Alzheimer's & Cognition

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

The study was published online in BMJ Medicine.
 

Naturally randomized research

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

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

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

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

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

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

Genetic proxy

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

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

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

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

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

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

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

The findings remained “consistent” in sensitivity analyses.
 

A modifiable risk factor?

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

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

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

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

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

Novel strategies

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

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

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

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

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

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

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

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

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

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

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

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

The study was published online in BMJ Medicine.
 

Naturally randomized research

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

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

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

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

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

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

Genetic proxy

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

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

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

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

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

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

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

The findings remained “consistent” in sensitivity analyses.
 

A modifiable risk factor?

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

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

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

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

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

Novel strategies

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

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

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

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

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

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

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

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

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

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

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

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

The study was published online in BMJ Medicine.
 

Naturally randomized research

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

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

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

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

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

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

Genetic proxy

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

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

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

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

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

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

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

The findings remained “consistent” in sensitivity analyses.
 

A modifiable risk factor?

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

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

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

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

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

Novel strategies

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

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

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

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

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

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

Roche has received Food and Drug Administration 510(k) clearance for additional cerebrospinal fluid (CSF) assays for Alzheimer’s disease (AD), supporting timely diagnosis and treatment decision-making.

The Elecsys beta-amyloid (1-42) CSF II (Abeta42) and Elecsys total-tau CSF assays (tTau) (used as a tTau/Abeta42 ratio) are for use in adults ages 55 and older being evaluated for AD.

They join the Elecsys beta-amyloid (1-42) CSF II (Abeta42) and Elecsys phospho-tau (181P) CSF (pTau181) assays (used as a pTau181/Abeta42 ratio) that received FDA 510(k) clearance in 2022.

Olivier Le Moal/Getty Images

“An early and accurate diagnosis can help patients, caregivers and physicians determine a path forward, and the Elecsys CSF assays support diagnosis at early disease stages, when treatment is most effective,” Brad Moore, president and CEO of Roche Diagnostics North America, said in a statement.

Appropriate use recommendations for new and emerging AD drugs call for confirmation of amyloid pathology. Currently, the only FDA-cleared methods to confirm amyloid pathology are CSF tests and PET scans.

“The Elecsys AD CSF assays are concordant with amyloid PET scan imaging and have the potential to provide a more affordable and accessible routine option to confirm the presence of amyloid pathology in the brain,” Roche said.

“They also offer detection of both amyloid and tau biomarkers from one draw, with no radiation and potential to detect Alzheimer’s pathology in early stages of disease,” the company added.

The previously approved Elecsys pTau181/Abeta42 ratio is currently available and the newly approved Elecsys tTau/Abeta42 ratio will be available in the fourth quarter of 2023.

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

Roche has received Food and Drug Administration 510(k) clearance for additional cerebrospinal fluid (CSF) assays for Alzheimer’s disease (AD), supporting timely diagnosis and treatment decision-making.

The Elecsys beta-amyloid (1-42) CSF II (Abeta42) and Elecsys total-tau CSF assays (tTau) (used as a tTau/Abeta42 ratio) are for use in adults ages 55 and older being evaluated for AD.

They join the Elecsys beta-amyloid (1-42) CSF II (Abeta42) and Elecsys phospho-tau (181P) CSF (pTau181) assays (used as a pTau181/Abeta42 ratio) that received FDA 510(k) clearance in 2022.

Olivier Le Moal/Getty Images

“An early and accurate diagnosis can help patients, caregivers and physicians determine a path forward, and the Elecsys CSF assays support diagnosis at early disease stages, when treatment is most effective,” Brad Moore, president and CEO of Roche Diagnostics North America, said in a statement.

Appropriate use recommendations for new and emerging AD drugs call for confirmation of amyloid pathology. Currently, the only FDA-cleared methods to confirm amyloid pathology are CSF tests and PET scans.

“The Elecsys AD CSF assays are concordant with amyloid PET scan imaging and have the potential to provide a more affordable and accessible routine option to confirm the presence of amyloid pathology in the brain,” Roche said.

“They also offer detection of both amyloid and tau biomarkers from one draw, with no radiation and potential to detect Alzheimer’s pathology in early stages of disease,” the company added.

The previously approved Elecsys pTau181/Abeta42 ratio is currently available and the newly approved Elecsys tTau/Abeta42 ratio will be available in the fourth quarter of 2023.

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

Roche has received Food and Drug Administration 510(k) clearance for additional cerebrospinal fluid (CSF) assays for Alzheimer’s disease (AD), supporting timely diagnosis and treatment decision-making.

The Elecsys beta-amyloid (1-42) CSF II (Abeta42) and Elecsys total-tau CSF assays (tTau) (used as a tTau/Abeta42 ratio) are for use in adults ages 55 and older being evaluated for AD.

They join the Elecsys beta-amyloid (1-42) CSF II (Abeta42) and Elecsys phospho-tau (181P) CSF (pTau181) assays (used as a pTau181/Abeta42 ratio) that received FDA 510(k) clearance in 2022.

Olivier Le Moal/Getty Images

“An early and accurate diagnosis can help patients, caregivers and physicians determine a path forward, and the Elecsys CSF assays support diagnosis at early disease stages, when treatment is most effective,” Brad Moore, president and CEO of Roche Diagnostics North America, said in a statement.

Appropriate use recommendations for new and emerging AD drugs call for confirmation of amyloid pathology. Currently, the only FDA-cleared methods to confirm amyloid pathology are CSF tests and PET scans.

“The Elecsys AD CSF assays are concordant with amyloid PET scan imaging and have the potential to provide a more affordable and accessible routine option to confirm the presence of amyloid pathology in the brain,” Roche said.

“They also offer detection of both amyloid and tau biomarkers from one draw, with no radiation and potential to detect Alzheimer’s pathology in early stages of disease,” the company added.

The previously approved Elecsys pTau181/Abeta42 ratio is currently available and the newly approved Elecsys tTau/Abeta42 ratio will be available in the fourth quarter of 2023.

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

A new study provides reassurance about the safety of long-term proton pump inhibitor (PPIs) and histamine-2 receptor antagonist (H2RA) use in older adults, finding no increased risk for dementia or cognitive changes.

It was published online in Gastroenterology.

The post hoc observational study was led by Raaj Mehta, MD, PhD, with Massachusetts General Hospital and Harvard Medical School in Boston.

The researchers analyzed results from the Aspirin in Reducing Events in the Elderly clinical trial. The randomized trial of aspirin included 18,934 adults aged 65 and older from the United States and Australia. Patients’ use of PPI and H2RA was tracked, along with dementia incidence and cognitive changes.

The results showed that there was no link to new dementia diagnoses in patients who used PPIs (25%) and H2RA (2%) at baseline, versus those who did not use either heartburn medication.

Limitations of prior studies are referenced, including the potential for residual confounding and underestimation of PPI and H2RA use, the lack of data on medication dose and duration, and the absence of apo E4 allele status.

The study was funded by grants from the National Institute on Aging, the National Cancer Institute, and other institutions. Dr. Mehta has disclosed no relevant conflicts of interest.

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

A new study provides reassurance about the safety of long-term proton pump inhibitor (PPIs) and histamine-2 receptor antagonist (H2RA) use in older adults, finding no increased risk for dementia or cognitive changes.

It was published online in Gastroenterology.

The post hoc observational study was led by Raaj Mehta, MD, PhD, with Massachusetts General Hospital and Harvard Medical School in Boston.

The researchers analyzed results from the Aspirin in Reducing Events in the Elderly clinical trial. The randomized trial of aspirin included 18,934 adults aged 65 and older from the United States and Australia. Patients’ use of PPI and H2RA was tracked, along with dementia incidence and cognitive changes.

The results showed that there was no link to new dementia diagnoses in patients who used PPIs (25%) and H2RA (2%) at baseline, versus those who did not use either heartburn medication.

Limitations of prior studies are referenced, including the potential for residual confounding and underestimation of PPI and H2RA use, the lack of data on medication dose and duration, and the absence of apo E4 allele status.

The study was funded by grants from the National Institute on Aging, the National Cancer Institute, and other institutions. Dr. Mehta has disclosed no relevant conflicts of interest.

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

A new study provides reassurance about the safety of long-term proton pump inhibitor (PPIs) and histamine-2 receptor antagonist (H2RA) use in older adults, finding no increased risk for dementia or cognitive changes.

It was published online in Gastroenterology.

The post hoc observational study was led by Raaj Mehta, MD, PhD, with Massachusetts General Hospital and Harvard Medical School in Boston.

The researchers analyzed results from the Aspirin in Reducing Events in the Elderly clinical trial. The randomized trial of aspirin included 18,934 adults aged 65 and older from the United States and Australia. Patients’ use of PPI and H2RA was tracked, along with dementia incidence and cognitive changes.

The results showed that there was no link to new dementia diagnoses in patients who used PPIs (25%) and H2RA (2%) at baseline, versus those who did not use either heartburn medication.

Limitations of prior studies are referenced, including the potential for residual confounding and underestimation of PPI and H2RA use, the lack of data on medication dose and duration, and the absence of apo E4 allele status.

The study was funded by grants from the National Institute on Aging, the National Cancer Institute, and other institutions. Dr. Mehta has disclosed no relevant conflicts of interest.

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

Daily napping may help preserve brain health, new research suggests.

Investigators at University College London, and the University of the Republic of Uruguay, Montevideo, found individuals genetically predisposed to regular napping had larger total brain volume, a surrogate of better cognitive health.

“Our results suggest that napping may improve brain health,” first author Valentina Paz, MSc, a PhD candidate at the University of the Republic of Uruguay said in an interview. “Specifically, our work revealed a 15.8 cubic cm increase in total brain volume with more frequent daytime napping,” she said.

The findings were published online in Sleep Health.
 

Higher brain volume

Previous studies examining the potential link between napping and cognition in older adults have yielded conflicting results.

To clarify this association, Ms. Paz and colleagues used Mendelian randomization to study DNA samples, cognitive outcomes, and functional magnetic resonance imaging data in participants from the ongoing UK Biobank Study.  

Starting with data from 378,932 study participants (mean age 57), investigators compared measures of brain health and cognition of those who are more genetically programmed to nap with people who did not have these genetic variations.

More specifically, the investigators examined 97 sections of genetic code previously linked to the likelihood of regular napping and correlated these results with fMRI and cognitive outcomes between those genetically predisposed to take regular naps and those who weren’t.

Study outcomes included total brain volume, hippocampal volume, reaction time, and visual memory.

The final study sample included 35,080 with neuroimaging, cognitive assessment, and genotype data.

The researchers estimated that the average difference in brain volume between individuals genetically programmed to be habitual nappers and those who were not was equivalent to 15.8 cubic cm, or 2.6-6.5 years of aging.

However, there was no difference in the other three outcomes – hippocampal volume, reaction time, and visual processing – between the two study groups.

Since investigators did not have information on the length of time participants napped, Ms. Paz suggested that “taking a short nap in the early afternoon may help cognition in those needing it.”

However, she added, the study’s findings need to be replicated before any firm conclusions can be made.

“More work is needed to examine the associations between napping and cognition, and the replication of these findings using other datasets and methods,” she said.

The investigators note that the study’s findings augment the knowledge of the “impact of habitual daytime napping on brain health, which is essential to understanding cognitive impairment in the aging population. The lack of evidence for an association between napping and hippocampal volume and cognitive outcomes (for example, alertness) may be affected by habitual daytime napping and should be studied in the future.”
 

Strengths, limitations

Tara Spires-Jones, PhD, president of the British Neuroscience Association and group leader at the UK Dementia Research Institute, said, “the study shows a small but significant increase in brain volume in people who have a genetic signature associated with taking daytime naps.”

Dr. Spires-Jones, who was not involved in the research, noted that while the study is well-conducted, it has limitations. Because Mendelian randomization uses a genetic signature, she noted, outcomes depend on the accuracy of the signature. 

“The napping habits of UK Biobank participants were self-reported, which might not be entirely accurate, and the ‘napping’ signature overlapped substantially with the signature for cognitive outcomes in the study, which makes the causal link weaker,” she said.

“Even with those limitations, this study is interesting because it adds to the data indicating that sleep is important for brain health,” said Dr. Spires-Jones.

The study was supported by Diabetes UK, the British Heart Foundation, and the Diabetes Research and Wellness Foundation. In Uruguay, it was supported by Programa de Desarrollo de las Ciencias Básicas, Agencia Nacional de Investigación e Innovación, Comisión Sectorial de Investigación Científica, and Comisión Académica de Posgrado. In the United States it was supported by the National Heart, Lung, and Blood Institute. There were no disclosures reported.

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

Daily napping may help preserve brain health, new research suggests.

Investigators at University College London, and the University of the Republic of Uruguay, Montevideo, found individuals genetically predisposed to regular napping had larger total brain volume, a surrogate of better cognitive health.

“Our results suggest that napping may improve brain health,” first author Valentina Paz, MSc, a PhD candidate at the University of the Republic of Uruguay said in an interview. “Specifically, our work revealed a 15.8 cubic cm increase in total brain volume with more frequent daytime napping,” she said.

The findings were published online in Sleep Health.
 

Higher brain volume

Previous studies examining the potential link between napping and cognition in older adults have yielded conflicting results.

To clarify this association, Ms. Paz and colleagues used Mendelian randomization to study DNA samples, cognitive outcomes, and functional magnetic resonance imaging data in participants from the ongoing UK Biobank Study.  

Starting with data from 378,932 study participants (mean age 57), investigators compared measures of brain health and cognition of those who are more genetically programmed to nap with people who did not have these genetic variations.

More specifically, the investigators examined 97 sections of genetic code previously linked to the likelihood of regular napping and correlated these results with fMRI and cognitive outcomes between those genetically predisposed to take regular naps and those who weren’t.

Study outcomes included total brain volume, hippocampal volume, reaction time, and visual memory.

The final study sample included 35,080 with neuroimaging, cognitive assessment, and genotype data.

The researchers estimated that the average difference in brain volume between individuals genetically programmed to be habitual nappers and those who were not was equivalent to 15.8 cubic cm, or 2.6-6.5 years of aging.

However, there was no difference in the other three outcomes – hippocampal volume, reaction time, and visual processing – between the two study groups.

Since investigators did not have information on the length of time participants napped, Ms. Paz suggested that “taking a short nap in the early afternoon may help cognition in those needing it.”

However, she added, the study’s findings need to be replicated before any firm conclusions can be made.

“More work is needed to examine the associations between napping and cognition, and the replication of these findings using other datasets and methods,” she said.

The investigators note that the study’s findings augment the knowledge of the “impact of habitual daytime napping on brain health, which is essential to understanding cognitive impairment in the aging population. The lack of evidence for an association between napping and hippocampal volume and cognitive outcomes (for example, alertness) may be affected by habitual daytime napping and should be studied in the future.”
 

Strengths, limitations

Tara Spires-Jones, PhD, president of the British Neuroscience Association and group leader at the UK Dementia Research Institute, said, “the study shows a small but significant increase in brain volume in people who have a genetic signature associated with taking daytime naps.”

Dr. Spires-Jones, who was not involved in the research, noted that while the study is well-conducted, it has limitations. Because Mendelian randomization uses a genetic signature, she noted, outcomes depend on the accuracy of the signature. 

“The napping habits of UK Biobank participants were self-reported, which might not be entirely accurate, and the ‘napping’ signature overlapped substantially with the signature for cognitive outcomes in the study, which makes the causal link weaker,” she said.

“Even with those limitations, this study is interesting because it adds to the data indicating that sleep is important for brain health,” said Dr. Spires-Jones.

The study was supported by Diabetes UK, the British Heart Foundation, and the Diabetes Research and Wellness Foundation. In Uruguay, it was supported by Programa de Desarrollo de las Ciencias Básicas, Agencia Nacional de Investigación e Innovación, Comisión Sectorial de Investigación Científica, and Comisión Académica de Posgrado. In the United States it was supported by the National Heart, Lung, and Blood Institute. There were no disclosures reported.

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

Daily napping may help preserve brain health, new research suggests.

Investigators at University College London, and the University of the Republic of Uruguay, Montevideo, found individuals genetically predisposed to regular napping had larger total brain volume, a surrogate of better cognitive health.

“Our results suggest that napping may improve brain health,” first author Valentina Paz, MSc, a PhD candidate at the University of the Republic of Uruguay said in an interview. “Specifically, our work revealed a 15.8 cubic cm increase in total brain volume with more frequent daytime napping,” she said.

The findings were published online in Sleep Health.
 

Higher brain volume

Previous studies examining the potential link between napping and cognition in older adults have yielded conflicting results.

To clarify this association, Ms. Paz and colleagues used Mendelian randomization to study DNA samples, cognitive outcomes, and functional magnetic resonance imaging data in participants from the ongoing UK Biobank Study.  

Starting with data from 378,932 study participants (mean age 57), investigators compared measures of brain health and cognition of those who are more genetically programmed to nap with people who did not have these genetic variations.

More specifically, the investigators examined 97 sections of genetic code previously linked to the likelihood of regular napping and correlated these results with fMRI and cognitive outcomes between those genetically predisposed to take regular naps and those who weren’t.

Study outcomes included total brain volume, hippocampal volume, reaction time, and visual memory.

The final study sample included 35,080 with neuroimaging, cognitive assessment, and genotype data.

The researchers estimated that the average difference in brain volume between individuals genetically programmed to be habitual nappers and those who were not was equivalent to 15.8 cubic cm, or 2.6-6.5 years of aging.

However, there was no difference in the other three outcomes – hippocampal volume, reaction time, and visual processing – between the two study groups.

Since investigators did not have information on the length of time participants napped, Ms. Paz suggested that “taking a short nap in the early afternoon may help cognition in those needing it.”

However, she added, the study’s findings need to be replicated before any firm conclusions can be made.

“More work is needed to examine the associations between napping and cognition, and the replication of these findings using other datasets and methods,” she said.

The investigators note that the study’s findings augment the knowledge of the “impact of habitual daytime napping on brain health, which is essential to understanding cognitive impairment in the aging population. The lack of evidence for an association between napping and hippocampal volume and cognitive outcomes (for example, alertness) may be affected by habitual daytime napping and should be studied in the future.”
 

Strengths, limitations

Tara Spires-Jones, PhD, president of the British Neuroscience Association and group leader at the UK Dementia Research Institute, said, “the study shows a small but significant increase in brain volume in people who have a genetic signature associated with taking daytime naps.”

Dr. Spires-Jones, who was not involved in the research, noted that while the study is well-conducted, it has limitations. Because Mendelian randomization uses a genetic signature, she noted, outcomes depend on the accuracy of the signature. 

“The napping habits of UK Biobank participants were self-reported, which might not be entirely accurate, and the ‘napping’ signature overlapped substantially with the signature for cognitive outcomes in the study, which makes the causal link weaker,” she said.

“Even with those limitations, this study is interesting because it adds to the data indicating that sleep is important for brain health,” said Dr. Spires-Jones.

The study was supported by Diabetes UK, the British Heart Foundation, and the Diabetes Research and Wellness Foundation. In Uruguay, it was supported by Programa de Desarrollo de las Ciencias Básicas, Agencia Nacional de Investigación e Innovación, Comisión Sectorial de Investigación Científica, and Comisión Académica de Posgrado. In the United States it was supported by the National Heart, Lung, and Blood Institute. There were no disclosures reported.

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

TOPLINE:

A new study provides reassurance about the long-term safety of proton pump inhibitors (PPIs) and histamine-2 receptor antagonist (H2RA) use in older adults, finding no increased risk for dementia or cognitive changes.

METHODOLOGY:

• Post hoc observational study within the Aspirin in Reducing Events in the Elderly (ASPREE) clinical trial.
• 18,934 adults aged 65+ from the United States and Australia without dementia at baseline.
• 4,667 (25%) PPI users and 368 (2%) H2RA users at baseline.
• PPI and H2RA use, dementia incidence, and cognitive changes were tracked.

TAKEAWAY:

• In multivariable analysis, baseline PPI use was not associated with incident dementia (hazard ratio, 0.88) or cognitive impairment (HR, 1.00).
• PPI use was not linked to changes in overall cognitive test scores over time (beta –0.002).
• No associations were found between H2RA use and cognitive endpoints.

IN PRACTICE:

“Long-term use of PPIs in older adults is unlikely to have negative effects on cognition,” the study team concludes.

STUDY DETAILS:

The study was led by Raaj Mehta, MD, PhD, with Massachusetts General Hospital and Harvard Medical School in Boston. The study was published online in Gastroenterology. Funding was provided by grants from the National Institute on Aging, the National Cancer Institute, and other institutions.

LIMITATIONS:

Potential for residual confounding and underestimation of PPI and H2RA use, lack of data on medication dose and duration, and the absence of ApoE4 allele status.

DISCLOSURES:

Dr. Mehta has disclosed no relevant conflicts of interest.

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

TOPLINE:

A new study provides reassurance about the long-term safety of proton pump inhibitors (PPIs) and histamine-2 receptor antagonist (H2RA) use in older adults, finding no increased risk for dementia or cognitive changes.

METHODOLOGY:

• Post hoc observational study within the Aspirin in Reducing Events in the Elderly (ASPREE) clinical trial.
• 18,934 adults aged 65+ from the United States and Australia without dementia at baseline.
• 4,667 (25%) PPI users and 368 (2%) H2RA users at baseline.
• PPI and H2RA use, dementia incidence, and cognitive changes were tracked.

TAKEAWAY:

• In multivariable analysis, baseline PPI use was not associated with incident dementia (hazard ratio, 0.88) or cognitive impairment (HR, 1.00).
• PPI use was not linked to changes in overall cognitive test scores over time (beta –0.002).
• No associations were found between H2RA use and cognitive endpoints.

IN PRACTICE:

“Long-term use of PPIs in older adults is unlikely to have negative effects on cognition,” the study team concludes.

STUDY DETAILS:

The study was led by Raaj Mehta, MD, PhD, with Massachusetts General Hospital and Harvard Medical School in Boston. The study was published online in Gastroenterology. Funding was provided by grants from the National Institute on Aging, the National Cancer Institute, and other institutions.

LIMITATIONS:

Potential for residual confounding and underestimation of PPI and H2RA use, lack of data on medication dose and duration, and the absence of ApoE4 allele status.

DISCLOSURES:

Dr. Mehta has disclosed no relevant conflicts of interest.

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

TOPLINE:

A new study provides reassurance about the long-term safety of proton pump inhibitors (PPIs) and histamine-2 receptor antagonist (H2RA) use in older adults, finding no increased risk for dementia or cognitive changes.

METHODOLOGY:

• Post hoc observational study within the Aspirin in Reducing Events in the Elderly (ASPREE) clinical trial.
• 18,934 adults aged 65+ from the United States and Australia without dementia at baseline.
• 4,667 (25%) PPI users and 368 (2%) H2RA users at baseline.
• PPI and H2RA use, dementia incidence, and cognitive changes were tracked.

TAKEAWAY:

• In multivariable analysis, baseline PPI use was not associated with incident dementia (hazard ratio, 0.88) or cognitive impairment (HR, 1.00).
• PPI use was not linked to changes in overall cognitive test scores over time (beta –0.002).
• No associations were found between H2RA use and cognitive endpoints.

IN PRACTICE:

“Long-term use of PPIs in older adults is unlikely to have negative effects on cognition,” the study team concludes.

STUDY DETAILS:

The study was led by Raaj Mehta, MD, PhD, with Massachusetts General Hospital and Harvard Medical School in Boston. The study was published online in Gastroenterology. Funding was provided by grants from the National Institute on Aging, the National Cancer Institute, and other institutions.

LIMITATIONS:

Potential for residual confounding and underestimation of PPI and H2RA use, lack of data on medication dose and duration, and the absence of ApoE4 allele status.

DISCLOSURES:

Dr. Mehta has disclosed no relevant conflicts of interest.

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

TOPLINE:

Vortioxetine significantly improves depressive symptoms, cognitive performance, functioning, and quality of life at 12 weeks in patients with both major depressive disorder (MDD) and early-stage dementia.

METHODOLOGY:

• The multicenter MEMORY study included 82 subjects with MDD and early-stage dementia, mean age 70.3 years, mostly female (66%) and White (95%).
• Vortioxetine, a modulator of 5-hydroxytryptamine receptor activity and an inhibitor of the 5-HT transporter, initiated at 5 mg/day (recommended starting dose in older adults) with the dose up-titrated to 10 mg/day after a week and flexible dosing thereafter.
• Depression was assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS), and cognition with the Digit Symbol Substitution Test (DSST) and Rey Auditory Verbal Learning Test.

TAKEAWAY:

• There was significant and clinically meaningful improvement in the severity of depressive symptoms, as measured by MADRS total score (the primary outcome), at all assessment time points (P < .0001).
• Improvements in depressive symptoms were irrespective of dementia type.
• There were also significant improvements in DSST total score (P < .0001) and in daily functioning and health-related quality of life (HRQoL).
• Vortioxetine was well tolerated; side effects, including nausea and abdominal pain, were mostly mild to moderate.

IN PRACTICE:

“Vortioxetine demonstrated effectiveness in clinically significantly improving depressive symptoms, cognitive performance, daily and global functioning, and HRQoL in patients with MDD and comorbid early-stage dementia treated for 12 weeks” the researchers noted. 

STUDY DETAILS:

The study was conducted by Michael Cronquist Christensen from pharmaceutical company H. Lundbeck, Valby, Denmark, and colleagues. It was published online in the Journal of Affective Disorders.

LIMITATIONS:

The study is open label and lacked a control group. Learning effects were possible, which could contribute to improved cognitive performance, although significant improvement on the RAVLT was not observed until week 4, suggesting earning effects were minimal.
 

DISCLOSURES:

The study was funded by H. Lundbeck. Mr. Christensen is an employee of H. Lundbeck.

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

TOPLINE:

Vortioxetine significantly improves depressive symptoms, cognitive performance, functioning, and quality of life at 12 weeks in patients with both major depressive disorder (MDD) and early-stage dementia.

METHODOLOGY:

• The multicenter MEMORY study included 82 subjects with MDD and early-stage dementia, mean age 70.3 years, mostly female (66%) and White (95%).
• Vortioxetine, a modulator of 5-hydroxytryptamine receptor activity and an inhibitor of the 5-HT transporter, initiated at 5 mg/day (recommended starting dose in older adults) with the dose up-titrated to 10 mg/day after a week and flexible dosing thereafter.
• Depression was assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS), and cognition with the Digit Symbol Substitution Test (DSST) and Rey Auditory Verbal Learning Test.

TAKEAWAY:

• There was significant and clinically meaningful improvement in the severity of depressive symptoms, as measured by MADRS total score (the primary outcome), at all assessment time points (P < .0001).
• Improvements in depressive symptoms were irrespective of dementia type.
• There were also significant improvements in DSST total score (P < .0001) and in daily functioning and health-related quality of life (HRQoL).
• Vortioxetine was well tolerated; side effects, including nausea and abdominal pain, were mostly mild to moderate.

IN PRACTICE:

“Vortioxetine demonstrated effectiveness in clinically significantly improving depressive symptoms, cognitive performance, daily and global functioning, and HRQoL in patients with MDD and comorbid early-stage dementia treated for 12 weeks” the researchers noted. 

STUDY DETAILS:

The study was conducted by Michael Cronquist Christensen from pharmaceutical company H. Lundbeck, Valby, Denmark, and colleagues. It was published online in the Journal of Affective Disorders.

LIMITATIONS:

The study is open label and lacked a control group. Learning effects were possible, which could contribute to improved cognitive performance, although significant improvement on the RAVLT was not observed until week 4, suggesting earning effects were minimal.
 

DISCLOSURES:

The study was funded by H. Lundbeck. Mr. Christensen is an employee of H. Lundbeck.

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

TOPLINE:

Vortioxetine significantly improves depressive symptoms, cognitive performance, functioning, and quality of life at 12 weeks in patients with both major depressive disorder (MDD) and early-stage dementia.

METHODOLOGY:

• The multicenter MEMORY study included 82 subjects with MDD and early-stage dementia, mean age 70.3 years, mostly female (66%) and White (95%).
• Vortioxetine, a modulator of 5-hydroxytryptamine receptor activity and an inhibitor of the 5-HT transporter, initiated at 5 mg/day (recommended starting dose in older adults) with the dose up-titrated to 10 mg/day after a week and flexible dosing thereafter.
• Depression was assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS), and cognition with the Digit Symbol Substitution Test (DSST) and Rey Auditory Verbal Learning Test.

TAKEAWAY:

• There was significant and clinically meaningful improvement in the severity of depressive symptoms, as measured by MADRS total score (the primary outcome), at all assessment time points (P < .0001).
• Improvements in depressive symptoms were irrespective of dementia type.
• There were also significant improvements in DSST total score (P < .0001) and in daily functioning and health-related quality of life (HRQoL).
• Vortioxetine was well tolerated; side effects, including nausea and abdominal pain, were mostly mild to moderate.

IN PRACTICE:

“Vortioxetine demonstrated effectiveness in clinically significantly improving depressive symptoms, cognitive performance, daily and global functioning, and HRQoL in patients with MDD and comorbid early-stage dementia treated for 12 weeks” the researchers noted. 

STUDY DETAILS:

The study was conducted by Michael Cronquist Christensen from pharmaceutical company H. Lundbeck, Valby, Denmark, and colleagues. It was published online in the Journal of Affective Disorders.

LIMITATIONS:

The study is open label and lacked a control group. Learning effects were possible, which could contribute to improved cognitive performance, although significant improvement on the RAVLT was not observed until week 4, suggesting earning effects were minimal.
 

DISCLOSURES:

The study was funded by H. Lundbeck. Mr. Christensen is an employee of H. Lundbeck.

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

The composition of gut bacteria in people with preclinical Alzheimer’s disease (AD) differs from that of healthy people, a new study shows.

The findings open up the possibility of analyzing the gut microbiome to identify individuals at a higher risk for dementia and perhaps designing microbiome-altering preventive treatments to help stave off cognitive decline, researchers noted.

Study investigator Gautam Dantas, PhD, cautioned that it’s not known whether the gut is influencing the brain, or the brain is influencing the gut, “but this association is valuable to know in either case.

“It could be that the changes in the gut microbiome are just a readout of pathological changes in the brain. The other alternative is that the gut microbiome is contributing to AD, in which case, altering the gut microbiome with probiotics or fecal transfers might help change the course of the disease,” Dr. Dantas, Washington University, St. Louis, said in a news release.

The study was published online in Science Translational Medicine.
 

Stool test?

Multiple lines of evidence suggest a role for gut microbes in the evolution of AD pathogenesis. However, less is known about gut microbiome changes in the preclinical (presymptomatic) phase of AD.

To investigate, Dr. Dantas and colleagues studied 164 cognitively normal adults, 49 of whom had biomarker evidence of preclinical AD.

After the researchers accounted for clinical covariates and diet, those with preclinical AD had distinct gut microbial taxonomic profiles compared with their healthy controls.

The observed microbiome features correlated with amyloid and tau but not neurodegeneration biomarkers, “suggesting that the gut microbial community changes early in the disease process,” the researchers suggested.

They identified specific taxa that were associated with preclinical AD and including these microbiome features improved the accuracy, sensitivity, and specificity of machine learning classifiers for predicting preclinical AD status.

The findings suggest “markers in the stool might complement early screening measures for preclinical AD,” the researchers noted.

“The nice thing about using the gut microbiome as a screening tool is its simplicity and ease,” Beau Ances, MD, PhD, professor of neurology, at Washington University, St. Louis, said in the release.

“One day, individuals may be able to provide a stool sample and find out if they are at increased risk for developing AD. It would be much easier and less invasive and more accessible for a large proportion of the population, especially underrepresented groups, compared to brain scans or spinal taps,” Dr. Ances added.

The researchers have launched a 5-year follow-up study designed to help determine whether the differences in the gut microbiome are a cause or a result of the brain changes seen in early AD.
 

Caveats, cautionary notes

In a comment, Claire Sexton, DPhil, Alzheimer’s Association senior director of scientific programs and outreach, cautioned that the study design means that it’s “not possible to prove one thing causes another. What it can show is that two or more aspects are in some way related, thus setting the stage for further research.”

Dr. Sexton noted that though the authors accounted for a number of variables in their models, including age, sex, race, education, body mass index, hypertension, and diabetes, and observed no differences in intake of any major nutrient group, “it’s still not possible to rule out that additional factors beyond the variations in gut microbiome contributed to the changes in brain markers of Alzheimer’s.”

Dr. Sexton also noted that the study population is not representative of all people living with AD, with the vast majority of those with preclinical AD in the study being White.

“If these findings are replicated and confirmed in study groups that are representative of our communities, it is possible that gut microbiome signatures could be a further addition to the suite of diagnostic tools employed in certain settings,” Dr. Sexton said.

This research was supported by the Infection Disease Society of America Foundation, the National Institute on Aging, the Brennan Fund and the Paula and Rodger Riney Foundation. Dr. Dantas, Dr. Ances and Dr. Sexton have no relevant disclosures.

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

The composition of gut bacteria in people with preclinical Alzheimer’s disease (AD) differs from that of healthy people, a new study shows.

The findings open up the possibility of analyzing the gut microbiome to identify individuals at a higher risk for dementia and perhaps designing microbiome-altering preventive treatments to help stave off cognitive decline, researchers noted.

Study investigator Gautam Dantas, PhD, cautioned that it’s not known whether the gut is influencing the brain, or the brain is influencing the gut, “but this association is valuable to know in either case.

“It could be that the changes in the gut microbiome are just a readout of pathological changes in the brain. The other alternative is that the gut microbiome is contributing to AD, in which case, altering the gut microbiome with probiotics or fecal transfers might help change the course of the disease,” Dr. Dantas, Washington University, St. Louis, said in a news release.

The study was published online in Science Translational Medicine.
 

Stool test?

Multiple lines of evidence suggest a role for gut microbes in the evolution of AD pathogenesis. However, less is known about gut microbiome changes in the preclinical (presymptomatic) phase of AD.

To investigate, Dr. Dantas and colleagues studied 164 cognitively normal adults, 49 of whom had biomarker evidence of preclinical AD.

After the researchers accounted for clinical covariates and diet, those with preclinical AD had distinct gut microbial taxonomic profiles compared with their healthy controls.

The observed microbiome features correlated with amyloid and tau but not neurodegeneration biomarkers, “suggesting that the gut microbial community changes early in the disease process,” the researchers suggested.

They identified specific taxa that were associated with preclinical AD and including these microbiome features improved the accuracy, sensitivity, and specificity of machine learning classifiers for predicting preclinical AD status.

The findings suggest “markers in the stool might complement early screening measures for preclinical AD,” the researchers noted.

“The nice thing about using the gut microbiome as a screening tool is its simplicity and ease,” Beau Ances, MD, PhD, professor of neurology, at Washington University, St. Louis, said in the release.

“One day, individuals may be able to provide a stool sample and find out if they are at increased risk for developing AD. It would be much easier and less invasive and more accessible for a large proportion of the population, especially underrepresented groups, compared to brain scans or spinal taps,” Dr. Ances added.

The researchers have launched a 5-year follow-up study designed to help determine whether the differences in the gut microbiome are a cause or a result of the brain changes seen in early AD.
 

Caveats, cautionary notes

In a comment, Claire Sexton, DPhil, Alzheimer’s Association senior director of scientific programs and outreach, cautioned that the study design means that it’s “not possible to prove one thing causes another. What it can show is that two or more aspects are in some way related, thus setting the stage for further research.”

Dr. Sexton noted that though the authors accounted for a number of variables in their models, including age, sex, race, education, body mass index, hypertension, and diabetes, and observed no differences in intake of any major nutrient group, “it’s still not possible to rule out that additional factors beyond the variations in gut microbiome contributed to the changes in brain markers of Alzheimer’s.”

Dr. Sexton also noted that the study population is not representative of all people living with AD, with the vast majority of those with preclinical AD in the study being White.

“If these findings are replicated and confirmed in study groups that are representative of our communities, it is possible that gut microbiome signatures could be a further addition to the suite of diagnostic tools employed in certain settings,” Dr. Sexton said.

This research was supported by the Infection Disease Society of America Foundation, the National Institute on Aging, the Brennan Fund and the Paula and Rodger Riney Foundation. Dr. Dantas, Dr. Ances and Dr. Sexton have no relevant disclosures.

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

The composition of gut bacteria in people with preclinical Alzheimer’s disease (AD) differs from that of healthy people, a new study shows.

The findings open up the possibility of analyzing the gut microbiome to identify individuals at a higher risk for dementia and perhaps designing microbiome-altering preventive treatments to help stave off cognitive decline, researchers noted.

Study investigator Gautam Dantas, PhD, cautioned that it’s not known whether the gut is influencing the brain, or the brain is influencing the gut, “but this association is valuable to know in either case.

“It could be that the changes in the gut microbiome are just a readout of pathological changes in the brain. The other alternative is that the gut microbiome is contributing to AD, in which case, altering the gut microbiome with probiotics or fecal transfers might help change the course of the disease,” Dr. Dantas, Washington University, St. Louis, said in a news release.

The study was published online in Science Translational Medicine.
 

Stool test?

Multiple lines of evidence suggest a role for gut microbes in the evolution of AD pathogenesis. However, less is known about gut microbiome changes in the preclinical (presymptomatic) phase of AD.

To investigate, Dr. Dantas and colleagues studied 164 cognitively normal adults, 49 of whom had biomarker evidence of preclinical AD.

After the researchers accounted for clinical covariates and diet, those with preclinical AD had distinct gut microbial taxonomic profiles compared with their healthy controls.

The observed microbiome features correlated with amyloid and tau but not neurodegeneration biomarkers, “suggesting that the gut microbial community changes early in the disease process,” the researchers suggested.

They identified specific taxa that were associated with preclinical AD and including these microbiome features improved the accuracy, sensitivity, and specificity of machine learning classifiers for predicting preclinical AD status.

The findings suggest “markers in the stool might complement early screening measures for preclinical AD,” the researchers noted.

“The nice thing about using the gut microbiome as a screening tool is its simplicity and ease,” Beau Ances, MD, PhD, professor of neurology, at Washington University, St. Louis, said in the release.

“One day, individuals may be able to provide a stool sample and find out if they are at increased risk for developing AD. It would be much easier and less invasive and more accessible for a large proportion of the population, especially underrepresented groups, compared to brain scans or spinal taps,” Dr. Ances added.

The researchers have launched a 5-year follow-up study designed to help determine whether the differences in the gut microbiome are a cause or a result of the brain changes seen in early AD.
 

Caveats, cautionary notes

In a comment, Claire Sexton, DPhil, Alzheimer’s Association senior director of scientific programs and outreach, cautioned that the study design means that it’s “not possible to prove one thing causes another. What it can show is that two or more aspects are in some way related, thus setting the stage for further research.”

Dr. Sexton noted that though the authors accounted for a number of variables in their models, including age, sex, race, education, body mass index, hypertension, and diabetes, and observed no differences in intake of any major nutrient group, “it’s still not possible to rule out that additional factors beyond the variations in gut microbiome contributed to the changes in brain markers of Alzheimer’s.”

Dr. Sexton also noted that the study population is not representative of all people living with AD, with the vast majority of those with preclinical AD in the study being White.

“If these findings are replicated and confirmed in study groups that are representative of our communities, it is possible that gut microbiome signatures could be a further addition to the suite of diagnostic tools employed in certain settings,” Dr. Sexton said.

This research was supported by the Infection Disease Society of America Foundation, the National Institute on Aging, the Brennan Fund and the Paula and Rodger Riney Foundation. Dr. Dantas, Dr. Ances and Dr. Sexton have no relevant disclosures.

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

Patients with persistent depressive or cognitive symptoms after mild to moderate COVID-19 (COVID-DC) may have gliosis and inflammation, data suggest.

In a case-control study of 40 patients who were treated at a tertiary care psychiatric hospital in Canada, the level of translocator protein total distribution volume (TSPO VT), a marker of gliosis, was 9.23 mL/cm³ among patients with COVID-DC and 7.72 mL/cm³ among control persons. Differences were particularly notable in the ventral striatum and dorsal putamen.

“Most theories assume there is inflammation in the brain [with] long COVID,” but that assumption had not been studied, author Jeffrey H. Meyer, MD, PhD, Canada Research Chair in Neurochemistry of Major Depressive Disorder at the University of Toronto, said in an interview. “Such information is pivotal to developing treatments.”

The study was published online in JAMA Psychiatry.
 

Quantifiable marker

The investigators sought to determine whether levels of TSPO VT, which are quantifiable with PET, are elevated in the dorsal putamen, ventral striatum, prefrontal cortex, anterior cingulate cortex, and hippocampus of patients with COVID-DC, compared with patients without this syndrome. These brain regions were chosen, according to the authors, “because injury in these regions, which can cause gliosis, also induces symptoms of COVID-DC.”

The study was conducted from April 2021 through June 30, 2022. The investigators compared levels of TSPO VT in the selected brain regions of 20 participants with COVID-DC (mean age, 32.7 years; 60% women) with that of 20 control persons (mean age, 33.3 years; 55% women). TSPO VT was measured with fluorine F18–labeled N-(2-(2-fluoroethoxy)benzyl)-N-(4-phenoxypyridin-3-yl)acetamide PET.

The difference in TSPO VT was most noticeable in the ventral striatum (mean difference, 1.97 mL/cm³) and dorsal putamen (mean difference, 1.70 mL/cm³). The study authors suggest that gliosis in these areas may explain some of the persistent symptoms reported in structured clinical interviews and assessed on neuropsychological and psychological testing.

For patients with COVID-DC, motor speed on the finger-tapping test was negatively associated with dorsal putamen TSPO VT (r, −0.53). The 10 participants with COVID-DC whose speed was lowest had higher mean dorsal putamen TSPO VT levels than those of control persons by 2.3 mL/cm³.

The investigators could not assess a possible association between the ventral striatum TSPO VT and anhedonia because all participants had these symptoms. No significant correlations were found between depression and TSPO VT in the prefrontal cortex or anterior cingulate cortex.

The authors acknowledged that the study was cross-sectional, and so the duration of persistently elevated TSPO VT is not yet known. In addition, elevation in TSPO VT is not completely specific to glial cells, and although correlations with finger-tapping test performance reflect associations between brain changes and symptoms, they do not prove cause and effect.

“Presently, clinicians can use treatments for symptoms in other illnesses that are [also] common with long COVID. We need better than this,” said Dr. Meyer. “Clients with long COVID should be able to state their symptoms, and the practitioner should have an evidence-based matching treatment to recommend.”

Research is ongoing. “We are acquiring more information regarding different types of inflammation in the brain, whether there is ongoing injury, and whether treatments that influence inflammation are helpful,” said Dr. Meyer.
 

Jigsaw puzzle

“While this is an important piece in the jigsaw puzzle of neuroinflammation in chronic neurological disease, it is important to keep in mind that we still lack understanding of the complex picture for several reasons,” Alexander Gerhard, MD, honorary senior lecturer in neuroscience at the University of Manchester, England, wrote in an accompanying editorial.

Among these reasons is that the PET technique used in the study is noisy and not restricted to glial cells, he wrote. TSPO expression is only one part of the brain’s neuroinflammatory response, but PET techniques “do not currently allow us to distinguish between different states of microglial activation.” In addition, “a much more detailed understanding of microglial activation at different time points” is needed before neuroinflammatory changes can be targeted therapeutically, Dr. Gerhard wrote.

In a comment, Vilma Gabbay, MD, professor of psychiatry and neuroscience and director of biomarkers and dimensional psychiatry in the Psychiatry Research Institute at Montefiore Einstein, Albert Einstein College of Medicine, New York, said that “this is an important initial step to better understand the neuropsychiatric consequences of COVID even in only a mild and moderate viral illness.” TSPO imaging through PET scanning has been used as an index for neuroinflammation and gliosis. Researchers have used it to study neurodegenerative diseases, but as the authors noted, the ligand is not specific for gliosis.

“Follow-up large cohort studies including other measures of neuroimaging modalities assessing circuitry and neurochemistry are needed,” she said. “Similarly, studying the blood-brain barrier will also allow us to better understand how the immune reaction in the blood transitions to the brain.”

This field of research is evolving, and clinical trials are ongoing, Dr. Gabbay added. Meanwhile, clinicians should monitor for, assess, and treat neuropsychiatric symptoms and “follow the literature for new research and management recommendations.”

The study was primarily funded by a Canadian Institutes of Health Research Project grant to the authors, with some funding from the Canadian Institute for Military and Veteran Health Research. Dr. Meyer received support from their Canada Research Chair awards and received grants and support from several pharmaceutical companies outside of the submitted work. Dr. Gerhard and Dr. Gabbay disclosed no relevant financial relationships.

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

Patients with persistent depressive or cognitive symptoms after mild to moderate COVID-19 (COVID-DC) may have gliosis and inflammation, data suggest.

In a case-control study of 40 patients who were treated at a tertiary care psychiatric hospital in Canada, the level of translocator protein total distribution volume (TSPO VT), a marker of gliosis, was 9.23 mL/cm³ among patients with COVID-DC and 7.72 mL/cm³ among control persons. Differences were particularly notable in the ventral striatum and dorsal putamen.

“Most theories assume there is inflammation in the brain [with] long COVID,” but that assumption had not been studied, author Jeffrey H. Meyer, MD, PhD, Canada Research Chair in Neurochemistry of Major Depressive Disorder at the University of Toronto, said in an interview. “Such information is pivotal to developing treatments.”

The study was published online in JAMA Psychiatry.
 

Quantifiable marker

The investigators sought to determine whether levels of TSPO VT, which are quantifiable with PET, are elevated in the dorsal putamen, ventral striatum, prefrontal cortex, anterior cingulate cortex, and hippocampus of patients with COVID-DC, compared with patients without this syndrome. These brain regions were chosen, according to the authors, “because injury in these regions, which can cause gliosis, also induces symptoms of COVID-DC.”

The study was conducted from April 2021 through June 30, 2022. The investigators compared levels of TSPO VT in the selected brain regions of 20 participants with COVID-DC (mean age, 32.7 years; 60% women) with that of 20 control persons (mean age, 33.3 years; 55% women). TSPO VT was measured with fluorine F18–labeled N-(2-(2-fluoroethoxy)benzyl)-N-(4-phenoxypyridin-3-yl)acetamide PET.

The difference in TSPO VT was most noticeable in the ventral striatum (mean difference, 1.97 mL/cm³) and dorsal putamen (mean difference, 1.70 mL/cm³). The study authors suggest that gliosis in these areas may explain some of the persistent symptoms reported in structured clinical interviews and assessed on neuropsychological and psychological testing.

For patients with COVID-DC, motor speed on the finger-tapping test was negatively associated with dorsal putamen TSPO VT (r, −0.53). The 10 participants with COVID-DC whose speed was lowest had higher mean dorsal putamen TSPO VT levels than those of control persons by 2.3 mL/cm³.

The investigators could not assess a possible association between the ventral striatum TSPO VT and anhedonia because all participants had these symptoms. No significant correlations were found between depression and TSPO VT in the prefrontal cortex or anterior cingulate cortex.

The authors acknowledged that the study was cross-sectional, and so the duration of persistently elevated TSPO VT is not yet known. In addition, elevation in TSPO VT is not completely specific to glial cells, and although correlations with finger-tapping test performance reflect associations between brain changes and symptoms, they do not prove cause and effect.

“Presently, clinicians can use treatments for symptoms in other illnesses that are [also] common with long COVID. We need better than this,” said Dr. Meyer. “Clients with long COVID should be able to state their symptoms, and the practitioner should have an evidence-based matching treatment to recommend.”

Research is ongoing. “We are acquiring more information regarding different types of inflammation in the brain, whether there is ongoing injury, and whether treatments that influence inflammation are helpful,” said Dr. Meyer.
 

Jigsaw puzzle

“While this is an important piece in the jigsaw puzzle of neuroinflammation in chronic neurological disease, it is important to keep in mind that we still lack understanding of the complex picture for several reasons,” Alexander Gerhard, MD, honorary senior lecturer in neuroscience at the University of Manchester, England, wrote in an accompanying editorial.

Among these reasons is that the PET technique used in the study is noisy and not restricted to glial cells, he wrote. TSPO expression is only one part of the brain’s neuroinflammatory response, but PET techniques “do not currently allow us to distinguish between different states of microglial activation.” In addition, “a much more detailed understanding of microglial activation at different time points” is needed before neuroinflammatory changes can be targeted therapeutically, Dr. Gerhard wrote.

In a comment, Vilma Gabbay, MD, professor of psychiatry and neuroscience and director of biomarkers and dimensional psychiatry in the Psychiatry Research Institute at Montefiore Einstein, Albert Einstein College of Medicine, New York, said that “this is an important initial step to better understand the neuropsychiatric consequences of COVID even in only a mild and moderate viral illness.” TSPO imaging through PET scanning has been used as an index for neuroinflammation and gliosis. Researchers have used it to study neurodegenerative diseases, but as the authors noted, the ligand is not specific for gliosis.

“Follow-up large cohort studies including other measures of neuroimaging modalities assessing circuitry and neurochemistry are needed,” she said. “Similarly, studying the blood-brain barrier will also allow us to better understand how the immune reaction in the blood transitions to the brain.”

This field of research is evolving, and clinical trials are ongoing, Dr. Gabbay added. Meanwhile, clinicians should monitor for, assess, and treat neuropsychiatric symptoms and “follow the literature for new research and management recommendations.”

The study was primarily funded by a Canadian Institutes of Health Research Project grant to the authors, with some funding from the Canadian Institute for Military and Veteran Health Research. Dr. Meyer received support from their Canada Research Chair awards and received grants and support from several pharmaceutical companies outside of the submitted work. Dr. Gerhard and Dr. Gabbay disclosed no relevant financial relationships.

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

Patients with persistent depressive or cognitive symptoms after mild to moderate COVID-19 (COVID-DC) may have gliosis and inflammation, data suggest.

In a case-control study of 40 patients who were treated at a tertiary care psychiatric hospital in Canada, the level of translocator protein total distribution volume (TSPO VT), a marker of gliosis, was 9.23 mL/cm³ among patients with COVID-DC and 7.72 mL/cm³ among control persons. Differences were particularly notable in the ventral striatum and dorsal putamen.

“Most theories assume there is inflammation in the brain [with] long COVID,” but that assumption had not been studied, author Jeffrey H. Meyer, MD, PhD, Canada Research Chair in Neurochemistry of Major Depressive Disorder at the University of Toronto, said in an interview. “Such information is pivotal to developing treatments.”

The study was published online in JAMA Psychiatry.
 

Quantifiable marker

The investigators sought to determine whether levels of TSPO VT, which are quantifiable with PET, are elevated in the dorsal putamen, ventral striatum, prefrontal cortex, anterior cingulate cortex, and hippocampus of patients with COVID-DC, compared with patients without this syndrome. These brain regions were chosen, according to the authors, “because injury in these regions, which can cause gliosis, also induces symptoms of COVID-DC.”

The study was conducted from April 2021 through June 30, 2022. The investigators compared levels of TSPO VT in the selected brain regions of 20 participants with COVID-DC (mean age, 32.7 years; 60% women) with that of 20 control persons (mean age, 33.3 years; 55% women). TSPO VT was measured with fluorine F18–labeled N-(2-(2-fluoroethoxy)benzyl)-N-(4-phenoxypyridin-3-yl)acetamide PET.

The difference in TSPO VT was most noticeable in the ventral striatum (mean difference, 1.97 mL/cm³) and dorsal putamen (mean difference, 1.70 mL/cm³). The study authors suggest that gliosis in these areas may explain some of the persistent symptoms reported in structured clinical interviews and assessed on neuropsychological and psychological testing.

For patients with COVID-DC, motor speed on the finger-tapping test was negatively associated with dorsal putamen TSPO VT (r, −0.53). The 10 participants with COVID-DC whose speed was lowest had higher mean dorsal putamen TSPO VT levels than those of control persons by 2.3 mL/cm³.

The investigators could not assess a possible association between the ventral striatum TSPO VT and anhedonia because all participants had these symptoms. No significant correlations were found between depression and TSPO VT in the prefrontal cortex or anterior cingulate cortex.

The authors acknowledged that the study was cross-sectional, and so the duration of persistently elevated TSPO VT is not yet known. In addition, elevation in TSPO VT is not completely specific to glial cells, and although correlations with finger-tapping test performance reflect associations between brain changes and symptoms, they do not prove cause and effect.

“Presently, clinicians can use treatments for symptoms in other illnesses that are [also] common with long COVID. We need better than this,” said Dr. Meyer. “Clients with long COVID should be able to state their symptoms, and the practitioner should have an evidence-based matching treatment to recommend.”

Research is ongoing. “We are acquiring more information regarding different types of inflammation in the brain, whether there is ongoing injury, and whether treatments that influence inflammation are helpful,” said Dr. Meyer.
 

Jigsaw puzzle

“While this is an important piece in the jigsaw puzzle of neuroinflammation in chronic neurological disease, it is important to keep in mind that we still lack understanding of the complex picture for several reasons,” Alexander Gerhard, MD, honorary senior lecturer in neuroscience at the University of Manchester, England, wrote in an accompanying editorial.

Among these reasons is that the PET technique used in the study is noisy and not restricted to glial cells, he wrote. TSPO expression is only one part of the brain’s neuroinflammatory response, but PET techniques “do not currently allow us to distinguish between different states of microglial activation.” In addition, “a much more detailed understanding of microglial activation at different time points” is needed before neuroinflammatory changes can be targeted therapeutically, Dr. Gerhard wrote.

In a comment, Vilma Gabbay, MD, professor of psychiatry and neuroscience and director of biomarkers and dimensional psychiatry in the Psychiatry Research Institute at Montefiore Einstein, Albert Einstein College of Medicine, New York, said that “this is an important initial step to better understand the neuropsychiatric consequences of COVID even in only a mild and moderate viral illness.” TSPO imaging through PET scanning has been used as an index for neuroinflammation and gliosis. Researchers have used it to study neurodegenerative diseases, but as the authors noted, the ligand is not specific for gliosis.

“Follow-up large cohort studies including other measures of neuroimaging modalities assessing circuitry and neurochemistry are needed,” she said. “Similarly, studying the blood-brain barrier will also allow us to better understand how the immune reaction in the blood transitions to the brain.”

This field of research is evolving, and clinical trials are ongoing, Dr. Gabbay added. Meanwhile, clinicians should monitor for, assess, and treat neuropsychiatric symptoms and “follow the literature for new research and management recommendations.”

The study was primarily funded by a Canadian Institutes of Health Research Project grant to the authors, with some funding from the Canadian Institute for Military and Veteran Health Research. Dr. Meyer received support from their Canada Research Chair awards and received grants and support from several pharmaceutical companies outside of the submitted work. Dr. Gerhard and Dr. Gabbay disclosed no relevant financial relationships.

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

MADRID – Recent research has confirmed the impact of periodontitis on risk of neurologic diseases, especially the increased risks for stroke and Alzheimer’s disease.

The Spanish Society of Dentistry and Osseointegration (SEPA) and the Spanish Society of Neurology (SEN) recently released a report with the latest data on this topic. The report reviews, updates, and presents the most recent scientific evidence regarding this link. It also provides practical recommendations that, on the basis of the evidence, should be applied in dental clinics and neurology centers.

As Yago Leira, DDS, PhD, periodontist and coordinator of the SEPA-SEN working group, told this news organization, “The main takeaway from this scientific report is that patients with periodontitis are at nearly twice the risk of developing Alzheimer’s disease and at triple the risk of ischemic stroke.”

Data from the report show that individuals with periodontitis are at 2.8 times’ higher risk of ischemic stroke. The available evidence regarding hemorrhagic stroke, however, is conflicting.

How does this dental condition affect the course of cardiovascular disease? Observational studies have shown that those who have had an ischemic stroke and have a confirmed diagnosis of periodontitis are at greater risk of suffering a recurrent vascular event, worse neurologic deficit, and postictal depression than are patients without periodontitis.
 

Immune‐mediated inflammation

As far as its link to Alzheimer’s disease, meta-analyses of epidemiologic studies show that periodontitis is associated with a 1.7 times greater risk of this type of dementia and that the risk triples among patients with more serious forms of periodontitis.

Likewise, studies suggest that individuals with dementia or neurocognitive impairment are at a greater risk of suffering periodontitis. Other studies indicate that individuals with periodontitis have worse outcomes on various neuropsychological tests of cognitive function.

The current report presents the evidence from three clearly defined perspectives: The epidemiologic association between periodontitis and these neurologic diseases, the biological mechanisms that may explain this link, and interventional studies of dental treatment as a means of preventing stroke and Alzheimer’s disease.

“There is a possible biological explanation for these epidemiological findings. The report concludes that the low-grade chronic, systemic, immune-mediated inflammatory response induced by the bacteria and their endotoxins and the proinflammatory mediators circulating through the blood contributes to various biological processes that are involved in neurological impairment and cerebral ischemia,” said Dr. Leira, one of the report’s authors.

Ana Frank, MD, PhD, another author of this study, is head of the neurology department at the La Paz University Hospital in Madrid and a member of the SEPA-SEN group. She said in an interview that the main biological mechanism in stroke and Alzheimer’s disease is chronic exposure of the entire brain (vasculature, neurons, and astrocytes) to the harmful effects of periodontal infection. “Although low in intensity, this [exposure] is sufficient to set off a series of events that eventually lead to vascular endothelial injury, changes to neurons and astrocytes, and damage to the neuropil.”

As far as the evidence of an epidemiologic association between periodontitis and both neurologic diseases, Dr. Frank cited the exponential increase in risk brought on by periodontitis. She said that further epidemiologic studies are necessary to gain a better understanding of the magnitude of the problem.
 

A preventive alternative?

Dr. Leira cited evidence that periodontal treatment could provide a means of preventing stroke and dementia. He pointed out that numerous population studies have observed various oral health interventions (e.g., periodic dental prophylaxis or periodontal treatment) and regular dental visits to reduce the risk of developing dementia and stroke. “However, we don’t currently have randomized clinical trials that were designed to investigate whether periodontal treatment may be a primary or a secondary preventive measure against these neurological conditions.”

According to Dr. Leira, “There are currently several research groups in the United States and Europe, including ours, that are performing clinical trials to assess the impact of periodontal treatment on recurrent vascular events in patients with cerebrovascular disease.

“On the other hand, there are various interventional studies underway that are evaluating the potential effect of periodontal treatment on cognitive function in patients with dementia. Along these lines, there appear to be encouraging results from the 1-year follow-up in the GAIN study, which was a phase 2/3 clinical trial testing atuzaginstat. Atuzaginstat is an inhibitor of gingipain, the endotoxin produced by Porphyromonas gingivalis, which is one of the bacteria thought to be responsible for periodontitis. The drug reduces neurocognitive impairment in patients with high levels of antibodies against this periodontal pathogen.”
 

Toward clinical practice

The report has a practical focus. The intention is that this evidence will make its way into recommendations for dentists to implement in clinical practice, especially with elderly patients or patients with risk factors for stroke.

In this regard, Dr. Leira said, “On one hand, dentists have to know how to approach patients who have already suffered a stroke (most of whom have vascular risk factors like diabetes and hypertension), many of whom have polypharmacy and are [taking] certain drugs like blood thinners that could negatively impact various dental procedures. In such cases, it is important to maintain direct contact with a neurologist, since these patients ought to be treated with a multidisciplinary approach.

“On the other hand, each patient who comes to the dental office and has a diagnosis of periodontitis could be screened to identify potential vascular risk factors, even though the definitive diagnosis would need to be given by a specialist physician. To this end, SEPA is carrying out the Promosalud (“Health Promotion”) project, which will soon be applied in a large number of dental clinics in Spain,” added Dr. Leira.

“Lastly, specialists in odontology must understand the potential positive benefits surrounding systemic vascular inflammation that periodontal treatment could provide, including, for example, metabolic control and lowering blood pressure.”

For patients with cognitive impairment, the authors of the report recommended adhering to the following steps during dental visits: Inform the patient and the patient’s caregiver about the importance of good dental hygiene and monitor for any signs of infection or dental disease; address pain in every patient with cognitive impairment and dental problems, especially those with agitation, even if the patient isn’t specifically complaining of pain (also, try not to give opioids); finally, avoid sedation as much as possible and use the smallest effective dose if it becomes necessary.
 

Prescribe oral hygiene

Regarding recommendations that neurologists should follow during consultations in light of the link between these diseases and periodontitis, Dr. Frank said, “Regardless of how old our patients are, I believe it’s important to emphasize the importance of practicing good oral and dental hygiene. It’s a good strategy to put this in writing in medical reports, alongside the usual recommendations about healthy lifestyle habits and monitoring for diseases like high blood pressure, diabetes, or dyslipidemia. These, among other factors like smoking, a sedentary lifestyle, alcoholism, and other drug addictions, are vascular risk factors and are therefore risk factors for stroke and dementia.”

According to Dr. Frank, the public is largely unaware of the relationship between periodontitis and incident neurologic diseases. “We still have a long way to go before we can say that the public is aware of this potential link. And not just the public, either. I believe we must stress among our colleagues and among health care professionals in general the importance of promoting dental health to improve people’s overall health.”

In this regard, Dr. Leira emphasized the authors’ intention to make this report available not only to oral health and neurologic health care professionals but also to primary care physicians and nurses so that patients with cerebrovascular disease or Alzheimer’s disease and their caregivers can develop a greater awareness and thereby improve prevention.

“This study will also provide the scientific basis to support the SEPA-SEN working group as they implement their future activities and projects,” Dr. Leira concluded.

Dr. Leira and Dr. Frank have disclosed no relevant financial relationships.
 

This article was translated from the Medscape Spanish Edition. A version of this article appeared on Medscape.com.

MADRID – Recent research has confirmed the impact of periodontitis on risk of neurologic diseases, especially the increased risks for stroke and Alzheimer’s disease.

The Spanish Society of Dentistry and Osseointegration (SEPA) and the Spanish Society of Neurology (SEN) recently released a report with the latest data on this topic. The report reviews, updates, and presents the most recent scientific evidence regarding this link. It also provides practical recommendations that, on the basis of the evidence, should be applied in dental clinics and neurology centers.

As Yago Leira, DDS, PhD, periodontist and coordinator of the SEPA-SEN working group, told this news organization, “The main takeaway from this scientific report is that patients with periodontitis are at nearly twice the risk of developing Alzheimer’s disease and at triple the risk of ischemic stroke.”

Data from the report show that individuals with periodontitis are at 2.8 times’ higher risk of ischemic stroke. The available evidence regarding hemorrhagic stroke, however, is conflicting.

How does this dental condition affect the course of cardiovascular disease? Observational studies have shown that those who have had an ischemic stroke and have a confirmed diagnosis of periodontitis are at greater risk of suffering a recurrent vascular event, worse neurologic deficit, and postictal depression than are patients without periodontitis.
 

Immune‐mediated inflammation

As far as its link to Alzheimer’s disease, meta-analyses of epidemiologic studies show that periodontitis is associated with a 1.7 times greater risk of this type of dementia and that the risk triples among patients with more serious forms of periodontitis.

Likewise, studies suggest that individuals with dementia or neurocognitive impairment are at a greater risk of suffering periodontitis. Other studies indicate that individuals with periodontitis have worse outcomes on various neuropsychological tests of cognitive function.

The current report presents the evidence from three clearly defined perspectives: The epidemiologic association between periodontitis and these neurologic diseases, the biological mechanisms that may explain this link, and interventional studies of dental treatment as a means of preventing stroke and Alzheimer’s disease.

“There is a possible biological explanation for these epidemiological findings. The report concludes that the low-grade chronic, systemic, immune-mediated inflammatory response induced by the bacteria and their endotoxins and the proinflammatory mediators circulating through the blood contributes to various biological processes that are involved in neurological impairment and cerebral ischemia,” said Dr. Leira, one of the report’s authors.

Ana Frank, MD, PhD, another author of this study, is head of the neurology department at the La Paz University Hospital in Madrid and a member of the SEPA-SEN group. She said in an interview that the main biological mechanism in stroke and Alzheimer’s disease is chronic exposure of the entire brain (vasculature, neurons, and astrocytes) to the harmful effects of periodontal infection. “Although low in intensity, this [exposure] is sufficient to set off a series of events that eventually lead to vascular endothelial injury, changes to neurons and astrocytes, and damage to the neuropil.”

As far as the evidence of an epidemiologic association between periodontitis and both neurologic diseases, Dr. Frank cited the exponential increase in risk brought on by periodontitis. She said that further epidemiologic studies are necessary to gain a better understanding of the magnitude of the problem.
 

A preventive alternative?

Dr. Leira cited evidence that periodontal treatment could provide a means of preventing stroke and dementia. He pointed out that numerous population studies have observed various oral health interventions (e.g., periodic dental prophylaxis or periodontal treatment) and regular dental visits to reduce the risk of developing dementia and stroke. “However, we don’t currently have randomized clinical trials that were designed to investigate whether periodontal treatment may be a primary or a secondary preventive measure against these neurological conditions.”

According to Dr. Leira, “There are currently several research groups in the United States and Europe, including ours, that are performing clinical trials to assess the impact of periodontal treatment on recurrent vascular events in patients with cerebrovascular disease.

“On the other hand, there are various interventional studies underway that are evaluating the potential effect of periodontal treatment on cognitive function in patients with dementia. Along these lines, there appear to be encouraging results from the 1-year follow-up in the GAIN study, which was a phase 2/3 clinical trial testing atuzaginstat. Atuzaginstat is an inhibitor of gingipain, the endotoxin produced by Porphyromonas gingivalis, which is one of the bacteria thought to be responsible for periodontitis. The drug reduces neurocognitive impairment in patients with high levels of antibodies against this periodontal pathogen.”
 

Toward clinical practice

The report has a practical focus. The intention is that this evidence will make its way into recommendations for dentists to implement in clinical practice, especially with elderly patients or patients with risk factors for stroke.

In this regard, Dr. Leira said, “On one hand, dentists have to know how to approach patients who have already suffered a stroke (most of whom have vascular risk factors like diabetes and hypertension), many of whom have polypharmacy and are [taking] certain drugs like blood thinners that could negatively impact various dental procedures. In such cases, it is important to maintain direct contact with a neurologist, since these patients ought to be treated with a multidisciplinary approach.

“On the other hand, each patient who comes to the dental office and has a diagnosis of periodontitis could be screened to identify potential vascular risk factors, even though the definitive diagnosis would need to be given by a specialist physician. To this end, SEPA is carrying out the Promosalud (“Health Promotion”) project, which will soon be applied in a large number of dental clinics in Spain,” added Dr. Leira.

“Lastly, specialists in odontology must understand the potential positive benefits surrounding systemic vascular inflammation that periodontal treatment could provide, including, for example, metabolic control and lowering blood pressure.”

For patients with cognitive impairment, the authors of the report recommended adhering to the following steps during dental visits: Inform the patient and the patient’s caregiver about the importance of good dental hygiene and monitor for any signs of infection or dental disease; address pain in every patient with cognitive impairment and dental problems, especially those with agitation, even if the patient isn’t specifically complaining of pain (also, try not to give opioids); finally, avoid sedation as much as possible and use the smallest effective dose if it becomes necessary.
 

Prescribe oral hygiene

Regarding recommendations that neurologists should follow during consultations in light of the link between these diseases and periodontitis, Dr. Frank said, “Regardless of how old our patients are, I believe it’s important to emphasize the importance of practicing good oral and dental hygiene. It’s a good strategy to put this in writing in medical reports, alongside the usual recommendations about healthy lifestyle habits and monitoring for diseases like high blood pressure, diabetes, or dyslipidemia. These, among other factors like smoking, a sedentary lifestyle, alcoholism, and other drug addictions, are vascular risk factors and are therefore risk factors for stroke and dementia.”

According to Dr. Frank, the public is largely unaware of the relationship between periodontitis and incident neurologic diseases. “We still have a long way to go before we can say that the public is aware of this potential link. And not just the public, either. I believe we must stress among our colleagues and among health care professionals in general the importance of promoting dental health to improve people’s overall health.”

In this regard, Dr. Leira emphasized the authors’ intention to make this report available not only to oral health and neurologic health care professionals but also to primary care physicians and nurses so that patients with cerebrovascular disease or Alzheimer’s disease and their caregivers can develop a greater awareness and thereby improve prevention.

“This study will also provide the scientific basis to support the SEPA-SEN working group as they implement their future activities and projects,” Dr. Leira concluded.

Dr. Leira and Dr. Frank have disclosed no relevant financial relationships.
 

This article was translated from the Medscape Spanish Edition. A version of this article appeared on Medscape.com.

MADRID – Recent research has confirmed the impact of periodontitis on risk of neurologic diseases, especially the increased risks for stroke and Alzheimer’s disease.

The Spanish Society of Dentistry and Osseointegration (SEPA) and the Spanish Society of Neurology (SEN) recently released a report with the latest data on this topic. The report reviews, updates, and presents the most recent scientific evidence regarding this link. It also provides practical recommendations that, on the basis of the evidence, should be applied in dental clinics and neurology centers.

As Yago Leira, DDS, PhD, periodontist and coordinator of the SEPA-SEN working group, told this news organization, “The main takeaway from this scientific report is that patients with periodontitis are at nearly twice the risk of developing Alzheimer’s disease and at triple the risk of ischemic stroke.”

Data from the report show that individuals with periodontitis are at 2.8 times’ higher risk of ischemic stroke. The available evidence regarding hemorrhagic stroke, however, is conflicting.

How does this dental condition affect the course of cardiovascular disease? Observational studies have shown that those who have had an ischemic stroke and have a confirmed diagnosis of periodontitis are at greater risk of suffering a recurrent vascular event, worse neurologic deficit, and postictal depression than are patients without periodontitis.
 

Immune‐mediated inflammation

As far as its link to Alzheimer’s disease, meta-analyses of epidemiologic studies show that periodontitis is associated with a 1.7 times greater risk of this type of dementia and that the risk triples among patients with more serious forms of periodontitis.

Likewise, studies suggest that individuals with dementia or neurocognitive impairment are at a greater risk of suffering periodontitis. Other studies indicate that individuals with periodontitis have worse outcomes on various neuropsychological tests of cognitive function.

The current report presents the evidence from three clearly defined perspectives: The epidemiologic association between periodontitis and these neurologic diseases, the biological mechanisms that may explain this link, and interventional studies of dental treatment as a means of preventing stroke and Alzheimer’s disease.

“There is a possible biological explanation for these epidemiological findings. The report concludes that the low-grade chronic, systemic, immune-mediated inflammatory response induced by the bacteria and their endotoxins and the proinflammatory mediators circulating through the blood contributes to various biological processes that are involved in neurological impairment and cerebral ischemia,” said Dr. Leira, one of the report’s authors.

Ana Frank, MD, PhD, another author of this study, is head of the neurology department at the La Paz University Hospital in Madrid and a member of the SEPA-SEN group. She said in an interview that the main biological mechanism in stroke and Alzheimer’s disease is chronic exposure of the entire brain (vasculature, neurons, and astrocytes) to the harmful effects of periodontal infection. “Although low in intensity, this [exposure] is sufficient to set off a series of events that eventually lead to vascular endothelial injury, changes to neurons and astrocytes, and damage to the neuropil.”

As far as the evidence of an epidemiologic association between periodontitis and both neurologic diseases, Dr. Frank cited the exponential increase in risk brought on by periodontitis. She said that further epidemiologic studies are necessary to gain a better understanding of the magnitude of the problem.
 

A preventive alternative?

Dr. Leira cited evidence that periodontal treatment could provide a means of preventing stroke and dementia. He pointed out that numerous population studies have observed various oral health interventions (e.g., periodic dental prophylaxis or periodontal treatment) and regular dental visits to reduce the risk of developing dementia and stroke. “However, we don’t currently have randomized clinical trials that were designed to investigate whether periodontal treatment may be a primary or a secondary preventive measure against these neurological conditions.”

According to Dr. Leira, “There are currently several research groups in the United States and Europe, including ours, that are performing clinical trials to assess the impact of periodontal treatment on recurrent vascular events in patients with cerebrovascular disease.

“On the other hand, there are various interventional studies underway that are evaluating the potential effect of periodontal treatment on cognitive function in patients with dementia. Along these lines, there appear to be encouraging results from the 1-year follow-up in the GAIN study, which was a phase 2/3 clinical trial testing atuzaginstat. Atuzaginstat is an inhibitor of gingipain, the endotoxin produced by Porphyromonas gingivalis, which is one of the bacteria thought to be responsible for periodontitis. The drug reduces neurocognitive impairment in patients with high levels of antibodies against this periodontal pathogen.”
 

Toward clinical practice

The report has a practical focus. The intention is that this evidence will make its way into recommendations for dentists to implement in clinical practice, especially with elderly patients or patients with risk factors for stroke.

In this regard, Dr. Leira said, “On one hand, dentists have to know how to approach patients who have already suffered a stroke (most of whom have vascular risk factors like diabetes and hypertension), many of whom have polypharmacy and are [taking] certain drugs like blood thinners that could negatively impact various dental procedures. In such cases, it is important to maintain direct contact with a neurologist, since these patients ought to be treated with a multidisciplinary approach.

“On the other hand, each patient who comes to the dental office and has a diagnosis of periodontitis could be screened to identify potential vascular risk factors, even though the definitive diagnosis would need to be given by a specialist physician. To this end, SEPA is carrying out the Promosalud (“Health Promotion”) project, which will soon be applied in a large number of dental clinics in Spain,” added Dr. Leira.

“Lastly, specialists in odontology must understand the potential positive benefits surrounding systemic vascular inflammation that periodontal treatment could provide, including, for example, metabolic control and lowering blood pressure.”

For patients with cognitive impairment, the authors of the report recommended adhering to the following steps during dental visits: Inform the patient and the patient’s caregiver about the importance of good dental hygiene and monitor for any signs of infection or dental disease; address pain in every patient with cognitive impairment and dental problems, especially those with agitation, even if the patient isn’t specifically complaining of pain (also, try not to give opioids); finally, avoid sedation as much as possible and use the smallest effective dose if it becomes necessary.
 

Prescribe oral hygiene

Regarding recommendations that neurologists should follow during consultations in light of the link between these diseases and periodontitis, Dr. Frank said, “Regardless of how old our patients are, I believe it’s important to emphasize the importance of practicing good oral and dental hygiene. It’s a good strategy to put this in writing in medical reports, alongside the usual recommendations about healthy lifestyle habits and monitoring for diseases like high blood pressure, diabetes, or dyslipidemia. These, among other factors like smoking, a sedentary lifestyle, alcoholism, and other drug addictions, are vascular risk factors and are therefore risk factors for stroke and dementia.”

According to Dr. Frank, the public is largely unaware of the relationship between periodontitis and incident neurologic diseases. “We still have a long way to go before we can say that the public is aware of this potential link. And not just the public, either. I believe we must stress among our colleagues and among health care professionals in general the importance of promoting dental health to improve people’s overall health.”

In this regard, Dr. Leira emphasized the authors’ intention to make this report available not only to oral health and neurologic health care professionals but also to primary care physicians and nurses so that patients with cerebrovascular disease or Alzheimer’s disease and their caregivers can develop a greater awareness and thereby improve prevention.

“This study will also provide the scientific basis to support the SEPA-SEN working group as they implement their future activities and projects,” Dr. Leira concluded.

Dr. Leira and Dr. Frank have disclosed no relevant financial relationships.
 

This article was translated from the Medscape Spanish Edition. A version of this article appeared on Medscape.com.