Alzheimer's & Cognition

The study covered in this summary was published in Research Square as a preprint and has not yet been peer reviewed.

Key takeaways

• Focal cognitive deficits are more prevalent in hospitalized patients than ambulatory patients.
• Cognitive performance is related to neuropsychiatric symptoms in ambulatory but not hospitalized patients.
• Objective neurocognitive measures can supply crucial information to guide clinical decisions regarding the need for further imaging or neurologic workup and should be included as endpoints in clinical trials.

Why this matters

• Cognitive complaints commonly occur in patients convalescing from COVID-19, although their cause is frequently unclear.
• The researchers evaluated factors that play a role in cognitive impairment in ambulatory versus hospitalized patients during the subacute stage of recovery.
• These results underscore the significance of assessing both subjective and objective complaints in ascertaining the prevalence of cognitive impairment in recovering patients and research participants.
• The drivers of cognitive complaints are likely different in hospitalized COVID-19 patients in comparison with ambulatory COVID-19 patients, so it’s important to understand these factors in making treatment decisions.
• Biopsychosocial factors appear to be a powerful driver of cognitive complaints in recovering ambulatory patients. They can be treated with interventions targeting anxiety, depression, sleep disturbances, and pain, which may prove to be the most efficient and cost-effective approach to prevent disability in individuals with mild manifestations of COVID-19.
• Objective neurocognitive deficits were more prevalent in hospitalized patients – a marker of greater disease severity – with mainly deficits in memory and psychomotor speed. Factors that contribute to focal cognitive deficits in these individuals are emerging and represent a noteworthy realm for future investigation.

Study design

• The trial prospectively recruited patients from a hospital-wide registry at the Mayo Clinic in Jacksonville, Fla.
• All patients tested positive for SARS-CoV-2 infection on a real-time reverse transcriptase polymerase chain-reaction assay between June 2020 and March 2021.
• Patients were 18 years of age or older.
• The researchers excluded those with a pre-existing major neurocognitive disorder.
• To participate, patients needed access to a desktop or laptop computer to complete a test and survey.
• They responded to a comprehensive neuropsychological questionnaire and a computerized cognitive screen using a remote telemedicine platform.
• The researchers compared rates of subjective and objective neuropsychological impairment between the ambulatory and hospitalized groups. Factors linked to impairment were analyzed separately within each group.

Key results

• After laboratory confirmation of SARS-CoV-2 infection, a total of 102 patients (76 ambulatory, 26 hospitalized) completed the symptom inventory and neurocognitive tests in 24 ± 22 days.
• Hospitalized and ambulatory patients self-reported high rates of cognitive impairment (27%-40%). There were no variations between the groups.
• However, hospitalized patients had more significant rates of objective impairment in visual memory (30% vs. 4%; P = .001) and psychomotor speed (41% vs. 15%; P = .008).
• Objective cognitive test performance was linked to anxiety, depression, fatigue, and pain in the ambulatory but not the hospitalized group.

Limitations

• The sample size of hospitalized patients was small.
• A larger fraction of hospitalized patients in the sample completed outcome assessments, compared with ambulatory patients, indicating that remote computerized testing did not present a disproportionate access barrier for patients with more severe illness.
• Owing to limited instances of delirium, seizures, and stroke, it was not possible to directly consider the contributions of these events to post–COVID-19 subjective complaints and objective impairment.
• The researchers depended on a 45-minute computerized test battery, which eliminates exposure risk and is available to patients in remote locations, but it necessitates computer literacy and access to a home desktop computer. While this requirement may have skewed the sample toward a more socioeconomically advantaged and younger population, there were no differences in age, race, or ethnicity between those who completed the computerized outcome assessments and those who did not. For patients who are able to give consent electronically, computerized testing does not pose an additional barrier.
• As a result of this study’s cross-sectional nature, the researchers could not comment on the natural history and long-term risk of COVID-19 cognitive impairment. It will be crucial to monitor cognitive progression at future time points to assess the rate and predictors of cognitive normalization versus decline.

Study disclosures

• Gregory S. Day, a coauthor, owns stock (greater than $10,000) in ANI Pharmaceuticals, a generic pharmaceutical company. He serves as a topic editor for DynaMed (EBSCO), overseeing development of evidence-based educational content, a consultant for Parabon Nanolabs (advice relevant to National Institutes of Health small business grant submission), and as the clinical director of the Anti-NMDA Receptor Encephalitis Foundation, Canada (uncompensated). The other authors have disclosed no relevant financial relationships.

This is a summary of a preprint research study, “Neurocognitive Screening in Patients Following SARS-CoV-2 Infection: Tools for Triage,” written by Karen Blackmon from Mayo Clinic in Florida, on medRxiv. This study has not yet been peer reviewed. The full text of the study can be found on medRxiv.org. A version of this article first appeared on Medscape.com.

The study covered in this summary was published in Research Square as a preprint and has not yet been peer reviewed.

Key takeaways

• Focal cognitive deficits are more prevalent in hospitalized patients than ambulatory patients.
• Cognitive performance is related to neuropsychiatric symptoms in ambulatory but not hospitalized patients.
• Objective neurocognitive measures can supply crucial information to guide clinical decisions regarding the need for further imaging or neurologic workup and should be included as endpoints in clinical trials.

Why this matters

• Cognitive complaints commonly occur in patients convalescing from COVID-19, although their cause is frequently unclear.
• The researchers evaluated factors that play a role in cognitive impairment in ambulatory versus hospitalized patients during the subacute stage of recovery.
• These results underscore the significance of assessing both subjective and objective complaints in ascertaining the prevalence of cognitive impairment in recovering patients and research participants.
• The drivers of cognitive complaints are likely different in hospitalized COVID-19 patients in comparison with ambulatory COVID-19 patients, so it’s important to understand these factors in making treatment decisions.
• Biopsychosocial factors appear to be a powerful driver of cognitive complaints in recovering ambulatory patients. They can be treated with interventions targeting anxiety, depression, sleep disturbances, and pain, which may prove to be the most efficient and cost-effective approach to prevent disability in individuals with mild manifestations of COVID-19.
• Objective neurocognitive deficits were more prevalent in hospitalized patients – a marker of greater disease severity – with mainly deficits in memory and psychomotor speed. Factors that contribute to focal cognitive deficits in these individuals are emerging and represent a noteworthy realm for future investigation.

Study design

• The trial prospectively recruited patients from a hospital-wide registry at the Mayo Clinic in Jacksonville, Fla.
• All patients tested positive for SARS-CoV-2 infection on a real-time reverse transcriptase polymerase chain-reaction assay between June 2020 and March 2021.
• Patients were 18 years of age or older.
• The researchers excluded those with a pre-existing major neurocognitive disorder.
• To participate, patients needed access to a desktop or laptop computer to complete a test and survey.
• They responded to a comprehensive neuropsychological questionnaire and a computerized cognitive screen using a remote telemedicine platform.
• The researchers compared rates of subjective and objective neuropsychological impairment between the ambulatory and hospitalized groups. Factors linked to impairment were analyzed separately within each group.

Key results

• After laboratory confirmation of SARS-CoV-2 infection, a total of 102 patients (76 ambulatory, 26 hospitalized) completed the symptom inventory and neurocognitive tests in 24 ± 22 days.
• Hospitalized and ambulatory patients self-reported high rates of cognitive impairment (27%-40%). There were no variations between the groups.
• However, hospitalized patients had more significant rates of objective impairment in visual memory (30% vs. 4%; P = .001) and psychomotor speed (41% vs. 15%; P = .008).
• Objective cognitive test performance was linked to anxiety, depression, fatigue, and pain in the ambulatory but not the hospitalized group.

Limitations

• The sample size of hospitalized patients was small.
• A larger fraction of hospitalized patients in the sample completed outcome assessments, compared with ambulatory patients, indicating that remote computerized testing did not present a disproportionate access barrier for patients with more severe illness.
• Owing to limited instances of delirium, seizures, and stroke, it was not possible to directly consider the contributions of these events to post–COVID-19 subjective complaints and objective impairment.
• The researchers depended on a 45-minute computerized test battery, which eliminates exposure risk and is available to patients in remote locations, but it necessitates computer literacy and access to a home desktop computer. While this requirement may have skewed the sample toward a more socioeconomically advantaged and younger population, there were no differences in age, race, or ethnicity between those who completed the computerized outcome assessments and those who did not. For patients who are able to give consent electronically, computerized testing does not pose an additional barrier.
• As a result of this study’s cross-sectional nature, the researchers could not comment on the natural history and long-term risk of COVID-19 cognitive impairment. It will be crucial to monitor cognitive progression at future time points to assess the rate and predictors of cognitive normalization versus decline.

Study disclosures

• Gregory S. Day, a coauthor, owns stock (greater than $10,000) in ANI Pharmaceuticals, a generic pharmaceutical company. He serves as a topic editor for DynaMed (EBSCO), overseeing development of evidence-based educational content, a consultant for Parabon Nanolabs (advice relevant to National Institutes of Health small business grant submission), and as the clinical director of the Anti-NMDA Receptor Encephalitis Foundation, Canada (uncompensated). The other authors have disclosed no relevant financial relationships.

This is a summary of a preprint research study, “Neurocognitive Screening in Patients Following SARS-CoV-2 Infection: Tools for Triage,” written by Karen Blackmon from Mayo Clinic in Florida, on medRxiv. This study has not yet been peer reviewed. The full text of the study can be found on medRxiv.org. A version of this article first appeared on Medscape.com.

The study covered in this summary was published in Research Square as a preprint and has not yet been peer reviewed.

Key takeaways

• Focal cognitive deficits are more prevalent in hospitalized patients than ambulatory patients.
• Cognitive performance is related to neuropsychiatric symptoms in ambulatory but not hospitalized patients.
• Objective neurocognitive measures can supply crucial information to guide clinical decisions regarding the need for further imaging or neurologic workup and should be included as endpoints in clinical trials.

Why this matters

• Cognitive complaints commonly occur in patients convalescing from COVID-19, although their cause is frequently unclear.
• The researchers evaluated factors that play a role in cognitive impairment in ambulatory versus hospitalized patients during the subacute stage of recovery.
• These results underscore the significance of assessing both subjective and objective complaints in ascertaining the prevalence of cognitive impairment in recovering patients and research participants.
• The drivers of cognitive complaints are likely different in hospitalized COVID-19 patients in comparison with ambulatory COVID-19 patients, so it’s important to understand these factors in making treatment decisions.
• Biopsychosocial factors appear to be a powerful driver of cognitive complaints in recovering ambulatory patients. They can be treated with interventions targeting anxiety, depression, sleep disturbances, and pain, which may prove to be the most efficient and cost-effective approach to prevent disability in individuals with mild manifestations of COVID-19.
• Objective neurocognitive deficits were more prevalent in hospitalized patients – a marker of greater disease severity – with mainly deficits in memory and psychomotor speed. Factors that contribute to focal cognitive deficits in these individuals are emerging and represent a noteworthy realm for future investigation.

Study design

• The trial prospectively recruited patients from a hospital-wide registry at the Mayo Clinic in Jacksonville, Fla.
• All patients tested positive for SARS-CoV-2 infection on a real-time reverse transcriptase polymerase chain-reaction assay between June 2020 and March 2021.
• Patients were 18 years of age or older.
• The researchers excluded those with a pre-existing major neurocognitive disorder.
• To participate, patients needed access to a desktop or laptop computer to complete a test and survey.
• They responded to a comprehensive neuropsychological questionnaire and a computerized cognitive screen using a remote telemedicine platform.
• The researchers compared rates of subjective and objective neuropsychological impairment between the ambulatory and hospitalized groups. Factors linked to impairment were analyzed separately within each group.

Key results

• After laboratory confirmation of SARS-CoV-2 infection, a total of 102 patients (76 ambulatory, 26 hospitalized) completed the symptom inventory and neurocognitive tests in 24 ± 22 days.
• Hospitalized and ambulatory patients self-reported high rates of cognitive impairment (27%-40%). There were no variations between the groups.
• However, hospitalized patients had more significant rates of objective impairment in visual memory (30% vs. 4%; P = .001) and psychomotor speed (41% vs. 15%; P = .008).
• Objective cognitive test performance was linked to anxiety, depression, fatigue, and pain in the ambulatory but not the hospitalized group.

Limitations

• The sample size of hospitalized patients was small.
• A larger fraction of hospitalized patients in the sample completed outcome assessments, compared with ambulatory patients, indicating that remote computerized testing did not present a disproportionate access barrier for patients with more severe illness.
• Owing to limited instances of delirium, seizures, and stroke, it was not possible to directly consider the contributions of these events to post–COVID-19 subjective complaints and objective impairment.
• The researchers depended on a 45-minute computerized test battery, which eliminates exposure risk and is available to patients in remote locations, but it necessitates computer literacy and access to a home desktop computer. While this requirement may have skewed the sample toward a more socioeconomically advantaged and younger population, there were no differences in age, race, or ethnicity between those who completed the computerized outcome assessments and those who did not. For patients who are able to give consent electronically, computerized testing does not pose an additional barrier.
• As a result of this study’s cross-sectional nature, the researchers could not comment on the natural history and long-term risk of COVID-19 cognitive impairment. It will be crucial to monitor cognitive progression at future time points to assess the rate and predictors of cognitive normalization versus decline.

Study disclosures

• Gregory S. Day, a coauthor, owns stock (greater than $10,000) in ANI Pharmaceuticals, a generic pharmaceutical company. He serves as a topic editor for DynaMed (EBSCO), overseeing development of evidence-based educational content, a consultant for Parabon Nanolabs (advice relevant to National Institutes of Health small business grant submission), and as the clinical director of the Anti-NMDA Receptor Encephalitis Foundation, Canada (uncompensated). The other authors have disclosed no relevant financial relationships.

This is a summary of a preprint research study, “Neurocognitive Screening in Patients Following SARS-CoV-2 Infection: Tools for Triage,” written by Karen Blackmon from Mayo Clinic in Florida, on medRxiv. This study has not yet been peer reviewed. The full text of the study can be found on medRxiv.org. A version of this article first appeared on Medscape.com.

For the first time, neuroscientists have recorded the brain activity of a dying person, revealing a brain wave pattern similar to that seen when memories are recalled. Although only a single case study, researchers say the recording raises the possibility that as we die, our lives really do flash before our eyes.

“The same neurophysiological activity patterns that occur in our brains when we dream, remember, meditate, concentrate – these same patterns also appear just before we die,” study investigator Ajmal Zemmar, MD, PhD, assistant professor of neurosurgery at the University of Louisville (Ky.), said in an interview.

The research was published online Feb. 22, 2022, in the Frontiers in Aging Neuroscience.
 

Accidental finding

The recording of brain activity was captured inadvertently in 2016 when neuroscientists used continuous EEG to detect and treat seizures in an 87-year-old man who had developed epilepsy after a traumatic brain injury, While undergoing the EEG, the patient had a cardiac arrest and died.

In the 30 seconds before and after blood flow to the brain stopped, the EEG showed an increase in gamma oscillations. These are brain waves known to be involved in high cognitive functions, including conscious perception and memory flashbacks.

Researchers also noted changes in alpha, theta, delta, and beta wave activity just before and just after cardiac arrest, and that changes in one type modulated changes in others. That suggests a coordinated rhythm, which further suggests the activity is more than just the firing of neurons as they die.

“When you observe this and you observe the rhythmic oscillation, you are inclined to think this may be a coordinated activity pattern of the brain rather than a mere discharge when the brain dies,” Dr. Zemmar said.

Although they’ve had the data since 2016, Dr. Zemmar and colleagues held off on publishing in the hopes of finding similar recordings in other individuals. That their 5-year search yielded no results illustrates just how difficult a study like this is to conduct, Dr. Zemmar noted. “We’re trying to figure out how to do this in a predictable way, but obtaining datasets like this is going to be challenging,” he said.

Although Dr. Zemmar was unable to find recordings of activity in the dying brains of other humans, he did find a similar study conducted with rats in 2013. In that research, investigators reported a surge of brain activity in rats just prior to and immediately after experimental cardiac arrest. Changes in high- and low-frequency brain waves mirrored those documented in the current case study.
 

Bringing a picture together

Commenting on the new study, George Mashour, MD, PhD, professor and chair of anesthesiology and professor of neurosurgery and pharmacology at the University of Michigan, Ann Arbor, said the results are eerily similar to a 2013 study that he coauthored.

Although the current research is just a single case study, Dr. Mashour said when taken with his team’s findings in rats and other work, the new findings are “starting to put a picture together of what might be going on in the dying brain.”

“They were able to record throughout the process of cardiac arrest and death and what they found was strikingly similar to what we found in our highly controlled animal study,” said Dr. Mashour, who is also the founding director of the Center for Consciousness Science at the University of Michigan.

“There was a surge of higher-frequency activity and there was coherence across different parts of the brain,” he added. “That suggests that what we found in the rigorous controlled setting of a laboratory actually translates to humans who are undergoing the clinical process of dying.”

What remains unclear is whether this brain activity explains the near-death experiences described in the literature, which include “life recall” of memories, Dr. Mashour said. “This higher-frequency surge that’s happening around the time of death, is that correlated with experiencing something like this near-death experience? Or is it just a neural feature that can just as easily happen in an unconscious brain?”

The study was funded by the Heidi Demetriades Foundation, the ETH Zürich Foundation, and the Henan Provincial People’s Hospital Outstanding Talents Founding Grant Project. Dr. Zemmar and Dr. Mashour disclosed no relevant financial relationships.

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

For the first time, neuroscientists have recorded the brain activity of a dying person, revealing a brain wave pattern similar to that seen when memories are recalled. Although only a single case study, researchers say the recording raises the possibility that as we die, our lives really do flash before our eyes.

“The same neurophysiological activity patterns that occur in our brains when we dream, remember, meditate, concentrate – these same patterns also appear just before we die,” study investigator Ajmal Zemmar, MD, PhD, assistant professor of neurosurgery at the University of Louisville (Ky.), said in an interview.

The research was published online Feb. 22, 2022, in the Frontiers in Aging Neuroscience.
 

Accidental finding

The recording of brain activity was captured inadvertently in 2016 when neuroscientists used continuous EEG to detect and treat seizures in an 87-year-old man who had developed epilepsy after a traumatic brain injury, While undergoing the EEG, the patient had a cardiac arrest and died.

In the 30 seconds before and after blood flow to the brain stopped, the EEG showed an increase in gamma oscillations. These are brain waves known to be involved in high cognitive functions, including conscious perception and memory flashbacks.

Researchers also noted changes in alpha, theta, delta, and beta wave activity just before and just after cardiac arrest, and that changes in one type modulated changes in others. That suggests a coordinated rhythm, which further suggests the activity is more than just the firing of neurons as they die.

“When you observe this and you observe the rhythmic oscillation, you are inclined to think this may be a coordinated activity pattern of the brain rather than a mere discharge when the brain dies,” Dr. Zemmar said.

Although they’ve had the data since 2016, Dr. Zemmar and colleagues held off on publishing in the hopes of finding similar recordings in other individuals. That their 5-year search yielded no results illustrates just how difficult a study like this is to conduct, Dr. Zemmar noted. “We’re trying to figure out how to do this in a predictable way, but obtaining datasets like this is going to be challenging,” he said.

Although Dr. Zemmar was unable to find recordings of activity in the dying brains of other humans, he did find a similar study conducted with rats in 2013. In that research, investigators reported a surge of brain activity in rats just prior to and immediately after experimental cardiac arrest. Changes in high- and low-frequency brain waves mirrored those documented in the current case study.
 

Bringing a picture together

Commenting on the new study, George Mashour, MD, PhD, professor and chair of anesthesiology and professor of neurosurgery and pharmacology at the University of Michigan, Ann Arbor, said the results are eerily similar to a 2013 study that he coauthored.

Although the current research is just a single case study, Dr. Mashour said when taken with his team’s findings in rats and other work, the new findings are “starting to put a picture together of what might be going on in the dying brain.”

“They were able to record throughout the process of cardiac arrest and death and what they found was strikingly similar to what we found in our highly controlled animal study,” said Dr. Mashour, who is also the founding director of the Center for Consciousness Science at the University of Michigan.

“There was a surge of higher-frequency activity and there was coherence across different parts of the brain,” he added. “That suggests that what we found in the rigorous controlled setting of a laboratory actually translates to humans who are undergoing the clinical process of dying.”

What remains unclear is whether this brain activity explains the near-death experiences described in the literature, which include “life recall” of memories, Dr. Mashour said. “This higher-frequency surge that’s happening around the time of death, is that correlated with experiencing something like this near-death experience? Or is it just a neural feature that can just as easily happen in an unconscious brain?”

The study was funded by the Heidi Demetriades Foundation, the ETH Zürich Foundation, and the Henan Provincial People’s Hospital Outstanding Talents Founding Grant Project. Dr. Zemmar and Dr. Mashour disclosed no relevant financial relationships.

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

For the first time, neuroscientists have recorded the brain activity of a dying person, revealing a brain wave pattern similar to that seen when memories are recalled. Although only a single case study, researchers say the recording raises the possibility that as we die, our lives really do flash before our eyes.

“The same neurophysiological activity patterns that occur in our brains when we dream, remember, meditate, concentrate – these same patterns also appear just before we die,” study investigator Ajmal Zemmar, MD, PhD, assistant professor of neurosurgery at the University of Louisville (Ky.), said in an interview.

The research was published online Feb. 22, 2022, in the Frontiers in Aging Neuroscience.
 

Accidental finding

The recording of brain activity was captured inadvertently in 2016 when neuroscientists used continuous EEG to detect and treat seizures in an 87-year-old man who had developed epilepsy after a traumatic brain injury, While undergoing the EEG, the patient had a cardiac arrest and died.

In the 30 seconds before and after blood flow to the brain stopped, the EEG showed an increase in gamma oscillations. These are brain waves known to be involved in high cognitive functions, including conscious perception and memory flashbacks.

Researchers also noted changes in alpha, theta, delta, and beta wave activity just before and just after cardiac arrest, and that changes in one type modulated changes in others. That suggests a coordinated rhythm, which further suggests the activity is more than just the firing of neurons as they die.

“When you observe this and you observe the rhythmic oscillation, you are inclined to think this may be a coordinated activity pattern of the brain rather than a mere discharge when the brain dies,” Dr. Zemmar said.

Although they’ve had the data since 2016, Dr. Zemmar and colleagues held off on publishing in the hopes of finding similar recordings in other individuals. That their 5-year search yielded no results illustrates just how difficult a study like this is to conduct, Dr. Zemmar noted. “We’re trying to figure out how to do this in a predictable way, but obtaining datasets like this is going to be challenging,” he said.

Although Dr. Zemmar was unable to find recordings of activity in the dying brains of other humans, he did find a similar study conducted with rats in 2013. In that research, investigators reported a surge of brain activity in rats just prior to and immediately after experimental cardiac arrest. Changes in high- and low-frequency brain waves mirrored those documented in the current case study.
 

Bringing a picture together

Commenting on the new study, George Mashour, MD, PhD, professor and chair of anesthesiology and professor of neurosurgery and pharmacology at the University of Michigan, Ann Arbor, said the results are eerily similar to a 2013 study that he coauthored.

Although the current research is just a single case study, Dr. Mashour said when taken with his team’s findings in rats and other work, the new findings are “starting to put a picture together of what might be going on in the dying brain.”

“They were able to record throughout the process of cardiac arrest and death and what they found was strikingly similar to what we found in our highly controlled animal study,” said Dr. Mashour, who is also the founding director of the Center for Consciousness Science at the University of Michigan.

“There was a surge of higher-frequency activity and there was coherence across different parts of the brain,” he added. “That suggests that what we found in the rigorous controlled setting of a laboratory actually translates to humans who are undergoing the clinical process of dying.”

What remains unclear is whether this brain activity explains the near-death experiences described in the literature, which include “life recall” of memories, Dr. Mashour said. “This higher-frequency surge that’s happening around the time of death, is that correlated with experiencing something like this near-death experience? Or is it just a neural feature that can just as easily happen in an unconscious brain?”

The study was funded by the Heidi Demetriades Foundation, the ETH Zürich Foundation, and the Henan Provincial People’s Hospital Outstanding Talents Founding Grant Project. Dr. Zemmar and Dr. Mashour disclosed no relevant financial relationships.

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

A healthy, diverse gut microbiome is associated with better cognitive function in middle age, new research suggests.

Investigators conducted cognitive testing and analyzed stool samples in close to 600 adults and found that beta-diversity, which is a between-person measure of gut microbial community composition, was significantly associated with cognitive scores.

Three specific bacterial genera showed a positive association with performance on at least one cognitive test, while one showed a negative association.

“Data from our study support an association between the gut microbial community and measure of cognitive function – results that are consistent with findings from other human and animal research,” study investigator Katie Meyer, ScD, assistant professor, department of nutrition, UNC Gillings School of Public Health, Chapel Hill, N.C., told this news organization.

“However, it is also important to recognize that we are still learning about how to characterize the role of this dynamic ecological community and delineate mechanistic pathways,” she said.

The study was published online Feb 8 in JAMA Network Open.
 

‘Novel’ research

“Communication pathways between gut bacteria and neurologic function (referred to as the ‘gut-brain axis’) have emerged as a novel area of research into potential mechanisms regulating brain health through immunologic, metabolic, and endocrine pathways,” the authors wrote.

A number of studies have “shown associations between gut microbial measures and neurological outcomes, including cognitive function and dementia,” but mechanisms underlying these associations “have not been fully established.”

Animal and small-scale human studies have suggested that reduced microbial diversity is associated with poorer cognition, but studies have not been conducted in community-based large and diverse populations.

The researchers therefore examined cross-sectional associations of gut microbial diversity and taxonomic composition with cognitive status in a large group of community-dwelling, sociodemographically diverse Black and White adults living in four metropolitan areas who were participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study.

They hypothesized that microbial diversity would be positively associated with global as well as domain-specific cognitive status and that higher cognitive status would be associated with specific taxonomic groups involved in short-chain fatty acid production.

The CARDIA’s year 30 follow-up examination took place during 2015-2016, when the original participants ranged in age from 48 to 60 years. During that examination, participants took a battery of cognitive assessments, and 615 also provided a stool sample for a microbiome substudy; of these, 597 (mean [SD] age, 55.2 [3.5] years, 44.7% Black, 45.2% White) had both stool DNA available for sequencing and a complete complement of cognitive tests and were included in the current study.

The cognitive tests included the Digit Symbol Substitution Test (DSST); Rey-Auditory Verbal Learning Test (RAVLT); the timed Stroop test; letter fluency and category fluency; and the Montreal Cognitive Assessment (MoCA).

Covariates that might confound associations between microbial and cognitive measures, including body mass index, diabetes, age, sex, race, field center, education, physical activity, current smoking, diet quality, number of medications, and hypertension, were included in the analyses.

The investigators conducted three standard microbial analyses: within-person alpha-diversity; between-person beta-diversity; and individual taxa.
 

Potential pathways

The strongest associations in the variance tests for beta-diversity, which were significant for all cognition measures in multivariable-adjusted principal coordinates analysis (all Ps = .001 except for the Stroop, which was .007). However, the association with letter fluency was not deemed significant (P = .07).

After fully adjusting for sociodemographic variables, health behaviors, and clinical covariates, the researchers found that three genera were positively associated, while one was negatively associated with cognitive measures.

Starting point

Commenting for this news organization, Timothy Dinan, MD, PhD, professor of psychiatry and an investigator, APC Microbiome Institute, University College Cork, Ireland, said, “This is an important study, adding to the growing body of evidence that gut microbes influence brain function.”

Dr. Dinan, who was not involved with the study, continued: “In an impressively large sample, an association between cognition and gut microbiota architecture was demonstrated.”

He cautioned that the study “is limited by the fact that it is cross-sectional, and the relationships are correlational.” Nevertheless, “despite these obvious caveats, the paper undoubtedly advances the field.”

Dr. Meyer agreed, noting that there is “a paucity of biomarkers that can be used to predict cognitive decline and dementia,” but because their study was cross-sectional, “we cannot assess temporality (i.e., whether gut microbiota predicts cognitive decline); but, as a start, we can assess associations.”

She added that “at this point, we know far more about modifiable risk factors that have been shown to be positively associated with cognitive function,” including eating a Mediterranean diet and engaging in physical activity.

“It is possible that protective effects of diet and activity may, in part, operate thorough the gut microbiota,” Dr. Meyer suggested.

The CARDIA study is supported by the National Heart, Lung, and Blood Institute, the Intramural Research Program of the National Institute on Aging, and the University of North Carolina Nutrition Research Institute. Dr. Meyer and coauthors and Dr. Dinan report no relevant financial relationships.

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

A healthy, diverse gut microbiome is associated with better cognitive function in middle age, new research suggests.

Investigators conducted cognitive testing and analyzed stool samples in close to 600 adults and found that beta-diversity, which is a between-person measure of gut microbial community composition, was significantly associated with cognitive scores.

Three specific bacterial genera showed a positive association with performance on at least one cognitive test, while one showed a negative association.

“Data from our study support an association between the gut microbial community and measure of cognitive function – results that are consistent with findings from other human and animal research,” study investigator Katie Meyer, ScD, assistant professor, department of nutrition, UNC Gillings School of Public Health, Chapel Hill, N.C., told this news organization.

“However, it is also important to recognize that we are still learning about how to characterize the role of this dynamic ecological community and delineate mechanistic pathways,” she said.

The study was published online Feb 8 in JAMA Network Open.
 

‘Novel’ research

“Communication pathways between gut bacteria and neurologic function (referred to as the ‘gut-brain axis’) have emerged as a novel area of research into potential mechanisms regulating brain health through immunologic, metabolic, and endocrine pathways,” the authors wrote.

A number of studies have “shown associations between gut microbial measures and neurological outcomes, including cognitive function and dementia,” but mechanisms underlying these associations “have not been fully established.”

Animal and small-scale human studies have suggested that reduced microbial diversity is associated with poorer cognition, but studies have not been conducted in community-based large and diverse populations.

The researchers therefore examined cross-sectional associations of gut microbial diversity and taxonomic composition with cognitive status in a large group of community-dwelling, sociodemographically diverse Black and White adults living in four metropolitan areas who were participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study.

They hypothesized that microbial diversity would be positively associated with global as well as domain-specific cognitive status and that higher cognitive status would be associated with specific taxonomic groups involved in short-chain fatty acid production.

The CARDIA’s year 30 follow-up examination took place during 2015-2016, when the original participants ranged in age from 48 to 60 years. During that examination, participants took a battery of cognitive assessments, and 615 also provided a stool sample for a microbiome substudy; of these, 597 (mean [SD] age, 55.2 [3.5] years, 44.7% Black, 45.2% White) had both stool DNA available for sequencing and a complete complement of cognitive tests and were included in the current study.

The cognitive tests included the Digit Symbol Substitution Test (DSST); Rey-Auditory Verbal Learning Test (RAVLT); the timed Stroop test; letter fluency and category fluency; and the Montreal Cognitive Assessment (MoCA).

Covariates that might confound associations between microbial and cognitive measures, including body mass index, diabetes, age, sex, race, field center, education, physical activity, current smoking, diet quality, number of medications, and hypertension, were included in the analyses.

The investigators conducted three standard microbial analyses: within-person alpha-diversity; between-person beta-diversity; and individual taxa.
 

Potential pathways

The strongest associations in the variance tests for beta-diversity, which were significant for all cognition measures in multivariable-adjusted principal coordinates analysis (all Ps = .001 except for the Stroop, which was .007). However, the association with letter fluency was not deemed significant (P = .07).

After fully adjusting for sociodemographic variables, health behaviors, and clinical covariates, the researchers found that three genera were positively associated, while one was negatively associated with cognitive measures.

Starting point

Commenting for this news organization, Timothy Dinan, MD, PhD, professor of psychiatry and an investigator, APC Microbiome Institute, University College Cork, Ireland, said, “This is an important study, adding to the growing body of evidence that gut microbes influence brain function.”

Dr. Dinan, who was not involved with the study, continued: “In an impressively large sample, an association between cognition and gut microbiota architecture was demonstrated.”

He cautioned that the study “is limited by the fact that it is cross-sectional, and the relationships are correlational.” Nevertheless, “despite these obvious caveats, the paper undoubtedly advances the field.”

Dr. Meyer agreed, noting that there is “a paucity of biomarkers that can be used to predict cognitive decline and dementia,” but because their study was cross-sectional, “we cannot assess temporality (i.e., whether gut microbiota predicts cognitive decline); but, as a start, we can assess associations.”

She added that “at this point, we know far more about modifiable risk factors that have been shown to be positively associated with cognitive function,” including eating a Mediterranean diet and engaging in physical activity.

“It is possible that protective effects of diet and activity may, in part, operate thorough the gut microbiota,” Dr. Meyer suggested.

The CARDIA study is supported by the National Heart, Lung, and Blood Institute, the Intramural Research Program of the National Institute on Aging, and the University of North Carolina Nutrition Research Institute. Dr. Meyer and coauthors and Dr. Dinan report no relevant financial relationships.

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

A healthy, diverse gut microbiome is associated with better cognitive function in middle age, new research suggests.

Investigators conducted cognitive testing and analyzed stool samples in close to 600 adults and found that beta-diversity, which is a between-person measure of gut microbial community composition, was significantly associated with cognitive scores.

Three specific bacterial genera showed a positive association with performance on at least one cognitive test, while one showed a negative association.

“Data from our study support an association between the gut microbial community and measure of cognitive function – results that are consistent with findings from other human and animal research,” study investigator Katie Meyer, ScD, assistant professor, department of nutrition, UNC Gillings School of Public Health, Chapel Hill, N.C., told this news organization.

“However, it is also important to recognize that we are still learning about how to characterize the role of this dynamic ecological community and delineate mechanistic pathways,” she said.

The study was published online Feb 8 in JAMA Network Open.
 

‘Novel’ research

“Communication pathways between gut bacteria and neurologic function (referred to as the ‘gut-brain axis’) have emerged as a novel area of research into potential mechanisms regulating brain health through immunologic, metabolic, and endocrine pathways,” the authors wrote.

A number of studies have “shown associations between gut microbial measures and neurological outcomes, including cognitive function and dementia,” but mechanisms underlying these associations “have not been fully established.”

Animal and small-scale human studies have suggested that reduced microbial diversity is associated with poorer cognition, but studies have not been conducted in community-based large and diverse populations.

The researchers therefore examined cross-sectional associations of gut microbial diversity and taxonomic composition with cognitive status in a large group of community-dwelling, sociodemographically diverse Black and White adults living in four metropolitan areas who were participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study.

They hypothesized that microbial diversity would be positively associated with global as well as domain-specific cognitive status and that higher cognitive status would be associated with specific taxonomic groups involved in short-chain fatty acid production.

The CARDIA’s year 30 follow-up examination took place during 2015-2016, when the original participants ranged in age from 48 to 60 years. During that examination, participants took a battery of cognitive assessments, and 615 also provided a stool sample for a microbiome substudy; of these, 597 (mean [SD] age, 55.2 [3.5] years, 44.7% Black, 45.2% White) had both stool DNA available for sequencing and a complete complement of cognitive tests and were included in the current study.

The cognitive tests included the Digit Symbol Substitution Test (DSST); Rey-Auditory Verbal Learning Test (RAVLT); the timed Stroop test; letter fluency and category fluency; and the Montreal Cognitive Assessment (MoCA).

Covariates that might confound associations between microbial and cognitive measures, including body mass index, diabetes, age, sex, race, field center, education, physical activity, current smoking, diet quality, number of medications, and hypertension, were included in the analyses.

The investigators conducted three standard microbial analyses: within-person alpha-diversity; between-person beta-diversity; and individual taxa.
 

Potential pathways

The strongest associations in the variance tests for beta-diversity, which were significant for all cognition measures in multivariable-adjusted principal coordinates analysis (all Ps = .001 except for the Stroop, which was .007). However, the association with letter fluency was not deemed significant (P = .07).

After fully adjusting for sociodemographic variables, health behaviors, and clinical covariates, the researchers found that three genera were positively associated, while one was negatively associated with cognitive measures.

Starting point

Commenting for this news organization, Timothy Dinan, MD, PhD, professor of psychiatry and an investigator, APC Microbiome Institute, University College Cork, Ireland, said, “This is an important study, adding to the growing body of evidence that gut microbes influence brain function.”

Dr. Dinan, who was not involved with the study, continued: “In an impressively large sample, an association between cognition and gut microbiota architecture was demonstrated.”

He cautioned that the study “is limited by the fact that it is cross-sectional, and the relationships are correlational.” Nevertheless, “despite these obvious caveats, the paper undoubtedly advances the field.”

Dr. Meyer agreed, noting that there is “a paucity of biomarkers that can be used to predict cognitive decline and dementia,” but because their study was cross-sectional, “we cannot assess temporality (i.e., whether gut microbiota predicts cognitive decline); but, as a start, we can assess associations.”

She added that “at this point, we know far more about modifiable risk factors that have been shown to be positively associated with cognitive function,” including eating a Mediterranean diet and engaging in physical activity.

“It is possible that protective effects of diet and activity may, in part, operate thorough the gut microbiota,” Dr. Meyer suggested.

The CARDIA study is supported by the National Heart, Lung, and Blood Institute, the Intramural Research Program of the National Institute on Aging, and the University of North Carolina Nutrition Research Institute. Dr. Meyer and coauthors and Dr. Dinan report no relevant financial relationships.

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

 Patients who have had a myocardial infarction experience faster cognitive decline over time than immediately after the event, new research suggests.

Although cognition in the acute phase after MI was not different than those without an MI in large observational cohorts, cognitive decline became significantly different over a median 6.5 years of follow-up.

The results reinforce the idea that heart health is closely tied to brain health, lead study author Michelle C. Johansen, MD, PhD, assistant professor of neurology cerebrovascular division, Johns Hopkins University, Baltimore, said in an interview. “From a clinical standpoint, heart health affects brain health and there may be effective interventions to prevent heart attack from happening that could reduce the rate of cognitive decline.”

The study was presented during the International Stroke Conference sponsored by the American Heart Association.

Researchers are increasingly recognizing the vascular contribution to cognitive impairment, said Dr. Johansen. This could involve “silent” or subclinical strokes that go unrecognized until seen on imaging.

The study included 31,377 adults free of MI and dementia from six large, well-known cohort studies: the Atherosclerosis Risk in Communities Study, the Coronary Artery Risk Development in Young Adults Study, the Cardiovascular Health Study, the Framingham Offspring Study, the Multi-Ethnic Study of Atherosclerosis, and the Northern Manhattan Study

About 56% of study participants were women, 23% were Black, 8% were Hispanic, and 69% were White.

They were followed from 1971 to 2017 with investigators repeatedly measuring vascular risk factors. The median study follow-up was 6.5 years, but some were followed for up to 20 years. During that time, there were 1,047 incident MIs.

The researchers performed a pooled analysis from these studies “using some fancy statistical techniques,” said Dr. Johansen. “The unique thing about this study was we were able to harmonize the cognitive measures.”

This allowed the researchers to determine if incident MI affected cognitive decline soon after the event and then long-term after the event. The primary outcome was change in global cognition. Additional outcomes were memory and executive function.

The median time between the first MI and the cognitive assessment was about 1.8 years but ranged from about 6 months to 4 years, said Dr. Johansen. Participants were a median age of 60 years at the time of the first cognitive assessment.

The researchers adjusted results for demographic factors, heart disease risk factors, and cognitive test results prior to the MI. Participants who had a stroke during the follow-up period were excluded from the analysis as stroke can affect cognition.

The study showed incident MI was associated with significant decline in global cognition (–0.71; 95% confidence interval, –1.02 to 0.42; P < .0001) and executive function (–0.68; 95% CI, –0.97 to 0.39; P < .004), but not memory, after the MI.

As cognition naturally declines with age, the researchers took that into consideration. “We anticipated cognition over time was going to go down, which it did, but the question we asked was: ‘How did the slope, which we knew was going to decline over time, compare in people who did not have a MI versus those that did?’ ” said Dr. Johansen.

After adjusting the model accordingly, the effect estimates indicating declines in global cognition and executive function were not significant.

However, another model that looked at the effect of incident MI on decline in cognitive function over the years following the event found significant differences.

Compared with participants without MI, those with incident MI had significantly faster declines in global cognition (–0.15 points/year faster, 95% CI, –0.21 to –0.10; P < .002), memory (–0.13 points/year faster, 95% CI, –0.23 to –0.04; P = .004), and executive function (–0.14 points/year faster, 95% CI, –0.20 to –0.08; P < .0001).

Dr. Johansen surmised that MI may result in subclinical infarcts or inflammation, or that MI and cognitive decline have shared vascular risk factors.

She said she can only speculate about why there was not more of a cognitive decline surrounding the MI. “It may be that right after the event, subjects are kind of sick from other things so it’s hard to see exactly what’s going on. Sometimes people can have other problems just from being in the hospital and having a heart attack may make cognition difficult to assess.”

The researchers also looked at those who had a second MI. “We asked whether the decline we saw after the first heart attack among those who had two heart attacks was explained by the fact they had more than one heart attack, and the answer to that question is no,” Dr. Johansen said.

The next research steps for Dr. Johansen and associates are to look at differences in race and sex.

Karen L. Furie, MD, chair, department of neurology, Brown University, and chief of neurology at Rhode Island Hospital, the Miriam Hospital, and the Bradley Hospital, all in Providence, provided a comment on the research.

MI and cognitive decline have a number of common risk factors, including hypertension, diabetes, high cholesterol, smoking, physical inactivity, and poor diet that can lead to obesity, said Dr. Furie.

“It’s critically important to identify these risk factors as early as possible,” she said. “People in early and middle life may not be receiving optimal medical management or engaging in ideal lifestyle choices and these contribute to the development and progression of atherosclerotic disease over the subsequent decades.”

In theory, she said, if these risk factors were eliminated or adequately treated earlier in life, “both the heart and brain could age naturally and in a healthy manner, enabling a higher functioning and better quality of life.”

The study was funded by the National Institute of Neurological Disorders and Stroke and the National Institute of Aging of the National Institutes of Health. Dr. Johansen receives research funding from NINDS.

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

 Patients who have had a myocardial infarction experience faster cognitive decline over time than immediately after the event, new research suggests.

Although cognition in the acute phase after MI was not different than those without an MI in large observational cohorts, cognitive decline became significantly different over a median 6.5 years of follow-up.

The results reinforce the idea that heart health is closely tied to brain health, lead study author Michelle C. Johansen, MD, PhD, assistant professor of neurology cerebrovascular division, Johns Hopkins University, Baltimore, said in an interview. “From a clinical standpoint, heart health affects brain health and there may be effective interventions to prevent heart attack from happening that could reduce the rate of cognitive decline.”

The study was presented during the International Stroke Conference sponsored by the American Heart Association.

Researchers are increasingly recognizing the vascular contribution to cognitive impairment, said Dr. Johansen. This could involve “silent” or subclinical strokes that go unrecognized until seen on imaging.

The study included 31,377 adults free of MI and dementia from six large, well-known cohort studies: the Atherosclerosis Risk in Communities Study, the Coronary Artery Risk Development in Young Adults Study, the Cardiovascular Health Study, the Framingham Offspring Study, the Multi-Ethnic Study of Atherosclerosis, and the Northern Manhattan Study

About 56% of study participants were women, 23% were Black, 8% were Hispanic, and 69% were White.

They were followed from 1971 to 2017 with investigators repeatedly measuring vascular risk factors. The median study follow-up was 6.5 years, but some were followed for up to 20 years. During that time, there were 1,047 incident MIs.

The researchers performed a pooled analysis from these studies “using some fancy statistical techniques,” said Dr. Johansen. “The unique thing about this study was we were able to harmonize the cognitive measures.”

This allowed the researchers to determine if incident MI affected cognitive decline soon after the event and then long-term after the event. The primary outcome was change in global cognition. Additional outcomes were memory and executive function.

The median time between the first MI and the cognitive assessment was about 1.8 years but ranged from about 6 months to 4 years, said Dr. Johansen. Participants were a median age of 60 years at the time of the first cognitive assessment.

The researchers adjusted results for demographic factors, heart disease risk factors, and cognitive test results prior to the MI. Participants who had a stroke during the follow-up period were excluded from the analysis as stroke can affect cognition.

The study showed incident MI was associated with significant decline in global cognition (–0.71; 95% confidence interval, –1.02 to 0.42; P < .0001) and executive function (–0.68; 95% CI, –0.97 to 0.39; P < .004), but not memory, after the MI.

As cognition naturally declines with age, the researchers took that into consideration. “We anticipated cognition over time was going to go down, which it did, but the question we asked was: ‘How did the slope, which we knew was going to decline over time, compare in people who did not have a MI versus those that did?’ ” said Dr. Johansen.

After adjusting the model accordingly, the effect estimates indicating declines in global cognition and executive function were not significant.

However, another model that looked at the effect of incident MI on decline in cognitive function over the years following the event found significant differences.

Compared with participants without MI, those with incident MI had significantly faster declines in global cognition (–0.15 points/year faster, 95% CI, –0.21 to –0.10; P < .002), memory (–0.13 points/year faster, 95% CI, –0.23 to –0.04; P = .004), and executive function (–0.14 points/year faster, 95% CI, –0.20 to –0.08; P < .0001).

Dr. Johansen surmised that MI may result in subclinical infarcts or inflammation, or that MI and cognitive decline have shared vascular risk factors.

She said she can only speculate about why there was not more of a cognitive decline surrounding the MI. “It may be that right after the event, subjects are kind of sick from other things so it’s hard to see exactly what’s going on. Sometimes people can have other problems just from being in the hospital and having a heart attack may make cognition difficult to assess.”

The researchers also looked at those who had a second MI. “We asked whether the decline we saw after the first heart attack among those who had two heart attacks was explained by the fact they had more than one heart attack, and the answer to that question is no,” Dr. Johansen said.

The next research steps for Dr. Johansen and associates are to look at differences in race and sex.

Karen L. Furie, MD, chair, department of neurology, Brown University, and chief of neurology at Rhode Island Hospital, the Miriam Hospital, and the Bradley Hospital, all in Providence, provided a comment on the research.

MI and cognitive decline have a number of common risk factors, including hypertension, diabetes, high cholesterol, smoking, physical inactivity, and poor diet that can lead to obesity, said Dr. Furie.

“It’s critically important to identify these risk factors as early as possible,” she said. “People in early and middle life may not be receiving optimal medical management or engaging in ideal lifestyle choices and these contribute to the development and progression of atherosclerotic disease over the subsequent decades.”

In theory, she said, if these risk factors were eliminated or adequately treated earlier in life, “both the heart and brain could age naturally and in a healthy manner, enabling a higher functioning and better quality of life.”

The study was funded by the National Institute of Neurological Disorders and Stroke and the National Institute of Aging of the National Institutes of Health. Dr. Johansen receives research funding from NINDS.

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

 Patients who have had a myocardial infarction experience faster cognitive decline over time than immediately after the event, new research suggests.

Although cognition in the acute phase after MI was not different than those without an MI in large observational cohorts, cognitive decline became significantly different over a median 6.5 years of follow-up.

The results reinforce the idea that heart health is closely tied to brain health, lead study author Michelle C. Johansen, MD, PhD, assistant professor of neurology cerebrovascular division, Johns Hopkins University, Baltimore, said in an interview. “From a clinical standpoint, heart health affects brain health and there may be effective interventions to prevent heart attack from happening that could reduce the rate of cognitive decline.”

The study was presented during the International Stroke Conference sponsored by the American Heart Association.

Researchers are increasingly recognizing the vascular contribution to cognitive impairment, said Dr. Johansen. This could involve “silent” or subclinical strokes that go unrecognized until seen on imaging.

The study included 31,377 adults free of MI and dementia from six large, well-known cohort studies: the Atherosclerosis Risk in Communities Study, the Coronary Artery Risk Development in Young Adults Study, the Cardiovascular Health Study, the Framingham Offspring Study, the Multi-Ethnic Study of Atherosclerosis, and the Northern Manhattan Study

About 56% of study participants were women, 23% were Black, 8% were Hispanic, and 69% were White.

They were followed from 1971 to 2017 with investigators repeatedly measuring vascular risk factors. The median study follow-up was 6.5 years, but some were followed for up to 20 years. During that time, there were 1,047 incident MIs.

The researchers performed a pooled analysis from these studies “using some fancy statistical techniques,” said Dr. Johansen. “The unique thing about this study was we were able to harmonize the cognitive measures.”

This allowed the researchers to determine if incident MI affected cognitive decline soon after the event and then long-term after the event. The primary outcome was change in global cognition. Additional outcomes were memory and executive function.

The median time between the first MI and the cognitive assessment was about 1.8 years but ranged from about 6 months to 4 years, said Dr. Johansen. Participants were a median age of 60 years at the time of the first cognitive assessment.

The researchers adjusted results for demographic factors, heart disease risk factors, and cognitive test results prior to the MI. Participants who had a stroke during the follow-up period were excluded from the analysis as stroke can affect cognition.

The study showed incident MI was associated with significant decline in global cognition (–0.71; 95% confidence interval, –1.02 to 0.42; P < .0001) and executive function (–0.68; 95% CI, –0.97 to 0.39; P < .004), but not memory, after the MI.

As cognition naturally declines with age, the researchers took that into consideration. “We anticipated cognition over time was going to go down, which it did, but the question we asked was: ‘How did the slope, which we knew was going to decline over time, compare in people who did not have a MI versus those that did?’ ” said Dr. Johansen.

After adjusting the model accordingly, the effect estimates indicating declines in global cognition and executive function were not significant.

However, another model that looked at the effect of incident MI on decline in cognitive function over the years following the event found significant differences.

Compared with participants without MI, those with incident MI had significantly faster declines in global cognition (–0.15 points/year faster, 95% CI, –0.21 to –0.10; P < .002), memory (–0.13 points/year faster, 95% CI, –0.23 to –0.04; P = .004), and executive function (–0.14 points/year faster, 95% CI, –0.20 to –0.08; P < .0001).

Dr. Johansen surmised that MI may result in subclinical infarcts or inflammation, or that MI and cognitive decline have shared vascular risk factors.

She said she can only speculate about why there was not more of a cognitive decline surrounding the MI. “It may be that right after the event, subjects are kind of sick from other things so it’s hard to see exactly what’s going on. Sometimes people can have other problems just from being in the hospital and having a heart attack may make cognition difficult to assess.”

The researchers also looked at those who had a second MI. “We asked whether the decline we saw after the first heart attack among those who had two heart attacks was explained by the fact they had more than one heart attack, and the answer to that question is no,” Dr. Johansen said.

The next research steps for Dr. Johansen and associates are to look at differences in race and sex.

Karen L. Furie, MD, chair, department of neurology, Brown University, and chief of neurology at Rhode Island Hospital, the Miriam Hospital, and the Bradley Hospital, all in Providence, provided a comment on the research.

MI and cognitive decline have a number of common risk factors, including hypertension, diabetes, high cholesterol, smoking, physical inactivity, and poor diet that can lead to obesity, said Dr. Furie.

“It’s critically important to identify these risk factors as early as possible,” she said. “People in early and middle life may not be receiving optimal medical management or engaging in ideal lifestyle choices and these contribute to the development and progression of atherosclerotic disease over the subsequent decades.”

In theory, she said, if these risk factors were eliminated or adequately treated earlier in life, “both the heart and brain could age naturally and in a healthy manner, enabling a higher functioning and better quality of life.”

The study was funded by the National Institute of Neurological Disorders and Stroke and the National Institute of Aging of the National Institutes of Health. Dr. Johansen receives research funding from NINDS.

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

Medicare has received a key endorsement of its plan to restrict payment for the controversial Alzheimer’s disease (AD) drug aducanumab (Aduhelm) – but also drew pleas from other groups for more generous reimbursement of the drug, as well as expected similar medications currently in development.

The Centers for Medicare & Medicaid Services received more than 9,900 comments on its plan, according to the current tally posted on its website. However, it is unclear when the final count will be available.

CMS intends to limit federal payment for monoclonal antibodies that target amyloid to clinical trials. Among supporters of this approach is the influential Medicare Payment Advisory Commission, an expert panel that helps Congress and CMS manage the federal health program.

Opponents of the CMS plan include several pharmaceutical companies. Patient and consumer groups, individuals, and lawmakers had mixed views.

CMS officials will weigh the feedback provided in the comments when setting a final coverage policy for aducanumab. It is expected the agency’s final decision will be announced on April 11.
 

Ongoing debate

The comments submitted to CMS reflect ongoing debate about whether the evidence proves aducanumab provides significant clinical benefit.

The Food and Drug Administration’s unusual approach to clearing the drug for U.S. sales triggered a review of its management of the accelerated approval process by the Office of Inspector General for the Department of Health & Human Services.

The FDA granted an accelerated approval for aducanumab in June based on evidence that the drug clears amyloid in the brain. However, it is unclear whether clearing the protein from the brain results in clinical benefit.

Usually, accelerated approvals precede the completion of phase 3 drug trials, with the FDA allowing early access to a medicine while awaiting confirmatory trials.

In the case of aducanumab, results of the phase 3 confirmatory trials ENGAGE and EMERGE were available at the time of FDA approval. However, interpretation of the findings is controversial.

Biogen contends that the amyloid-clearing effect of the higher dose of aducanumab shown in EMERGE indicates the drug has clinical potential. However, others argue that amyloid clearance does not indicate clinical benefit.

Limiting Medicare coverage of aducanumab for treatment of AD means “the progression of disease, for nearly all beneficiaries, would continue unabated,” Biogen wrote in its comment to CMS.
 

Conflicting data

Supporters of the CMS plan have a different view of the trial data. They note the failure of aducanumab in the companion ENGAGE trial, while also questioning the magnitude of benefit suggested by even the most positive data cited for the drug in the EMERGE trial.

Both studies used the Clinical Dementia Rating-Sum of Boxes (CDR-SB) score, an 18-point scale measuring cognition and function.

In his comment to CMS, MedPAC chairman Michael E. Chernew, PhD, noted the change in CDR-SB score of 0.39 in EMERGE’s high-dose aducanumab group. CMS has described this as being “less than the 1-2 point change that has been suggested as a minimal clinically important difference,” Dr. Chernew wrote.

MedPAC does not normally comment on Medicare coverage decisions, but did so in this case because of its significance and because of the potential fiscal implications, he noted.

“Though there is only limited, conflicting data on Aduhelm’s clinical effectiveness, Medicare would pay a high price for the product,” Dr. Chernew wrote, pointing out the $28,200 annual U.S. price of the drug.

MedPAC thus endorsed the coverage-with-evidence-development (CED) pathway. Under this approach, Medicare would pay for these drugs when used in clinical trials that meet certain criteria.
 

Legal challenge?

In its comment to CMS, Biogen questioned the agency’s legal grounds for limiting coverage of aducanumab. A mandate on clinical trials as part of the CED proposal “runs afoul of the Administrative Procedure Act’s prohibition against arbitrary and capricious agency action,” Biogen said.

The drug company argued that its own planned follow-on studies would provide the kind of data Medicare officials want to see. It also argued for greater use of observational data, including real-world evidence, and of information from Medicare claims.

Roche’s Genentech, which is also developing antiamyloid drugs for AD, echoed some of Biogen’s concerns about the aducanumab plan.

CMS’ CED plan would be “unnecessarily restrictive and discouraging for patients living with this destructive disease,” David Burt, executive director for federal government affairs at Genentech, wrote in a comment to CMS.

CMS should clarify that the CED requirement would not apply to cases of FDA-approved antiamyloid therapies that have demonstrated “clinically meaningful improvement,” Mr. Burt added. He noted there are phase 3 trials of drugs in this class that could soon produce data.

CMS should “fully consider the broad ramifications and significant unintended consequences of prematurely placing unduly severe restrictions on the entire class of antiamyloid monoclonal antibodies,” Mr. Burt wrote.
 

Health care inequity

In its comment to CMS, Biogen also noted the Medicare proposal would “compound the already pervasive inequities in access to treatment and will ultimately prove highly detrimental to health equity.”

There are already concerns about the access of Black and Latinx patients to clinical trials. The planned CED approach would tightly restrict access to aducanumab, as well as expected follow-ons in the amyloid-directed monoclonal antibody (mAb) drug class, the company said.

“Many of the trial sites for Aduhelm, as well as for other amyloid-directed [monoclonal antibodies] are not hospital-based outpatient settings, but include infusion centers, private practices, and medical research centers,” Biogen wrote.

Patient groups such as UsAgainstAlzheimer’s told CMS the CED approach would worsen disparities, despite the aim of Medicare officials to increase participation of Black and Latinx patients in future testing.

“CMS will be hard-pressed to achieve diversity if such hospitals are the only locations where Medicare beneficiaries are able to access mAbs,” USAgainstAlzheimer’s wrote in a Feb. 10 comment.

In contrast, the nonprofit National Center for Health Research praised CMS for what it described as an effort to address a lack of representation of Black and Latinx patients in earlier aducanumab research.

However, the NCHR also suggested CMS revise its plan to mandate that clinical trials include patients who are representative of the national population diagnosed with AD.

“Rather than being concerned about the percentage of patients in specific racial and ethnic groups, we propose that CMS include sufficient numbers of patients in different racial, ethnic, and age groups to ensure that there is enough statistical power for subgroup analyses to determine safety and efficacy for each of the major demographic groups,” the NCHR wrote.
 

Patient health, Medicare at risk

On Feb. 8, a group of House Republican lawmakers asked CMS to reverse its stance. In a publicly released letter, Rep. Cathy McMorris Rodgers of Washington state, the ranking Republican on the House Energy and Commerce Committee, and colleagues urged broader coverage of aducanumab.

In the letter, the group emphasized the idea of aducanumab as a potential treatment for patients with Down syndrome who are at risk for AD.

“The link between Down Syndrome and AD is still being researched by scientists,” Rep. Rodgers and colleagues wrote.

“However, there appears to be a correlation between the additional 21st chromosome present in people with Down Syndrome and the chromosome’s gene that makes amyloid precursor proteins and can cause a build-up of the beta-amyloid plaques common amongst those with AD,” they add.

On the other hand, CMS garnered earlier support from influential Democrats. On Jan. 13, House Energy and Commerce Chairman Frank Pallone Jr (D-N.J.) and House Oversight and Reform Chairwoman Carolyn B. Maloney (D-N.Y.) released a letter praising CMS for its plan for covering aducanumab.

In addition to the HHS-OIG review of the FDA’s approval of the drug, the two House committees are in the midst of their own investigation of the agency’s decision to clear the drug.

“Any broader coverage determination before there is clarity on Aduhelm’s approval process and findings from the myriad ongoing investigations may put the health of millions of Alzheimer’s patients on the line and the financial stability of the nation’s health insurance program for American seniors at risk,” Rep. Pallone and Rep. Maloney wrote.

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

Medicare has received a key endorsement of its plan to restrict payment for the controversial Alzheimer’s disease (AD) drug aducanumab (Aduhelm) – but also drew pleas from other groups for more generous reimbursement of the drug, as well as expected similar medications currently in development.

The Centers for Medicare & Medicaid Services received more than 9,900 comments on its plan, according to the current tally posted on its website. However, it is unclear when the final count will be available.

CMS intends to limit federal payment for monoclonal antibodies that target amyloid to clinical trials. Among supporters of this approach is the influential Medicare Payment Advisory Commission, an expert panel that helps Congress and CMS manage the federal health program.

Opponents of the CMS plan include several pharmaceutical companies. Patient and consumer groups, individuals, and lawmakers had mixed views.

CMS officials will weigh the feedback provided in the comments when setting a final coverage policy for aducanumab. It is expected the agency’s final decision will be announced on April 11.
 

Ongoing debate

The comments submitted to CMS reflect ongoing debate about whether the evidence proves aducanumab provides significant clinical benefit.

The Food and Drug Administration’s unusual approach to clearing the drug for U.S. sales triggered a review of its management of the accelerated approval process by the Office of Inspector General for the Department of Health & Human Services.

The FDA granted an accelerated approval for aducanumab in June based on evidence that the drug clears amyloid in the brain. However, it is unclear whether clearing the protein from the brain results in clinical benefit.

Usually, accelerated approvals precede the completion of phase 3 drug trials, with the FDA allowing early access to a medicine while awaiting confirmatory trials.

In the case of aducanumab, results of the phase 3 confirmatory trials ENGAGE and EMERGE were available at the time of FDA approval. However, interpretation of the findings is controversial.

Biogen contends that the amyloid-clearing effect of the higher dose of aducanumab shown in EMERGE indicates the drug has clinical potential. However, others argue that amyloid clearance does not indicate clinical benefit.

Limiting Medicare coverage of aducanumab for treatment of AD means “the progression of disease, for nearly all beneficiaries, would continue unabated,” Biogen wrote in its comment to CMS.
 

Conflicting data

Supporters of the CMS plan have a different view of the trial data. They note the failure of aducanumab in the companion ENGAGE trial, while also questioning the magnitude of benefit suggested by even the most positive data cited for the drug in the EMERGE trial.

Both studies used the Clinical Dementia Rating-Sum of Boxes (CDR-SB) score, an 18-point scale measuring cognition and function.

In his comment to CMS, MedPAC chairman Michael E. Chernew, PhD, noted the change in CDR-SB score of 0.39 in EMERGE’s high-dose aducanumab group. CMS has described this as being “less than the 1-2 point change that has been suggested as a minimal clinically important difference,” Dr. Chernew wrote.

MedPAC does not normally comment on Medicare coverage decisions, but did so in this case because of its significance and because of the potential fiscal implications, he noted.

“Though there is only limited, conflicting data on Aduhelm’s clinical effectiveness, Medicare would pay a high price for the product,” Dr. Chernew wrote, pointing out the $28,200 annual U.S. price of the drug.

MedPAC thus endorsed the coverage-with-evidence-development (CED) pathway. Under this approach, Medicare would pay for these drugs when used in clinical trials that meet certain criteria.
 

Legal challenge?

In its comment to CMS, Biogen questioned the agency’s legal grounds for limiting coverage of aducanumab. A mandate on clinical trials as part of the CED proposal “runs afoul of the Administrative Procedure Act’s prohibition against arbitrary and capricious agency action,” Biogen said.

The drug company argued that its own planned follow-on studies would provide the kind of data Medicare officials want to see. It also argued for greater use of observational data, including real-world evidence, and of information from Medicare claims.

Roche’s Genentech, which is also developing antiamyloid drugs for AD, echoed some of Biogen’s concerns about the aducanumab plan.

CMS’ CED plan would be “unnecessarily restrictive and discouraging for patients living with this destructive disease,” David Burt, executive director for federal government affairs at Genentech, wrote in a comment to CMS.

CMS should clarify that the CED requirement would not apply to cases of FDA-approved antiamyloid therapies that have demonstrated “clinically meaningful improvement,” Mr. Burt added. He noted there are phase 3 trials of drugs in this class that could soon produce data.

CMS should “fully consider the broad ramifications and significant unintended consequences of prematurely placing unduly severe restrictions on the entire class of antiamyloid monoclonal antibodies,” Mr. Burt wrote.
 

Health care inequity

In its comment to CMS, Biogen also noted the Medicare proposal would “compound the already pervasive inequities in access to treatment and will ultimately prove highly detrimental to health equity.”

There are already concerns about the access of Black and Latinx patients to clinical trials. The planned CED approach would tightly restrict access to aducanumab, as well as expected follow-ons in the amyloid-directed monoclonal antibody (mAb) drug class, the company said.

“Many of the trial sites for Aduhelm, as well as for other amyloid-directed [monoclonal antibodies] are not hospital-based outpatient settings, but include infusion centers, private practices, and medical research centers,” Biogen wrote.

Patient groups such as UsAgainstAlzheimer’s told CMS the CED approach would worsen disparities, despite the aim of Medicare officials to increase participation of Black and Latinx patients in future testing.

“CMS will be hard-pressed to achieve diversity if such hospitals are the only locations where Medicare beneficiaries are able to access mAbs,” USAgainstAlzheimer’s wrote in a Feb. 10 comment.

In contrast, the nonprofit National Center for Health Research praised CMS for what it described as an effort to address a lack of representation of Black and Latinx patients in earlier aducanumab research.

However, the NCHR also suggested CMS revise its plan to mandate that clinical trials include patients who are representative of the national population diagnosed with AD.

“Rather than being concerned about the percentage of patients in specific racial and ethnic groups, we propose that CMS include sufficient numbers of patients in different racial, ethnic, and age groups to ensure that there is enough statistical power for subgroup analyses to determine safety and efficacy for each of the major demographic groups,” the NCHR wrote.
 

Patient health, Medicare at risk

On Feb. 8, a group of House Republican lawmakers asked CMS to reverse its stance. In a publicly released letter, Rep. Cathy McMorris Rodgers of Washington state, the ranking Republican on the House Energy and Commerce Committee, and colleagues urged broader coverage of aducanumab.

In the letter, the group emphasized the idea of aducanumab as a potential treatment for patients with Down syndrome who are at risk for AD.

“The link between Down Syndrome and AD is still being researched by scientists,” Rep. Rodgers and colleagues wrote.

“However, there appears to be a correlation between the additional 21st chromosome present in people with Down Syndrome and the chromosome’s gene that makes amyloid precursor proteins and can cause a build-up of the beta-amyloid plaques common amongst those with AD,” they add.

On the other hand, CMS garnered earlier support from influential Democrats. On Jan. 13, House Energy and Commerce Chairman Frank Pallone Jr (D-N.J.) and House Oversight and Reform Chairwoman Carolyn B. Maloney (D-N.Y.) released a letter praising CMS for its plan for covering aducanumab.

In addition to the HHS-OIG review of the FDA’s approval of the drug, the two House committees are in the midst of their own investigation of the agency’s decision to clear the drug.

“Any broader coverage determination before there is clarity on Aduhelm’s approval process and findings from the myriad ongoing investigations may put the health of millions of Alzheimer’s patients on the line and the financial stability of the nation’s health insurance program for American seniors at risk,” Rep. Pallone and Rep. Maloney wrote.

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

Medicare has received a key endorsement of its plan to restrict payment for the controversial Alzheimer’s disease (AD) drug aducanumab (Aduhelm) – but also drew pleas from other groups for more generous reimbursement of the drug, as well as expected similar medications currently in development.

The Centers for Medicare & Medicaid Services received more than 9,900 comments on its plan, according to the current tally posted on its website. However, it is unclear when the final count will be available.

CMS intends to limit federal payment for monoclonal antibodies that target amyloid to clinical trials. Among supporters of this approach is the influential Medicare Payment Advisory Commission, an expert panel that helps Congress and CMS manage the federal health program.

Opponents of the CMS plan include several pharmaceutical companies. Patient and consumer groups, individuals, and lawmakers had mixed views.

CMS officials will weigh the feedback provided in the comments when setting a final coverage policy for aducanumab. It is expected the agency’s final decision will be announced on April 11.
 

Ongoing debate

The comments submitted to CMS reflect ongoing debate about whether the evidence proves aducanumab provides significant clinical benefit.

The Food and Drug Administration’s unusual approach to clearing the drug for U.S. sales triggered a review of its management of the accelerated approval process by the Office of Inspector General for the Department of Health & Human Services.

The FDA granted an accelerated approval for aducanumab in June based on evidence that the drug clears amyloid in the brain. However, it is unclear whether clearing the protein from the brain results in clinical benefit.

Usually, accelerated approvals precede the completion of phase 3 drug trials, with the FDA allowing early access to a medicine while awaiting confirmatory trials.

In the case of aducanumab, results of the phase 3 confirmatory trials ENGAGE and EMERGE were available at the time of FDA approval. However, interpretation of the findings is controversial.

Biogen contends that the amyloid-clearing effect of the higher dose of aducanumab shown in EMERGE indicates the drug has clinical potential. However, others argue that amyloid clearance does not indicate clinical benefit.

Limiting Medicare coverage of aducanumab for treatment of AD means “the progression of disease, for nearly all beneficiaries, would continue unabated,” Biogen wrote in its comment to CMS.
 

Conflicting data

Supporters of the CMS plan have a different view of the trial data. They note the failure of aducanumab in the companion ENGAGE trial, while also questioning the magnitude of benefit suggested by even the most positive data cited for the drug in the EMERGE trial.

Both studies used the Clinical Dementia Rating-Sum of Boxes (CDR-SB) score, an 18-point scale measuring cognition and function.

In his comment to CMS, MedPAC chairman Michael E. Chernew, PhD, noted the change in CDR-SB score of 0.39 in EMERGE’s high-dose aducanumab group. CMS has described this as being “less than the 1-2 point change that has been suggested as a minimal clinically important difference,” Dr. Chernew wrote.

MedPAC does not normally comment on Medicare coverage decisions, but did so in this case because of its significance and because of the potential fiscal implications, he noted.

“Though there is only limited, conflicting data on Aduhelm’s clinical effectiveness, Medicare would pay a high price for the product,” Dr. Chernew wrote, pointing out the $28,200 annual U.S. price of the drug.

MedPAC thus endorsed the coverage-with-evidence-development (CED) pathway. Under this approach, Medicare would pay for these drugs when used in clinical trials that meet certain criteria.
 

Legal challenge?

In its comment to CMS, Biogen questioned the agency’s legal grounds for limiting coverage of aducanumab. A mandate on clinical trials as part of the CED proposal “runs afoul of the Administrative Procedure Act’s prohibition against arbitrary and capricious agency action,” Biogen said.

The drug company argued that its own planned follow-on studies would provide the kind of data Medicare officials want to see. It also argued for greater use of observational data, including real-world evidence, and of information from Medicare claims.

Roche’s Genentech, which is also developing antiamyloid drugs for AD, echoed some of Biogen’s concerns about the aducanumab plan.

CMS’ CED plan would be “unnecessarily restrictive and discouraging for patients living with this destructive disease,” David Burt, executive director for federal government affairs at Genentech, wrote in a comment to CMS.

CMS should clarify that the CED requirement would not apply to cases of FDA-approved antiamyloid therapies that have demonstrated “clinically meaningful improvement,” Mr. Burt added. He noted there are phase 3 trials of drugs in this class that could soon produce data.

CMS should “fully consider the broad ramifications and significant unintended consequences of prematurely placing unduly severe restrictions on the entire class of antiamyloid monoclonal antibodies,” Mr. Burt wrote.
 

Health care inequity

In its comment to CMS, Biogen also noted the Medicare proposal would “compound the already pervasive inequities in access to treatment and will ultimately prove highly detrimental to health equity.”

There are already concerns about the access of Black and Latinx patients to clinical trials. The planned CED approach would tightly restrict access to aducanumab, as well as expected follow-ons in the amyloid-directed monoclonal antibody (mAb) drug class, the company said.

“Many of the trial sites for Aduhelm, as well as for other amyloid-directed [monoclonal antibodies] are not hospital-based outpatient settings, but include infusion centers, private practices, and medical research centers,” Biogen wrote.

Patient groups such as UsAgainstAlzheimer’s told CMS the CED approach would worsen disparities, despite the aim of Medicare officials to increase participation of Black and Latinx patients in future testing.

“CMS will be hard-pressed to achieve diversity if such hospitals are the only locations where Medicare beneficiaries are able to access mAbs,” USAgainstAlzheimer’s wrote in a Feb. 10 comment.

In contrast, the nonprofit National Center for Health Research praised CMS for what it described as an effort to address a lack of representation of Black and Latinx patients in earlier aducanumab research.

However, the NCHR also suggested CMS revise its plan to mandate that clinical trials include patients who are representative of the national population diagnosed with AD.

“Rather than being concerned about the percentage of patients in specific racial and ethnic groups, we propose that CMS include sufficient numbers of patients in different racial, ethnic, and age groups to ensure that there is enough statistical power for subgroup analyses to determine safety and efficacy for each of the major demographic groups,” the NCHR wrote.
 

Patient health, Medicare at risk

On Feb. 8, a group of House Republican lawmakers asked CMS to reverse its stance. In a publicly released letter, Rep. Cathy McMorris Rodgers of Washington state, the ranking Republican on the House Energy and Commerce Committee, and colleagues urged broader coverage of aducanumab.

In the letter, the group emphasized the idea of aducanumab as a potential treatment for patients with Down syndrome who are at risk for AD.

“The link between Down Syndrome and AD is still being researched by scientists,” Rep. Rodgers and colleagues wrote.

“However, there appears to be a correlation between the additional 21st chromosome present in people with Down Syndrome and the chromosome’s gene that makes amyloid precursor proteins and can cause a build-up of the beta-amyloid plaques common amongst those with AD,” they add.

On the other hand, CMS garnered earlier support from influential Democrats. On Jan. 13, House Energy and Commerce Chairman Frank Pallone Jr (D-N.J.) and House Oversight and Reform Chairwoman Carolyn B. Maloney (D-N.Y.) released a letter praising CMS for its plan for covering aducanumab.

In addition to the HHS-OIG review of the FDA’s approval of the drug, the two House committees are in the midst of their own investigation of the agency’s decision to clear the drug.

“Any broader coverage determination before there is clarity on Aduhelm’s approval process and findings from the myriad ongoing investigations may put the health of millions of Alzheimer’s patients on the line and the financial stability of the nation’s health insurance program for American seniors at risk,” Rep. Pallone and Rep. Maloney wrote.

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

A high level of education, superior academic performance, and excellent written language skills may predict the reversal of mild cognitive impairment (MCI) to normal cognitive function, new research shows.

The investigators found individuals with these factors, which are all markers of cognitive reserve, had a significantly greater chance of reversion from MCI to normal cognition (NC) than progression from MCI to dementia.

In a cohort study of more than 600 women aged 75 years or older, about a third of those with MCI reverted to NC at some point during follow-up, which sends “an encouraging message,” study author Suzanne Tyas, PhD, associate professor, University of Waterloo (Ont.), said in an interview.

“That’s a positive thing for people to keep in mind when they’re thinking about prognosis. Some of these novel characteristics we’ve identified might be useful in thinking about how likely a particular patient might be to improve versus decline cognitively,” Dr. Tyas added.

The findings were published online Feb. 4, 2022, in the journal Neurology.
 

Highly educated cohort

As the population ages, the number of individuals experiencing age-related conditions, including dementia, increases. There is no cure for most dementia types so prevention is key – and preventing dementia requires understanding its risk factors, Dr. Tyas noted.

The analysis included participants from the Nun Study, a longitudinal study of aging and cognition among members of the School Sisters of Notre Dame in the United States. All were 75 and older at baseline, which was from 1991 to 1993; about 14.5% were older than 90 years.

Participants were generally highly educated, with 84.5% attaining an undergraduate or graduate degree. They also had a similar socioeconomic status, level of social supports, marital and reproductive history, and alcohol and tobacco use.

Researchers examined cognitive function at baseline and then about annually until death or end of the 12th round of assessments. They used five measures from the Consortium to Establish a Registry for Alzheimer’s Disease neuropsychological battery to categorize subjects into NC, MCI, or dementia: Delayed Word Recall, Verbal Fluency, Boston Naming, Constructional Praxis, and the Mini-Mental State Exam.

The current analysis focused on the 619 participants with data on apolipoprotein E (apo E) epsilon-4 genotyping and education. From convent archives, investigators also had access to the nuns’ early high school academic performance in English, Latin, algebra, and geometry.

“Typically we only have data for [overall] education. But I know from teaching that there’s a difference between people who just pass my courses and graduate with a university degree versus those who really excel,” Dr. Tyas said.

The researchers also assessed handwriting samples from before the participants entered the religious order. From these, they scored “idea density,” which is the number of ideas contained in the writing and “grammatical complexity,” which includes structure, use of clauses, subclauses, and so on.
 

Dementia not inevitable

Results showed 472 of the 619 participants had MCI during the study period. About 30.3% of these showed at least one reverse transition from MCI to NC during a mean follow-up of 8.6 years; 83.9% went on to develop dementia.

This shows converting from MCI to NC occurs relatively frequently, Dr. Tyas noted.

“This is encouraging because some people think that if they have a diagnosis of MCI they are inevitably going to decline to dementia,” she added.

The researchers also used complicated modeling of transition rates over time between NC, MCI, and dementia and adjusted for participants who died. They estimated relative risk of reversion versus progression for age, apo E, and potential cognitive reserve indicators.

Not surprisingly, younger age (90 years or less) and absence of apo E epsilon-4 allele contributed to a significantly higher rate for reversion from MCI to NC versus progression from MCI to dementia.

However, although age and apo E are known risk factors for dementia, these have not been examined in the context of whether individuals with MCI are more likely to improve or decline, said Dr. Tyas.

Higher educational attainment, the traditional indicator of cognitive reserve, was associated with a significantly higher relative risk for reversion from MCI to NC versus progression from MCI to dementia (RR, 2.6) for a bachelor’s degree versus less education.

There was a greater RR for even higher education after adjusting for age and apo E epsilon-4 status.
 

Language skills key

Interestingly, the investigators also found a significant association with good grades in high school English but not other subjects (RR for higher vs. lower English grades, 1.83; 95% confidence interval, 1.07-3.14).

In addition, they found both characteristics of written language skills (idea density and grammatical complexity) were significant predictors of conversion to NC.

“Those with high levels of idea density were four times more likely to improve to normal cognition than progress to dementia, and the effect was even stronger for grammatical structure. Those individuals with higher levels were almost six times more likely to improve than decline,” Dr. Tyas reported.

The RR for higher versus lower idea density was 3.93 (95% CI, 1.3-11.9) and the RR for higher versus lower grammatical complexity was 5.78 (95% CI, 1.56-21.42).

These new results could be useful when planning future clinical trials, Dr. Tyas noted. “MCI in some people is going to improve even without any treatment, and this should be taken into consideration when recruiting participants to a study and when interpreting the results.

“You don’t want something to look like it’s a benefit of the treatment when in fact these individuals would have just reverted on their own,” she added.
 

Research implications

Commenting on the findings, Claire Sexton, DPhil, director of scientific programs and outreach at the Alzheimer’s Association, noted that, in “this study of highly educated, older women,” transitions from MCI to NC “were about equally common” as transitions from MCI to dementia.

“As advances are made in early detection of dementia, and treatments are developed and marketed for people living with MCI, this article’s findings are important to inform discussions of prognosis with patients and [to the] design of clinical trials,” Dr. Sexton said.

The study was funded by the Canadian Institutes of Health Research and the Natural Sciences and Engineering Research Council of Canada. Funding for the Nun Study at the University of Kentucky was provided by the U.S. National Institute of Aging and the Kleberg Foundation. Dr. Tyas has disclosed no relevant financial relationships.

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

A high level of education, superior academic performance, and excellent written language skills may predict the reversal of mild cognitive impairment (MCI) to normal cognitive function, new research shows.

The investigators found individuals with these factors, which are all markers of cognitive reserve, had a significantly greater chance of reversion from MCI to normal cognition (NC) than progression from MCI to dementia.

In a cohort study of more than 600 women aged 75 years or older, about a third of those with MCI reverted to NC at some point during follow-up, which sends “an encouraging message,” study author Suzanne Tyas, PhD, associate professor, University of Waterloo (Ont.), said in an interview.

“That’s a positive thing for people to keep in mind when they’re thinking about prognosis. Some of these novel characteristics we’ve identified might be useful in thinking about how likely a particular patient might be to improve versus decline cognitively,” Dr. Tyas added.

The findings were published online Feb. 4, 2022, in the journal Neurology.
 

Highly educated cohort

As the population ages, the number of individuals experiencing age-related conditions, including dementia, increases. There is no cure for most dementia types so prevention is key – and preventing dementia requires understanding its risk factors, Dr. Tyas noted.

The analysis included participants from the Nun Study, a longitudinal study of aging and cognition among members of the School Sisters of Notre Dame in the United States. All were 75 and older at baseline, which was from 1991 to 1993; about 14.5% were older than 90 years.

Participants were generally highly educated, with 84.5% attaining an undergraduate or graduate degree. They also had a similar socioeconomic status, level of social supports, marital and reproductive history, and alcohol and tobacco use.

Researchers examined cognitive function at baseline and then about annually until death or end of the 12th round of assessments. They used five measures from the Consortium to Establish a Registry for Alzheimer’s Disease neuropsychological battery to categorize subjects into NC, MCI, or dementia: Delayed Word Recall, Verbal Fluency, Boston Naming, Constructional Praxis, and the Mini-Mental State Exam.

The current analysis focused on the 619 participants with data on apolipoprotein E (apo E) epsilon-4 genotyping and education. From convent archives, investigators also had access to the nuns’ early high school academic performance in English, Latin, algebra, and geometry.

“Typically we only have data for [overall] education. But I know from teaching that there’s a difference between people who just pass my courses and graduate with a university degree versus those who really excel,” Dr. Tyas said.

The researchers also assessed handwriting samples from before the participants entered the religious order. From these, they scored “idea density,” which is the number of ideas contained in the writing and “grammatical complexity,” which includes structure, use of clauses, subclauses, and so on.
 

Dementia not inevitable

Results showed 472 of the 619 participants had MCI during the study period. About 30.3% of these showed at least one reverse transition from MCI to NC during a mean follow-up of 8.6 years; 83.9% went on to develop dementia.

This shows converting from MCI to NC occurs relatively frequently, Dr. Tyas noted.

“This is encouraging because some people think that if they have a diagnosis of MCI they are inevitably going to decline to dementia,” she added.

The researchers also used complicated modeling of transition rates over time between NC, MCI, and dementia and adjusted for participants who died. They estimated relative risk of reversion versus progression for age, apo E, and potential cognitive reserve indicators.

Not surprisingly, younger age (90 years or less) and absence of apo E epsilon-4 allele contributed to a significantly higher rate for reversion from MCI to NC versus progression from MCI to dementia.

However, although age and apo E are known risk factors for dementia, these have not been examined in the context of whether individuals with MCI are more likely to improve or decline, said Dr. Tyas.

Higher educational attainment, the traditional indicator of cognitive reserve, was associated with a significantly higher relative risk for reversion from MCI to NC versus progression from MCI to dementia (RR, 2.6) for a bachelor’s degree versus less education.

There was a greater RR for even higher education after adjusting for age and apo E epsilon-4 status.
 

Language skills key

Interestingly, the investigators also found a significant association with good grades in high school English but not other subjects (RR for higher vs. lower English grades, 1.83; 95% confidence interval, 1.07-3.14).

In addition, they found both characteristics of written language skills (idea density and grammatical complexity) were significant predictors of conversion to NC.

“Those with high levels of idea density were four times more likely to improve to normal cognition than progress to dementia, and the effect was even stronger for grammatical structure. Those individuals with higher levels were almost six times more likely to improve than decline,” Dr. Tyas reported.

The RR for higher versus lower idea density was 3.93 (95% CI, 1.3-11.9) and the RR for higher versus lower grammatical complexity was 5.78 (95% CI, 1.56-21.42).

These new results could be useful when planning future clinical trials, Dr. Tyas noted. “MCI in some people is going to improve even without any treatment, and this should be taken into consideration when recruiting participants to a study and when interpreting the results.

“You don’t want something to look like it’s a benefit of the treatment when in fact these individuals would have just reverted on their own,” she added.
 

Research implications

Commenting on the findings, Claire Sexton, DPhil, director of scientific programs and outreach at the Alzheimer’s Association, noted that, in “this study of highly educated, older women,” transitions from MCI to NC “were about equally common” as transitions from MCI to dementia.

“As advances are made in early detection of dementia, and treatments are developed and marketed for people living with MCI, this article’s findings are important to inform discussions of prognosis with patients and [to the] design of clinical trials,” Dr. Sexton said.

The study was funded by the Canadian Institutes of Health Research and the Natural Sciences and Engineering Research Council of Canada. Funding for the Nun Study at the University of Kentucky was provided by the U.S. National Institute of Aging and the Kleberg Foundation. Dr. Tyas has disclosed no relevant financial relationships.

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

A high level of education, superior academic performance, and excellent written language skills may predict the reversal of mild cognitive impairment (MCI) to normal cognitive function, new research shows.

The investigators found individuals with these factors, which are all markers of cognitive reserve, had a significantly greater chance of reversion from MCI to normal cognition (NC) than progression from MCI to dementia.

In a cohort study of more than 600 women aged 75 years or older, about a third of those with MCI reverted to NC at some point during follow-up, which sends “an encouraging message,” study author Suzanne Tyas, PhD, associate professor, University of Waterloo (Ont.), said in an interview.

“That’s a positive thing for people to keep in mind when they’re thinking about prognosis. Some of these novel characteristics we’ve identified might be useful in thinking about how likely a particular patient might be to improve versus decline cognitively,” Dr. Tyas added.

The findings were published online Feb. 4, 2022, in the journal Neurology.
 

Highly educated cohort

As the population ages, the number of individuals experiencing age-related conditions, including dementia, increases. There is no cure for most dementia types so prevention is key – and preventing dementia requires understanding its risk factors, Dr. Tyas noted.

The analysis included participants from the Nun Study, a longitudinal study of aging and cognition among members of the School Sisters of Notre Dame in the United States. All were 75 and older at baseline, which was from 1991 to 1993; about 14.5% were older than 90 years.

Participants were generally highly educated, with 84.5% attaining an undergraduate or graduate degree. They also had a similar socioeconomic status, level of social supports, marital and reproductive history, and alcohol and tobacco use.

Researchers examined cognitive function at baseline and then about annually until death or end of the 12th round of assessments. They used five measures from the Consortium to Establish a Registry for Alzheimer’s Disease neuropsychological battery to categorize subjects into NC, MCI, or dementia: Delayed Word Recall, Verbal Fluency, Boston Naming, Constructional Praxis, and the Mini-Mental State Exam.

The current analysis focused on the 619 participants with data on apolipoprotein E (apo E) epsilon-4 genotyping and education. From convent archives, investigators also had access to the nuns’ early high school academic performance in English, Latin, algebra, and geometry.

“Typically we only have data for [overall] education. But I know from teaching that there’s a difference between people who just pass my courses and graduate with a university degree versus those who really excel,” Dr. Tyas said.

The researchers also assessed handwriting samples from before the participants entered the religious order. From these, they scored “idea density,” which is the number of ideas contained in the writing and “grammatical complexity,” which includes structure, use of clauses, subclauses, and so on.
 

Dementia not inevitable

Results showed 472 of the 619 participants had MCI during the study period. About 30.3% of these showed at least one reverse transition from MCI to NC during a mean follow-up of 8.6 years; 83.9% went on to develop dementia.

This shows converting from MCI to NC occurs relatively frequently, Dr. Tyas noted.

“This is encouraging because some people think that if they have a diagnosis of MCI they are inevitably going to decline to dementia,” she added.

The researchers also used complicated modeling of transition rates over time between NC, MCI, and dementia and adjusted for participants who died. They estimated relative risk of reversion versus progression for age, apo E, and potential cognitive reserve indicators.

Not surprisingly, younger age (90 years or less) and absence of apo E epsilon-4 allele contributed to a significantly higher rate for reversion from MCI to NC versus progression from MCI to dementia.

However, although age and apo E are known risk factors for dementia, these have not been examined in the context of whether individuals with MCI are more likely to improve or decline, said Dr. Tyas.

Higher educational attainment, the traditional indicator of cognitive reserve, was associated with a significantly higher relative risk for reversion from MCI to NC versus progression from MCI to dementia (RR, 2.6) for a bachelor’s degree versus less education.

There was a greater RR for even higher education after adjusting for age and apo E epsilon-4 status.
 

Language skills key

Interestingly, the investigators also found a significant association with good grades in high school English but not other subjects (RR for higher vs. lower English grades, 1.83; 95% confidence interval, 1.07-3.14).

In addition, they found both characteristics of written language skills (idea density and grammatical complexity) were significant predictors of conversion to NC.

“Those with high levels of idea density were four times more likely to improve to normal cognition than progress to dementia, and the effect was even stronger for grammatical structure. Those individuals with higher levels were almost six times more likely to improve than decline,” Dr. Tyas reported.

The RR for higher versus lower idea density was 3.93 (95% CI, 1.3-11.9) and the RR for higher versus lower grammatical complexity was 5.78 (95% CI, 1.56-21.42).

These new results could be useful when planning future clinical trials, Dr. Tyas noted. “MCI in some people is going to improve even without any treatment, and this should be taken into consideration when recruiting participants to a study and when interpreting the results.

“You don’t want something to look like it’s a benefit of the treatment when in fact these individuals would have just reverted on their own,” she added.
 

Research implications

Commenting on the findings, Claire Sexton, DPhil, director of scientific programs and outreach at the Alzheimer’s Association, noted that, in “this study of highly educated, older women,” transitions from MCI to NC “were about equally common” as transitions from MCI to dementia.

“As advances are made in early detection of dementia, and treatments are developed and marketed for people living with MCI, this article’s findings are important to inform discussions of prognosis with patients and [to the] design of clinical trials,” Dr. Sexton said.

The study was funded by the Canadian Institutes of Health Research and the Natural Sciences and Engineering Research Council of Canada. Funding for the Nun Study at the University of Kentucky was provided by the U.S. National Institute of Aging and the Kleberg Foundation. Dr. Tyas has disclosed no relevant financial relationships.

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

Nearly one-third of adults over age 65 developed one or more new medical conditions in the weeks following a COVID-19 infection, according to new research.

The findings of the observational study, which were published in the BMJ, show the risk of a new condition being triggered by COVID is more than twice as high in seniors, compared with younger patients. Plus, the researchers observed an even higher risk among those who were hospitalized, with nearly half (46%) of patients having developed new conditions after the acute COVID-19 infection period.

Respiratory failure with shortness of breath was the most common postacute sequela, but a wide range of heart, kidney, lung, liver, cognitive, mental health, and other conditions were diagnosed at least 3 weeks after initial infection and persisted beyond 30 days.

This is one of the first studies to specifically describe the incidence and severity of new conditions triggered by COVID-19 infection in a general sample of older adults, said study author Ken Cohen MD, FACP, executive director of translational research at Optum Labs and national senior medical director at Optum Care.

“Much of what has been published on the postacute sequelae of COVID-19 has been predominantly from a younger population, and many of the patients had been hospitalized,” Dr. Cohen noted. “This was the first study to focus on a large population of seniors, most of whom did not require hospitalization.”

Dr. Cohen and colleagues reviewed the health insurance records of more than 133,000 Medicare beneficiaries aged 65 or older who were diagnosed with COVID-19 before April 2020. They also matched individuals by age, race, sex, hospitalization status, and other factors to comparison groups without COVID-19 (one from 2020 and one from 2019), and to a group diagnosed with other lower respiratory tract viral infections before the pandemic.
 

Risk of developing new conditions was higher in hospitalized

After acute COVID-19 infection, 32% of seniors sought medical care for at least one new medical condition in 2020, compared with 21% of uninfected people in the same year.

The most commonly observed conditions included:

• Respiratory failure (7.55% higher risk).
• Fatigue (5.66% higher risk).
• High blood pressure (4.43% higher risk).
• Memory problems (2.63% higher risk).
• Kidney injury (2.59% higher risk).
• Mental health diagnoses (2.5% higher risk).
• Blood-clotting disorders (1.47 % higher risk).
• Heart rhythm disorders (2.9% higher risk).

The risk of developing new conditions was even higher among those 23,486 who were hospitalized in 2020. Those individuals showed a 23.6% higher risk for developing at least one new condition, compared with uninfected seniors in the same year. Also, patients older than 75 had a higher risk for neurological disorders, including dementia, encephalopathy, and memory problems. The researchers also found that respiratory failure and kidney injury were significantly more likely to affect men and Black patients.

When those who had COVID were compared with the group with other lower respiratory viral infections before the pandemic, only the risks of respiratory failure (2.39% higher), dementia (0.71% higher), and fatigue (0.18% higher) were higher.

Primary care providers can learn from these data to better evaluate and manage their geriatric patients with COVID-19 infection, said Amit Shah, MD, a geriatrician with the Mayo Clinic in Phoenix, in an interview.

“We must assess older patients who have had COVID-19 for more than just improvement from the respiratory symptoms of COVID-19 in post-COVID follow-up visits,” he said. “Older individuals with frailty have vulnerability to subsequent complications from severe illnesses and it is common to see post-illness diagnoses, such as new diagnosis of delirium; dementia; or renal, respiratory, or cardiac issues that is precipitated by the original illness. This study confirms that this is likely the case with COVID-19 as well.

“Primary care physicians should be vigilant for these complications, including attention to the rehabilitation needs of older patients with longer-term postviral fatigue from COVID-19,” Dr. Shah added.
 

Data predates ‘Omicron wave’

It remains uncertain whether sequelae will differ with the Omicron variant, but the findings remain applicable, Dr. Cohen said.

“We know that illness from the Omicron variant is on average less severe in those that have been vaccinated. However, throughout the Omicron wave, individuals who have not been vaccinated continue to have significant rates of serious illness and hospitalization,” he said.

“Our findings showed that serious illness with hospitalization was associated with a higher rate of sequelae. It can therefore be inferred that the rates of sequelae seen in our study would continue to occur in unvaccinated individuals who contract Omicron, but might occur less frequently in vaccinated individuals who contract Omicron and have less severe illness.”

Dr. Cohen serves as a consultant for Pfizer. Dr. Shah has disclosed no relevant financial relationships.

Nearly one-third of adults over age 65 developed one or more new medical conditions in the weeks following a COVID-19 infection, according to new research.

The findings of the observational study, which were published in the BMJ, show the risk of a new condition being triggered by COVID is more than twice as high in seniors, compared with younger patients. Plus, the researchers observed an even higher risk among those who were hospitalized, with nearly half (46%) of patients having developed new conditions after the acute COVID-19 infection period.

Respiratory failure with shortness of breath was the most common postacute sequela, but a wide range of heart, kidney, lung, liver, cognitive, mental health, and other conditions were diagnosed at least 3 weeks after initial infection and persisted beyond 30 days.

This is one of the first studies to specifically describe the incidence and severity of new conditions triggered by COVID-19 infection in a general sample of older adults, said study author Ken Cohen MD, FACP, executive director of translational research at Optum Labs and national senior medical director at Optum Care.

“Much of what has been published on the postacute sequelae of COVID-19 has been predominantly from a younger population, and many of the patients had been hospitalized,” Dr. Cohen noted. “This was the first study to focus on a large population of seniors, most of whom did not require hospitalization.”

Dr. Cohen and colleagues reviewed the health insurance records of more than 133,000 Medicare beneficiaries aged 65 or older who were diagnosed with COVID-19 before April 2020. They also matched individuals by age, race, sex, hospitalization status, and other factors to comparison groups without COVID-19 (one from 2020 and one from 2019), and to a group diagnosed with other lower respiratory tract viral infections before the pandemic.
 

Risk of developing new conditions was higher in hospitalized

After acute COVID-19 infection, 32% of seniors sought medical care for at least one new medical condition in 2020, compared with 21% of uninfected people in the same year.

The most commonly observed conditions included:

• Respiratory failure (7.55% higher risk).
• Fatigue (5.66% higher risk).
• High blood pressure (4.43% higher risk).
• Memory problems (2.63% higher risk).
• Kidney injury (2.59% higher risk).
• Mental health diagnoses (2.5% higher risk).
• Blood-clotting disorders (1.47 % higher risk).
• Heart rhythm disorders (2.9% higher risk).

The risk of developing new conditions was even higher among those 23,486 who were hospitalized in 2020. Those individuals showed a 23.6% higher risk for developing at least one new condition, compared with uninfected seniors in the same year. Also, patients older than 75 had a higher risk for neurological disorders, including dementia, encephalopathy, and memory problems. The researchers also found that respiratory failure and kidney injury were significantly more likely to affect men and Black patients.

When those who had COVID were compared with the group with other lower respiratory viral infections before the pandemic, only the risks of respiratory failure (2.39% higher), dementia (0.71% higher), and fatigue (0.18% higher) were higher.

Primary care providers can learn from these data to better evaluate and manage their geriatric patients with COVID-19 infection, said Amit Shah, MD, a geriatrician with the Mayo Clinic in Phoenix, in an interview.

“We must assess older patients who have had COVID-19 for more than just improvement from the respiratory symptoms of COVID-19 in post-COVID follow-up visits,” he said. “Older individuals with frailty have vulnerability to subsequent complications from severe illnesses and it is common to see post-illness diagnoses, such as new diagnosis of delirium; dementia; or renal, respiratory, or cardiac issues that is precipitated by the original illness. This study confirms that this is likely the case with COVID-19 as well.

“Primary care physicians should be vigilant for these complications, including attention to the rehabilitation needs of older patients with longer-term postviral fatigue from COVID-19,” Dr. Shah added.
 

Data predates ‘Omicron wave’

It remains uncertain whether sequelae will differ with the Omicron variant, but the findings remain applicable, Dr. Cohen said.

“We know that illness from the Omicron variant is on average less severe in those that have been vaccinated. However, throughout the Omicron wave, individuals who have not been vaccinated continue to have significant rates of serious illness and hospitalization,” he said.

“Our findings showed that serious illness with hospitalization was associated with a higher rate of sequelae. It can therefore be inferred that the rates of sequelae seen in our study would continue to occur in unvaccinated individuals who contract Omicron, but might occur less frequently in vaccinated individuals who contract Omicron and have less severe illness.”

Dr. Cohen serves as a consultant for Pfizer. Dr. Shah has disclosed no relevant financial relationships.

Nearly one-third of adults over age 65 developed one or more new medical conditions in the weeks following a COVID-19 infection, according to new research.

The findings of the observational study, which were published in the BMJ, show the risk of a new condition being triggered by COVID is more than twice as high in seniors, compared with younger patients. Plus, the researchers observed an even higher risk among those who were hospitalized, with nearly half (46%) of patients having developed new conditions after the acute COVID-19 infection period.

Respiratory failure with shortness of breath was the most common postacute sequela, but a wide range of heart, kidney, lung, liver, cognitive, mental health, and other conditions were diagnosed at least 3 weeks after initial infection and persisted beyond 30 days.

This is one of the first studies to specifically describe the incidence and severity of new conditions triggered by COVID-19 infection in a general sample of older adults, said study author Ken Cohen MD, FACP, executive director of translational research at Optum Labs and national senior medical director at Optum Care.

“Much of what has been published on the postacute sequelae of COVID-19 has been predominantly from a younger population, and many of the patients had been hospitalized,” Dr. Cohen noted. “This was the first study to focus on a large population of seniors, most of whom did not require hospitalization.”

Dr. Cohen and colleagues reviewed the health insurance records of more than 133,000 Medicare beneficiaries aged 65 or older who were diagnosed with COVID-19 before April 2020. They also matched individuals by age, race, sex, hospitalization status, and other factors to comparison groups without COVID-19 (one from 2020 and one from 2019), and to a group diagnosed with other lower respiratory tract viral infections before the pandemic.
 

Risk of developing new conditions was higher in hospitalized

After acute COVID-19 infection, 32% of seniors sought medical care for at least one new medical condition in 2020, compared with 21% of uninfected people in the same year.

The most commonly observed conditions included:

• Respiratory failure (7.55% higher risk).
• Fatigue (5.66% higher risk).
• High blood pressure (4.43% higher risk).
• Memory problems (2.63% higher risk).
• Kidney injury (2.59% higher risk).
• Mental health diagnoses (2.5% higher risk).
• Blood-clotting disorders (1.47 % higher risk).
• Heart rhythm disorders (2.9% higher risk).

The risk of developing new conditions was even higher among those 23,486 who were hospitalized in 2020. Those individuals showed a 23.6% higher risk for developing at least one new condition, compared with uninfected seniors in the same year. Also, patients older than 75 had a higher risk for neurological disorders, including dementia, encephalopathy, and memory problems. The researchers also found that respiratory failure and kidney injury were significantly more likely to affect men and Black patients.

When those who had COVID were compared with the group with other lower respiratory viral infections before the pandemic, only the risks of respiratory failure (2.39% higher), dementia (0.71% higher), and fatigue (0.18% higher) were higher.

Primary care providers can learn from these data to better evaluate and manage their geriatric patients with COVID-19 infection, said Amit Shah, MD, a geriatrician with the Mayo Clinic in Phoenix, in an interview.

“We must assess older patients who have had COVID-19 for more than just improvement from the respiratory symptoms of COVID-19 in post-COVID follow-up visits,” he said. “Older individuals with frailty have vulnerability to subsequent complications from severe illnesses and it is common to see post-illness diagnoses, such as new diagnosis of delirium; dementia; or renal, respiratory, or cardiac issues that is precipitated by the original illness. This study confirms that this is likely the case with COVID-19 as well.

“Primary care physicians should be vigilant for these complications, including attention to the rehabilitation needs of older patients with longer-term postviral fatigue from COVID-19,” Dr. Shah added.
 

Data predates ‘Omicron wave’

It remains uncertain whether sequelae will differ with the Omicron variant, but the findings remain applicable, Dr. Cohen said.

“We know that illness from the Omicron variant is on average less severe in those that have been vaccinated. However, throughout the Omicron wave, individuals who have not been vaccinated continue to have significant rates of serious illness and hospitalization,” he said.

“Our findings showed that serious illness with hospitalization was associated with a higher rate of sequelae. It can therefore be inferred that the rates of sequelae seen in our study would continue to occur in unvaccinated individuals who contract Omicron, but might occur less frequently in vaccinated individuals who contract Omicron and have less severe illness.”

Dr. Cohen serves as a consultant for Pfizer. Dr. Shah has disclosed no relevant financial relationships.

Dietary intake of polyunsaturated fatty acids (PUFA), particularly omega 6, is associated with improved cognitive function in older adults, new research suggests.

The study provides important “pieces of the puzzle” of the diet and cognition connection, but the results aren’t “ready for prime time,” study investigator Roger S. McIntyre, MD, professor of psychiatry and pharmacology, University of Toronto, said in an interview.

“I don’t think we’re there yet when it comes to recommending supplementation to the general public,” said Dr. McIntyre, adding a larger “more compelling study” is needed.

The study was published online Jan. 14 in The American Journal of Geriatric Psychiatry.
 

Clinically meaningful?

Research shows that 25%-50% of community-dwelling adults aged 65-85 years have some cognitive impairment. Other evidence indicates cognition is affected by dietary fat intake.

Many lines of research show that alterations in lipid homeostasis can cause brain dysfunction, said Dr. McIntyre. “This shouldn’t surprise us because our brain is made up of protein, water, and fat.”

This new analysis used combined data from the 2011-2012 and 2013-2014 cycles of the National Health and Nutrition Examination Survey (NHANES), a series of ongoing cross-sectional surveys conducted by the Centers for Disease Control and Prevention. The data are collected in two phases, an in-home face-to-face interview and a physical examination.

Researchers obtained dietary intake information through two 24-hour dietary recall interviews. Dietary information included total energy (kcal/d), intakes in grams per day (g/d) of total fat, saturated fatty acid (SFAT), monounsaturated fatty acid (MUFA), PUFA, total omega-3 and total omega-6 fatty acids, and milligrams per day (mg/d) of cholesterol.

For cognitive function, the researchers used total and delayed recall scores of the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD), the animal fluency test, and the digit symbol substitution test (DSST).

The study included 2,253 adults aged 60 years and older (mean age, 69.4 years) and 51% were non-Hispanic White individuals.

After adjustment for age, sex, race/ethnicity, educational attainment, smoking status, alcohol consumption, income, and total energy, dietary intake of PUFA and omega-6 fatty acid was positively associated with DSST.

The DSST score increased about 0.06 standard deviation (SD) (about 1 score) with each SD increase in these fatty acids (8.8 g/d for PUFA and 7.9 g/d for omega-6) (P values were .02 for PUFA and .01 for omega-6).

However, it’s unclear what an improvement of 1 DSST score means clinically, said Dr. McIntyre. “The P value is significant, but how does that translate? Does this mean a person can now think more clearly or function better?”
 

‘Million dollar question’ remains unanswered

The fact that omega-6, considered neuroinflammatory, was associated with improved DSST score illustrates the complexity of this field, said Dr. McIntyre.

“We’re learning that when it comes to inflammation, many of the molecules in our brain that are implicated as anti-inflammatory can also be pro-inflammatory, so bad guys can be good guys and good guys can be bad guys.”

It speaks to the notion of homeostasis, he added. “Just like a seesaw; when you push this part down, that part goes up.”

The analysis showed the animal fluency score increased about 0.05 SD (around 0.3 score) with each SD (1.1 g/d) increase in dietary intake of omega-3.

There were no significant associations between other dietary fat intake and cognitive performance.

The researchers investigated the role of oxidative stress and antioxidant biomarkers (gamma glutamyl transpeptidase [GGT], bilirubin, uric acid, and vitamin D).

Cells produce oxidative radicals that are normally “mopped up” by our “innate antioxidant capability,” said Dr. McIntyre. “But in states of cognitive impairment, these oxidative stress markers accumulate and they exceed what the normal innate response is able to manage.”

The study showed GGT levels decreased with increased PUFA and omega-6 fatty acid intakes; levels of bilirubin decreased with increase in most dietary fat intakes; uric acid levels decreased with MUFA intake and omega-6/omega-3 ratio; and vitamin D levels increased with omega-3 fatty acid intake but decreased with SFAT intake.

Causal mediation analysis showed the association between dietary intake of fatty acids and DSST performance was partially mediated by GGT levels. However, Dr. McIntyre emphasized that this does not prove causality.

“The million dollar question is, is this the sole explanation for the association? In other words, is it the oxidative stress that caused the cognitive impairment and therefore correcting it improved it, or is it the case that oxidative stress is a proxy of other activities that are also taking place?”
 

A ‘plausible’ link

In an editorial, Candida Rebello, PhD, of the department of integrated physiology and molecular medicine at Pennington Biomedical Research Center, Baton Rouge, La., said the finding that omega-3 and omega-6 fatty acids are positively associated with cognition in older adults makes some sense.

She noted that aging is associated with an overt inflammatory phenotype, and evidence shows these fatty acids are precursors for bioactive molecules that play a role in self-limiting the acute inflammatory response.

Dr. Rebello said the positive association of omega-6 fatty acid with cognition shown in this study contrasts with the “common belief” that increasing dietary intake of these fatty acids enhances inflammation, but agreed the association is “plausible.”

She said it’s “essential” to determine “the underlying mechanisms that regulate the diverse features of inflammation and sort out the processes that protect from neuronal damage and those that contribute towards it.”

She noted the ratio of omega-6 to omega-3 is about 15:1 in the present day Western diet, as opposed to a 1:1 ratio in diets of the past. Omega-3 fatty acids are found in fish oil supplements and fatty fish like mackerel and salmon, while cereal, grains, and vegetable oil are sources of omega-6.

Attaining a measure of balance of fatty acids in the diet may be a “prudent approach,” said Dr. Rebello. “Substituting some meat entrées with fatty fish and polyunsaturated vegetable oils with monounsaturated fats such as olive oil are small changes that are likely to garner adherence.”

Dr. Rebello noted that the study used NHANES food intake data, which rely on participant self-report and so may not be accurate.

The study received funding from the MOE (Ministry of Education in China) Project of Humanities and Social Sciences and the Research Startup Fund of Southwest University. Dr. McIntyre has received research grant support from CIHR/GACD/Chinese National Natural Research Foundation and speaker/consultation fees from Lundbeck, Janssen, Purdue, Pfizer, Otsuka, Takeda, Neurocrine, Sunovion, Bausch Health, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular, NewBridge Pharmaceuticals, and AbbVie. He is a CEO of Braxia Scientific Corp.

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

Dietary intake of polyunsaturated fatty acids (PUFA), particularly omega 6, is associated with improved cognitive function in older adults, new research suggests.

The study provides important “pieces of the puzzle” of the diet and cognition connection, but the results aren’t “ready for prime time,” study investigator Roger S. McIntyre, MD, professor of psychiatry and pharmacology, University of Toronto, said in an interview.

“I don’t think we’re there yet when it comes to recommending supplementation to the general public,” said Dr. McIntyre, adding a larger “more compelling study” is needed.

The study was published online Jan. 14 in The American Journal of Geriatric Psychiatry.
 

Clinically meaningful?

Research shows that 25%-50% of community-dwelling adults aged 65-85 years have some cognitive impairment. Other evidence indicates cognition is affected by dietary fat intake.

Many lines of research show that alterations in lipid homeostasis can cause brain dysfunction, said Dr. McIntyre. “This shouldn’t surprise us because our brain is made up of protein, water, and fat.”

This new analysis used combined data from the 2011-2012 and 2013-2014 cycles of the National Health and Nutrition Examination Survey (NHANES), a series of ongoing cross-sectional surveys conducted by the Centers for Disease Control and Prevention. The data are collected in two phases, an in-home face-to-face interview and a physical examination.

Researchers obtained dietary intake information through two 24-hour dietary recall interviews. Dietary information included total energy (kcal/d), intakes in grams per day (g/d) of total fat, saturated fatty acid (SFAT), monounsaturated fatty acid (MUFA), PUFA, total omega-3 and total omega-6 fatty acids, and milligrams per day (mg/d) of cholesterol.

For cognitive function, the researchers used total and delayed recall scores of the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD), the animal fluency test, and the digit symbol substitution test (DSST).

The study included 2,253 adults aged 60 years and older (mean age, 69.4 years) and 51% were non-Hispanic White individuals.

After adjustment for age, sex, race/ethnicity, educational attainment, smoking status, alcohol consumption, income, and total energy, dietary intake of PUFA and omega-6 fatty acid was positively associated with DSST.

The DSST score increased about 0.06 standard deviation (SD) (about 1 score) with each SD increase in these fatty acids (8.8 g/d for PUFA and 7.9 g/d for omega-6) (P values were .02 for PUFA and .01 for omega-6).

However, it’s unclear what an improvement of 1 DSST score means clinically, said Dr. McIntyre. “The P value is significant, but how does that translate? Does this mean a person can now think more clearly or function better?”
 

‘Million dollar question’ remains unanswered

The fact that omega-6, considered neuroinflammatory, was associated with improved DSST score illustrates the complexity of this field, said Dr. McIntyre.

“We’re learning that when it comes to inflammation, many of the molecules in our brain that are implicated as anti-inflammatory can also be pro-inflammatory, so bad guys can be good guys and good guys can be bad guys.”

It speaks to the notion of homeostasis, he added. “Just like a seesaw; when you push this part down, that part goes up.”

The analysis showed the animal fluency score increased about 0.05 SD (around 0.3 score) with each SD (1.1 g/d) increase in dietary intake of omega-3.

There were no significant associations between other dietary fat intake and cognitive performance.

The researchers investigated the role of oxidative stress and antioxidant biomarkers (gamma glutamyl transpeptidase [GGT], bilirubin, uric acid, and vitamin D).

Cells produce oxidative radicals that are normally “mopped up” by our “innate antioxidant capability,” said Dr. McIntyre. “But in states of cognitive impairment, these oxidative stress markers accumulate and they exceed what the normal innate response is able to manage.”

The study showed GGT levels decreased with increased PUFA and omega-6 fatty acid intakes; levels of bilirubin decreased with increase in most dietary fat intakes; uric acid levels decreased with MUFA intake and omega-6/omega-3 ratio; and vitamin D levels increased with omega-3 fatty acid intake but decreased with SFAT intake.

Causal mediation analysis showed the association between dietary intake of fatty acids and DSST performance was partially mediated by GGT levels. However, Dr. McIntyre emphasized that this does not prove causality.

“The million dollar question is, is this the sole explanation for the association? In other words, is it the oxidative stress that caused the cognitive impairment and therefore correcting it improved it, or is it the case that oxidative stress is a proxy of other activities that are also taking place?”
 

A ‘plausible’ link

In an editorial, Candida Rebello, PhD, of the department of integrated physiology and molecular medicine at Pennington Biomedical Research Center, Baton Rouge, La., said the finding that omega-3 and omega-6 fatty acids are positively associated with cognition in older adults makes some sense.

She noted that aging is associated with an overt inflammatory phenotype, and evidence shows these fatty acids are precursors for bioactive molecules that play a role in self-limiting the acute inflammatory response.

Dr. Rebello said the positive association of omega-6 fatty acid with cognition shown in this study contrasts with the “common belief” that increasing dietary intake of these fatty acids enhances inflammation, but agreed the association is “plausible.”

She said it’s “essential” to determine “the underlying mechanisms that regulate the diverse features of inflammation and sort out the processes that protect from neuronal damage and those that contribute towards it.”

She noted the ratio of omega-6 to omega-3 is about 15:1 in the present day Western diet, as opposed to a 1:1 ratio in diets of the past. Omega-3 fatty acids are found in fish oil supplements and fatty fish like mackerel and salmon, while cereal, grains, and vegetable oil are sources of omega-6.

Attaining a measure of balance of fatty acids in the diet may be a “prudent approach,” said Dr. Rebello. “Substituting some meat entrées with fatty fish and polyunsaturated vegetable oils with monounsaturated fats such as olive oil are small changes that are likely to garner adherence.”

Dr. Rebello noted that the study used NHANES food intake data, which rely on participant self-report and so may not be accurate.

The study received funding from the MOE (Ministry of Education in China) Project of Humanities and Social Sciences and the Research Startup Fund of Southwest University. Dr. McIntyre has received research grant support from CIHR/GACD/Chinese National Natural Research Foundation and speaker/consultation fees from Lundbeck, Janssen, Purdue, Pfizer, Otsuka, Takeda, Neurocrine, Sunovion, Bausch Health, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular, NewBridge Pharmaceuticals, and AbbVie. He is a CEO of Braxia Scientific Corp.

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

Dietary intake of polyunsaturated fatty acids (PUFA), particularly omega 6, is associated with improved cognitive function in older adults, new research suggests.

The study provides important “pieces of the puzzle” of the diet and cognition connection, but the results aren’t “ready for prime time,” study investigator Roger S. McIntyre, MD, professor of psychiatry and pharmacology, University of Toronto, said in an interview.

“I don’t think we’re there yet when it comes to recommending supplementation to the general public,” said Dr. McIntyre, adding a larger “more compelling study” is needed.

The study was published online Jan. 14 in The American Journal of Geriatric Psychiatry.
 

Clinically meaningful?

Research shows that 25%-50% of community-dwelling adults aged 65-85 years have some cognitive impairment. Other evidence indicates cognition is affected by dietary fat intake.

Many lines of research show that alterations in lipid homeostasis can cause brain dysfunction, said Dr. McIntyre. “This shouldn’t surprise us because our brain is made up of protein, water, and fat.”

This new analysis used combined data from the 2011-2012 and 2013-2014 cycles of the National Health and Nutrition Examination Survey (NHANES), a series of ongoing cross-sectional surveys conducted by the Centers for Disease Control and Prevention. The data are collected in two phases, an in-home face-to-face interview and a physical examination.

Researchers obtained dietary intake information through two 24-hour dietary recall interviews. Dietary information included total energy (kcal/d), intakes in grams per day (g/d) of total fat, saturated fatty acid (SFAT), monounsaturated fatty acid (MUFA), PUFA, total omega-3 and total omega-6 fatty acids, and milligrams per day (mg/d) of cholesterol.

For cognitive function, the researchers used total and delayed recall scores of the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD), the animal fluency test, and the digit symbol substitution test (DSST).

The study included 2,253 adults aged 60 years and older (mean age, 69.4 years) and 51% were non-Hispanic White individuals.

After adjustment for age, sex, race/ethnicity, educational attainment, smoking status, alcohol consumption, income, and total energy, dietary intake of PUFA and omega-6 fatty acid was positively associated with DSST.

The DSST score increased about 0.06 standard deviation (SD) (about 1 score) with each SD increase in these fatty acids (8.8 g/d for PUFA and 7.9 g/d for omega-6) (P values were .02 for PUFA and .01 for omega-6).

However, it’s unclear what an improvement of 1 DSST score means clinically, said Dr. McIntyre. “The P value is significant, but how does that translate? Does this mean a person can now think more clearly or function better?”
 

‘Million dollar question’ remains unanswered

The fact that omega-6, considered neuroinflammatory, was associated with improved DSST score illustrates the complexity of this field, said Dr. McIntyre.

“We’re learning that when it comes to inflammation, many of the molecules in our brain that are implicated as anti-inflammatory can also be pro-inflammatory, so bad guys can be good guys and good guys can be bad guys.”

It speaks to the notion of homeostasis, he added. “Just like a seesaw; when you push this part down, that part goes up.”

The analysis showed the animal fluency score increased about 0.05 SD (around 0.3 score) with each SD (1.1 g/d) increase in dietary intake of omega-3.

There were no significant associations between other dietary fat intake and cognitive performance.

The researchers investigated the role of oxidative stress and antioxidant biomarkers (gamma glutamyl transpeptidase [GGT], bilirubin, uric acid, and vitamin D).

Cells produce oxidative radicals that are normally “mopped up” by our “innate antioxidant capability,” said Dr. McIntyre. “But in states of cognitive impairment, these oxidative stress markers accumulate and they exceed what the normal innate response is able to manage.”

The study showed GGT levels decreased with increased PUFA and omega-6 fatty acid intakes; levels of bilirubin decreased with increase in most dietary fat intakes; uric acid levels decreased with MUFA intake and omega-6/omega-3 ratio; and vitamin D levels increased with omega-3 fatty acid intake but decreased with SFAT intake.

Causal mediation analysis showed the association between dietary intake of fatty acids and DSST performance was partially mediated by GGT levels. However, Dr. McIntyre emphasized that this does not prove causality.

“The million dollar question is, is this the sole explanation for the association? In other words, is it the oxidative stress that caused the cognitive impairment and therefore correcting it improved it, or is it the case that oxidative stress is a proxy of other activities that are also taking place?”
 

A ‘plausible’ link

In an editorial, Candida Rebello, PhD, of the department of integrated physiology and molecular medicine at Pennington Biomedical Research Center, Baton Rouge, La., said the finding that omega-3 and omega-6 fatty acids are positively associated with cognition in older adults makes some sense.

She noted that aging is associated with an overt inflammatory phenotype, and evidence shows these fatty acids are precursors for bioactive molecules that play a role in self-limiting the acute inflammatory response.

Dr. Rebello said the positive association of omega-6 fatty acid with cognition shown in this study contrasts with the “common belief” that increasing dietary intake of these fatty acids enhances inflammation, but agreed the association is “plausible.”

She said it’s “essential” to determine “the underlying mechanisms that regulate the diverse features of inflammation and sort out the processes that protect from neuronal damage and those that contribute towards it.”

She noted the ratio of omega-6 to omega-3 is about 15:1 in the present day Western diet, as opposed to a 1:1 ratio in diets of the past. Omega-3 fatty acids are found in fish oil supplements and fatty fish like mackerel and salmon, while cereal, grains, and vegetable oil are sources of omega-6.

Attaining a measure of balance of fatty acids in the diet may be a “prudent approach,” said Dr. Rebello. “Substituting some meat entrées with fatty fish and polyunsaturated vegetable oils with monounsaturated fats such as olive oil are small changes that are likely to garner adherence.”

Dr. Rebello noted that the study used NHANES food intake data, which rely on participant self-report and so may not be accurate.

The study received funding from the MOE (Ministry of Education in China) Project of Humanities and Social Sciences and the Research Startup Fund of Southwest University. Dr. McIntyre has received research grant support from CIHR/GACD/Chinese National Natural Research Foundation and speaker/consultation fees from Lundbeck, Janssen, Purdue, Pfizer, Otsuka, Takeda, Neurocrine, Sunovion, Bausch Health, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular, NewBridge Pharmaceuticals, and AbbVie. He is a CEO of Braxia Scientific Corp.

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

The American Heart Association (AHA) draws attention to the important bidirectional link between cardiovascular health and brain health in its annual statistical update on heart disease and stroke.

“For several years now, the AHA and the scientific community have increasingly recognized the connections between cardiovascular health and brain health, so it was time for us to cement this into its own chapter, which we highlight as the brain health chapter,” Connie W. Tsao, MD, MPH, chair of the statistical update writing group, with Harvard Medical School, Boston, said in an AHA podcast.

“The global rate of brain disease is quickly outpacing heart disease,” Mitchell S. V. Elkind, MD, immediate past president of the AHA, added in a news release.

“The rate of deaths from Alzheimer’s disease and other dementias rose more than twice as much in the past decade compared to the rate of deaths from heart disease, and that is something we must address,” said Dr. Elkind, with Columbia University Vagelos College of Physicians and Surgeons in New York.

“It’s becoming more evident that reducing vascular disease risk factors can make a real difference in helping people live longer, healthier lives, free of heart disease and brain disease,” Dr. Elkind added.

The AHA’s Heart Disease and Stroke Statistics – 2022 Update was published online January 26 in Circulation).

The report highlights some of the research connecting heart and brain health, including the following:

• A meta-analysis of 139 studies showed that people with midlife hypertension were five times more likely to experience impairment on global cognition and about twice as likely to experience reduced executive function, dementia, and Alzheimer’s disease.
• A meta-analysis of four longitudinal studies found that the risk for dementia associated with heart failure was increased nearly twofold.
• In the large prospective Atherosclerosis Risk in Communities (ARIC) Neurocognitive Study, atrial fibrillation was associated with greater cognitive decline and dementia over 20 years.
• A meta-analysis of 10 prospective studies (including 24,801 participants) showed that coronary heart disease (CHD) was associated with a 40% increased risk of poor cognitive outcomes, including dementia, cognitive impairment, or cognitive decline.

“This new chapter on brain health was a critical one to add,” Dr. Tsao said in the news release.

“The data we’ve collected brings to light the strong correlations between heart health and brain health and makes it an easy story to tell -- what’s good for the heart is good for the brain,” Dr. Tsao added.

Along with the new chapter on brain health, the 2022 statistical update provides the latest statistics and heart disease and stroke. Among the highlights:

• Cardiovascular disease (CVD) remains the leading cause of death worldwide. In the United States in 2019, CVD, listed as the underlying cause of death, accounted for 874,613 deaths, about 2,396 deaths each day. On average, someone dies of CVD every 36 seconds.
• CVD claims more lives each year in the United States than all forms of cancer and chronic lower respiratory disease combined.
• In 2019, CHD was the leading cause (41.3%) of deaths attributable to CVD, followed by other CVD (17.3%), stroke (17.2%), hypertension (11.7%), heart failure (9.9%), and diseases of the arteries (2.8%).
• In 2019, stroke accounted for roughly 1 in every 19 deaths in the United States. On average, someone in the United States has a stroke every 40 seconds and someone dies of stroke every 3 minutes 30 seconds. When considered separately from other CVD, stroke ranks number five among all causes of death in the United States.

While the annual statistics update aims to be a contemporary update of annual heart disease and stroke statistics over the past year, it also examines trends over time, Dr. Tsao explains in the podcast.

“One noteworthy point is that we saw a decline in the rate of cardiovascular mortality over the past three decades or so until about 2010. But over the past decade now, we’re also seeing a rise in these numbers,” she said.

This could be due to rising rates of obesity, diabetes, and poor hypertension control, as well as other lifestyle behaviors, Tsao said.
 

Key risk factor data

Each year, the statistical update gauges the cardiovascular health of Americans by tracking seven key health factors and behaviors that increase risk for heart disease and stroke. Below is a snapshot of the latest risk factor data.

Smoking

In 2019, smoking was the leading risk factor for years of life lost to premature death and the third leading risk factor for years of life lived with disability or injury.

According to the 2020 surgeon general’s report on smoking cessation, more than 480,000 Americans die as a result of cigarette smoking, and more than 41,000 die of secondhand smoke exposure each year (roughly 1 in 5 deaths annually).

One in 7 adults are current smokers, 1 in 6 female adults are current smokers, and 1 in 5 high school students use e-cigarettes.
 

Physical inactivity

In 2018, 25.4% of U.S. adults did not engage in leisure-time physical activity, and only 24.0% met the 2018 Physical Activity Guidelines for Americans for both aerobic and muscle strengthening.

Among U.S. high school students in 2019, only 44.1% were physically active for 60 minutes or more on at least 5 days of the week.
 

Nutrition

While there is some evidence that Americans are improving their diet, fewer than 10% of U.S. adults met guidelines for whole grain, whole fruit, and nonstarchy vegetable consumption each day in 2017–2018.

Overweight/obesity

The prevalence of obesity among adults increased from 1999–2000 through 2017–2018 from 30.5% to 42.4%. Overall prevalence of obesity and severe obesity in U.S. youth 2 to 19 years of age increased from 13.9% to 19.3% and 2.6% to 6.1% between 1999–2000 and 2017–2018.

Cholesterol

Close to 94 million (38.1%) U.S. adults have total cholesterol of 200 mg/dL or higher, according to 2015–2018 data; about 28.0 million (11.5%) have total cholesterol of 240 mg/dL or higher; and 27.8% have high levels of low-density lipoprotein cholesterol (130 mg/dL or higher).

Diabetes

In 2019, 87,647 U.S. deaths were attributed to diabetes; data show that 9.8 million U.S. adults have undiagnosed diabetes, 28.2 million have diagnosed diabetes, and 113.6 million have prediabetes.

Hypertension

A total of 121.5 million (47.3%) U.S. adults have hypertension, based on 2015–2018 data. In 2019, 102,072 U.S. deaths were primarily attributable to hypertension.

This statistical update was prepared by a volunteer writing group on behalf of the American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee. Disclosures for the writing committee are listed with the original article.



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

The American Heart Association (AHA) draws attention to the important bidirectional link between cardiovascular health and brain health in its annual statistical update on heart disease and stroke.

“For several years now, the AHA and the scientific community have increasingly recognized the connections between cardiovascular health and brain health, so it was time for us to cement this into its own chapter, which we highlight as the brain health chapter,” Connie W. Tsao, MD, MPH, chair of the statistical update writing group, with Harvard Medical School, Boston, said in an AHA podcast.

“The global rate of brain disease is quickly outpacing heart disease,” Mitchell S. V. Elkind, MD, immediate past president of the AHA, added in a news release.

“The rate of deaths from Alzheimer’s disease and other dementias rose more than twice as much in the past decade compared to the rate of deaths from heart disease, and that is something we must address,” said Dr. Elkind, with Columbia University Vagelos College of Physicians and Surgeons in New York.

“It’s becoming more evident that reducing vascular disease risk factors can make a real difference in helping people live longer, healthier lives, free of heart disease and brain disease,” Dr. Elkind added.

The AHA’s Heart Disease and Stroke Statistics – 2022 Update was published online January 26 in Circulation).

The report highlights some of the research connecting heart and brain health, including the following:

• A meta-analysis of 139 studies showed that people with midlife hypertension were five times more likely to experience impairment on global cognition and about twice as likely to experience reduced executive function, dementia, and Alzheimer’s disease.
• A meta-analysis of four longitudinal studies found that the risk for dementia associated with heart failure was increased nearly twofold.
• In the large prospective Atherosclerosis Risk in Communities (ARIC) Neurocognitive Study, atrial fibrillation was associated with greater cognitive decline and dementia over 20 years.
• A meta-analysis of 10 prospective studies (including 24,801 participants) showed that coronary heart disease (CHD) was associated with a 40% increased risk of poor cognitive outcomes, including dementia, cognitive impairment, or cognitive decline.

“This new chapter on brain health was a critical one to add,” Dr. Tsao said in the news release.

“The data we’ve collected brings to light the strong correlations between heart health and brain health and makes it an easy story to tell -- what’s good for the heart is good for the brain,” Dr. Tsao added.

Along with the new chapter on brain health, the 2022 statistical update provides the latest statistics and heart disease and stroke. Among the highlights:

• Cardiovascular disease (CVD) remains the leading cause of death worldwide. In the United States in 2019, CVD, listed as the underlying cause of death, accounted for 874,613 deaths, about 2,396 deaths each day. On average, someone dies of CVD every 36 seconds.
• CVD claims more lives each year in the United States than all forms of cancer and chronic lower respiratory disease combined.
• In 2019, CHD was the leading cause (41.3%) of deaths attributable to CVD, followed by other CVD (17.3%), stroke (17.2%), hypertension (11.7%), heart failure (9.9%), and diseases of the arteries (2.8%).
• In 2019, stroke accounted for roughly 1 in every 19 deaths in the United States. On average, someone in the United States has a stroke every 40 seconds and someone dies of stroke every 3 minutes 30 seconds. When considered separately from other CVD, stroke ranks number five among all causes of death in the United States.

While the annual statistics update aims to be a contemporary update of annual heart disease and stroke statistics over the past year, it also examines trends over time, Dr. Tsao explains in the podcast.

“One noteworthy point is that we saw a decline in the rate of cardiovascular mortality over the past three decades or so until about 2010. But over the past decade now, we’re also seeing a rise in these numbers,” she said.

This could be due to rising rates of obesity, diabetes, and poor hypertension control, as well as other lifestyle behaviors, Tsao said.
 

Key risk factor data

Each year, the statistical update gauges the cardiovascular health of Americans by tracking seven key health factors and behaviors that increase risk for heart disease and stroke. Below is a snapshot of the latest risk factor data.

Smoking

In 2019, smoking was the leading risk factor for years of life lost to premature death and the third leading risk factor for years of life lived with disability or injury.

According to the 2020 surgeon general’s report on smoking cessation, more than 480,000 Americans die as a result of cigarette smoking, and more than 41,000 die of secondhand smoke exposure each year (roughly 1 in 5 deaths annually).

One in 7 adults are current smokers, 1 in 6 female adults are current smokers, and 1 in 5 high school students use e-cigarettes.
 

Physical inactivity

In 2018, 25.4% of U.S. adults did not engage in leisure-time physical activity, and only 24.0% met the 2018 Physical Activity Guidelines for Americans for both aerobic and muscle strengthening.

Among U.S. high school students in 2019, only 44.1% were physically active for 60 minutes or more on at least 5 days of the week.
 

Nutrition

While there is some evidence that Americans are improving their diet, fewer than 10% of U.S. adults met guidelines for whole grain, whole fruit, and nonstarchy vegetable consumption each day in 2017–2018.

Overweight/obesity

The prevalence of obesity among adults increased from 1999–2000 through 2017–2018 from 30.5% to 42.4%. Overall prevalence of obesity and severe obesity in U.S. youth 2 to 19 years of age increased from 13.9% to 19.3% and 2.6% to 6.1% between 1999–2000 and 2017–2018.

Cholesterol

Close to 94 million (38.1%) U.S. adults have total cholesterol of 200 mg/dL or higher, according to 2015–2018 data; about 28.0 million (11.5%) have total cholesterol of 240 mg/dL or higher; and 27.8% have high levels of low-density lipoprotein cholesterol (130 mg/dL or higher).

Diabetes

In 2019, 87,647 U.S. deaths were attributed to diabetes; data show that 9.8 million U.S. adults have undiagnosed diabetes, 28.2 million have diagnosed diabetes, and 113.6 million have prediabetes.

Hypertension

A total of 121.5 million (47.3%) U.S. adults have hypertension, based on 2015–2018 data. In 2019, 102,072 U.S. deaths were primarily attributable to hypertension.

This statistical update was prepared by a volunteer writing group on behalf of the American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee. Disclosures for the writing committee are listed with the original article.



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

The American Heart Association (AHA) draws attention to the important bidirectional link between cardiovascular health and brain health in its annual statistical update on heart disease and stroke.

“For several years now, the AHA and the scientific community have increasingly recognized the connections between cardiovascular health and brain health, so it was time for us to cement this into its own chapter, which we highlight as the brain health chapter,” Connie W. Tsao, MD, MPH, chair of the statistical update writing group, with Harvard Medical School, Boston, said in an AHA podcast.

“The global rate of brain disease is quickly outpacing heart disease,” Mitchell S. V. Elkind, MD, immediate past president of the AHA, added in a news release.

“The rate of deaths from Alzheimer’s disease and other dementias rose more than twice as much in the past decade compared to the rate of deaths from heart disease, and that is something we must address,” said Dr. Elkind, with Columbia University Vagelos College of Physicians and Surgeons in New York.

“It’s becoming more evident that reducing vascular disease risk factors can make a real difference in helping people live longer, healthier lives, free of heart disease and brain disease,” Dr. Elkind added.

The AHA’s Heart Disease and Stroke Statistics – 2022 Update was published online January 26 in Circulation).

The report highlights some of the research connecting heart and brain health, including the following:

• A meta-analysis of 139 studies showed that people with midlife hypertension were five times more likely to experience impairment on global cognition and about twice as likely to experience reduced executive function, dementia, and Alzheimer’s disease.
• A meta-analysis of four longitudinal studies found that the risk for dementia associated with heart failure was increased nearly twofold.
• In the large prospective Atherosclerosis Risk in Communities (ARIC) Neurocognitive Study, atrial fibrillation was associated with greater cognitive decline and dementia over 20 years.
• A meta-analysis of 10 prospective studies (including 24,801 participants) showed that coronary heart disease (CHD) was associated with a 40% increased risk of poor cognitive outcomes, including dementia, cognitive impairment, or cognitive decline.

“This new chapter on brain health was a critical one to add,” Dr. Tsao said in the news release.

“The data we’ve collected brings to light the strong correlations between heart health and brain health and makes it an easy story to tell -- what’s good for the heart is good for the brain,” Dr. Tsao added.

Along with the new chapter on brain health, the 2022 statistical update provides the latest statistics and heart disease and stroke. Among the highlights:

• Cardiovascular disease (CVD) remains the leading cause of death worldwide. In the United States in 2019, CVD, listed as the underlying cause of death, accounted for 874,613 deaths, about 2,396 deaths each day. On average, someone dies of CVD every 36 seconds.
• CVD claims more lives each year in the United States than all forms of cancer and chronic lower respiratory disease combined.
• In 2019, CHD was the leading cause (41.3%) of deaths attributable to CVD, followed by other CVD (17.3%), stroke (17.2%), hypertension (11.7%), heart failure (9.9%), and diseases of the arteries (2.8%).
• In 2019, stroke accounted for roughly 1 in every 19 deaths in the United States. On average, someone in the United States has a stroke every 40 seconds and someone dies of stroke every 3 minutes 30 seconds. When considered separately from other CVD, stroke ranks number five among all causes of death in the United States.

While the annual statistics update aims to be a contemporary update of annual heart disease and stroke statistics over the past year, it also examines trends over time, Dr. Tsao explains in the podcast.

“One noteworthy point is that we saw a decline in the rate of cardiovascular mortality over the past three decades or so until about 2010. But over the past decade now, we’re also seeing a rise in these numbers,” she said.

This could be due to rising rates of obesity, diabetes, and poor hypertension control, as well as other lifestyle behaviors, Tsao said.
 

Key risk factor data

Each year, the statistical update gauges the cardiovascular health of Americans by tracking seven key health factors and behaviors that increase risk for heart disease and stroke. Below is a snapshot of the latest risk factor data.

Smoking

In 2019, smoking was the leading risk factor for years of life lost to premature death and the third leading risk factor for years of life lived with disability or injury.

According to the 2020 surgeon general’s report on smoking cessation, more than 480,000 Americans die as a result of cigarette smoking, and more than 41,000 die of secondhand smoke exposure each year (roughly 1 in 5 deaths annually).

One in 7 adults are current smokers, 1 in 6 female adults are current smokers, and 1 in 5 high school students use e-cigarettes.
 

Physical inactivity

In 2018, 25.4% of U.S. adults did not engage in leisure-time physical activity, and only 24.0% met the 2018 Physical Activity Guidelines for Americans for both aerobic and muscle strengthening.

Among U.S. high school students in 2019, only 44.1% were physically active for 60 minutes or more on at least 5 days of the week.
 

Nutrition

While there is some evidence that Americans are improving their diet, fewer than 10% of U.S. adults met guidelines for whole grain, whole fruit, and nonstarchy vegetable consumption each day in 2017–2018.

Overweight/obesity

The prevalence of obesity among adults increased from 1999–2000 through 2017–2018 from 30.5% to 42.4%. Overall prevalence of obesity and severe obesity in U.S. youth 2 to 19 years of age increased from 13.9% to 19.3% and 2.6% to 6.1% between 1999–2000 and 2017–2018.

Cholesterol

Close to 94 million (38.1%) U.S. adults have total cholesterol of 200 mg/dL or higher, according to 2015–2018 data; about 28.0 million (11.5%) have total cholesterol of 240 mg/dL or higher; and 27.8% have high levels of low-density lipoprotein cholesterol (130 mg/dL or higher).

Diabetes

In 2019, 87,647 U.S. deaths were attributed to diabetes; data show that 9.8 million U.S. adults have undiagnosed diabetes, 28.2 million have diagnosed diabetes, and 113.6 million have prediabetes.

Hypertension

A total of 121.5 million (47.3%) U.S. adults have hypertension, based on 2015–2018 data. In 2019, 102,072 U.S. deaths were primarily attributable to hypertension.

This statistical update was prepared by a volunteer writing group on behalf of the American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee. Disclosures for the writing committee are listed with the original article.



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

It all started with genetic data. A gene here, a gene there. Eventually the story became clearer: If scientists are to one day find a cure for Alzheimer’s disease, they should look to the immune system.

Over the past couple decades, researchers have identified numerous genes involved in various immune system functions that may also contribute to Alzheimer’s disease. Some of the prime suspects are genes that control microglia, now the focus of intense research in developing new Alzheimer’s drugs.

Microglia are amoeba-like cells that scour the brain for injuries and invaders. They help clear dead or impaired brain cells and literally gobble up invading microbes. Without them, we’d be in trouble.

In a normal brain, a protein called beta-amyloid is cleared away through our lymphatic system by microglia as molecular junk. But sometimes it builds up. Certain gene mutations are one culprit in this toxic accumulation. Traumatic brain injury is another, and, perhaps, impaired microglial function.

One thing everyone agrees on is that in people with Alzheimer’s disease, too much amyloid accumulates between their brain cells and in the vessels that supply the brain with blood. Once amyloid begins to clog networks of neurons, it triggers the accumulation of another protein, called tau, inside of these brain cells. The presence of tau sends microglia and other immune mechanisms into overdrive, resulting in the inflammatory immune response that many experts believe ultimately saps brain vitality in Alzheimer’s disease.
 

The gene scene

To date, nearly a dozen genes involved in immune and microglial function have been tied to Alzheimer’s disease. The first was CD33, identified in 2008.

“When we got the results, I literally ran to my colleague’s office next door and said, you gotta see this!” said Harvard neuroscientist Rudolph Tanzi. Dr. Tanzi, who goes by Rudy, led the CD33 research. The discovery was quickly named a top medical breakthrough of 2008 by Time magazine.

“We were laughing because what they didn’t know is we had no idea what this gene did,” he joked. But over time, research by Dr. Tanzi and his group revealed that CD33 is a kind of microglial on-off switch, activating the cells as part of an inflammatory pathway.

“We kind of got it all going when it came to the genetics,” he said.

Microglia normally recognize molecular patterns associated with microbes and cellular damage as unwanted. This is how they know to take action – to devour unfamiliar pathogens and dead tissue. Dr. Tanzi believes microglia sense any sign of brain damage as an infection, which causes them to become hyperactive.

Much of our modern human immune system, he explained, evolved many hundreds of thousands of years ago. Our lifespans at the time were far shorter than they are today, and the majority of people didn’t live long enough to develop dementia or the withered brain cells that come with it. So our immune system, he said, assumes any faulty brain tissue is due to a microbe, not dementia. Microglia react aggressively, clearing the area to prevent the spread of infection.

“They say, ‘We better wipe out this part of the brain that’s infected, even if it’s not.’ They don’t know,” quipped Dr. Tanzi. “That’s what causes neuroinflammation. And CD33 turns this response on. The microglia become killers, not just janitors.”
 

A brake on overactive microglia

If CD33 is the yin, a gene called TREM2 is the yang. Discovered a few years after CD33, TREM2 reins in microglial activation, returning them to their role as cellular housekeepers.

Neurologist David Holtzman, MD, of Washington University in St. Louis, who studies TREM2, agrees that wherever you find amyloid, tau, or dead brain cells, there are microglia raring to go and ready to scavenge.

“I think at first a lot of people thought these cells were reacting to Alzheimer’s pathology, and not necessarily a cause of the disease,” he said.

It was the discovery of TREM2 on the heels of CD33 that really shifted the thinking, in part because it produces a protein that in the brain is only found in microglia. “Many of us [in the field] immediately said, ‘Look, there’s now a risk factor that is only expressed in microglia. It must be that innate immune cells are important in some way in the pathogenesis of the disease,’ “ he added.

Dr. Holtzman sees microglial activation in impending dementia as a double-edged sword. In the beginning, microglia clear unwanted amyloid to maintain brain health. But once accumulated amyloid and tau have done enough damage, the neuroinflammation that comes with microglial activation does more harm than good. Neurons die en masse and dementia sets in.

But not all researchers are convinced.

Serge Revist, PhD, is a professor in the department of molecular medicine at the Laval University Medical School in Quebec. Based on his lab’s research, he believes that while impaired immune activity is involved in Alzheimer’s disease, it is not the root cause. “I don’t think it is the immune cells that do the damage, I still think it is the beta-amyloid itself,” he said, “In my lab, in mouse studies, we’ve never found that immune cells were directly responsible for killing neurons.”

He does believe that in some patients with Alzheimer’s disease, microglia may not be able to handle the excess amyloid that accumulates in the disease and that developing treatments that improve the ability of microglia and the immune system to clear the protein could be effective.
 

Microglial medicines

The biological cascade leading to Alzheimer’s disease is a tangled one. Gene variants influencing the accumulation and clearance of amyloid are likely a major contributor. But immune activity caused by early life infection might also be involved, at least in some cases. This infectious theory of Alzheimer’s disease was first proposed by Dr. Tanzi’s now-deceased colleague Robert Moir, PhD. Dr. Tanzi’s group even has evidence that amyloid itself is antimicrobial and evolved to protect us from pathogens, only to become a problem when overactive and aggregated.

And the same goes for microglia, cells whose over-ambition might cause much of the brain degeneration seen in Alzheimer’s disease.

In theory, if a treatment could decrease CD33 activity or increase that of TREM2, doctors might one day may be able to slow or even stop the progression of dementia. Instead of going after amyloid itself – the mechanism behind so many failed investigational Alzheimer’s drugs – a therapy that quells the immune response to amyloid might be the answer in treating dementia.

“There are a number of scientists and companies trying to figure out how to influence genes like TREM2 and CD33 and to both decrease amyloid and act on the downstream consequences of the protein,” said Dr. Holtzman. “All of this is to say that somewhere in the biology that causes Alzheimer’s disease, the immune system is involved.”

It seems that in many cases, the most common form of a dementia might be due to a well-intentioned immune cell going rogue. “I think you’d hear this from basically any researcher worth their salt,” said Dr. Tanzi. “I feel strongly that without microglial activation, you will not get Alzheimer’s disease.”

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

It all started with genetic data. A gene here, a gene there. Eventually the story became clearer: If scientists are to one day find a cure for Alzheimer’s disease, they should look to the immune system.

Over the past couple decades, researchers have identified numerous genes involved in various immune system functions that may also contribute to Alzheimer’s disease. Some of the prime suspects are genes that control microglia, now the focus of intense research in developing new Alzheimer’s drugs.

Microglia are amoeba-like cells that scour the brain for injuries and invaders. They help clear dead or impaired brain cells and literally gobble up invading microbes. Without them, we’d be in trouble.

In a normal brain, a protein called beta-amyloid is cleared away through our lymphatic system by microglia as molecular junk. But sometimes it builds up. Certain gene mutations are one culprit in this toxic accumulation. Traumatic brain injury is another, and, perhaps, impaired microglial function.

One thing everyone agrees on is that in people with Alzheimer’s disease, too much amyloid accumulates between their brain cells and in the vessels that supply the brain with blood. Once amyloid begins to clog networks of neurons, it triggers the accumulation of another protein, called tau, inside of these brain cells. The presence of tau sends microglia and other immune mechanisms into overdrive, resulting in the inflammatory immune response that many experts believe ultimately saps brain vitality in Alzheimer’s disease.
 

The gene scene

To date, nearly a dozen genes involved in immune and microglial function have been tied to Alzheimer’s disease. The first was CD33, identified in 2008.

“When we got the results, I literally ran to my colleague’s office next door and said, you gotta see this!” said Harvard neuroscientist Rudolph Tanzi. Dr. Tanzi, who goes by Rudy, led the CD33 research. The discovery was quickly named a top medical breakthrough of 2008 by Time magazine.

“We were laughing because what they didn’t know is we had no idea what this gene did,” he joked. But over time, research by Dr. Tanzi and his group revealed that CD33 is a kind of microglial on-off switch, activating the cells as part of an inflammatory pathway.

“We kind of got it all going when it came to the genetics,” he said.

Microglia normally recognize molecular patterns associated with microbes and cellular damage as unwanted. This is how they know to take action – to devour unfamiliar pathogens and dead tissue. Dr. Tanzi believes microglia sense any sign of brain damage as an infection, which causes them to become hyperactive.

Much of our modern human immune system, he explained, evolved many hundreds of thousands of years ago. Our lifespans at the time were far shorter than they are today, and the majority of people didn’t live long enough to develop dementia or the withered brain cells that come with it. So our immune system, he said, assumes any faulty brain tissue is due to a microbe, not dementia. Microglia react aggressively, clearing the area to prevent the spread of infection.

“They say, ‘We better wipe out this part of the brain that’s infected, even if it’s not.’ They don’t know,” quipped Dr. Tanzi. “That’s what causes neuroinflammation. And CD33 turns this response on. The microglia become killers, not just janitors.”
 

A brake on overactive microglia

If CD33 is the yin, a gene called TREM2 is the yang. Discovered a few years after CD33, TREM2 reins in microglial activation, returning them to their role as cellular housekeepers.

Neurologist David Holtzman, MD, of Washington University in St. Louis, who studies TREM2, agrees that wherever you find amyloid, tau, or dead brain cells, there are microglia raring to go and ready to scavenge.

“I think at first a lot of people thought these cells were reacting to Alzheimer’s pathology, and not necessarily a cause of the disease,” he said.

It was the discovery of TREM2 on the heels of CD33 that really shifted the thinking, in part because it produces a protein that in the brain is only found in microglia. “Many of us [in the field] immediately said, ‘Look, there’s now a risk factor that is only expressed in microglia. It must be that innate immune cells are important in some way in the pathogenesis of the disease,’ “ he added.

Dr. Holtzman sees microglial activation in impending dementia as a double-edged sword. In the beginning, microglia clear unwanted amyloid to maintain brain health. But once accumulated amyloid and tau have done enough damage, the neuroinflammation that comes with microglial activation does more harm than good. Neurons die en masse and dementia sets in.

But not all researchers are convinced.

Serge Revist, PhD, is a professor in the department of molecular medicine at the Laval University Medical School in Quebec. Based on his lab’s research, he believes that while impaired immune activity is involved in Alzheimer’s disease, it is not the root cause. “I don’t think it is the immune cells that do the damage, I still think it is the beta-amyloid itself,” he said, “In my lab, in mouse studies, we’ve never found that immune cells were directly responsible for killing neurons.”

He does believe that in some patients with Alzheimer’s disease, microglia may not be able to handle the excess amyloid that accumulates in the disease and that developing treatments that improve the ability of microglia and the immune system to clear the protein could be effective.
 

Microglial medicines

The biological cascade leading to Alzheimer’s disease is a tangled one. Gene variants influencing the accumulation and clearance of amyloid are likely a major contributor. But immune activity caused by early life infection might also be involved, at least in some cases. This infectious theory of Alzheimer’s disease was first proposed by Dr. Tanzi’s now-deceased colleague Robert Moir, PhD. Dr. Tanzi’s group even has evidence that amyloid itself is antimicrobial and evolved to protect us from pathogens, only to become a problem when overactive and aggregated.

And the same goes for microglia, cells whose over-ambition might cause much of the brain degeneration seen in Alzheimer’s disease.

In theory, if a treatment could decrease CD33 activity or increase that of TREM2, doctors might one day may be able to slow or even stop the progression of dementia. Instead of going after amyloid itself – the mechanism behind so many failed investigational Alzheimer’s drugs – a therapy that quells the immune response to amyloid might be the answer in treating dementia.

“There are a number of scientists and companies trying to figure out how to influence genes like TREM2 and CD33 and to both decrease amyloid and act on the downstream consequences of the protein,” said Dr. Holtzman. “All of this is to say that somewhere in the biology that causes Alzheimer’s disease, the immune system is involved.”

It seems that in many cases, the most common form of a dementia might be due to a well-intentioned immune cell going rogue. “I think you’d hear this from basically any researcher worth their salt,” said Dr. Tanzi. “I feel strongly that without microglial activation, you will not get Alzheimer’s disease.”

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

It all started with genetic data. A gene here, a gene there. Eventually the story became clearer: If scientists are to one day find a cure for Alzheimer’s disease, they should look to the immune system.

Over the past couple decades, researchers have identified numerous genes involved in various immune system functions that may also contribute to Alzheimer’s disease. Some of the prime suspects are genes that control microglia, now the focus of intense research in developing new Alzheimer’s drugs.

Microglia are amoeba-like cells that scour the brain for injuries and invaders. They help clear dead or impaired brain cells and literally gobble up invading microbes. Without them, we’d be in trouble.

In a normal brain, a protein called beta-amyloid is cleared away through our lymphatic system by microglia as molecular junk. But sometimes it builds up. Certain gene mutations are one culprit in this toxic accumulation. Traumatic brain injury is another, and, perhaps, impaired microglial function.

One thing everyone agrees on is that in people with Alzheimer’s disease, too much amyloid accumulates between their brain cells and in the vessels that supply the brain with blood. Once amyloid begins to clog networks of neurons, it triggers the accumulation of another protein, called tau, inside of these brain cells. The presence of tau sends microglia and other immune mechanisms into overdrive, resulting in the inflammatory immune response that many experts believe ultimately saps brain vitality in Alzheimer’s disease.
 

The gene scene

To date, nearly a dozen genes involved in immune and microglial function have been tied to Alzheimer’s disease. The first was CD33, identified in 2008.

“When we got the results, I literally ran to my colleague’s office next door and said, you gotta see this!” said Harvard neuroscientist Rudolph Tanzi. Dr. Tanzi, who goes by Rudy, led the CD33 research. The discovery was quickly named a top medical breakthrough of 2008 by Time magazine.

“We were laughing because what they didn’t know is we had no idea what this gene did,” he joked. But over time, research by Dr. Tanzi and his group revealed that CD33 is a kind of microglial on-off switch, activating the cells as part of an inflammatory pathway.

“We kind of got it all going when it came to the genetics,” he said.

Microglia normally recognize molecular patterns associated with microbes and cellular damage as unwanted. This is how they know to take action – to devour unfamiliar pathogens and dead tissue. Dr. Tanzi believes microglia sense any sign of brain damage as an infection, which causes them to become hyperactive.

Much of our modern human immune system, he explained, evolved many hundreds of thousands of years ago. Our lifespans at the time were far shorter than they are today, and the majority of people didn’t live long enough to develop dementia or the withered brain cells that come with it. So our immune system, he said, assumes any faulty brain tissue is due to a microbe, not dementia. Microglia react aggressively, clearing the area to prevent the spread of infection.

“They say, ‘We better wipe out this part of the brain that’s infected, even if it’s not.’ They don’t know,” quipped Dr. Tanzi. “That’s what causes neuroinflammation. And CD33 turns this response on. The microglia become killers, not just janitors.”
 

A brake on overactive microglia

If CD33 is the yin, a gene called TREM2 is the yang. Discovered a few years after CD33, TREM2 reins in microglial activation, returning them to their role as cellular housekeepers.

Neurologist David Holtzman, MD, of Washington University in St. Louis, who studies TREM2, agrees that wherever you find amyloid, tau, or dead brain cells, there are microglia raring to go and ready to scavenge.

“I think at first a lot of people thought these cells were reacting to Alzheimer’s pathology, and not necessarily a cause of the disease,” he said.

It was the discovery of TREM2 on the heels of CD33 that really shifted the thinking, in part because it produces a protein that in the brain is only found in microglia. “Many of us [in the field] immediately said, ‘Look, there’s now a risk factor that is only expressed in microglia. It must be that innate immune cells are important in some way in the pathogenesis of the disease,’ “ he added.

Dr. Holtzman sees microglial activation in impending dementia as a double-edged sword. In the beginning, microglia clear unwanted amyloid to maintain brain health. But once accumulated amyloid and tau have done enough damage, the neuroinflammation that comes with microglial activation does more harm than good. Neurons die en masse and dementia sets in.

But not all researchers are convinced.

Serge Revist, PhD, is a professor in the department of molecular medicine at the Laval University Medical School in Quebec. Based on his lab’s research, he believes that while impaired immune activity is involved in Alzheimer’s disease, it is not the root cause. “I don’t think it is the immune cells that do the damage, I still think it is the beta-amyloid itself,” he said, “In my lab, in mouse studies, we’ve never found that immune cells were directly responsible for killing neurons.”

He does believe that in some patients with Alzheimer’s disease, microglia may not be able to handle the excess amyloid that accumulates in the disease and that developing treatments that improve the ability of microglia and the immune system to clear the protein could be effective.
 

Microglial medicines

The biological cascade leading to Alzheimer’s disease is a tangled one. Gene variants influencing the accumulation and clearance of amyloid are likely a major contributor. But immune activity caused by early life infection might also be involved, at least in some cases. This infectious theory of Alzheimer’s disease was first proposed by Dr. Tanzi’s now-deceased colleague Robert Moir, PhD. Dr. Tanzi’s group even has evidence that amyloid itself is antimicrobial and evolved to protect us from pathogens, only to become a problem when overactive and aggregated.

And the same goes for microglia, cells whose over-ambition might cause much of the brain degeneration seen in Alzheimer’s disease.

In theory, if a treatment could decrease CD33 activity or increase that of TREM2, doctors might one day may be able to slow or even stop the progression of dementia. Instead of going after amyloid itself – the mechanism behind so many failed investigational Alzheimer’s drugs – a therapy that quells the immune response to amyloid might be the answer in treating dementia.

“There are a number of scientists and companies trying to figure out how to influence genes like TREM2 and CD33 and to both decrease amyloid and act on the downstream consequences of the protein,” said Dr. Holtzman. “All of this is to say that somewhere in the biology that causes Alzheimer’s disease, the immune system is involved.”

It seems that in many cases, the most common form of a dementia might be due to a well-intentioned immune cell going rogue. “I think you’d hear this from basically any researcher worth their salt,” said Dr. Tanzi. “I feel strongly that without microglial activation, you will not get Alzheimer’s disease.”

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