — it’s an economic and humanitarian one,” Dr. Lakhan said. 

Masud Husain, PhD, with the University of Oxford in England, agreed. 

The conclusions in this report are “very important for all of us, but particularly for health policy makers and government,” he said. 

“If we did simple things well such as screening for some of the factors identified in this report, with adequate resources to perform this, we have the potential to prevent dementia on a national scale. This would be far more cost effective than developing high-tech treatments, which so far have been disappointing in their impacts on people with established dementia,” Dr. Husain said. 

The Lancet Commission was funded by University College London, Alzheimer’s Society, Alzheimer’s Research UK, and the Economic and Social Research Council. A complete list of author disclosures is available with the original article. Dr. Snyder, Dr. Lakhan, Dr. Husain and Dr. Spires-Jones have no relevant disclosures.

A version of this article appeared on Medscape.com.

PHILADELPHIA – Nearly half of dementia cases worldwide could theoretically be prevented or delayed by eliminating 14 modifiable risk factors during an individual’s lifetime, a report from the Lancet Commission on dementia prevention, intervention, and care.

The report adds two new modifiable risk factors for dementia — high cholesterol and vision loss — to the 12 risk factors identified in the 2020 Lancet Commission report, which were linked to about 40% of all dementia cases. 

The original Lancet Commission report, published in 2017, identified nine modifiable risk factors that were estimated to be responsible for one third of dementia cases. 

“Our new report reveals that there is much more that can and should be done to reduce the risk of dementia. It’s never too early or too late to act, with opportunities to make an impact at any stage of life,” lead author Gill Livingston, MD, from University College London in England, said in a statement. 

The 57-page report was published online in The Lancet Neurology (to coincide with its presentation at the 2024 Alzheimer’s Association International Conference (AAIC).
 

‘Compelling’ New Evidence 

The 12 risk factors cited in the 2020 report are lower levels of education, hearing loss, hypertension, smoking, obesity, depression, physical inactivity, diabetes, excessive alcohol consumption, traumatic brain injury (TBI), air pollution, and social isolation. 

According to the authors of the current report, there is “new compelling evidence” that untreated vision loss and elevated low-density lipoprotein (LDL) cholesterol are also risk factors for dementia.

These two added risk factors are associated with 9% of all dementia cases — with an estimated 7% of cases caused by high LDL cholesterol from about age 40 years, and 2% of cases caused by untreated vision loss in later life, the authors said.

Out of all 14 risk factors, those tied to the greatest proportion of dementia in the global population are hearing impairment and high LDL cholesterol (7% each), along with less education in early life, and social isolation in later life (5% each), the report estimates. 

The new report also outlines 13 recommendations aimed at individuals and governments to help guard against dementia. They include preventing and treating hearing loss, vision loss, and depression; being cognitively active throughout life; using head protection in contact sports; reducing vascular risk factors (high cholesterol, diabetes, obesity, hypertension); improving air quality; and providing supportive community environments to increase social contact. 

Tara Spires-Jones, PhD, president of the British Neuroscience Association, emphasized that, while this research doesn’t directly link specific factors to dementia, it supports evidence that a healthy lifestyle — encompassing education, social activities, exercise, cognitive engagement, and avoiding head injuries and harmful factors for heart and lung health — can enhance brain resilience and prevent dementia.

In an interview, Heather M. Snyder, PhD, senior vice president of medical and scientific relations, Alzheimer’s Association, said: “Our brains are complex and what happens throughout our lives may increase or decrease our risk for dementia as we age. Protecting brain health as we age requires a comprehensive approach that includes discussions on diet, exercise, heart health, hearing, and vision.”

Also weighing in on the new report, Shaheen Lakhan, MD, PhD, neurologist and researcher based in Miami, Florida, said the addition of high cholesterol is “particularly noteworthy as it reinforces the intricate connection between vascular health and brain health — a link we’ve long suspected but can now target more effectively.”

As for vision loss, “it’s not just a matter of seeing clearly; it’s a matter of thinking clearly. Untreated vision loss can lead to social isolation, reduced physical activity, and cognitive decline,” said Dr. Lakhan. 
 

Dementia Is Not Inevitable

In his view, “the potential to prevent or delay nearly half of dementia cases by addressing these risk factors is nothing short of revolutionary. It shifts our perspective from viewing dementia as an inevitable part of aging to seeing it as a condition we can actively work to prevent,” Dr. Lakhan added.

He said the report’s emphasis on health equity is also important. 

“Dementia risk factors disproportionately affect socioeconomically disadvantaged groups and low- and middle-income countries. Addressing these disparities isn’t just a matter of fairness in the fight against dementia, equality in prevention is as important as equality in treatment,” Dr. Lakhan commented.

While the report offers hope, it also presents a challenge, he said. 

Implementing the recommended preventive measures requires a “coordinated effort from individuals, healthcare systems, and policymakers. The potential benefits, both in terms of quality of life and economic savings, make this effort not just worthwhile but imperative. Preventing dementia is not just a medical imperative — it’s an economic and humanitarian one,” Dr. Lakhan said. 

Masud Husain, PhD, with the University of Oxford in England, agreed. 

The conclusions in this report are “very important for all of us, but particularly for health policy makers and government,” he said. 

“If we did simple things well such as screening for some of the factors identified in this report, with adequate resources to perform this, we have the potential to prevent dementia on a national scale. This would be far more cost effective than developing high-tech treatments, which so far have been disappointing in their impacts on people with established dementia,” Dr. Husain said. 

The Lancet Commission was funded by University College London, Alzheimer’s Society, Alzheimer’s Research UK, and the Economic and Social Research Council. A complete list of author disclosures is available with the original article. Dr. Snyder, Dr. Lakhan, Dr. Husain and Dr. Spires-Jones have no relevant disclosures.

A version of this article appeared on Medscape.com.

PHILADELPHIA – Nearly half of dementia cases worldwide could theoretically be prevented or delayed by eliminating 14 modifiable risk factors during an individual’s lifetime, a report from the Lancet Commission on dementia prevention, intervention, and care.

The report adds two new modifiable risk factors for dementia — high cholesterol and vision loss — to the 12 risk factors identified in the 2020 Lancet Commission report, which were linked to about 40% of all dementia cases. 

The original Lancet Commission report, published in 2017, identified nine modifiable risk factors that were estimated to be responsible for one third of dementia cases. 

“Our new report reveals that there is much more that can and should be done to reduce the risk of dementia. It’s never too early or too late to act, with opportunities to make an impact at any stage of life,” lead author Gill Livingston, MD, from University College London in England, said in a statement. 

The 57-page report was published online in The Lancet Neurology (to coincide with its presentation at the 2024 Alzheimer’s Association International Conference (AAIC).
 

‘Compelling’ New Evidence 

The 12 risk factors cited in the 2020 report are lower levels of education, hearing loss, hypertension, smoking, obesity, depression, physical inactivity, diabetes, excessive alcohol consumption, traumatic brain injury (TBI), air pollution, and social isolation. 

According to the authors of the current report, there is “new compelling evidence” that untreated vision loss and elevated low-density lipoprotein (LDL) cholesterol are also risk factors for dementia.

These two added risk factors are associated with 9% of all dementia cases — with an estimated 7% of cases caused by high LDL cholesterol from about age 40 years, and 2% of cases caused by untreated vision loss in later life, the authors said.

Out of all 14 risk factors, those tied to the greatest proportion of dementia in the global population are hearing impairment and high LDL cholesterol (7% each), along with less education in early life, and social isolation in later life (5% each), the report estimates. 

The new report also outlines 13 recommendations aimed at individuals and governments to help guard against dementia. They include preventing and treating hearing loss, vision loss, and depression; being cognitively active throughout life; using head protection in contact sports; reducing vascular risk factors (high cholesterol, diabetes, obesity, hypertension); improving air quality; and providing supportive community environments to increase social contact. 

Tara Spires-Jones, PhD, president of the British Neuroscience Association, emphasized that, while this research doesn’t directly link specific factors to dementia, it supports evidence that a healthy lifestyle — encompassing education, social activities, exercise, cognitive engagement, and avoiding head injuries and harmful factors for heart and lung health — can enhance brain resilience and prevent dementia.

In an interview, Heather M. Snyder, PhD, senior vice president of medical and scientific relations, Alzheimer’s Association, said: “Our brains are complex and what happens throughout our lives may increase or decrease our risk for dementia as we age. Protecting brain health as we age requires a comprehensive approach that includes discussions on diet, exercise, heart health, hearing, and vision.”

Also weighing in on the new report, Shaheen Lakhan, MD, PhD, neurologist and researcher based in Miami, Florida, said the addition of high cholesterol is “particularly noteworthy as it reinforces the intricate connection between vascular health and brain health — a link we’ve long suspected but can now target more effectively.”

As for vision loss, “it’s not just a matter of seeing clearly; it’s a matter of thinking clearly. Untreated vision loss can lead to social isolation, reduced physical activity, and cognitive decline,” said Dr. Lakhan. 
 

Dementia Is Not Inevitable

In his view, “the potential to prevent or delay nearly half of dementia cases by addressing these risk factors is nothing short of revolutionary. It shifts our perspective from viewing dementia as an inevitable part of aging to seeing it as a condition we can actively work to prevent,” Dr. Lakhan added.

He said the report’s emphasis on health equity is also important. 

“Dementia risk factors disproportionately affect socioeconomically disadvantaged groups and low- and middle-income countries. Addressing these disparities isn’t just a matter of fairness in the fight against dementia, equality in prevention is as important as equality in treatment,” Dr. Lakhan commented.

While the report offers hope, it also presents a challenge, he said. 

Implementing the recommended preventive measures requires a “coordinated effort from individuals, healthcare systems, and policymakers. The potential benefits, both in terms of quality of life and economic savings, make this effort not just worthwhile but imperative. Preventing dementia is not just a medical imperative — it’s an economic and humanitarian one,” Dr. Lakhan said. 

Masud Husain, PhD, with the University of Oxford in England, agreed. 

The conclusions in this report are “very important for all of us, but particularly for health policy makers and government,” he said. 

“If we did simple things well such as screening for some of the factors identified in this report, with adequate resources to perform this, we have the potential to prevent dementia on a national scale. This would be far more cost effective than developing high-tech treatments, which so far have been disappointing in their impacts on people with established dementia,” Dr. Husain said. 

The Lancet Commission was funded by University College London, Alzheimer’s Society, Alzheimer’s Research UK, and the Economic and Social Research Council. A complete list of author disclosures is available with the original article. Dr. Snyder, Dr. Lakhan, Dr. Husain and Dr. Spires-Jones have no relevant disclosures.

A version of this article appeared on Medscape.com.

I need a hobby. Any suggestions?

Due to the annual summertime slowdown, I find myself with less to do and catch up on during weekends. My kids are grown. Nowadays, when I have free time, I have no idea what to do with myself.

That’s not to say I don’t do things to relax. Jigsaw puzzles, reading P.G. Wodehouse ... but there’s only so long I can sit there, maybe 30 minutes, before I get bored. Then I go back to my desk, check email, log in to see if any prescription refills need to be addressed ...

I look online for ideas. No, I don’t want to collect things. Or start gardening. Or learn an instrument. Or paint. Or take up photography. The last thing I want is a hobby that involves a significant financial outlay for stuff I may be selling on eBay in 3 months.

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

I need a hobby. Any suggestions?

Due to the annual summertime slowdown, I find myself with less to do and catch up on during weekends. My kids are grown. Nowadays, when I have free time, I have no idea what to do with myself.

That’s not to say I don’t do things to relax. Jigsaw puzzles, reading P.G. Wodehouse ... but there’s only so long I can sit there, maybe 30 minutes, before I get bored. Then I go back to my desk, check email, log in to see if any prescription refills need to be addressed ...

I look online for ideas. No, I don’t want to collect things. Or start gardening. Or learn an instrument. Or paint. Or take up photography. The last thing I want is a hobby that involves a significant financial outlay for stuff I may be selling on eBay in 3 months.

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

I need a hobby. Any suggestions?

Due to the annual summertime slowdown, I find myself with less to do and catch up on during weekends. My kids are grown. Nowadays, when I have free time, I have no idea what to do with myself.

That’s not to say I don’t do things to relax. Jigsaw puzzles, reading P.G. Wodehouse ... but there’s only so long I can sit there, maybe 30 minutes, before I get bored. Then I go back to my desk, check email, log in to see if any prescription refills need to be addressed ...

I look online for ideas. No, I don’t want to collect things. Or start gardening. Or learn an instrument. Or paint. Or take up photography. The last thing I want is a hobby that involves a significant financial outlay for stuff I may be selling on eBay in 3 months.

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

PHILADELPHIA – A new study supports the potential to repurpose glucagon-like peptide 1 (GLP-1) receptor agonists, used to treat type 2 diabetes and obesity, for dementia prevention.

In the phase 2b ELAD clinical trial, adults with early-stage Alzheimer’s disease taking the GLP-1 receptor agonist liraglutide exhibited slower decline in memory and thinking and experienced less brain atrophy over 12 months, compared with placebo.

“The slower loss of brain volume suggests liraglutide protects the brain, much like statins protect the heart,” study chief Paul Edison, MD, PhD, with Imperial College London, London, England, said in a statement.

“While further research is needed, liraglutide may work through various mechanisms, such as reducing inflammation in the brain, lowering insulin resistance and the toxic effects of Alzheimer’s biomarkers amyloid beta and tau, and improving how the brain’s nerve cells communicate,” Dr. Edison said.

He presented the study results at the 2024 Alzheimer’s Association International Conference (AAIC).

Brain Benefits

Liraglutide has previously demonstrated promising neuroprotective effects in animal models of Alzheimer’s disease and epidemiologic studies. 

In ELAD, 204 patients with mild to moderate Alzheimer’s disease were randomly allocated (1:1) to a daily subcutaneous injection of up to 1.8 mg of liraglutide or placebo for 12 months; 80 patients in the liraglutide group and 89 in the placebo group completed the study. 

Brain MRI was performed at baseline and at 12 months, along with neuropsychometric evaluation and 18F-fludeoxyglucose PET. 

The study’s primary endpoint — change in the cerebral glucose metabolic rate in the cortical regions of the brain (hippocampus, medial temporal lobe, and posterior cingulate) — was not met. 

However, patients taking liraglutide experienced a significant slowing of cognitive decline, compared with placebo group (P = .01), which was a key secondary outcome, calculated as a composite score of 18 different tests of memory, comprehension, language, and spatial orientation. 

Although the study was not powered to assess cognitive changes, adults taking liraglutide had an 18% slower decline in cognitive function over 12 months, compared with those on placebo, Dr. Edison reported. 

In addition, patients treated with liraglutide had nearly 50% less volume loss in several areas of the brain involved in memory, language, and decision-making, including frontal, temporal, parietal, and total gray matter, as measured by MRI. 

Liraglutide daily subcutaneous injections were safe and well tolerated in patients with Alzheimer’s disease, Dr. Edison reported. There were 25 serious side effects — 18 in the placebo group and 7 in the liraglutide group — and most were considered unlikely to be related to the study treatment. There were no deaths. 
 

Promising, Preliminary

This study shows a positive effect of liraglutide on the brain in terms of “slowing down of brain atrophy and slowing down the rate of cognitive decline,” said Howard Fillit, MD, founding executive director of the Alzheimer’s Drug Discovery Foundation, who wasn’t involved in the study.

Heather Snyder, PhD, vice-president of medical and scientific relations at the Alzheimer’s Association, said it’s “interesting” to see slowing of brain volume loss and some cognitive benefit “especially as the study was not powered necessarily to see some of those changes. The fact that they did see these changes in this small study provides a window into what may happen, but we certainly need larger phase 3 studies.”

In a statement from the UK nonprofit Science Media Centre, Tara Spires-Jones, PhD, president of the British Neuroscience Association and group leader at the UK Dementia Research Institute, called the data “promising.”

“There are clear links from strong data in the field between vascular risk factors including diabetes and obesity being associated with increased risk of dementia. The GLP-1 drug should help reduce these risk factors as well as potentially directly protecting brain cells,” Dr. Spires-Jones said. 

However, she said “more research in bigger trials is needed to confirm whether this type of treatment will be effective in people with Alzheimer’s disease.”

Stephen Evans, MSc, emeritus professor, London School of Hygiene and Tropical Medicine, noted that the repurposing of drugs is “an important avenue of research but there is a lot of uncertainty here.”

He cautioned that the “50% brain volume change may not translate to important cognitive effects, and reporting only on those who completed the full 52 weeks of treatment could bring bias into the results. It sounds like it is worth pursuing a larger trial, but these results cannot demonstrate that liraglutide can protect against dementia.”

The ongoing phase 3 EVOKE trial is investigating the effects of the GLP-1 receptor agonist semaglutide in early Alzheimer’s disease.

Funding for the study was provided by Alzheimer’s Society UK, Alzheimer’s Drug Discovery Foundation, Novo Nordisk, John and Lucille Van Geest Foundation, and the National Institute for Health and Care Research Biomedical Research Centre. Dr. Edison, Dr. Fillit, Dr. Snyder, Mr. Evans, and Dr. Spires-Jones had no relevant conflicts of interest.

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

PHILADELPHIA – A new study supports the potential to repurpose glucagon-like peptide 1 (GLP-1) receptor agonists, used to treat type 2 diabetes and obesity, for dementia prevention.

In the phase 2b ELAD clinical trial, adults with early-stage Alzheimer’s disease taking the GLP-1 receptor agonist liraglutide exhibited slower decline in memory and thinking and experienced less brain atrophy over 12 months, compared with placebo.

“The slower loss of brain volume suggests liraglutide protects the brain, much like statins protect the heart,” study chief Paul Edison, MD, PhD, with Imperial College London, London, England, said in a statement.

“While further research is needed, liraglutide may work through various mechanisms, such as reducing inflammation in the brain, lowering insulin resistance and the toxic effects of Alzheimer’s biomarkers amyloid beta and tau, and improving how the brain’s nerve cells communicate,” Dr. Edison said.

He presented the study results at the 2024 Alzheimer’s Association International Conference (AAIC).

Brain Benefits

Liraglutide has previously demonstrated promising neuroprotective effects in animal models of Alzheimer’s disease and epidemiologic studies. 

In ELAD, 204 patients with mild to moderate Alzheimer’s disease were randomly allocated (1:1) to a daily subcutaneous injection of up to 1.8 mg of liraglutide or placebo for 12 months; 80 patients in the liraglutide group and 89 in the placebo group completed the study. 

Brain MRI was performed at baseline and at 12 months, along with neuropsychometric evaluation and 18F-fludeoxyglucose PET. 

The study’s primary endpoint — change in the cerebral glucose metabolic rate in the cortical regions of the brain (hippocampus, medial temporal lobe, and posterior cingulate) — was not met. 

However, patients taking liraglutide experienced a significant slowing of cognitive decline, compared with placebo group (P = .01), which was a key secondary outcome, calculated as a composite score of 18 different tests of memory, comprehension, language, and spatial orientation. 

Although the study was not powered to assess cognitive changes, adults taking liraglutide had an 18% slower decline in cognitive function over 12 months, compared with those on placebo, Dr. Edison reported. 

In addition, patients treated with liraglutide had nearly 50% less volume loss in several areas of the brain involved in memory, language, and decision-making, including frontal, temporal, parietal, and total gray matter, as measured by MRI. 

Liraglutide daily subcutaneous injections were safe and well tolerated in patients with Alzheimer’s disease, Dr. Edison reported. There were 25 serious side effects — 18 in the placebo group and 7 in the liraglutide group — and most were considered unlikely to be related to the study treatment. There were no deaths. 
 

Promising, Preliminary

This study shows a positive effect of liraglutide on the brain in terms of “slowing down of brain atrophy and slowing down the rate of cognitive decline,” said Howard Fillit, MD, founding executive director of the Alzheimer’s Drug Discovery Foundation, who wasn’t involved in the study.

Heather Snyder, PhD, vice-president of medical and scientific relations at the Alzheimer’s Association, said it’s “interesting” to see slowing of brain volume loss and some cognitive benefit “especially as the study was not powered necessarily to see some of those changes. The fact that they did see these changes in this small study provides a window into what may happen, but we certainly need larger phase 3 studies.”

In a statement from the UK nonprofit Science Media Centre, Tara Spires-Jones, PhD, president of the British Neuroscience Association and group leader at the UK Dementia Research Institute, called the data “promising.”

“There are clear links from strong data in the field between vascular risk factors including diabetes and obesity being associated with increased risk of dementia. The GLP-1 drug should help reduce these risk factors as well as potentially directly protecting brain cells,” Dr. Spires-Jones said. 

However, she said “more research in bigger trials is needed to confirm whether this type of treatment will be effective in people with Alzheimer’s disease.”

Stephen Evans, MSc, emeritus professor, London School of Hygiene and Tropical Medicine, noted that the repurposing of drugs is “an important avenue of research but there is a lot of uncertainty here.”

He cautioned that the “50% brain volume change may not translate to important cognitive effects, and reporting only on those who completed the full 52 weeks of treatment could bring bias into the results. It sounds like it is worth pursuing a larger trial, but these results cannot demonstrate that liraglutide can protect against dementia.”

The ongoing phase 3 EVOKE trial is investigating the effects of the GLP-1 receptor agonist semaglutide in early Alzheimer’s disease.

Funding for the study was provided by Alzheimer’s Society UK, Alzheimer’s Drug Discovery Foundation, Novo Nordisk, John and Lucille Van Geest Foundation, and the National Institute for Health and Care Research Biomedical Research Centre. Dr. Edison, Dr. Fillit, Dr. Snyder, Mr. Evans, and Dr. Spires-Jones had no relevant conflicts of interest.

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

PHILADELPHIA – A new study supports the potential to repurpose glucagon-like peptide 1 (GLP-1) receptor agonists, used to treat type 2 diabetes and obesity, for dementia prevention.

In the phase 2b ELAD clinical trial, adults with early-stage Alzheimer’s disease taking the GLP-1 receptor agonist liraglutide exhibited slower decline in memory and thinking and experienced less brain atrophy over 12 months, compared with placebo.

“The slower loss of brain volume suggests liraglutide protects the brain, much like statins protect the heart,” study chief Paul Edison, MD, PhD, with Imperial College London, London, England, said in a statement.

“While further research is needed, liraglutide may work through various mechanisms, such as reducing inflammation in the brain, lowering insulin resistance and the toxic effects of Alzheimer’s biomarkers amyloid beta and tau, and improving how the brain’s nerve cells communicate,” Dr. Edison said.

He presented the study results at the 2024 Alzheimer’s Association International Conference (AAIC).

Brain Benefits

Liraglutide has previously demonstrated promising neuroprotective effects in animal models of Alzheimer’s disease and epidemiologic studies. 

In ELAD, 204 patients with mild to moderate Alzheimer’s disease were randomly allocated (1:1) to a daily subcutaneous injection of up to 1.8 mg of liraglutide or placebo for 12 months; 80 patients in the liraglutide group and 89 in the placebo group completed the study. 

Brain MRI was performed at baseline and at 12 months, along with neuropsychometric evaluation and 18F-fludeoxyglucose PET. 

The study’s primary endpoint — change in the cerebral glucose metabolic rate in the cortical regions of the brain (hippocampus, medial temporal lobe, and posterior cingulate) — was not met. 

However, patients taking liraglutide experienced a significant slowing of cognitive decline, compared with placebo group (P = .01), which was a key secondary outcome, calculated as a composite score of 18 different tests of memory, comprehension, language, and spatial orientation. 

Although the study was not powered to assess cognitive changes, adults taking liraglutide had an 18% slower decline in cognitive function over 12 months, compared with those on placebo, Dr. Edison reported. 

In addition, patients treated with liraglutide had nearly 50% less volume loss in several areas of the brain involved in memory, language, and decision-making, including frontal, temporal, parietal, and total gray matter, as measured by MRI. 

Liraglutide daily subcutaneous injections were safe and well tolerated in patients with Alzheimer’s disease, Dr. Edison reported. There were 25 serious side effects — 18 in the placebo group and 7 in the liraglutide group — and most were considered unlikely to be related to the study treatment. There were no deaths. 
 

Promising, Preliminary

This study shows a positive effect of liraglutide on the brain in terms of “slowing down of brain atrophy and slowing down the rate of cognitive decline,” said Howard Fillit, MD, founding executive director of the Alzheimer’s Drug Discovery Foundation, who wasn’t involved in the study.

Heather Snyder, PhD, vice-president of medical and scientific relations at the Alzheimer’s Association, said it’s “interesting” to see slowing of brain volume loss and some cognitive benefit “especially as the study was not powered necessarily to see some of those changes. The fact that they did see these changes in this small study provides a window into what may happen, but we certainly need larger phase 3 studies.”

In a statement from the UK nonprofit Science Media Centre, Tara Spires-Jones, PhD, president of the British Neuroscience Association and group leader at the UK Dementia Research Institute, called the data “promising.”

“There are clear links from strong data in the field between vascular risk factors including diabetes and obesity being associated with increased risk of dementia. The GLP-1 drug should help reduce these risk factors as well as potentially directly protecting brain cells,” Dr. Spires-Jones said. 

However, she said “more research in bigger trials is needed to confirm whether this type of treatment will be effective in people with Alzheimer’s disease.”

Stephen Evans, MSc, emeritus professor, London School of Hygiene and Tropical Medicine, noted that the repurposing of drugs is “an important avenue of research but there is a lot of uncertainty here.”

He cautioned that the “50% brain volume change may not translate to important cognitive effects, and reporting only on those who completed the full 52 weeks of treatment could bring bias into the results. It sounds like it is worth pursuing a larger trial, but these results cannot demonstrate that liraglutide can protect against dementia.”

The ongoing phase 3 EVOKE trial is investigating the effects of the GLP-1 receptor agonist semaglutide in early Alzheimer’s disease.

Funding for the study was provided by Alzheimer’s Society UK, Alzheimer’s Drug Discovery Foundation, Novo Nordisk, John and Lucille Van Geest Foundation, and the National Institute for Health and Care Research Biomedical Research Centre. Dr. Edison, Dr. Fillit, Dr. Snyder, Mr. Evans, and Dr. Spires-Jones had no relevant conflicts of interest.

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

PHILADELPHIA – Higher intake of processed red meat, including bacon, hot dogs, and sausages, is associated with an elevated dementia risk, preliminary research shows.

Study participants who consumed 0.25 or more servings of processed meat per day, or roughly two servings per week, had a 15% higher risk for dementia, compared with those who consumed less than 0.10 serving per day, which is about three servings per month. 

“Our study found a higher intake of red meat — particularly processed red meat — was associated with a higher risk of developing dementia, as well as worse cognition,” said study author Yuhan Li, MHS, research assistant, Channing Division of Network Medicine, Brigham and Women’s Hospital, Boston, Massachusetts.

However, the study also showed that replacing processed red meat with nuts and legumes could potentially lower this increased risk.

The findings were presented on at the 2024 Alzheimer’s Association International Conference (AAIC).

Inconsistent Research 

Previous studies have shown an inconsistent association between red meat intake and cognitive health.

To assess the relationship between diet and dementia, the researchers used data from the Nurses’ Health Study, which began recruiting female registered nurses aged 30-55 years in 1976, and the Health Professionals Follow-Up Study, which began recruiting male health professionals aged 40-75 in 1986.

They assessed processed red meat intake by validated semi-quantitative food frequency questionnaires administered every 2-4 years. Participants were asked how often they consumed a serving of processed red meat.

Investigators also assessed intake of unprocessed red meat, including beef, pork, or lamb as a main dish, in a sandwich or hamburger, or in a mixed dish. 

The investigators also looked at participants’ intake of nuts and legumes.

Dementia outcome was a composite endpoint of self-reported dementia and dementia-related death. “Specifically, participants reported a physician diagnosis of Alzheimer’s disease or other forms of dementia by questionnaire. Deaths were identified through state vital statistics records, the National Death Index, family reports, and the postal system,” said Ms. Li.
 

Three Cognitive Outcomes

Researchers examined three outcomes: dementia, subjective cognitive decline, and objective cognitive function. For dementia, they ascertained incident cases in 87,424 individuals in the UK’s National Health Service database without Parkinson’s disease or baseline dementia, stroke, or cancer. 

They longitudinally collected information on subjective cognitive decline from 33,908 Nurses’ Health Study participants and 10,058 participants in the Health Professionals Follow-Up Study.

Cognitive function was assessed using the Telephone Interview for Cognitive Status (1995-2008) in a subset of 17,458 Nurses’ Health Study participants.

Over a follow-up of 38 years (1980-2018), there were 6856 dementia cases in the Nurses’ Health Study. Participants with processed red meat intake of 0.25 or more serving/day, compared with less than 0.10 serving/day, had 15% higher risk for dementia (hazard ratio [HR], 1.15; 95% CI, 1.08-1.23; P < .001). 

In addition to an increased risk for dementia, intake of processed red meat was associated with accelerated cognitive aging in global cognition (1.61 years per 1–serving/day increment; 95% CI, 0.20, 3.03) and verbal memory (1.69 years per 1–serving/day increment; 95% CI, 0.13, 3.25; both P = .03).

Participants with processed red meat intake of 0.25 or more serving/day had a 14% higher likelihood of subjective cognitive decline, compared with those with intake less than 0.10 serving/day (odds ratio [OR], 1.14; 95% CI, 1.04-1.24; P = .004). 

For unprocessed red meat, consuming 1.00 or more serving/day versus less than 0.50 serving/day was associated with a 16% higher likelihood of subjective cognitive decline (OR, 1.16; 95% CI, 1.04-1.30; P = .02). 
 

Substitution Analysis

Researchers modeled the effects of replacing 1 serving/day of processed red meat with 1 serving/day of nuts and legumes on cognitive outcomes. They did this by treating food intakes as continuous variables and calculating the differences in coefficients of the two food items.

They found that substituting legumes and nuts was associated with a 23% lower risk for dementia (HR, 0.77; 95% CI, 0.69-0.86), 1.37 fewer years of cognitive aging (95% CI, –2.49 to –0.25), and 20% lower odds of subjective cognitive decline (OR, 0.80, 95% CI, 0.69-0.92).

The research cannot determine whether it’s the processing method itself or the type of red meat that affects cognition, Ms. Li cautioned. 

“Our study is an epidemiologic study, not a biological mechanism study, but based on our findings, red meat may be related to worse cognition, and processed red meat may add additional risk,” she said. 

She also noted that because the study focused solely on red meats, the study cannot determine the potential on the impact of other processed meats on cognition.

Although the study doesn’t address a possible mechanism linking processed red meat with cognition, Ms. Li said it’s possible such meats have high levels of relatively harmful substances, such as nitrites, N-nitroso compounds, and sodium, and that “these carry the additional risk to brain health.”

There are currently no specific guidelines regarding the “safe” amount of processed meat consumption specifically related to cognition, she said.

The study is important because of its large sample size, long follow-up period, and inclusion of repeated measurements of diet, the investigators noted. In addition, researchers assessed both processed and unprocessed red meat and evaluated multiple cognitive outcomes.

The investigators plan to assess the association between other modifiable factors and cognitive health.
 

Experts Weigh In 

In a comment, Claire Sexton, DPhil, senior director of scientific programs and outreach at the Alzheimer’s Association, agreed past studies on the topic have been “mixed,” with only some studies reporting links between cognition or dementia and processed red meat. 

Another unique aspect of the study, said Dr. Sexton, was the replacement analysis showing the brain benefits of eating nuts and legumes in place of processed red meat. “So, it’s not just suggesting to people what not to do, but also what they can be doing instead.”

That’s why this large study with more than 130,000 adults that tracked individuals for close to 40 years in some cases “is so valuable,” she added.

In a release from the Science Media Centre in the United Kingdom, several other experts commented on the study. Among them, Kevin McConway, PhD, emeritus professor of applied statistics at the Open University, Milton Keynes, England, said that “it’s pretty well impossible to get a clear message from the information that is available so far about this research. It is a conference paper, and all we have seen so far is a press release, a brief summary of the research, and a diagram. There isn’t a detailed, peer-reviewed research report, not yet anyway. Putting out limited information like this isn’t the right way to report science.”

Dr. McConway also noted that the observational study recorded participants’ diets and dementia diagnoses over several years without assigning specific diets. Those who ate more red processed meat had higher rates of dementia and cognitive decline. However, it’s unclear if these differences are caused by red meat consumption or other factors, such as diet, age, ethnicity, or location.

Researchers typically adjust for these factors, but the available information doesn’t specify what adjustments were made or their impact, he noted, and without detailed data, it’s impossible to evaluate the study’s quality. Although eating more red processed meat might increase dementia risk, more research is needed to confirm this, Dr. McConway added. 

Also commenting, Sebastian Walsh, a National Institute for Health and Care Research doctoral fellow who researches population-level approaches to dementia risk reduction at University of Cambridge, Cambridge, England, said that without seeing the full paper, it’s difficult to know exactly what to make of the study’s findings. 

“On the surface, this is a large and long study. But it isn’t clear how the analysis was done — specifically what other factors were taken into account when looking at this apparent relationship between red meat and dementia.

“Despite a lot of research looking at specific foods and different diseases, the basic public health advice that eating a healthy, balanced diet is good for health is essentially unchanged. Most people know and accept this. What is most important is to find ways of supporting people, particularly those from poorer backgrounds, to follow this advice and address the obesity epidemic,” said Mr. Walsh. 

The study was funded by a National Institutes of Health research grant. Ms. Li reports no relevant conflicts of interest. Dr. Sexton, Dr. McConway, and Mr. Walsh report no relevant disclosures.

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

PHILADELPHIA – Higher intake of processed red meat, including bacon, hot dogs, and sausages, is associated with an elevated dementia risk, preliminary research shows.

Study participants who consumed 0.25 or more servings of processed meat per day, or roughly two servings per week, had a 15% higher risk for dementia, compared with those who consumed less than 0.10 serving per day, which is about three servings per month. 

“Our study found a higher intake of red meat — particularly processed red meat — was associated with a higher risk of developing dementia, as well as worse cognition,” said study author Yuhan Li, MHS, research assistant, Channing Division of Network Medicine, Brigham and Women’s Hospital, Boston, Massachusetts.

However, the study also showed that replacing processed red meat with nuts and legumes could potentially lower this increased risk.

The findings were presented on at the 2024 Alzheimer’s Association International Conference (AAIC).

Inconsistent Research 

Previous studies have shown an inconsistent association between red meat intake and cognitive health.

To assess the relationship between diet and dementia, the researchers used data from the Nurses’ Health Study, which began recruiting female registered nurses aged 30-55 years in 1976, and the Health Professionals Follow-Up Study, which began recruiting male health professionals aged 40-75 in 1986.

They assessed processed red meat intake by validated semi-quantitative food frequency questionnaires administered every 2-4 years. Participants were asked how often they consumed a serving of processed red meat.

Investigators also assessed intake of unprocessed red meat, including beef, pork, or lamb as a main dish, in a sandwich or hamburger, or in a mixed dish. 

The investigators also looked at participants’ intake of nuts and legumes.

Dementia outcome was a composite endpoint of self-reported dementia and dementia-related death. “Specifically, participants reported a physician diagnosis of Alzheimer’s disease or other forms of dementia by questionnaire. Deaths were identified through state vital statistics records, the National Death Index, family reports, and the postal system,” said Ms. Li.
 

Three Cognitive Outcomes

Researchers examined three outcomes: dementia, subjective cognitive decline, and objective cognitive function. For dementia, they ascertained incident cases in 87,424 individuals in the UK’s National Health Service database without Parkinson’s disease or baseline dementia, stroke, or cancer. 

They longitudinally collected information on subjective cognitive decline from 33,908 Nurses’ Health Study participants and 10,058 participants in the Health Professionals Follow-Up Study.

Cognitive function was assessed using the Telephone Interview for Cognitive Status (1995-2008) in a subset of 17,458 Nurses’ Health Study participants.

Over a follow-up of 38 years (1980-2018), there were 6856 dementia cases in the Nurses’ Health Study. Participants with processed red meat intake of 0.25 or more serving/day, compared with less than 0.10 serving/day, had 15% higher risk for dementia (hazard ratio [HR], 1.15; 95% CI, 1.08-1.23; P < .001). 

In addition to an increased risk for dementia, intake of processed red meat was associated with accelerated cognitive aging in global cognition (1.61 years per 1–serving/day increment; 95% CI, 0.20, 3.03) and verbal memory (1.69 years per 1–serving/day increment; 95% CI, 0.13, 3.25; both P = .03).

Participants with processed red meat intake of 0.25 or more serving/day had a 14% higher likelihood of subjective cognitive decline, compared with those with intake less than 0.10 serving/day (odds ratio [OR], 1.14; 95% CI, 1.04-1.24; P = .004). 

For unprocessed red meat, consuming 1.00 or more serving/day versus less than 0.50 serving/day was associated with a 16% higher likelihood of subjective cognitive decline (OR, 1.16; 95% CI, 1.04-1.30; P = .02). 
 

Substitution Analysis

Researchers modeled the effects of replacing 1 serving/day of processed red meat with 1 serving/day of nuts and legumes on cognitive outcomes. They did this by treating food intakes as continuous variables and calculating the differences in coefficients of the two food items.

They found that substituting legumes and nuts was associated with a 23% lower risk for dementia (HR, 0.77; 95% CI, 0.69-0.86), 1.37 fewer years of cognitive aging (95% CI, –2.49 to –0.25), and 20% lower odds of subjective cognitive decline (OR, 0.80, 95% CI, 0.69-0.92).

The research cannot determine whether it’s the processing method itself or the type of red meat that affects cognition, Ms. Li cautioned. 

“Our study is an epidemiologic study, not a biological mechanism study, but based on our findings, red meat may be related to worse cognition, and processed red meat may add additional risk,” she said. 

She also noted that because the study focused solely on red meats, the study cannot determine the potential on the impact of other processed meats on cognition.

Although the study doesn’t address a possible mechanism linking processed red meat with cognition, Ms. Li said it’s possible such meats have high levels of relatively harmful substances, such as nitrites, N-nitroso compounds, and sodium, and that “these carry the additional risk to brain health.”

There are currently no specific guidelines regarding the “safe” amount of processed meat consumption specifically related to cognition, she said.

The study is important because of its large sample size, long follow-up period, and inclusion of repeated measurements of diet, the investigators noted. In addition, researchers assessed both processed and unprocessed red meat and evaluated multiple cognitive outcomes.

The investigators plan to assess the association between other modifiable factors and cognitive health.
 

Experts Weigh In 

In a comment, Claire Sexton, DPhil, senior director of scientific programs and outreach at the Alzheimer’s Association, agreed past studies on the topic have been “mixed,” with only some studies reporting links between cognition or dementia and processed red meat. 

Another unique aspect of the study, said Dr. Sexton, was the replacement analysis showing the brain benefits of eating nuts and legumes in place of processed red meat. “So, it’s not just suggesting to people what not to do, but also what they can be doing instead.”

That’s why this large study with more than 130,000 adults that tracked individuals for close to 40 years in some cases “is so valuable,” she added.

In a release from the Science Media Centre in the United Kingdom, several other experts commented on the study. Among them, Kevin McConway, PhD, emeritus professor of applied statistics at the Open University, Milton Keynes, England, said that “it’s pretty well impossible to get a clear message from the information that is available so far about this research. It is a conference paper, and all we have seen so far is a press release, a brief summary of the research, and a diagram. There isn’t a detailed, peer-reviewed research report, not yet anyway. Putting out limited information like this isn’t the right way to report science.”

Dr. McConway also noted that the observational study recorded participants’ diets and dementia diagnoses over several years without assigning specific diets. Those who ate more red processed meat had higher rates of dementia and cognitive decline. However, it’s unclear if these differences are caused by red meat consumption or other factors, such as diet, age, ethnicity, or location.

Researchers typically adjust for these factors, but the available information doesn’t specify what adjustments were made or their impact, he noted, and without detailed data, it’s impossible to evaluate the study’s quality. Although eating more red processed meat might increase dementia risk, more research is needed to confirm this, Dr. McConway added. 

Also commenting, Sebastian Walsh, a National Institute for Health and Care Research doctoral fellow who researches population-level approaches to dementia risk reduction at University of Cambridge, Cambridge, England, said that without seeing the full paper, it’s difficult to know exactly what to make of the study’s findings. 

“On the surface, this is a large and long study. But it isn’t clear how the analysis was done — specifically what other factors were taken into account when looking at this apparent relationship between red meat and dementia.

“Despite a lot of research looking at specific foods and different diseases, the basic public health advice that eating a healthy, balanced diet is good for health is essentially unchanged. Most people know and accept this. What is most important is to find ways of supporting people, particularly those from poorer backgrounds, to follow this advice and address the obesity epidemic,” said Mr. Walsh. 

The study was funded by a National Institutes of Health research grant. Ms. Li reports no relevant conflicts of interest. Dr. Sexton, Dr. McConway, and Mr. Walsh report no relevant disclosures.

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

PHILADELPHIA – Higher intake of processed red meat, including bacon, hot dogs, and sausages, is associated with an elevated dementia risk, preliminary research shows.

Study participants who consumed 0.25 or more servings of processed meat per day, or roughly two servings per week, had a 15% higher risk for dementia, compared with those who consumed less than 0.10 serving per day, which is about three servings per month. 

“Our study found a higher intake of red meat — particularly processed red meat — was associated with a higher risk of developing dementia, as well as worse cognition,” said study author Yuhan Li, MHS, research assistant, Channing Division of Network Medicine, Brigham and Women’s Hospital, Boston, Massachusetts.

However, the study also showed that replacing processed red meat with nuts and legumes could potentially lower this increased risk.

The findings were presented on at the 2024 Alzheimer’s Association International Conference (AAIC).

Inconsistent Research 

Previous studies have shown an inconsistent association between red meat intake and cognitive health.

To assess the relationship between diet and dementia, the researchers used data from the Nurses’ Health Study, which began recruiting female registered nurses aged 30-55 years in 1976, and the Health Professionals Follow-Up Study, which began recruiting male health professionals aged 40-75 in 1986.

They assessed processed red meat intake by validated semi-quantitative food frequency questionnaires administered every 2-4 years. Participants were asked how often they consumed a serving of processed red meat.

Investigators also assessed intake of unprocessed red meat, including beef, pork, or lamb as a main dish, in a sandwich or hamburger, or in a mixed dish. 

The investigators also looked at participants’ intake of nuts and legumes.

Dementia outcome was a composite endpoint of self-reported dementia and dementia-related death. “Specifically, participants reported a physician diagnosis of Alzheimer’s disease or other forms of dementia by questionnaire. Deaths were identified through state vital statistics records, the National Death Index, family reports, and the postal system,” said Ms. Li.
 

Three Cognitive Outcomes

Researchers examined three outcomes: dementia, subjective cognitive decline, and objective cognitive function. For dementia, they ascertained incident cases in 87,424 individuals in the UK’s National Health Service database without Parkinson’s disease or baseline dementia, stroke, or cancer. 

They longitudinally collected information on subjective cognitive decline from 33,908 Nurses’ Health Study participants and 10,058 participants in the Health Professionals Follow-Up Study.

Cognitive function was assessed using the Telephone Interview for Cognitive Status (1995-2008) in a subset of 17,458 Nurses’ Health Study participants.

Over a follow-up of 38 years (1980-2018), there were 6856 dementia cases in the Nurses’ Health Study. Participants with processed red meat intake of 0.25 or more serving/day, compared with less than 0.10 serving/day, had 15% higher risk for dementia (hazard ratio [HR], 1.15; 95% CI, 1.08-1.23; P < .001). 

In addition to an increased risk for dementia, intake of processed red meat was associated with accelerated cognitive aging in global cognition (1.61 years per 1–serving/day increment; 95% CI, 0.20, 3.03) and verbal memory (1.69 years per 1–serving/day increment; 95% CI, 0.13, 3.25; both P = .03).

Participants with processed red meat intake of 0.25 or more serving/day had a 14% higher likelihood of subjective cognitive decline, compared with those with intake less than 0.10 serving/day (odds ratio [OR], 1.14; 95% CI, 1.04-1.24; P = .004). 

For unprocessed red meat, consuming 1.00 or more serving/day versus less than 0.50 serving/day was associated with a 16% higher likelihood of subjective cognitive decline (OR, 1.16; 95% CI, 1.04-1.30; P = .02). 
 

Substitution Analysis

Researchers modeled the effects of replacing 1 serving/day of processed red meat with 1 serving/day of nuts and legumes on cognitive outcomes. They did this by treating food intakes as continuous variables and calculating the differences in coefficients of the two food items.

They found that substituting legumes and nuts was associated with a 23% lower risk for dementia (HR, 0.77; 95% CI, 0.69-0.86), 1.37 fewer years of cognitive aging (95% CI, –2.49 to –0.25), and 20% lower odds of subjective cognitive decline (OR, 0.80, 95% CI, 0.69-0.92).

The research cannot determine whether it’s the processing method itself or the type of red meat that affects cognition, Ms. Li cautioned. 

“Our study is an epidemiologic study, not a biological mechanism study, but based on our findings, red meat may be related to worse cognition, and processed red meat may add additional risk,” she said. 

She also noted that because the study focused solely on red meats, the study cannot determine the potential on the impact of other processed meats on cognition.

Although the study doesn’t address a possible mechanism linking processed red meat with cognition, Ms. Li said it’s possible such meats have high levels of relatively harmful substances, such as nitrites, N-nitroso compounds, and sodium, and that “these carry the additional risk to brain health.”

There are currently no specific guidelines regarding the “safe” amount of processed meat consumption specifically related to cognition, she said.

The study is important because of its large sample size, long follow-up period, and inclusion of repeated measurements of diet, the investigators noted. In addition, researchers assessed both processed and unprocessed red meat and evaluated multiple cognitive outcomes.

The investigators plan to assess the association between other modifiable factors and cognitive health.
 

Experts Weigh In 

In a comment, Claire Sexton, DPhil, senior director of scientific programs and outreach at the Alzheimer’s Association, agreed past studies on the topic have been “mixed,” with only some studies reporting links between cognition or dementia and processed red meat. 

Another unique aspect of the study, said Dr. Sexton, was the replacement analysis showing the brain benefits of eating nuts and legumes in place of processed red meat. “So, it’s not just suggesting to people what not to do, but also what they can be doing instead.”

That’s why this large study with more than 130,000 adults that tracked individuals for close to 40 years in some cases “is so valuable,” she added.

In a release from the Science Media Centre in the United Kingdom, several other experts commented on the study. Among them, Kevin McConway, PhD, emeritus professor of applied statistics at the Open University, Milton Keynes, England, said that “it’s pretty well impossible to get a clear message from the information that is available so far about this research. It is a conference paper, and all we have seen so far is a press release, a brief summary of the research, and a diagram. There isn’t a detailed, peer-reviewed research report, not yet anyway. Putting out limited information like this isn’t the right way to report science.”

Dr. McConway also noted that the observational study recorded participants’ diets and dementia diagnoses over several years without assigning specific diets. Those who ate more red processed meat had higher rates of dementia and cognitive decline. However, it’s unclear if these differences are caused by red meat consumption or other factors, such as diet, age, ethnicity, or location.

Researchers typically adjust for these factors, but the available information doesn’t specify what adjustments were made or their impact, he noted, and without detailed data, it’s impossible to evaluate the study’s quality. Although eating more red processed meat might increase dementia risk, more research is needed to confirm this, Dr. McConway added. 

Also commenting, Sebastian Walsh, a National Institute for Health and Care Research doctoral fellow who researches population-level approaches to dementia risk reduction at University of Cambridge, Cambridge, England, said that without seeing the full paper, it’s difficult to know exactly what to make of the study’s findings. 

“On the surface, this is a large and long study. But it isn’t clear how the analysis was done — specifically what other factors were taken into account when looking at this apparent relationship between red meat and dementia.

“Despite a lot of research looking at specific foods and different diseases, the basic public health advice that eating a healthy, balanced diet is good for health is essentially unchanged. Most people know and accept this. What is most important is to find ways of supporting people, particularly those from poorer backgrounds, to follow this advice and address the obesity epidemic,” said Mr. Walsh. 

The study was funded by a National Institutes of Health research grant. Ms. Li reports no relevant conflicts of interest. Dr. Sexton, Dr. McConway, and Mr. Walsh report no relevant disclosures.

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

Plasma phosphorylated (p)-tau217 testing can help identify preclinical Alzheimer’s disease, which could aid clinical trial recruitment.

Recruiting preclinical Alzheimer’s disease participants for clinical research is challenging, owing to a lack of symptoms and the high cost and invasiveness of cerebrospinal fluid (CSF) tests and brain amyloid PET imaging.

Plasma p-tau217 has consistently shown high performance in detecting Alzheimer’s disease pathology in patients with mild cognitive impairment and dementia, but there has been concern that it may have lower accuracy in cognitively unimpaired adults, said lead investigator Gemma Salvadó, PhD, with the Clinical Memory Research Unit, Lund University, Lund, Sweden.

However, “our study shows that plasma p-tau217, alone or in combination with invasive tests, can be used accurately to assess amyloid positivity in cognitively unimpaired participants, to streamline the inclusion of these participants in preventive clinical trials,” she said. 

The findings were presented at the 2024 Alzheimer’s Association International Conference (AAIC).
 

Correlation to CSF, PET Amyloid Status

The investigators assessed the clinical accuracy of plasma p-tau217 as a prescreening method in 2917 cognitively unimpaired adults (mean age, 67 years; 57% women) across 12 independent cohorts who had available plasma p-tau217 and amyloid beta PET imaging or CSF samples. 

They found that plasma p-tau217 levels correlated with amyloid beta CSF status and PET load. 

As a standalone test, plasma p-tau217 identified amyloid beta PET–positive cognitively normal adults with a positive predictive value of 80% or greater. 

The positive predictive value increased to 95% or greater when amyloid beta CSF or PET was used to confirm a positive plasma p-tau217 result. 

As a first step, plasma p-tau217 could significantly reduce the number of invasive tests performed because only individuals with a positive p-tau217 test would go on to PET imaging or CSF sampling, Dr. Salvadó told conference attendees. This may reduce trial recruitment costs and get more patients enrolled. 

Although the study had a large sample size, “these results should be replicated in independent studies, [in] more heterogeneous participants, and coming from the clinical setting instead of observational studies to avoid possible bias,” Dr. Salvadó added. 
 

A New Diagnostic Era 

Commenting on the research, Heather Snyder, PhD, vice president of medical and scientific relations at the Alzheimer’s Association, said what’s particularly interesting about this study is that the researchers examined multiple cohorts of cognitively unimpaired individuals and “consistently” found that plasma p-tau217 could identify individuals with amyloid-positive PET and CSF with high accuracy. 

“This may reduce the need for more expensive and more invasive scans or lumbar punctures to confirm if an individual has the biology,” Dr. Snyder said. 

“Blood tests are revolutionizing Alzheimer’s detection, diagnosis and ultimately treatment,” added Howard Fillit, MD, cofounder and chief science officer of the Alzheimer’s Drug Discovery Foundation. 

He predicted that blood tests will “soon replace more invasive and costly PET scans as the standard of care and serve as the first line of defense in diagnosing the disease.”

“After many years of research, the field is in a place where we have novel biomarkers and diagnostics to support a diagnosis,” the way cholesterol is used to help detect heart disease, said Dr. Fillit. 

“The diagnostic framework for Alzheimer’s — an incredibly complex disease — is constantly evolving. As we usher in the new era of care, we are moving closer to the day when blood tests will be complemented by digital tools to provide precise and timely diagnoses and risk assessments backed by numerous data points, complementing existing cognitive tests,” he added. 

Funding for the study was provided by the Alzheimer’s Association, the European Union’s Horizon 2020 Research and Innovation Program, Alzheimerfonden, and Strategic Research Area MultiPark. Dr. Salvadó, Dr. Snyder, and Dr. Fillit have no relevant disclosures.

A version of this article appeared on Medscape.com.

Plasma phosphorylated (p)-tau217 testing can help identify preclinical Alzheimer’s disease, which could aid clinical trial recruitment.

Recruiting preclinical Alzheimer’s disease participants for clinical research is challenging, owing to a lack of symptoms and the high cost and invasiveness of cerebrospinal fluid (CSF) tests and brain amyloid PET imaging.

Plasma p-tau217 has consistently shown high performance in detecting Alzheimer’s disease pathology in patients with mild cognitive impairment and dementia, but there has been concern that it may have lower accuracy in cognitively unimpaired adults, said lead investigator Gemma Salvadó, PhD, with the Clinical Memory Research Unit, Lund University, Lund, Sweden.

However, “our study shows that plasma p-tau217, alone or in combination with invasive tests, can be used accurately to assess amyloid positivity in cognitively unimpaired participants, to streamline the inclusion of these participants in preventive clinical trials,” she said. 

The findings were presented at the 2024 Alzheimer’s Association International Conference (AAIC).
 

Correlation to CSF, PET Amyloid Status

The investigators assessed the clinical accuracy of plasma p-tau217 as a prescreening method in 2917 cognitively unimpaired adults (mean age, 67 years; 57% women) across 12 independent cohorts who had available plasma p-tau217 and amyloid beta PET imaging or CSF samples. 

They found that plasma p-tau217 levels correlated with amyloid beta CSF status and PET load. 

As a standalone test, plasma p-tau217 identified amyloid beta PET–positive cognitively normal adults with a positive predictive value of 80% or greater. 

The positive predictive value increased to 95% or greater when amyloid beta CSF or PET was used to confirm a positive plasma p-tau217 result. 

As a first step, plasma p-tau217 could significantly reduce the number of invasive tests performed because only individuals with a positive p-tau217 test would go on to PET imaging or CSF sampling, Dr. Salvadó told conference attendees. This may reduce trial recruitment costs and get more patients enrolled. 

Although the study had a large sample size, “these results should be replicated in independent studies, [in] more heterogeneous participants, and coming from the clinical setting instead of observational studies to avoid possible bias,” Dr. Salvadó added. 
 

A New Diagnostic Era 

Commenting on the research, Heather Snyder, PhD, vice president of medical and scientific relations at the Alzheimer’s Association, said what’s particularly interesting about this study is that the researchers examined multiple cohorts of cognitively unimpaired individuals and “consistently” found that plasma p-tau217 could identify individuals with amyloid-positive PET and CSF with high accuracy. 

“This may reduce the need for more expensive and more invasive scans or lumbar punctures to confirm if an individual has the biology,” Dr. Snyder said. 

“Blood tests are revolutionizing Alzheimer’s detection, diagnosis and ultimately treatment,” added Howard Fillit, MD, cofounder and chief science officer of the Alzheimer’s Drug Discovery Foundation. 

He predicted that blood tests will “soon replace more invasive and costly PET scans as the standard of care and serve as the first line of defense in diagnosing the disease.”

“After many years of research, the field is in a place where we have novel biomarkers and diagnostics to support a diagnosis,” the way cholesterol is used to help detect heart disease, said Dr. Fillit. 

“The diagnostic framework for Alzheimer’s — an incredibly complex disease — is constantly evolving. As we usher in the new era of care, we are moving closer to the day when blood tests will be complemented by digital tools to provide precise and timely diagnoses and risk assessments backed by numerous data points, complementing existing cognitive tests,” he added. 

Funding for the study was provided by the Alzheimer’s Association, the European Union’s Horizon 2020 Research and Innovation Program, Alzheimerfonden, and Strategic Research Area MultiPark. Dr. Salvadó, Dr. Snyder, and Dr. Fillit have no relevant disclosures.

A version of this article appeared on Medscape.com.

Plasma phosphorylated (p)-tau217 testing can help identify preclinical Alzheimer’s disease, which could aid clinical trial recruitment.

Recruiting preclinical Alzheimer’s disease participants for clinical research is challenging, owing to a lack of symptoms and the high cost and invasiveness of cerebrospinal fluid (CSF) tests and brain amyloid PET imaging.

Plasma p-tau217 has consistently shown high performance in detecting Alzheimer’s disease pathology in patients with mild cognitive impairment and dementia, but there has been concern that it may have lower accuracy in cognitively unimpaired adults, said lead investigator Gemma Salvadó, PhD, with the Clinical Memory Research Unit, Lund University, Lund, Sweden.

However, “our study shows that plasma p-tau217, alone or in combination with invasive tests, can be used accurately to assess amyloid positivity in cognitively unimpaired participants, to streamline the inclusion of these participants in preventive clinical trials,” she said. 

The findings were presented at the 2024 Alzheimer’s Association International Conference (AAIC).
 

Correlation to CSF, PET Amyloid Status

The investigators assessed the clinical accuracy of plasma p-tau217 as a prescreening method in 2917 cognitively unimpaired adults (mean age, 67 years; 57% women) across 12 independent cohorts who had available plasma p-tau217 and amyloid beta PET imaging or CSF samples. 

They found that plasma p-tau217 levels correlated with amyloid beta CSF status and PET load. 

As a standalone test, plasma p-tau217 identified amyloid beta PET–positive cognitively normal adults with a positive predictive value of 80% or greater. 

The positive predictive value increased to 95% or greater when amyloid beta CSF or PET was used to confirm a positive plasma p-tau217 result. 

As a first step, plasma p-tau217 could significantly reduce the number of invasive tests performed because only individuals with a positive p-tau217 test would go on to PET imaging or CSF sampling, Dr. Salvadó told conference attendees. This may reduce trial recruitment costs and get more patients enrolled. 

Although the study had a large sample size, “these results should be replicated in independent studies, [in] more heterogeneous participants, and coming from the clinical setting instead of observational studies to avoid possible bias,” Dr. Salvadó added. 
 

A New Diagnostic Era 

Commenting on the research, Heather Snyder, PhD, vice president of medical and scientific relations at the Alzheimer’s Association, said what’s particularly interesting about this study is that the researchers examined multiple cohorts of cognitively unimpaired individuals and “consistently” found that plasma p-tau217 could identify individuals with amyloid-positive PET and CSF with high accuracy. 

“This may reduce the need for more expensive and more invasive scans or lumbar punctures to confirm if an individual has the biology,” Dr. Snyder said. 

“Blood tests are revolutionizing Alzheimer’s detection, diagnosis and ultimately treatment,” added Howard Fillit, MD, cofounder and chief science officer of the Alzheimer’s Drug Discovery Foundation. 

He predicted that blood tests will “soon replace more invasive and costly PET scans as the standard of care and serve as the first line of defense in diagnosing the disease.”

“After many years of research, the field is in a place where we have novel biomarkers and diagnostics to support a diagnosis,” the way cholesterol is used to help detect heart disease, said Dr. Fillit. 

“The diagnostic framework for Alzheimer’s — an incredibly complex disease — is constantly evolving. As we usher in the new era of care, we are moving closer to the day when blood tests will be complemented by digital tools to provide precise and timely diagnoses and risk assessments backed by numerous data points, complementing existing cognitive tests,” he added. 

Funding for the study was provided by the Alzheimer’s Association, the European Union’s Horizon 2020 Research and Innovation Program, Alzheimerfonden, and Strategic Research Area MultiPark. Dr. Salvadó, Dr. Snyder, and Dr. Fillit have no relevant disclosures.

A version of this article appeared on Medscape.com.

Fecal microbiota transplantation (FMT) for Parkinson’s disease is safe but does not offer clinically meaningful improvement in symptoms, results of a new, randomized placebo-controlled trial show.

However, investigators discovered some interesting insights from the study, which they believe may help in designing future “improved, and hopefully successful, trials” with the intervention.

“Further studies — for example, through modified fecal microbiota transplantation approaches or bowel cleansing — are warranted,” they concluded. 

The study was published online in JAMA Neurology. 
 

Gut Dysfunction: An Early Symptom

Investigators led by Filip Scheperjans, MD, Helsinki University Hospital, Finland, explained that gut dysfunction is a prevalent, early symptom in Parkinson’s disease and is associated with more rapid disease progression. 

Interventions targeting gut microbiota, such as FMT, have shown promising symptomatic, and potentially neuroprotective, effects in animal models of Parkinson’s disease. 

Although several randomized clinical trials suggest efficacy of probiotics for Parkinson’s disease-related constipation, only limited clinical information on FMT is available.

In the current trial, 48 patients with Parkinson’s disease aged 35-75 years with mild to moderate symptoms and dysbiosis of fecal microbiota were randomized in a 2:1 ratio to receive FMT or placebo infused into the cecum via colonoscopy.  

All patients had whole-bowel lavage starting the day before the colonoscopy. Fecal microbiota transplantation was administered as a single-dose and without antibiotic pretreatment. 

Active treatment was a freeze-stored preparation of 30 g of feces from one of two donors who were healthy individuals without dysbiosis. The preparation was mixed with 150 mL of sterile physiologic saline and 20 mL of 85% glycerol for cryoprotection to improve viability of microbes. Placebo was the carrier solution alone, consisting of 180 mL of sterile physiologic saline and 20 mL of 85% glycerol.

The primary endpoint, a change in Parkinson’s disease symptoms as assessed on the Unified Parkinson’s Disease Rating Scale (UPDRS) at 6 months, did not differ between the two study groups.

Gastrointestinal adverse events were more frequent in the FMT group, occurring in 16 patients (53%) versus one patient (7%) in the placebo group. But no major safety concerns were observed.

Secondary outcomes and post hoc analyses showed a greater increase in dopaminergic medication, which may indicate faster disease progression, but also improvement in certain motor and nonmotor outcomes in the placebo group. 

Microbiota changes were more pronounced after FMT, but dysbiosis status was reversed more frequently in the placebo group. 

The researchers noted that the apparent futility in this trial is in contrast to several previous small clinical studies of fecal transplant that have suggested the potential for improvement of Parkinson’s disease symptoms. 

In addition, encouraging results from the probiotics field suggest that an impact on motor and nonmotor Parkinson’s disease symptoms through gut microbiota manipulation is possible. 

The researchers raised the possibility that the placebo procedure was not an inert comparator, given the relatively strong and sustained gut microbiota alteration and dysbiosis conversion observed in the placebo group, and suggested that the colonic cleansing procedure may also have had some beneficial effect. 

“It seems possible that, after cleansing of a dysbiotic gut microbiota, recolonization leads to a more physiologic gut microbiota composition with symptom improvement in the placebo group. This warrants further exploration of modified fecal microbiota transplantation approaches and bowel cleansing in Parkinson’s disease,” they concluded. 
 

Distinct Gut Microbiome 

In an accompanying editorial, Timothy R. Sampson, PhD, assistant professor, Department of Cell Biology, Emory University School of Medicine, Atlanta, pointed out that dozens of independent studies have now demonstrated a distinct gut microbiome composition associated with Parkinson’s disease, and experimental data suggest that this has the capacity to incite inflammatory responses; degrade intestinal mucosa; and dysregulate a number of neuroactive and amyloidogenic molecules, which could contribute to the disease. 

He noted that three other small placebo-controlled studies of fecal transplantation in Parkinson’s disease showed slightly more robust responses in the active treatment group, including improvements in UPDRS scores and gastrointestinal symptoms.

However, these studies tested different FMT procedures, including lyophilized oral capsules given at different dosing frequencies and either nasojejunal or colonic transfusion following a standard bowel preparation.

In addition, there is no consensus on pretransplant procedures, such as antibiotics or bowel clearance, and the choice of donor microbiome is probably essential, because there may be certain microbes required to shift the entire community, Dr. Sampson wrote. 

Understanding how microbial contributions directly relate to Parkinson’s disease would identify individuals more likely to respond to peripheral interventions, and further exploration is needed to shed light on particular microbes that warrant targeting for either enrichment or depletion, he added. 

“Despite a lack of primary end point efficacy in this latest study, in-depth comparison across these studies may reveal opportunities to refine fecal microbiota transplantation approaches. Together, these studies will continue to refine the hypothesis of a microbial contribution to Parkinson’s disease and reveal new therapeutic avenues,” Dr. Sampson concluded.
 

‘Planting Grass in a Yard Full of Weeds’

Commenting on the research, James Beck, PhD, chief scientific officer of the Parkinson’s Foundation, New York, said that whether FMT are helpful remains to be determined. 

“The key question that needs to be solved is how to best perform these transplants. One issue is that you cannot plant grass when the yard is full of weeds. However, if you take too hard an approach killing the weeds — that is, with powerful antibiotics — you jeopardize the new grass, or in this case, the bacteria in the transplant. Solving that issue will be important as we consider whether this is effective or not.”

Dr. Beck added that there is still much to be learned from research into the gut microbiota. “I am hopeful with additional effort we will have answers soon.”
 

A version of this article appeared on Medscape.com.

Fecal microbiota transplantation (FMT) for Parkinson’s disease is safe but does not offer clinically meaningful improvement in symptoms, results of a new, randomized placebo-controlled trial show.

However, investigators discovered some interesting insights from the study, which they believe may help in designing future “improved, and hopefully successful, trials” with the intervention.

“Further studies — for example, through modified fecal microbiota transplantation approaches or bowel cleansing — are warranted,” they concluded. 

The study was published online in JAMA Neurology. 
 

Gut Dysfunction: An Early Symptom

Investigators led by Filip Scheperjans, MD, Helsinki University Hospital, Finland, explained that gut dysfunction is a prevalent, early symptom in Parkinson’s disease and is associated with more rapid disease progression. 

Interventions targeting gut microbiota, such as FMT, have shown promising symptomatic, and potentially neuroprotective, effects in animal models of Parkinson’s disease. 

Although several randomized clinical trials suggest efficacy of probiotics for Parkinson’s disease-related constipation, only limited clinical information on FMT is available.

In the current trial, 48 patients with Parkinson’s disease aged 35-75 years with mild to moderate symptoms and dysbiosis of fecal microbiota were randomized in a 2:1 ratio to receive FMT or placebo infused into the cecum via colonoscopy.  

All patients had whole-bowel lavage starting the day before the colonoscopy. Fecal microbiota transplantation was administered as a single-dose and without antibiotic pretreatment. 

Active treatment was a freeze-stored preparation of 30 g of feces from one of two donors who were healthy individuals without dysbiosis. The preparation was mixed with 150 mL of sterile physiologic saline and 20 mL of 85% glycerol for cryoprotection to improve viability of microbes. Placebo was the carrier solution alone, consisting of 180 mL of sterile physiologic saline and 20 mL of 85% glycerol.

The primary endpoint, a change in Parkinson’s disease symptoms as assessed on the Unified Parkinson’s Disease Rating Scale (UPDRS) at 6 months, did not differ between the two study groups.

Gastrointestinal adverse events were more frequent in the FMT group, occurring in 16 patients (53%) versus one patient (7%) in the placebo group. But no major safety concerns were observed.

Secondary outcomes and post hoc analyses showed a greater increase in dopaminergic medication, which may indicate faster disease progression, but also improvement in certain motor and nonmotor outcomes in the placebo group. 

Microbiota changes were more pronounced after FMT, but dysbiosis status was reversed more frequently in the placebo group. 

The researchers noted that the apparent futility in this trial is in contrast to several previous small clinical studies of fecal transplant that have suggested the potential for improvement of Parkinson’s disease symptoms. 

In addition, encouraging results from the probiotics field suggest that an impact on motor and nonmotor Parkinson’s disease symptoms through gut microbiota manipulation is possible. 

The researchers raised the possibility that the placebo procedure was not an inert comparator, given the relatively strong and sustained gut microbiota alteration and dysbiosis conversion observed in the placebo group, and suggested that the colonic cleansing procedure may also have had some beneficial effect. 

“It seems possible that, after cleansing of a dysbiotic gut microbiota, recolonization leads to a more physiologic gut microbiota composition with symptom improvement in the placebo group. This warrants further exploration of modified fecal microbiota transplantation approaches and bowel cleansing in Parkinson’s disease,” they concluded. 
 

Distinct Gut Microbiome 

In an accompanying editorial, Timothy R. Sampson, PhD, assistant professor, Department of Cell Biology, Emory University School of Medicine, Atlanta, pointed out that dozens of independent studies have now demonstrated a distinct gut microbiome composition associated with Parkinson’s disease, and experimental data suggest that this has the capacity to incite inflammatory responses; degrade intestinal mucosa; and dysregulate a number of neuroactive and amyloidogenic molecules, which could contribute to the disease. 

He noted that three other small placebo-controlled studies of fecal transplantation in Parkinson’s disease showed slightly more robust responses in the active treatment group, including improvements in UPDRS scores and gastrointestinal symptoms.

However, these studies tested different FMT procedures, including lyophilized oral capsules given at different dosing frequencies and either nasojejunal or colonic transfusion following a standard bowel preparation.

In addition, there is no consensus on pretransplant procedures, such as antibiotics or bowel clearance, and the choice of donor microbiome is probably essential, because there may be certain microbes required to shift the entire community, Dr. Sampson wrote. 

Understanding how microbial contributions directly relate to Parkinson’s disease would identify individuals more likely to respond to peripheral interventions, and further exploration is needed to shed light on particular microbes that warrant targeting for either enrichment or depletion, he added. 

“Despite a lack of primary end point efficacy in this latest study, in-depth comparison across these studies may reveal opportunities to refine fecal microbiota transplantation approaches. Together, these studies will continue to refine the hypothesis of a microbial contribution to Parkinson’s disease and reveal new therapeutic avenues,” Dr. Sampson concluded.
 

‘Planting Grass in a Yard Full of Weeds’

Commenting on the research, James Beck, PhD, chief scientific officer of the Parkinson’s Foundation, New York, said that whether FMT are helpful remains to be determined. 

“The key question that needs to be solved is how to best perform these transplants. One issue is that you cannot plant grass when the yard is full of weeds. However, if you take too hard an approach killing the weeds — that is, with powerful antibiotics — you jeopardize the new grass, or in this case, the bacteria in the transplant. Solving that issue will be important as we consider whether this is effective or not.”

Dr. Beck added that there is still much to be learned from research into the gut microbiota. “I am hopeful with additional effort we will have answers soon.”
 

A version of this article appeared on Medscape.com.

Fecal microbiota transplantation (FMT) for Parkinson’s disease is safe but does not offer clinically meaningful improvement in symptoms, results of a new, randomized placebo-controlled trial show.

However, investigators discovered some interesting insights from the study, which they believe may help in designing future “improved, and hopefully successful, trials” with the intervention.

“Further studies — for example, through modified fecal microbiota transplantation approaches or bowel cleansing — are warranted,” they concluded. 

The study was published online in JAMA Neurology. 
 

Gut Dysfunction: An Early Symptom

Investigators led by Filip Scheperjans, MD, Helsinki University Hospital, Finland, explained that gut dysfunction is a prevalent, early symptom in Parkinson’s disease and is associated with more rapid disease progression. 

Interventions targeting gut microbiota, such as FMT, have shown promising symptomatic, and potentially neuroprotective, effects in animal models of Parkinson’s disease. 

Although several randomized clinical trials suggest efficacy of probiotics for Parkinson’s disease-related constipation, only limited clinical information on FMT is available.

In the current trial, 48 patients with Parkinson’s disease aged 35-75 years with mild to moderate symptoms and dysbiosis of fecal microbiota were randomized in a 2:1 ratio to receive FMT or placebo infused into the cecum via colonoscopy.  

All patients had whole-bowel lavage starting the day before the colonoscopy. Fecal microbiota transplantation was administered as a single-dose and without antibiotic pretreatment. 

Active treatment was a freeze-stored preparation of 30 g of feces from one of two donors who were healthy individuals without dysbiosis. The preparation was mixed with 150 mL of sterile physiologic saline and 20 mL of 85% glycerol for cryoprotection to improve viability of microbes. Placebo was the carrier solution alone, consisting of 180 mL of sterile physiologic saline and 20 mL of 85% glycerol.

The primary endpoint, a change in Parkinson’s disease symptoms as assessed on the Unified Parkinson’s Disease Rating Scale (UPDRS) at 6 months, did not differ between the two study groups.

Gastrointestinal adverse events were more frequent in the FMT group, occurring in 16 patients (53%) versus one patient (7%) in the placebo group. But no major safety concerns were observed.

Secondary outcomes and post hoc analyses showed a greater increase in dopaminergic medication, which may indicate faster disease progression, but also improvement in certain motor and nonmotor outcomes in the placebo group. 

Microbiota changes were more pronounced after FMT, but dysbiosis status was reversed more frequently in the placebo group. 

The researchers noted that the apparent futility in this trial is in contrast to several previous small clinical studies of fecal transplant that have suggested the potential for improvement of Parkinson’s disease symptoms. 

In addition, encouraging results from the probiotics field suggest that an impact on motor and nonmotor Parkinson’s disease symptoms through gut microbiota manipulation is possible. 

The researchers raised the possibility that the placebo procedure was not an inert comparator, given the relatively strong and sustained gut microbiota alteration and dysbiosis conversion observed in the placebo group, and suggested that the colonic cleansing procedure may also have had some beneficial effect. 

“It seems possible that, after cleansing of a dysbiotic gut microbiota, recolonization leads to a more physiologic gut microbiota composition with symptom improvement in the placebo group. This warrants further exploration of modified fecal microbiota transplantation approaches and bowel cleansing in Parkinson’s disease,” they concluded. 
 

Distinct Gut Microbiome 

In an accompanying editorial, Timothy R. Sampson, PhD, assistant professor, Department of Cell Biology, Emory University School of Medicine, Atlanta, pointed out that dozens of independent studies have now demonstrated a distinct gut microbiome composition associated with Parkinson’s disease, and experimental data suggest that this has the capacity to incite inflammatory responses; degrade intestinal mucosa; and dysregulate a number of neuroactive and amyloidogenic molecules, which could contribute to the disease. 

He noted that three other small placebo-controlled studies of fecal transplantation in Parkinson’s disease showed slightly more robust responses in the active treatment group, including improvements in UPDRS scores and gastrointestinal symptoms.

However, these studies tested different FMT procedures, including lyophilized oral capsules given at different dosing frequencies and either nasojejunal or colonic transfusion following a standard bowel preparation.

In addition, there is no consensus on pretransplant procedures, such as antibiotics or bowel clearance, and the choice of donor microbiome is probably essential, because there may be certain microbes required to shift the entire community, Dr. Sampson wrote. 

Understanding how microbial contributions directly relate to Parkinson’s disease would identify individuals more likely to respond to peripheral interventions, and further exploration is needed to shed light on particular microbes that warrant targeting for either enrichment or depletion, he added. 

“Despite a lack of primary end point efficacy in this latest study, in-depth comparison across these studies may reveal opportunities to refine fecal microbiota transplantation approaches. Together, these studies will continue to refine the hypothesis of a microbial contribution to Parkinson’s disease and reveal new therapeutic avenues,” Dr. Sampson concluded.
 

‘Planting Grass in a Yard Full of Weeds’

Commenting on the research, James Beck, PhD, chief scientific officer of the Parkinson’s Foundation, New York, said that whether FMT are helpful remains to be determined. 

“The key question that needs to be solved is how to best perform these transplants. One issue is that you cannot plant grass when the yard is full of weeds. However, if you take too hard an approach killing the weeds — that is, with powerful antibiotics — you jeopardize the new grass, or in this case, the bacteria in the transplant. Solving that issue will be important as we consider whether this is effective or not.”

Dr. Beck added that there is still much to be learned from research into the gut microbiota. “I am hopeful with additional effort we will have answers soon.”
 

A version of this article appeared on Medscape.com.