Alzheimer's & Cognition

Novel, noninvasive testing is able to predict dementia onset with 80% accuracy up to 9 years before clinical diagnosis.

The results suggest resting-state functional MRI (rs-fMRI) could be used to identify a neural network signature of dementia risk early in the pathological course of the disease, an important advance as disease-modifying drugs such as those targeting amyloid beta are now becoming available.

“The brain has been changing for a long time before people get symptoms of dementia, and if we’re very precise about how we do it, we can actually, in principle, detect those changes, which could be really exciting,” study investigator Charles R. Marshall, PhD, professor of clinical neurology, Centre for Preventive Neurology, Wolfson Institute of Population Health, Queen Mary University of London, London, England, told this news organization.

“This could become a platform for screening people for risk status in the future, and it could one day make all the difference in terms of being able to prevent dementia,” he added.

The findings were published online in Nature Mental Health.

The rs-fMRI measures fluctuations in blood oxygen level–dependent signals across the brain, which reflect functional connectivity.

Brain regions commonly implicated in altered functional connectivity in Alzheimer’s disease (AD) are within the default-mode network (DMN). This is the group of regions “connecting with each other and communicating with each other when someone is just lying in an MRI scanner doing nothing, which is how it came to be called the default-mode network,” explained Dr. Marshall.

The DMN encompasses the medial prefrontal cortex, posterior cingulate cortex or precuneus, and bilateral inferior parietal cortices, as well as supplementary brain regions including the medial temporal lobes and temporal poles.

This network is believed to be selectively vulnerable to AD neuropathology. “Something about that network starts to be disrupted in the very earliest stages of Alzheimer’s disease,” said Dr. Marshall.

While this has been known for some time, “what we’ve not been able to do before is build a precise enough model of how the network is connected to be able to tell whether individual participants were going to get dementia or not,” he added.

The investigators used data from the UK Biobank, a large-scale biomedical database and research resource containing genetic and health information from about a half a million UK volunteer participants.

The analysis included 103 individuals with dementia (22 with prevalent dementia and 81 later diagnosed with dementia over a median of 3.7 years) and 1030 matched participants without dementia. All participants had MRI imaging between 2006 and 2010.

The total sample had a mean age of 70.4 years at the time of MRI data acquisition. For each participant, researchers extracted relevant data from 10 predefined regions of interest in the brain, which together defined their DMN. This included two midline regions and four regions in each hemisphere.
 

Greater Predictive Power

Researchers built a model using an approach related to how brain regions communicate with each other. “The model sort of incorporates what we know about how the changes that you see on a functional MRI scan relate to changes in the firing of brain cells, in a very precise way,” said Dr. Marshall.

The researchers then used a machine learning approach to develop a model for effective connectivity, which describes the causal influence of one brain region over another. “We trained a machine learning tool to recognize what a dementia-like pattern of connectivity looks like,” said Dr. Marshall.

Investigators controlled for potential confounders, including age, sex, handedness, in-scanner head motion, and geographical location of data acquisition.

The model was able to determine the difference in brain connectivity patterns between those who would go on to develop dementia and those who would not, with an accuracy of 82% up to 9 years before an official diagnosis was made.

When the researchers trained a model to use brain connections to predict time to diagnosis, the predicted time to diagnosis and actual time to diagnosis were within about 2 years.

This effective connectivity approach has much more predictive power than memory test scores or brain structural measures, said Dr. Marshall. “We looked at brain volumes and they performed very poorly, only just better than tossing a coin, and the same with cognitive test scores, which were only just better than chance.”

As for markers of amyloid beta and tau in the brain, these are “very useful diagnostically” but only when someone has symptoms, said Dr. Marshall. He noted people live for years with these proteins without developing dementia symptoms.

“We wouldn’t necessarily want to expose somebody who has a brain full of amyloid but was not going to get symptoms for the next 20 years to a treatment, but if we knew that person was highly likely to develop symptoms of dementia in the next 5 years, then we probably would,” he said.

Dr. Marshall believes the predictive power of all these diagnostic tools could be boosted if they were used together.
 

Potential for Early Detection, Treatment

Researchers examined a number of modifiable dementia risk factors, including hearing loss, depression, hypertension, and physical inactivity. They found self-reported social isolation was the only variable that showed a significant association with effective connectivity, meaning those who are socially isolated were more likely to have a “dementia-like” pattern of DMN effective connectivity. This finding suggests social isolation is a cause, rather than a consequence, of dementia.

The study also revealed associations between DMN effective connectivity and AD polygenic risk score, derived from meta-analysis of multiple external genome-wide association study sources.

A predictive tool that uses rs-fMRI could also help select participants at a high risk for dementia to investigate potential treatments. “There’s good reason to think that if we could go in earlier with, for example, anti-amyloid treatments, they’re more likely to be effective,” said Dr. Marshall.

The new test might eventually have value as a population screening tool, something akin to colon cancer screening, he added. “We don’t send everyone for a colonoscopy; you do a kind of pre-screening test at home, and if that’s positive, then you get called in for a colonoscopy.”

The researchers looked at all-cause dementia and not just AD because dementia subtype diagnoses in the UK Biobank “are not at all reliable,” said Dr. Marshall.

Study limitations included the fact that UK Biobank participants are healthier and less socioeconomically deprived than the general population and are predominantly White. Another study limitation was that labeling of cases and controls depended on clinician coding rather than on standardized diagnostic criteria.
 

Kudos, Caveats

In a release from the Science Media Center, a nonprofit organization promoting voices and views of the scientific community, Sebastian Walsh, National Institute for Health and Care Research doctoral fellow in Public Health Medicine, University of Cambridge, Cambridge, England, said the results are “potentially exciting,” and he praised the way the team conducted the study.

However, he noted some caveats, including the small sample size, with only about 100 people with dementia, and the relatively short time between the brain scan and diagnosis (an average of 3.7 years).

Dr. Walsh emphasized the importance of replicating the findings “in bigger samples with a much longer delay between scan and onset of cognitive symptoms.”

He also noted the average age of study participants was 70 years, whereas the average age at which individuals in the United Kingdom develop dementia is mid to late 80s, “so we need to see these results repeated for more diverse and older samples.”

He also noted that MRI scans are expensive, and the approach used in the study needs “a high-quality scan which requires people to keep their head still.”

Also commenting, Andrew Doig, PhD, professor, Division of Neuroscience, the University of Manchester, Manchester, England, said the MRI connectivity method used in the study might form part of a broader diagnostic approach.

“Dementia is a complex condition, and it is unlikely that we will ever find one simple test that can accurately diagnose it,” Dr. Doig noted. “Within a few years, however, there is good reason to believe that we will be routinely testing for dementia in middle-aged people, using a combination of methods, such as a blood test, followed by imaging.”

“The MRI connectivity method described here could form part of this diagnostic platform. We will then have an excellent understanding of which people are likely to benefit most from the new generation of dementia drugs,” he said.

Dr. Marshall and Dr. Walsh reported no relevant disclosures. Dr. Doig reported that he is a founder, shareholder, and consultant for PharmaKure Ltd, which is developing new diagnostics for neurodegenerative diseases using blood biomarkers.

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

Novel, noninvasive testing is able to predict dementia onset with 80% accuracy up to 9 years before clinical diagnosis.

The results suggest resting-state functional MRI (rs-fMRI) could be used to identify a neural network signature of dementia risk early in the pathological course of the disease, an important advance as disease-modifying drugs such as those targeting amyloid beta are now becoming available.

“The brain has been changing for a long time before people get symptoms of dementia, and if we’re very precise about how we do it, we can actually, in principle, detect those changes, which could be really exciting,” study investigator Charles R. Marshall, PhD, professor of clinical neurology, Centre for Preventive Neurology, Wolfson Institute of Population Health, Queen Mary University of London, London, England, told this news organization.

“This could become a platform for screening people for risk status in the future, and it could one day make all the difference in terms of being able to prevent dementia,” he added.

The findings were published online in Nature Mental Health.

The rs-fMRI measures fluctuations in blood oxygen level–dependent signals across the brain, which reflect functional connectivity.

Brain regions commonly implicated in altered functional connectivity in Alzheimer’s disease (AD) are within the default-mode network (DMN). This is the group of regions “connecting with each other and communicating with each other when someone is just lying in an MRI scanner doing nothing, which is how it came to be called the default-mode network,” explained Dr. Marshall.

The DMN encompasses the medial prefrontal cortex, posterior cingulate cortex or precuneus, and bilateral inferior parietal cortices, as well as supplementary brain regions including the medial temporal lobes and temporal poles.

This network is believed to be selectively vulnerable to AD neuropathology. “Something about that network starts to be disrupted in the very earliest stages of Alzheimer’s disease,” said Dr. Marshall.

While this has been known for some time, “what we’ve not been able to do before is build a precise enough model of how the network is connected to be able to tell whether individual participants were going to get dementia or not,” he added.

The investigators used data from the UK Biobank, a large-scale biomedical database and research resource containing genetic and health information from about a half a million UK volunteer participants.

The analysis included 103 individuals with dementia (22 with prevalent dementia and 81 later diagnosed with dementia over a median of 3.7 years) and 1030 matched participants without dementia. All participants had MRI imaging between 2006 and 2010.

The total sample had a mean age of 70.4 years at the time of MRI data acquisition. For each participant, researchers extracted relevant data from 10 predefined regions of interest in the brain, which together defined their DMN. This included two midline regions and four regions in each hemisphere.
 

Greater Predictive Power

Researchers built a model using an approach related to how brain regions communicate with each other. “The model sort of incorporates what we know about how the changes that you see on a functional MRI scan relate to changes in the firing of brain cells, in a very precise way,” said Dr. Marshall.

The researchers then used a machine learning approach to develop a model for effective connectivity, which describes the causal influence of one brain region over another. “We trained a machine learning tool to recognize what a dementia-like pattern of connectivity looks like,” said Dr. Marshall.

Investigators controlled for potential confounders, including age, sex, handedness, in-scanner head motion, and geographical location of data acquisition.

The model was able to determine the difference in brain connectivity patterns between those who would go on to develop dementia and those who would not, with an accuracy of 82% up to 9 years before an official diagnosis was made.

When the researchers trained a model to use brain connections to predict time to diagnosis, the predicted time to diagnosis and actual time to diagnosis were within about 2 years.

This effective connectivity approach has much more predictive power than memory test scores or brain structural measures, said Dr. Marshall. “We looked at brain volumes and they performed very poorly, only just better than tossing a coin, and the same with cognitive test scores, which were only just better than chance.”

As for markers of amyloid beta and tau in the brain, these are “very useful diagnostically” but only when someone has symptoms, said Dr. Marshall. He noted people live for years with these proteins without developing dementia symptoms.

“We wouldn’t necessarily want to expose somebody who has a brain full of amyloid but was not going to get symptoms for the next 20 years to a treatment, but if we knew that person was highly likely to develop symptoms of dementia in the next 5 years, then we probably would,” he said.

Dr. Marshall believes the predictive power of all these diagnostic tools could be boosted if they were used together.
 

Potential for Early Detection, Treatment

Researchers examined a number of modifiable dementia risk factors, including hearing loss, depression, hypertension, and physical inactivity. They found self-reported social isolation was the only variable that showed a significant association with effective connectivity, meaning those who are socially isolated were more likely to have a “dementia-like” pattern of DMN effective connectivity. This finding suggests social isolation is a cause, rather than a consequence, of dementia.

The study also revealed associations between DMN effective connectivity and AD polygenic risk score, derived from meta-analysis of multiple external genome-wide association study sources.

A predictive tool that uses rs-fMRI could also help select participants at a high risk for dementia to investigate potential treatments. “There’s good reason to think that if we could go in earlier with, for example, anti-amyloid treatments, they’re more likely to be effective,” said Dr. Marshall.

The new test might eventually have value as a population screening tool, something akin to colon cancer screening, he added. “We don’t send everyone for a colonoscopy; you do a kind of pre-screening test at home, and if that’s positive, then you get called in for a colonoscopy.”

The researchers looked at all-cause dementia and not just AD because dementia subtype diagnoses in the UK Biobank “are not at all reliable,” said Dr. Marshall.

Study limitations included the fact that UK Biobank participants are healthier and less socioeconomically deprived than the general population and are predominantly White. Another study limitation was that labeling of cases and controls depended on clinician coding rather than on standardized diagnostic criteria.
 

Kudos, Caveats

In a release from the Science Media Center, a nonprofit organization promoting voices and views of the scientific community, Sebastian Walsh, National Institute for Health and Care Research doctoral fellow in Public Health Medicine, University of Cambridge, Cambridge, England, said the results are “potentially exciting,” and he praised the way the team conducted the study.

However, he noted some caveats, including the small sample size, with only about 100 people with dementia, and the relatively short time between the brain scan and diagnosis (an average of 3.7 years).

Dr. Walsh emphasized the importance of replicating the findings “in bigger samples with a much longer delay between scan and onset of cognitive symptoms.”

He also noted the average age of study participants was 70 years, whereas the average age at which individuals in the United Kingdom develop dementia is mid to late 80s, “so we need to see these results repeated for more diverse and older samples.”

He also noted that MRI scans are expensive, and the approach used in the study needs “a high-quality scan which requires people to keep their head still.”

Also commenting, Andrew Doig, PhD, professor, Division of Neuroscience, the University of Manchester, Manchester, England, said the MRI connectivity method used in the study might form part of a broader diagnostic approach.

“Dementia is a complex condition, and it is unlikely that we will ever find one simple test that can accurately diagnose it,” Dr. Doig noted. “Within a few years, however, there is good reason to believe that we will be routinely testing for dementia in middle-aged people, using a combination of methods, such as a blood test, followed by imaging.”

“The MRI connectivity method described here could form part of this diagnostic platform. We will then have an excellent understanding of which people are likely to benefit most from the new generation of dementia drugs,” he said.

Dr. Marshall and Dr. Walsh reported no relevant disclosures. Dr. Doig reported that he is a founder, shareholder, and consultant for PharmaKure Ltd, which is developing new diagnostics for neurodegenerative diseases using blood biomarkers.

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

Novel, noninvasive testing is able to predict dementia onset with 80% accuracy up to 9 years before clinical diagnosis.

The results suggest resting-state functional MRI (rs-fMRI) could be used to identify a neural network signature of dementia risk early in the pathological course of the disease, an important advance as disease-modifying drugs such as those targeting amyloid beta are now becoming available.

“The brain has been changing for a long time before people get symptoms of dementia, and if we’re very precise about how we do it, we can actually, in principle, detect those changes, which could be really exciting,” study investigator Charles R. Marshall, PhD, professor of clinical neurology, Centre for Preventive Neurology, Wolfson Institute of Population Health, Queen Mary University of London, London, England, told this news organization.

“This could become a platform for screening people for risk status in the future, and it could one day make all the difference in terms of being able to prevent dementia,” he added.

The findings were published online in Nature Mental Health.

The rs-fMRI measures fluctuations in blood oxygen level–dependent signals across the brain, which reflect functional connectivity.

Brain regions commonly implicated in altered functional connectivity in Alzheimer’s disease (AD) are within the default-mode network (DMN). This is the group of regions “connecting with each other and communicating with each other when someone is just lying in an MRI scanner doing nothing, which is how it came to be called the default-mode network,” explained Dr. Marshall.

The DMN encompasses the medial prefrontal cortex, posterior cingulate cortex or precuneus, and bilateral inferior parietal cortices, as well as supplementary brain regions including the medial temporal lobes and temporal poles.

This network is believed to be selectively vulnerable to AD neuropathology. “Something about that network starts to be disrupted in the very earliest stages of Alzheimer’s disease,” said Dr. Marshall.

While this has been known for some time, “what we’ve not been able to do before is build a precise enough model of how the network is connected to be able to tell whether individual participants were going to get dementia or not,” he added.

The investigators used data from the UK Biobank, a large-scale biomedical database and research resource containing genetic and health information from about a half a million UK volunteer participants.

The analysis included 103 individuals with dementia (22 with prevalent dementia and 81 later diagnosed with dementia over a median of 3.7 years) and 1030 matched participants without dementia. All participants had MRI imaging between 2006 and 2010.

The total sample had a mean age of 70.4 years at the time of MRI data acquisition. For each participant, researchers extracted relevant data from 10 predefined regions of interest in the brain, which together defined their DMN. This included two midline regions and four regions in each hemisphere.
 

Greater Predictive Power

Researchers built a model using an approach related to how brain regions communicate with each other. “The model sort of incorporates what we know about how the changes that you see on a functional MRI scan relate to changes in the firing of brain cells, in a very precise way,” said Dr. Marshall.

The researchers then used a machine learning approach to develop a model for effective connectivity, which describes the causal influence of one brain region over another. “We trained a machine learning tool to recognize what a dementia-like pattern of connectivity looks like,” said Dr. Marshall.

Investigators controlled for potential confounders, including age, sex, handedness, in-scanner head motion, and geographical location of data acquisition.

The model was able to determine the difference in brain connectivity patterns between those who would go on to develop dementia and those who would not, with an accuracy of 82% up to 9 years before an official diagnosis was made.

When the researchers trained a model to use brain connections to predict time to diagnosis, the predicted time to diagnosis and actual time to diagnosis were within about 2 years.

This effective connectivity approach has much more predictive power than memory test scores or brain structural measures, said Dr. Marshall. “We looked at brain volumes and they performed very poorly, only just better than tossing a coin, and the same with cognitive test scores, which were only just better than chance.”

As for markers of amyloid beta and tau in the brain, these are “very useful diagnostically” but only when someone has symptoms, said Dr. Marshall. He noted people live for years with these proteins without developing dementia symptoms.

“We wouldn’t necessarily want to expose somebody who has a brain full of amyloid but was not going to get symptoms for the next 20 years to a treatment, but if we knew that person was highly likely to develop symptoms of dementia in the next 5 years, then we probably would,” he said.

Dr. Marshall believes the predictive power of all these diagnostic tools could be boosted if they were used together.
 

Potential for Early Detection, Treatment

Researchers examined a number of modifiable dementia risk factors, including hearing loss, depression, hypertension, and physical inactivity. They found self-reported social isolation was the only variable that showed a significant association with effective connectivity, meaning those who are socially isolated were more likely to have a “dementia-like” pattern of DMN effective connectivity. This finding suggests social isolation is a cause, rather than a consequence, of dementia.

The study also revealed associations between DMN effective connectivity and AD polygenic risk score, derived from meta-analysis of multiple external genome-wide association study sources.

A predictive tool that uses rs-fMRI could also help select participants at a high risk for dementia to investigate potential treatments. “There’s good reason to think that if we could go in earlier with, for example, anti-amyloid treatments, they’re more likely to be effective,” said Dr. Marshall.

The new test might eventually have value as a population screening tool, something akin to colon cancer screening, he added. “We don’t send everyone for a colonoscopy; you do a kind of pre-screening test at home, and if that’s positive, then you get called in for a colonoscopy.”

The researchers looked at all-cause dementia and not just AD because dementia subtype diagnoses in the UK Biobank “are not at all reliable,” said Dr. Marshall.

Study limitations included the fact that UK Biobank participants are healthier and less socioeconomically deprived than the general population and are predominantly White. Another study limitation was that labeling of cases and controls depended on clinician coding rather than on standardized diagnostic criteria.
 

Kudos, Caveats

In a release from the Science Media Center, a nonprofit organization promoting voices and views of the scientific community, Sebastian Walsh, National Institute for Health and Care Research doctoral fellow in Public Health Medicine, University of Cambridge, Cambridge, England, said the results are “potentially exciting,” and he praised the way the team conducted the study.

However, he noted some caveats, including the small sample size, with only about 100 people with dementia, and the relatively short time between the brain scan and diagnosis (an average of 3.7 years).

Dr. Walsh emphasized the importance of replicating the findings “in bigger samples with a much longer delay between scan and onset of cognitive symptoms.”

He also noted the average age of study participants was 70 years, whereas the average age at which individuals in the United Kingdom develop dementia is mid to late 80s, “so we need to see these results repeated for more diverse and older samples.”

He also noted that MRI scans are expensive, and the approach used in the study needs “a high-quality scan which requires people to keep their head still.”

Also commenting, Andrew Doig, PhD, professor, Division of Neuroscience, the University of Manchester, Manchester, England, said the MRI connectivity method used in the study might form part of a broader diagnostic approach.

“Dementia is a complex condition, and it is unlikely that we will ever find one simple test that can accurately diagnose it,” Dr. Doig noted. “Within a few years, however, there is good reason to believe that we will be routinely testing for dementia in middle-aged people, using a combination of methods, such as a blood test, followed by imaging.”

“The MRI connectivity method described here could form part of this diagnostic platform. We will then have an excellent understanding of which people are likely to benefit most from the new generation of dementia drugs,” he said.

Dr. Marshall and Dr. Walsh reported no relevant disclosures. Dr. Doig reported that he is a founder, shareholder, and consultant for PharmaKure Ltd, which is developing new diagnostics for neurodegenerative diseases using blood biomarkers.

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

TOPLINE:

Taking antidepressants in midlife was not associated with an increased risk of subsequent Alzheimer’s disease (AD) or AD-related dementias (ADRD), data from a large prospective study of US veterans show.

METHODOLOGY:

• Investigators analyzed data from 35,200 US veterans aged ≥ 55 years diagnosed with major depressive disorder from January 1, 2000, to June 1, 2022, and followed them for ≤ 20 years to track subsequent AD/ADRD diagnoses.
• Health information was pulled from electronic health records of the Veterans Health Administration (VHA) Corporate Data Warehouse, and veterans had to be at the VHA for ≥ 1 year before diagnosis.
• Participants were considered to be exposed to an antidepressant when a prescription lasted ≥ 3 months.

TAKEAWAY:

• A total of 32,500 individuals were diagnosed with MDD. The mean age was 65 years, and 91% were men. 17,000 patients received antidepressants for a median duration of 4 years. Median follow-up time was 3.2 years.
• There was no significant association between antidepressant exposure and the risk for AD/ADRD (events = 1056; hazard ratio, 0.93; 95% CI, 0.80-1.08) vs no exposure.
• In a subgroup analysis, investigators found no significant link between different classes of antidepressants and dementia risk. These included selective serotonin reuptake inhibitors, norepinephrine and dopamine reuptake inhibitors, and serotonin-norepinephrine reuptake inhibitors.
• Investigators emphasized the need for further research, particularly in populations with a larger representation of female patients.

IN PRACTICE:

“A possibility for the conflicting results in retrospective studies is that the heightened risk identified in participants on antidepressants may be attributed to depression itself, rather than the result of a potential pharmacological action. So, this and other clinical confounding factors need to be taken into account,” the investigators noted.

SOURCE:

The study was led by Jaime Ramos-Cejudo, PhD, VA Boston Healthcare System, Boston. It was published online May 8 in Alzheimer’s & Dementia.

LIMITATIONS:

The cohort’s relatively young age limited the number of dementia cases captured. Data from supplemental insurance, including Medicare, were not included, potentially limiting outcome capture.

DISCLOSURES:

The study was supported by the National Institutes of Health and the National Alzheimer’s Coordinating Center. The authors declared no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article appeared on Medscape.com.

TOPLINE:

Taking antidepressants in midlife was not associated with an increased risk of subsequent Alzheimer’s disease (AD) or AD-related dementias (ADRD), data from a large prospective study of US veterans show.

METHODOLOGY:

• Investigators analyzed data from 35,200 US veterans aged ≥ 55 years diagnosed with major depressive disorder from January 1, 2000, to June 1, 2022, and followed them for ≤ 20 years to track subsequent AD/ADRD diagnoses.
• Health information was pulled from electronic health records of the Veterans Health Administration (VHA) Corporate Data Warehouse, and veterans had to be at the VHA for ≥ 1 year before diagnosis.
• Participants were considered to be exposed to an antidepressant when a prescription lasted ≥ 3 months.

TAKEAWAY:

• A total of 32,500 individuals were diagnosed with MDD. The mean age was 65 years, and 91% were men. 17,000 patients received antidepressants for a median duration of 4 years. Median follow-up time was 3.2 years.
• There was no significant association between antidepressant exposure and the risk for AD/ADRD (events = 1056; hazard ratio, 0.93; 95% CI, 0.80-1.08) vs no exposure.
• In a subgroup analysis, investigators found no significant link between different classes of antidepressants and dementia risk. These included selective serotonin reuptake inhibitors, norepinephrine and dopamine reuptake inhibitors, and serotonin-norepinephrine reuptake inhibitors.
• Investigators emphasized the need for further research, particularly in populations with a larger representation of female patients.

IN PRACTICE:

“A possibility for the conflicting results in retrospective studies is that the heightened risk identified in participants on antidepressants may be attributed to depression itself, rather than the result of a potential pharmacological action. So, this and other clinical confounding factors need to be taken into account,” the investigators noted.

SOURCE:

The study was led by Jaime Ramos-Cejudo, PhD, VA Boston Healthcare System, Boston. It was published online May 8 in Alzheimer’s & Dementia.

LIMITATIONS:

The cohort’s relatively young age limited the number of dementia cases captured. Data from supplemental insurance, including Medicare, were not included, potentially limiting outcome capture.

DISCLOSURES:

The study was supported by the National Institutes of Health and the National Alzheimer’s Coordinating Center. The authors declared no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article appeared on Medscape.com.

TOPLINE:

Taking antidepressants in midlife was not associated with an increased risk of subsequent Alzheimer’s disease (AD) or AD-related dementias (ADRD), data from a large prospective study of US veterans show.

METHODOLOGY:

• Investigators analyzed data from 35,200 US veterans aged ≥ 55 years diagnosed with major depressive disorder from January 1, 2000, to June 1, 2022, and followed them for ≤ 20 years to track subsequent AD/ADRD diagnoses.
• Health information was pulled from electronic health records of the Veterans Health Administration (VHA) Corporate Data Warehouse, and veterans had to be at the VHA for ≥ 1 year before diagnosis.
• Participants were considered to be exposed to an antidepressant when a prescription lasted ≥ 3 months.

TAKEAWAY:

• A total of 32,500 individuals were diagnosed with MDD. The mean age was 65 years, and 91% were men. 17,000 patients received antidepressants for a median duration of 4 years. Median follow-up time was 3.2 years.
• There was no significant association between antidepressant exposure and the risk for AD/ADRD (events = 1056; hazard ratio, 0.93; 95% CI, 0.80-1.08) vs no exposure.
• In a subgroup analysis, investigators found no significant link between different classes of antidepressants and dementia risk. These included selective serotonin reuptake inhibitors, norepinephrine and dopamine reuptake inhibitors, and serotonin-norepinephrine reuptake inhibitors.
• Investigators emphasized the need for further research, particularly in populations with a larger representation of female patients.

IN PRACTICE:

“A possibility for the conflicting results in retrospective studies is that the heightened risk identified in participants on antidepressants may be attributed to depression itself, rather than the result of a potential pharmacological action. So, this and other clinical confounding factors need to be taken into account,” the investigators noted.

SOURCE:

The study was led by Jaime Ramos-Cejudo, PhD, VA Boston Healthcare System, Boston. It was published online May 8 in Alzheimer’s & Dementia.

LIMITATIONS:

The cohort’s relatively young age limited the number of dementia cases captured. Data from supplemental insurance, including Medicare, were not included, potentially limiting outcome capture.

DISCLOSURES:

The study was supported by the National Institutes of Health and the National Alzheimer’s Coordinating Center. The authors declared no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article appeared on Medscape.com.

Reports from older adults and their partners of early memory issues are associated with higher levels of tau neurofibrillary tangles in the brain, new research suggests. 

The findings show that in addition to beta-amyloid, tau is implicated in cognitive decline even in the absence of overt clinical symptoms.

“Understanding the earliest signs of Alzheimer’s disease is even more important now that new disease-modifying drugs are becoming available,” study author 

Rebecca E. Amariglio, PhD, clinical neuropsychologist at Brigham and Women’s Hospital and the Massachusetts General Hospital and assistant professor in neurology at Harvard Medical School, Boston, said in a news release. “Our study found early suspicions of memory problems by both participants and the people who knew them well were linked to higher levels of tau tangles in the brain.”

The study was published online in Neurology.
 

Subjective Cognitive Decline

Beta-amyloid plaque accumulations and tau neurofibrillary tangles both underlie the clinical continuum of Alzheimer’s disease (AD). Previous studies have investigated beta-amyloid burden and self- and partner-reported cognitive decline, but fewer have examined regional tau.

Subjective cognitive decline may be an early sign of AD, but self-awareness declines as individuals become increasingly symptomatic. So, a report from a partner about the participant’s level of cognitive functioning is often required in studies of mild cognitive impairment and dementia. The relevance of this model during the preclinical stage is less clear.

For the multicohort, cross-sectional study, investigators studied 675 cognitively unimpaired older adults (mean age, 72 years; 59% female), including persons with nonelevated beta-amyloid levels and those with elevated beta-amyloid levels, as determined by PET. 

Participants brought a spouse, adult child, or other study partner with them to answer questions about the participant’s cognitive abilities and their ability to complete daily tasks. About 65% of participants lived with their partners and both completed the Cognitive Function Index (CFI) to assess cognitive decline, with higher scores indicating greater cognitive decline. 

Covariates included age, sex, education, and cohort as well as objective cognitive performance.
 

The Value of Partner Reporting

Investigators found that higher tau levels were associated with greater self- and partner-reported cognitive decline (P < .001 for both).

Significant associations between self- and partner-reported CFI measures were driven by elevated beta-amyloid levels, with continuous beta-amyloid levels showing an independent effect on CFI in addition to tau. 

“Our findings suggest that asking older people who have elevated Alzheimer’s disease biomarkers about subjective cognitive decline may be valuable for early detection,” Dr. Amariglio said.

Limitations include the fact that most participants were White and highly educated. Future studies should include participants from more diverse racial and ethnic groups and people with diverse levels of education, researchers noted.

“Although this study was cross-sectional, findings suggest that among older CU individuals who at risk for AD dementia, capturing self-report and study partner report of cognitive function may be valuable for understanding the relationship between early pathophysiologic progression and the emergence of functional impairment,” the authors concluded.

The study was funded in part by the National Institute on Aging, Eli Lily, and the Alzheimer’s Association, among others. Dr. Amariglio receives research funding from the National Institute on Aging. Complete study funding and other authors’ disclosures are listed in the original paper.

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

Reports from older adults and their partners of early memory issues are associated with higher levels of tau neurofibrillary tangles in the brain, new research suggests. 

The findings show that in addition to beta-amyloid, tau is implicated in cognitive decline even in the absence of overt clinical symptoms.

“Understanding the earliest signs of Alzheimer’s disease is even more important now that new disease-modifying drugs are becoming available,” study author 

Rebecca E. Amariglio, PhD, clinical neuropsychologist at Brigham and Women’s Hospital and the Massachusetts General Hospital and assistant professor in neurology at Harvard Medical School, Boston, said in a news release. “Our study found early suspicions of memory problems by both participants and the people who knew them well were linked to higher levels of tau tangles in the brain.”

The study was published online in Neurology.
 

Subjective Cognitive Decline

Beta-amyloid plaque accumulations and tau neurofibrillary tangles both underlie the clinical continuum of Alzheimer’s disease (AD). Previous studies have investigated beta-amyloid burden and self- and partner-reported cognitive decline, but fewer have examined regional tau.

Subjective cognitive decline may be an early sign of AD, but self-awareness declines as individuals become increasingly symptomatic. So, a report from a partner about the participant’s level of cognitive functioning is often required in studies of mild cognitive impairment and dementia. The relevance of this model during the preclinical stage is less clear.

For the multicohort, cross-sectional study, investigators studied 675 cognitively unimpaired older adults (mean age, 72 years; 59% female), including persons with nonelevated beta-amyloid levels and those with elevated beta-amyloid levels, as determined by PET. 

Participants brought a spouse, adult child, or other study partner with them to answer questions about the participant’s cognitive abilities and their ability to complete daily tasks. About 65% of participants lived with their partners and both completed the Cognitive Function Index (CFI) to assess cognitive decline, with higher scores indicating greater cognitive decline. 

Covariates included age, sex, education, and cohort as well as objective cognitive performance.
 

The Value of Partner Reporting

Investigators found that higher tau levels were associated with greater self- and partner-reported cognitive decline (P < .001 for both).

Significant associations between self- and partner-reported CFI measures were driven by elevated beta-amyloid levels, with continuous beta-amyloid levels showing an independent effect on CFI in addition to tau. 

“Our findings suggest that asking older people who have elevated Alzheimer’s disease biomarkers about subjective cognitive decline may be valuable for early detection,” Dr. Amariglio said.

Limitations include the fact that most participants were White and highly educated. Future studies should include participants from more diverse racial and ethnic groups and people with diverse levels of education, researchers noted.

“Although this study was cross-sectional, findings suggest that among older CU individuals who at risk for AD dementia, capturing self-report and study partner report of cognitive function may be valuable for understanding the relationship between early pathophysiologic progression and the emergence of functional impairment,” the authors concluded.

The study was funded in part by the National Institute on Aging, Eli Lily, and the Alzheimer’s Association, among others. Dr. Amariglio receives research funding from the National Institute on Aging. Complete study funding and other authors’ disclosures are listed in the original paper.

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

Reports from older adults and their partners of early memory issues are associated with higher levels of tau neurofibrillary tangles in the brain, new research suggests. 

The findings show that in addition to beta-amyloid, tau is implicated in cognitive decline even in the absence of overt clinical symptoms.

“Understanding the earliest signs of Alzheimer’s disease is even more important now that new disease-modifying drugs are becoming available,” study author 

Rebecca E. Amariglio, PhD, clinical neuropsychologist at Brigham and Women’s Hospital and the Massachusetts General Hospital and assistant professor in neurology at Harvard Medical School, Boston, said in a news release. “Our study found early suspicions of memory problems by both participants and the people who knew them well were linked to higher levels of tau tangles in the brain.”

The study was published online in Neurology.
 

Subjective Cognitive Decline

Beta-amyloid plaque accumulations and tau neurofibrillary tangles both underlie the clinical continuum of Alzheimer’s disease (AD). Previous studies have investigated beta-amyloid burden and self- and partner-reported cognitive decline, but fewer have examined regional tau.

Subjective cognitive decline may be an early sign of AD, but self-awareness declines as individuals become increasingly symptomatic. So, a report from a partner about the participant’s level of cognitive functioning is often required in studies of mild cognitive impairment and dementia. The relevance of this model during the preclinical stage is less clear.

For the multicohort, cross-sectional study, investigators studied 675 cognitively unimpaired older adults (mean age, 72 years; 59% female), including persons with nonelevated beta-amyloid levels and those with elevated beta-amyloid levels, as determined by PET. 

Participants brought a spouse, adult child, or other study partner with them to answer questions about the participant’s cognitive abilities and their ability to complete daily tasks. About 65% of participants lived with their partners and both completed the Cognitive Function Index (CFI) to assess cognitive decline, with higher scores indicating greater cognitive decline. 

Covariates included age, sex, education, and cohort as well as objective cognitive performance.
 

The Value of Partner Reporting

Investigators found that higher tau levels were associated with greater self- and partner-reported cognitive decline (P < .001 for both).

Significant associations between self- and partner-reported CFI measures were driven by elevated beta-amyloid levels, with continuous beta-amyloid levels showing an independent effect on CFI in addition to tau. 

“Our findings suggest that asking older people who have elevated Alzheimer’s disease biomarkers about subjective cognitive decline may be valuable for early detection,” Dr. Amariglio said.

Limitations include the fact that most participants were White and highly educated. Future studies should include participants from more diverse racial and ethnic groups and people with diverse levels of education, researchers noted.

“Although this study was cross-sectional, findings suggest that among older CU individuals who at risk for AD dementia, capturing self-report and study partner report of cognitive function may be valuable for understanding the relationship between early pathophysiologic progression and the emergence of functional impairment,” the authors concluded.

The study was funded in part by the National Institute on Aging, Eli Lily, and the Alzheimer’s Association, among others. Dr. Amariglio receives research funding from the National Institute on Aging. Complete study funding and other authors’ disclosures are listed in the original paper.

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

Irisin levels in cerebrospinal fluid (CSF) are significantly lower among patients with Alzheimer’s disease, and levels positively correlate with amyloid beta 1-42 (Abeta42), increasing support for this emerging Alzheimer’s disease biomarker, according to investigators.

Irisin, a hormone released by muscles during physical exercise, also negatively correlated with Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB) in female patients, pointing to a sex-specific disease phenomenon, reported by co-lead authors Manuela Dicarlo, PhD, and Patrizia Pignataro, MSc, of the University of Bari “A. Moro,” Bari, Italy, and colleagues.

Regular physical exercise can slow cognitive decline in individuals at risk for or with Alzheimer’s disease, and irisin appears to play a key role in this process, the investigators wrote in Annals of Neurology. Previous studies have shown that increased irisin levels in the brain are associated with improved cognitive function and reduced amyloid beta levels, suggesting the hormone’s potential as a biomarker and therapeutic target for Alzheimer’s disease.

“Based on the protective effect of irisin in Alzheimer’s disease shown in animal and cell models, the goal of the present study was to investigate the levels of irisin in the biological fluids of a large cohort of patients biologically characterized according to the amyloid/tau/neurodegeneration (ATN) scheme of the National Institute on Aging–Alzheimer’s Association (NIA-AA),” Dr. Dicarlo and colleagues wrote. “We aimed to understand whether there may be variations of irisin levels across the disease stages, identified through the ATN system.”
 

Lower Levels of Irisin Seen in Patients With Alzheimer’s Disease

The study included 82 patients with Alzheimer’s disease, 44 individuals with mild cognitive impairment (MCI), and 20 with subjective memory complaints (SMC). Participants underwent comprehensive assessments, including neurological and neuropsychological exams, nutritional evaluations, MRI scans, and routine lab tests. Cognitive impairment severity was measured using the CDR-SOB and other metrics.

Blood and CSF samples were collected from all patients, the latter via lumbar puncture. These samples were analyzed for irisin levels and known Alzheimer’s disease biomarkers, including Abeta42, total tau (t-tau), and hyperphosphorylated tau (p-tau).

Mean CSF irisin levels were significantly lower among patients with Alzheimer’s disease than those with SMC (0.80 vs 1.23 pg/mL; P < .0001), and among those with MCI vs SMC (0.95 vs 1.23 pg/mL; P = .046). Among patients with Alzheimer’s disease, irisin levels were significantly lower among women than men (0.70 vs 0.96 pg/mL; P = .031).

Further analyses revealed positive correlations between CSF irisin level and Abeta42 in both males (r = 0.262; P < 005) and females (r = 0.379; P < .001). Conversely, in female patients, a significant negative correlation was found between CSF irisin level and CDR-SOB score (r = −0.234; P < .05).

Although a negative trend was observed between CSF irisin and total tau (t-tau) in the overall patient population (r = −0.144; P = 0.082), and more notably in female patients (r = −0.189; P = 0.084), these results were not statistically significant.

Plasma irisin levels were not significantly correlated with any of the other biomarkers.
 

Clinical Implications

This study “verifies that irisin levels do have a relationship to the Alzheimer’s disease process,” said Dylan Wint, MD, director of Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas.

In a written comment, Dr. Wint speculated that measuring irisin levels could theoretically help individualize physical exercise routines designed to combat cognitive decline.

“For example, maybe someone who is exercising but has a low irisin level would need to change the type of exercise they’re doing in order to optimally protect their brain health,” he said. “Or maybe they won’t get the same benefits for brain health as someone whose irisin shoots up every time they walk a flight of stairs.”

dowukidronesifrawrebrisevushuvaricofrishouejufrucraslibrispoclaweprivawadidespoduswupiwofrephibrocuwuthovatrukoshobavaphastedoslethudrivitriphatropapukiuidrebiprudiwaphiwawrekocledrudofrophidruphawrocrebrelutiwicliswocevastifrugo

It’s “near-impossible to tell,” however, if irisin will be employed in clinical trials or real-world practice, he added.

“I don’t see this being a highly useful serum biomarker for Alzheimer’s disease itself because other serum biomarkers are so far ahead and have more face validity,” Dr. Wint said.

The route of collection could also cause challenges.

“In the United States, CSF-based biomarkers can be a difficult sell, especially for serial testing,” Dr. Wint said. “But we have usable serum biomarkers for Alzheimer’s disease only because we have had CSF biomarkers against which to evaluate them. They may develop a way to evaluate this in the serum.”

Dr. Dicarlo and colleagues suggested that more work is needed to determine the ultimate value of irisin measurement.“The true ability of irisin to represent a biomarker of disease progression and severity remains to be further investigated,” they concluded. “However, our findings might offer interesting perspectives toward the potential role of irisin in the modulation of AD pathology and can guide the exploration of medication targeting the irisin system.”

The study was supported by Regione Puglia and CNR for Tecnopolo per la Medicina di Precisione, CIREMIC, the University of Bari, and Next Generation EU. The investigators and Dr. Wint disclosed no conflicts of interest.

Irisin levels in cerebrospinal fluid (CSF) are significantly lower among patients with Alzheimer’s disease, and levels positively correlate with amyloid beta 1-42 (Abeta42), increasing support for this emerging Alzheimer’s disease biomarker, according to investigators.

Irisin, a hormone released by muscles during physical exercise, also negatively correlated with Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB) in female patients, pointing to a sex-specific disease phenomenon, reported by co-lead authors Manuela Dicarlo, PhD, and Patrizia Pignataro, MSc, of the University of Bari “A. Moro,” Bari, Italy, and colleagues.

Regular physical exercise can slow cognitive decline in individuals at risk for or with Alzheimer’s disease, and irisin appears to play a key role in this process, the investigators wrote in Annals of Neurology. Previous studies have shown that increased irisin levels in the brain are associated with improved cognitive function and reduced amyloid beta levels, suggesting the hormone’s potential as a biomarker and therapeutic target for Alzheimer’s disease.

“Based on the protective effect of irisin in Alzheimer’s disease shown in animal and cell models, the goal of the present study was to investigate the levels of irisin in the biological fluids of a large cohort of patients biologically characterized according to the amyloid/tau/neurodegeneration (ATN) scheme of the National Institute on Aging–Alzheimer’s Association (NIA-AA),” Dr. Dicarlo and colleagues wrote. “We aimed to understand whether there may be variations of irisin levels across the disease stages, identified through the ATN system.”
 

Lower Levels of Irisin Seen in Patients With Alzheimer’s Disease

The study included 82 patients with Alzheimer’s disease, 44 individuals with mild cognitive impairment (MCI), and 20 with subjective memory complaints (SMC). Participants underwent comprehensive assessments, including neurological and neuropsychological exams, nutritional evaluations, MRI scans, and routine lab tests. Cognitive impairment severity was measured using the CDR-SOB and other metrics.

Blood and CSF samples were collected from all patients, the latter via lumbar puncture. These samples were analyzed for irisin levels and known Alzheimer’s disease biomarkers, including Abeta42, total tau (t-tau), and hyperphosphorylated tau (p-tau).

Mean CSF irisin levels were significantly lower among patients with Alzheimer’s disease than those with SMC (0.80 vs 1.23 pg/mL; P < .0001), and among those with MCI vs SMC (0.95 vs 1.23 pg/mL; P = .046). Among patients with Alzheimer’s disease, irisin levels were significantly lower among women than men (0.70 vs 0.96 pg/mL; P = .031).

Further analyses revealed positive correlations between CSF irisin level and Abeta42 in both males (r = 0.262; P < 005) and females (r = 0.379; P < .001). Conversely, in female patients, a significant negative correlation was found between CSF irisin level and CDR-SOB score (r = −0.234; P < .05).

Although a negative trend was observed between CSF irisin and total tau (t-tau) in the overall patient population (r = −0.144; P = 0.082), and more notably in female patients (r = −0.189; P = 0.084), these results were not statistically significant.

Plasma irisin levels were not significantly correlated with any of the other biomarkers.
 

Clinical Implications

This study “verifies that irisin levels do have a relationship to the Alzheimer’s disease process,” said Dylan Wint, MD, director of Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas.

In a written comment, Dr. Wint speculated that measuring irisin levels could theoretically help individualize physical exercise routines designed to combat cognitive decline.

“For example, maybe someone who is exercising but has a low irisin level would need to change the type of exercise they’re doing in order to optimally protect their brain health,” he said. “Or maybe they won’t get the same benefits for brain health as someone whose irisin shoots up every time they walk a flight of stairs.”

dowukidronesifrawrebrisevushuvaricofrishouejufrucraslibrispoclaweprivawadidespoduswupiwofrephibrocuwuthovatrukoshobavaphastedoslethudrivitriphatropapukiuidrebiprudiwaphiwawrekocledrudofrophidruphawrocrebrelutiwicliswocevastifrugo

It’s “near-impossible to tell,” however, if irisin will be employed in clinical trials or real-world practice, he added.

“I don’t see this being a highly useful serum biomarker for Alzheimer’s disease itself because other serum biomarkers are so far ahead and have more face validity,” Dr. Wint said.

The route of collection could also cause challenges.

“In the United States, CSF-based biomarkers can be a difficult sell, especially for serial testing,” Dr. Wint said. “But we have usable serum biomarkers for Alzheimer’s disease only because we have had CSF biomarkers against which to evaluate them. They may develop a way to evaluate this in the serum.”

Dr. Dicarlo and colleagues suggested that more work is needed to determine the ultimate value of irisin measurement.“The true ability of irisin to represent a biomarker of disease progression and severity remains to be further investigated,” they concluded. “However, our findings might offer interesting perspectives toward the potential role of irisin in the modulation of AD pathology and can guide the exploration of medication targeting the irisin system.”

The study was supported by Regione Puglia and CNR for Tecnopolo per la Medicina di Precisione, CIREMIC, the University of Bari, and Next Generation EU. The investigators and Dr. Wint disclosed no conflicts of interest.

Irisin levels in cerebrospinal fluid (CSF) are significantly lower among patients with Alzheimer’s disease, and levels positively correlate with amyloid beta 1-42 (Abeta42), increasing support for this emerging Alzheimer’s disease biomarker, according to investigators.

Irisin, a hormone released by muscles during physical exercise, also negatively correlated with Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB) in female patients, pointing to a sex-specific disease phenomenon, reported by co-lead authors Manuela Dicarlo, PhD, and Patrizia Pignataro, MSc, of the University of Bari “A. Moro,” Bari, Italy, and colleagues.

Regular physical exercise can slow cognitive decline in individuals at risk for or with Alzheimer’s disease, and irisin appears to play a key role in this process, the investigators wrote in Annals of Neurology. Previous studies have shown that increased irisin levels in the brain are associated with improved cognitive function and reduced amyloid beta levels, suggesting the hormone’s potential as a biomarker and therapeutic target for Alzheimer’s disease.

“Based on the protective effect of irisin in Alzheimer’s disease shown in animal and cell models, the goal of the present study was to investigate the levels of irisin in the biological fluids of a large cohort of patients biologically characterized according to the amyloid/tau/neurodegeneration (ATN) scheme of the National Institute on Aging–Alzheimer’s Association (NIA-AA),” Dr. Dicarlo and colleagues wrote. “We aimed to understand whether there may be variations of irisin levels across the disease stages, identified through the ATN system.”
 

Lower Levels of Irisin Seen in Patients With Alzheimer’s Disease

The study included 82 patients with Alzheimer’s disease, 44 individuals with mild cognitive impairment (MCI), and 20 with subjective memory complaints (SMC). Participants underwent comprehensive assessments, including neurological and neuropsychological exams, nutritional evaluations, MRI scans, and routine lab tests. Cognitive impairment severity was measured using the CDR-SOB and other metrics.

Blood and CSF samples were collected from all patients, the latter via lumbar puncture. These samples were analyzed for irisin levels and known Alzheimer’s disease biomarkers, including Abeta42, total tau (t-tau), and hyperphosphorylated tau (p-tau).

Mean CSF irisin levels were significantly lower among patients with Alzheimer’s disease than those with SMC (0.80 vs 1.23 pg/mL; P < .0001), and among those with MCI vs SMC (0.95 vs 1.23 pg/mL; P = .046). Among patients with Alzheimer’s disease, irisin levels were significantly lower among women than men (0.70 vs 0.96 pg/mL; P = .031).

Further analyses revealed positive correlations between CSF irisin level and Abeta42 in both males (r = 0.262; P < 005) and females (r = 0.379; P < .001). Conversely, in female patients, a significant negative correlation was found between CSF irisin level and CDR-SOB score (r = −0.234; P < .05).

Although a negative trend was observed between CSF irisin and total tau (t-tau) in the overall patient population (r = −0.144; P = 0.082), and more notably in female patients (r = −0.189; P = 0.084), these results were not statistically significant.

Plasma irisin levels were not significantly correlated with any of the other biomarkers.
 

Clinical Implications

This study “verifies that irisin levels do have a relationship to the Alzheimer’s disease process,” said Dylan Wint, MD, director of Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas.

In a written comment, Dr. Wint speculated that measuring irisin levels could theoretically help individualize physical exercise routines designed to combat cognitive decline.

“For example, maybe someone who is exercising but has a low irisin level would need to change the type of exercise they’re doing in order to optimally protect their brain health,” he said. “Or maybe they won’t get the same benefits for brain health as someone whose irisin shoots up every time they walk a flight of stairs.”

dowukidronesifrawrebrisevushuvaricofrishouejufrucraslibrispoclaweprivawadidespoduswupiwofrephibrocuwuthovatrukoshobavaphastedoslethudrivitriphatropapukiuidrebiprudiwaphiwawrekocledrudofrophidruphawrocrebrelutiwicliswocevastifrugo

It’s “near-impossible to tell,” however, if irisin will be employed in clinical trials or real-world practice, he added.

“I don’t see this being a highly useful serum biomarker for Alzheimer’s disease itself because other serum biomarkers are so far ahead and have more face validity,” Dr. Wint said.

The route of collection could also cause challenges.

“In the United States, CSF-based biomarkers can be a difficult sell, especially for serial testing,” Dr. Wint said. “But we have usable serum biomarkers for Alzheimer’s disease only because we have had CSF biomarkers against which to evaluate them. They may develop a way to evaluate this in the serum.”

Dr. Dicarlo and colleagues suggested that more work is needed to determine the ultimate value of irisin measurement.“The true ability of irisin to represent a biomarker of disease progression and severity remains to be further investigated,” they concluded. “However, our findings might offer interesting perspectives toward the potential role of irisin in the modulation of AD pathology and can guide the exploration of medication targeting the irisin system.”

The study was supported by Regione Puglia and CNR for Tecnopolo per la Medicina di Precisione, CIREMIC, the University of Bari, and Next Generation EU. The investigators and Dr. Wint disclosed no conflicts of interest.

Consuming highly processed foods may be harmful to the aging brain, independent of other risk factors for adverse neurologic outcomes and adherence to recommended dietary patterns, new research suggests.

Observations from a large cohort of adults followed for more than 10 years suggested that eating more ultraprocessed foods (UPFs) may increase the risk for cognitive decline and stroke, while eating more unprocessed or minimally processed foods may lower the risk.

“The first key takeaway is that the type of food that we eat matters for brain health, but it’s equally important to think about how it’s made and handled when thinking about brain health,” said study investigator W. Taylor Kimberly, MD, PhD, with Massachusetts General Hospital in Boston.

“The second is that it’s not just all a bad news story because while increased consumption of ultra-processed foods is associated with a higher risk of cognitive impairment and stroke, unprocessed foods appear to be protective,” Dr. Kimberly added.

The study was published online on May 22 in Neurology.
 

Food Processing Matters

UPFs are highly manipulated, low in protein and fiber, and packed with added ingredients, including sugar, fat, and salt. Examples of UPFs are soft drinks, chips, chocolate, candy, ice cream, sweetened breakfast cereals, packaged soups, chicken nuggets, hot dogs, and fries.

Unprocessed or minimally processed foods include meats such as simple cuts of beef, pork, and chicken, and vegetables and fruits.

Research has shown associations between high UPF consumption and increased risk for metabolic and neurologic disorders.

As reported previously, in the ELSA-Brasil study, higher intake of UPFs was significantly associated with a faster rate of decline in executive and global cognitive function.

Yet, it’s unclear whether the extent of food processing contributes to the risk of adverse neurologic outcomes independent of dietary patterns.

Dr. Kimberly and colleagues examined the association of food processing levels with the risk for cognitive impairment and stroke in the long-running REGARDS study, a large prospective US cohort of Black and White adults aged 45 years and older.

Food processing levels were defined by the NOVA food classification system, which ranges from unprocessed or minimally processed foods (NOVA1) to UPFs (NOVA4). Dietary patterns were characterized based on food frequency questionnaires.

In the cognitive impairment cohort, 768 of 14,175 adults without evidence of impairment at baseline who underwent follow-up testing developed cognitive impairment.
 

Diet an Opportunity to Protect Brain Health

In multivariable Cox proportional hazards models adjusting for age, sex, high blood pressure, and other factors, a 10% increase in relative intake of UPFs was associated with a 16% higher risk for cognitive impairment (hazard ratio [HR], 1.16). Conversely, a higher intake of unprocessed or minimally processed foods correlated with a 12% lower risk for cognitive impairment (HR, 0.88).

In the stroke cohort, 1108 of 20,243 adults without a history of stroke had a stroke during the follow-up.

In multivariable Cox models, greater intake of UPFs was associated with an 8% increased risk for stroke (HR, 1.08), while greater intake of unprocessed or minimally processed foods correlated with a 9% lower risk for stroke (HR, 0.91).

The effect of UPFs on stroke risk was greater among Black than among White adults (UPF-by-race interaction HR, 1.15).

The associations between UPFs and both cognitive impairment and stroke were independent of adherence to the Mediterranean diet, the Dietary Approaches to Stop Hypertension (DASH) diet, and the Mediterranean-DASH Intervention for Neurodegenerative Delay diet.

These results “highlight the possibility that we have the capacity to maintain our brain health and prevent poor brain health outcomes by focusing on unprocessed foods in the long term,” Dr. Kimberly said.

He cautioned that this was “an observational study and not an interventional study, so we can’t say with certainty that substituting ultra-processed foods with unprocessed foods will definitively improve brain health,” Dr. Kimberly said. “That’s a clinical trial question that has not been done but our results certainly are provocative.”
 

Consider UPFs in National Guidelines?

The coauthors of an accompanying editorial said the “robust” results from Kimberly and colleagues highlight the “significant role of food processing levels and their relationship with adverse neurologic outcomes, independent of conventional dietary patterns.”

Peipei Gao, MS, with Harvard T.H. Chan School of Public Health, and Zhendong Mei, PhD, with Harvard Medical School, both in Boston, noted that the mechanisms underlying the impact of UPFs on adverse neurologic outcomes “can be attributed not only to their nutritional profiles,” including poor nutrient composition and high glycemic load, “but also to the presence of additives including emulsifiers, colorants, sweeteners, and nitrates/nitrites, which have been associated with disruptions in the gut microbial ecosystem and inflammation.

“Understanding how food processing levels are associated with human health offers a fresh take on the saying ‘you are what you eat,’ ” the editorialists wrote.

This new study, they noted, adds to the evidence by highlighting the link between UPFs and brain health, independent of traditional dietary patterns and “raises questions about whether considerations of UPFs should be included in dietary guidelines, as well as national and global public health policies for improving brain health.”

The editorialists called for large prospective population studies and randomized controlled trials to better understand the link between UPF consumption and brain health. “In addition, mechanistic studies are warranted to identify specific foods, detrimental processes, and additives that play a role in UPFs and their association with neurologic disorders,” they concluded.

Funding for the study was provided by the National Institute of Neurological Disorders and Stroke, the National Institute on Aging, National Institutes of Health, and Department of Health and Human Services. The authors and editorial writers had no relevant disclosures.

A version of this article appeared on Medscape.com.

Consuming highly processed foods may be harmful to the aging brain, independent of other risk factors for adverse neurologic outcomes and adherence to recommended dietary patterns, new research suggests.

Observations from a large cohort of adults followed for more than 10 years suggested that eating more ultraprocessed foods (UPFs) may increase the risk for cognitive decline and stroke, while eating more unprocessed or minimally processed foods may lower the risk.

“The first key takeaway is that the type of food that we eat matters for brain health, but it’s equally important to think about how it’s made and handled when thinking about brain health,” said study investigator W. Taylor Kimberly, MD, PhD, with Massachusetts General Hospital in Boston.

“The second is that it’s not just all a bad news story because while increased consumption of ultra-processed foods is associated with a higher risk of cognitive impairment and stroke, unprocessed foods appear to be protective,” Dr. Kimberly added.

The study was published online on May 22 in Neurology.
 

Food Processing Matters

UPFs are highly manipulated, low in protein and fiber, and packed with added ingredients, including sugar, fat, and salt. Examples of UPFs are soft drinks, chips, chocolate, candy, ice cream, sweetened breakfast cereals, packaged soups, chicken nuggets, hot dogs, and fries.

Unprocessed or minimally processed foods include meats such as simple cuts of beef, pork, and chicken, and vegetables and fruits.

Research has shown associations between high UPF consumption and increased risk for metabolic and neurologic disorders.

As reported previously, in the ELSA-Brasil study, higher intake of UPFs was significantly associated with a faster rate of decline in executive and global cognitive function.

Yet, it’s unclear whether the extent of food processing contributes to the risk of adverse neurologic outcomes independent of dietary patterns.

Dr. Kimberly and colleagues examined the association of food processing levels with the risk for cognitive impairment and stroke in the long-running REGARDS study, a large prospective US cohort of Black and White adults aged 45 years and older.

Food processing levels were defined by the NOVA food classification system, which ranges from unprocessed or minimally processed foods (NOVA1) to UPFs (NOVA4). Dietary patterns were characterized based on food frequency questionnaires.

In the cognitive impairment cohort, 768 of 14,175 adults without evidence of impairment at baseline who underwent follow-up testing developed cognitive impairment.
 

Diet an Opportunity to Protect Brain Health

In multivariable Cox proportional hazards models adjusting for age, sex, high blood pressure, and other factors, a 10% increase in relative intake of UPFs was associated with a 16% higher risk for cognitive impairment (hazard ratio [HR], 1.16). Conversely, a higher intake of unprocessed or minimally processed foods correlated with a 12% lower risk for cognitive impairment (HR, 0.88).

In the stroke cohort, 1108 of 20,243 adults without a history of stroke had a stroke during the follow-up.

In multivariable Cox models, greater intake of UPFs was associated with an 8% increased risk for stroke (HR, 1.08), while greater intake of unprocessed or minimally processed foods correlated with a 9% lower risk for stroke (HR, 0.91).

The effect of UPFs on stroke risk was greater among Black than among White adults (UPF-by-race interaction HR, 1.15).

The associations between UPFs and both cognitive impairment and stroke were independent of adherence to the Mediterranean diet, the Dietary Approaches to Stop Hypertension (DASH) diet, and the Mediterranean-DASH Intervention for Neurodegenerative Delay diet.

These results “highlight the possibility that we have the capacity to maintain our brain health and prevent poor brain health outcomes by focusing on unprocessed foods in the long term,” Dr. Kimberly said.

He cautioned that this was “an observational study and not an interventional study, so we can’t say with certainty that substituting ultra-processed foods with unprocessed foods will definitively improve brain health,” Dr. Kimberly said. “That’s a clinical trial question that has not been done but our results certainly are provocative.”
 

Consider UPFs in National Guidelines?

The coauthors of an accompanying editorial said the “robust” results from Kimberly and colleagues highlight the “significant role of food processing levels and their relationship with adverse neurologic outcomes, independent of conventional dietary patterns.”

Peipei Gao, MS, with Harvard T.H. Chan School of Public Health, and Zhendong Mei, PhD, with Harvard Medical School, both in Boston, noted that the mechanisms underlying the impact of UPFs on adverse neurologic outcomes “can be attributed not only to their nutritional profiles,” including poor nutrient composition and high glycemic load, “but also to the presence of additives including emulsifiers, colorants, sweeteners, and nitrates/nitrites, which have been associated with disruptions in the gut microbial ecosystem and inflammation.

“Understanding how food processing levels are associated with human health offers a fresh take on the saying ‘you are what you eat,’ ” the editorialists wrote.

This new study, they noted, adds to the evidence by highlighting the link between UPFs and brain health, independent of traditional dietary patterns and “raises questions about whether considerations of UPFs should be included in dietary guidelines, as well as national and global public health policies for improving brain health.”

The editorialists called for large prospective population studies and randomized controlled trials to better understand the link between UPF consumption and brain health. “In addition, mechanistic studies are warranted to identify specific foods, detrimental processes, and additives that play a role in UPFs and their association with neurologic disorders,” they concluded.

Funding for the study was provided by the National Institute of Neurological Disorders and Stroke, the National Institute on Aging, National Institutes of Health, and Department of Health and Human Services. The authors and editorial writers had no relevant disclosures.

A version of this article appeared on Medscape.com.

Consuming highly processed foods may be harmful to the aging brain, independent of other risk factors for adverse neurologic outcomes and adherence to recommended dietary patterns, new research suggests.

Observations from a large cohort of adults followed for more than 10 years suggested that eating more ultraprocessed foods (UPFs) may increase the risk for cognitive decline and stroke, while eating more unprocessed or minimally processed foods may lower the risk.

“The first key takeaway is that the type of food that we eat matters for brain health, but it’s equally important to think about how it’s made and handled when thinking about brain health,” said study investigator W. Taylor Kimberly, MD, PhD, with Massachusetts General Hospital in Boston.

“The second is that it’s not just all a bad news story because while increased consumption of ultra-processed foods is associated with a higher risk of cognitive impairment and stroke, unprocessed foods appear to be protective,” Dr. Kimberly added.

The study was published online on May 22 in Neurology.
 

Food Processing Matters

UPFs are highly manipulated, low in protein and fiber, and packed with added ingredients, including sugar, fat, and salt. Examples of UPFs are soft drinks, chips, chocolate, candy, ice cream, sweetened breakfast cereals, packaged soups, chicken nuggets, hot dogs, and fries.

Unprocessed or minimally processed foods include meats such as simple cuts of beef, pork, and chicken, and vegetables and fruits.

Research has shown associations between high UPF consumption and increased risk for metabolic and neurologic disorders.

As reported previously, in the ELSA-Brasil study, higher intake of UPFs was significantly associated with a faster rate of decline in executive and global cognitive function.

Yet, it’s unclear whether the extent of food processing contributes to the risk of adverse neurologic outcomes independent of dietary patterns.

Dr. Kimberly and colleagues examined the association of food processing levels with the risk for cognitive impairment and stroke in the long-running REGARDS study, a large prospective US cohort of Black and White adults aged 45 years and older.

Food processing levels were defined by the NOVA food classification system, which ranges from unprocessed or minimally processed foods (NOVA1) to UPFs (NOVA4). Dietary patterns were characterized based on food frequency questionnaires.

In the cognitive impairment cohort, 768 of 14,175 adults without evidence of impairment at baseline who underwent follow-up testing developed cognitive impairment.
 

Diet an Opportunity to Protect Brain Health

In multivariable Cox proportional hazards models adjusting for age, sex, high blood pressure, and other factors, a 10% increase in relative intake of UPFs was associated with a 16% higher risk for cognitive impairment (hazard ratio [HR], 1.16). Conversely, a higher intake of unprocessed or minimally processed foods correlated with a 12% lower risk for cognitive impairment (HR, 0.88).

In the stroke cohort, 1108 of 20,243 adults without a history of stroke had a stroke during the follow-up.

In multivariable Cox models, greater intake of UPFs was associated with an 8% increased risk for stroke (HR, 1.08), while greater intake of unprocessed or minimally processed foods correlated with a 9% lower risk for stroke (HR, 0.91).

The effect of UPFs on stroke risk was greater among Black than among White adults (UPF-by-race interaction HR, 1.15).

The associations between UPFs and both cognitive impairment and stroke were independent of adherence to the Mediterranean diet, the Dietary Approaches to Stop Hypertension (DASH) diet, and the Mediterranean-DASH Intervention for Neurodegenerative Delay diet.

These results “highlight the possibility that we have the capacity to maintain our brain health and prevent poor brain health outcomes by focusing on unprocessed foods in the long term,” Dr. Kimberly said.

He cautioned that this was “an observational study and not an interventional study, so we can’t say with certainty that substituting ultra-processed foods with unprocessed foods will definitively improve brain health,” Dr. Kimberly said. “That’s a clinical trial question that has not been done but our results certainly are provocative.”
 

Consider UPFs in National Guidelines?

The coauthors of an accompanying editorial said the “robust” results from Kimberly and colleagues highlight the “significant role of food processing levels and their relationship with adverse neurologic outcomes, independent of conventional dietary patterns.”

Peipei Gao, MS, with Harvard T.H. Chan School of Public Health, and Zhendong Mei, PhD, with Harvard Medical School, both in Boston, noted that the mechanisms underlying the impact of UPFs on adverse neurologic outcomes “can be attributed not only to their nutritional profiles,” including poor nutrient composition and high glycemic load, “but also to the presence of additives including emulsifiers, colorants, sweeteners, and nitrates/nitrites, which have been associated with disruptions in the gut microbial ecosystem and inflammation.

“Understanding how food processing levels are associated with human health offers a fresh take on the saying ‘you are what you eat,’ ” the editorialists wrote.

This new study, they noted, adds to the evidence by highlighting the link between UPFs and brain health, independent of traditional dietary patterns and “raises questions about whether considerations of UPFs should be included in dietary guidelines, as well as national and global public health policies for improving brain health.”

The editorialists called for large prospective population studies and randomized controlled trials to better understand the link between UPF consumption and brain health. “In addition, mechanistic studies are warranted to identify specific foods, detrimental processes, and additives that play a role in UPFs and their association with neurologic disorders,” they concluded.

Funding for the study was provided by the National Institute of Neurological Disorders and Stroke, the National Institute on Aging, National Institutes of Health, and Department of Health and Human Services. The authors and editorial writers had no relevant disclosures.

A version of this article appeared on Medscape.com.

Seniors are increasingly targeted in ever-sophisticated online financial cybercrimes, but mental health clinicians can play a key role in protecting their patients.

Elizabeth J. Santos, MD, clinical chief, Division of Geriatric Mental Health & Memory Care, and associate professor of psychiatry, neurology & medicine, University of Rochester School of Medicine and Dentistry, Rochester, New York, provided tips to attendees of the American Psychiatric Association (APA) 2024 Annual Meeting, and elaborated on these for this news organization.

Cybercrimes targeting seniors are common. A 2023 University of Michigan National Poll on Healthy Aging found 75% of adults aged 50-80 years experienced a fraud attempt either online or by phone, text, email, or mail in the past 2 years.

The poll found about 30% of respondents reported experiencing financial fraud, which could involve compromising credit cards, hacking bank accounts, or identity theft.

Older age is a risk factor for cybercrime. Seniors may have lower cognitive functioning and/or impaired decision-making. In addition, they are often socially isolated, dependent on others, and have poor health and financial literacy.
 

Romance Scams Common

Romance scams are another common financial fraud. Stephanie Garayalde, MD, a geriatric psychiatrist at the University of Florida, Gainesville, Florida, and another presenter at the APA session, used the example of Mr. L, a 74-year-old outpatient under treatment for depression who was unable to pay his rent.

Mr. L was giving money to his “girlfriend” he met online. Their relationship was totally virtual; she always had constant excuses for not meeting in person. He was funneling increasing funds to pay what he believed were medical bills and to bail her out of various other emergencies.

Once the fraud was discovered, Mr. L not only felt the loneliness of a lost romantic connection but also grappled with feelings of embarrassment and guilt.

“I see older patients who have been scammed who feel ashamed that they haven’t left enough money for their families,” said Dr. Santos.

Another well-known scam targets grandparents. Fraudsters sometimes use an artificial intelligence–generated voice mimicking a young family member and pretend to need money right away for bail or another problem.

In such situations, Dr. Santos advises patients to “hang up and call your family” to verify the call “no matter what the person says or who they sound like.”

Scammers may impersonate government officials to try to get social insurance information. Dr. Santos stresses the importance of never giving out this information. “If someone says they’re from your bank or a government agency like the IRS, hang up and call the bank or agency yourself.”

Evidence suggests this and other cybercrimes are on the rise. The Federal Bureau of Investigation’s Internet Crime Complaint Center received 888,000 complaints in 2023, a 10% increase from 2022, and losses of about $12.5 billion, which is a 22% increase over 2022.

It’s not that uncommon for the same older person to be scammed by numerous people and fall for it again and again, said Dr. Santos.

To mitigate the risk to this vulnerable group, researchers at the University of Central Florida, Orlando, Florida, are developing a scam screener for the elderly that will provide tools to help doctors screen older adults. The screen will focus on identifying factors that make victims most vulnerable, including seniors’ ability to think critically, a necessary skill for guarding against cybercrime.
 

Red Flags

In the meantime, Dr. Santos identified red flags for clinicians. Patients may show deviations in their typical behaviors; for example, they may seem sadder, more subdued, or more withdrawn than usual.

As loneliness and isolation can be a signal of victimization, “ask patients about their connectedness and be suspicious if the connectedness is all virtual,” she said.

Learning about the quality of their relationships is also important. “Instead of asking the superficial question of ‘Do you have friends’, ask ‘How do you talk to your friends? Are you actually getting out and meeting them?’”

If patients report they have never actually seen these so-called friends in-person, it should raise a red flag.

Another clue something may be amiss is “needing to be on their device or be home to get a call at a certain time.” Dr. Santos recalled a patient whose cell phone rang constantly during an evaluation, even after she had changed her phone number several times. “The scammers kept tracking her down,” she said.

Patients who are victims of cybercrime may stop taking their medications, fail to follow up on ordered tests, or miss paying for medical services.

Dr. Santos recommended screening for conditions known to be linked to cybercrime victimization such as depression. One of her patients was attending her memory clinic, but their cognitive issues were due to depression, not dementia.

It is important to identify subtle cognitive impairments. Dr. Santos recommended using the Saint Louis University Mental Status Examination, which she says is easier to use than the Montreal Cognitive Assessment.
 

Avoid Shaming

When managing patients who are potential cybercrime victims, she also suggests doctors be careful about their tone and their attitude. “Don’t shame someone for becoming a victim because it happens to everyone.”

When patients show signs of victimization, physicians could consider asking about their Internet use, social media practices, and general safety surrounding their finances.

They should emphasize the importance of protecting accounts through strong passwords, multifactor authentication when possible, and avoidance of sharing personal information with anyone who calls, emails, or texts.

Clinicians might also consider asking patients to review bills for new or unusual charges, check their bank account statements for withdrawals they didn’t make, and review credit reports for accounts in their name they don’t recognize.

Clinicians should also encourage patients to have a healthcare proxy, power of attorney, and advanced directives and recommend resources that can help victims. These include:

Federal Trade Commission (to report identity theft): https://reportfraud.ftc.gov;  https://www.identitytheft.gov

Federal Bureau of Investigation – Internet Crime and Complaint Center https://www.ic3.gov

National Elder Fraud Hotline (1-833-372-8311) or 1-833-FRAUD-11

http://ovc.ojp.gov/program/stop-elder-fraud/providing-help-restoring-hope

A version of this article appeared on Medscape.com.

Seniors are increasingly targeted in ever-sophisticated online financial cybercrimes, but mental health clinicians can play a key role in protecting their patients.

Elizabeth J. Santos, MD, clinical chief, Division of Geriatric Mental Health & Memory Care, and associate professor of psychiatry, neurology & medicine, University of Rochester School of Medicine and Dentistry, Rochester, New York, provided tips to attendees of the American Psychiatric Association (APA) 2024 Annual Meeting, and elaborated on these for this news organization.

Cybercrimes targeting seniors are common. A 2023 University of Michigan National Poll on Healthy Aging found 75% of adults aged 50-80 years experienced a fraud attempt either online or by phone, text, email, or mail in the past 2 years.

The poll found about 30% of respondents reported experiencing financial fraud, which could involve compromising credit cards, hacking bank accounts, or identity theft.

Older age is a risk factor for cybercrime. Seniors may have lower cognitive functioning and/or impaired decision-making. In addition, they are often socially isolated, dependent on others, and have poor health and financial literacy.
 

Romance Scams Common

Romance scams are another common financial fraud. Stephanie Garayalde, MD, a geriatric psychiatrist at the University of Florida, Gainesville, Florida, and another presenter at the APA session, used the example of Mr. L, a 74-year-old outpatient under treatment for depression who was unable to pay his rent.

Mr. L was giving money to his “girlfriend” he met online. Their relationship was totally virtual; she always had constant excuses for not meeting in person. He was funneling increasing funds to pay what he believed were medical bills and to bail her out of various other emergencies.

Once the fraud was discovered, Mr. L not only felt the loneliness of a lost romantic connection but also grappled with feelings of embarrassment and guilt.

“I see older patients who have been scammed who feel ashamed that they haven’t left enough money for their families,” said Dr. Santos.

Another well-known scam targets grandparents. Fraudsters sometimes use an artificial intelligence–generated voice mimicking a young family member and pretend to need money right away for bail or another problem.

In such situations, Dr. Santos advises patients to “hang up and call your family” to verify the call “no matter what the person says or who they sound like.”

Scammers may impersonate government officials to try to get social insurance information. Dr. Santos stresses the importance of never giving out this information. “If someone says they’re from your bank or a government agency like the IRS, hang up and call the bank or agency yourself.”

Evidence suggests this and other cybercrimes are on the rise. The Federal Bureau of Investigation’s Internet Crime Complaint Center received 888,000 complaints in 2023, a 10% increase from 2022, and losses of about $12.5 billion, which is a 22% increase over 2022.

It’s not that uncommon for the same older person to be scammed by numerous people and fall for it again and again, said Dr. Santos.

To mitigate the risk to this vulnerable group, researchers at the University of Central Florida, Orlando, Florida, are developing a scam screener for the elderly that will provide tools to help doctors screen older adults. The screen will focus on identifying factors that make victims most vulnerable, including seniors’ ability to think critically, a necessary skill for guarding against cybercrime.
 

Red Flags

In the meantime, Dr. Santos identified red flags for clinicians. Patients may show deviations in their typical behaviors; for example, they may seem sadder, more subdued, or more withdrawn than usual.

As loneliness and isolation can be a signal of victimization, “ask patients about their connectedness and be suspicious if the connectedness is all virtual,” she said.

Learning about the quality of their relationships is also important. “Instead of asking the superficial question of ‘Do you have friends’, ask ‘How do you talk to your friends? Are you actually getting out and meeting them?’”

If patients report they have never actually seen these so-called friends in-person, it should raise a red flag.

Another clue something may be amiss is “needing to be on their device or be home to get a call at a certain time.” Dr. Santos recalled a patient whose cell phone rang constantly during an evaluation, even after she had changed her phone number several times. “The scammers kept tracking her down,” she said.

Patients who are victims of cybercrime may stop taking their medications, fail to follow up on ordered tests, or miss paying for medical services.

Dr. Santos recommended screening for conditions known to be linked to cybercrime victimization such as depression. One of her patients was attending her memory clinic, but their cognitive issues were due to depression, not dementia.

It is important to identify subtle cognitive impairments. Dr. Santos recommended using the Saint Louis University Mental Status Examination, which she says is easier to use than the Montreal Cognitive Assessment.
 

Avoid Shaming

When managing patients who are potential cybercrime victims, she also suggests doctors be careful about their tone and their attitude. “Don’t shame someone for becoming a victim because it happens to everyone.”

When patients show signs of victimization, physicians could consider asking about their Internet use, social media practices, and general safety surrounding their finances.

They should emphasize the importance of protecting accounts through strong passwords, multifactor authentication when possible, and avoidance of sharing personal information with anyone who calls, emails, or texts.

Clinicians might also consider asking patients to review bills for new or unusual charges, check their bank account statements for withdrawals they didn’t make, and review credit reports for accounts in their name they don’t recognize.

Clinicians should also encourage patients to have a healthcare proxy, power of attorney, and advanced directives and recommend resources that can help victims. These include:

Federal Trade Commission (to report identity theft): https://reportfraud.ftc.gov;  https://www.identitytheft.gov

Federal Bureau of Investigation – Internet Crime and Complaint Center https://www.ic3.gov

National Elder Fraud Hotline (1-833-372-8311) or 1-833-FRAUD-11

http://ovc.ojp.gov/program/stop-elder-fraud/providing-help-restoring-hope

A version of this article appeared on Medscape.com.

Seniors are increasingly targeted in ever-sophisticated online financial cybercrimes, but mental health clinicians can play a key role in protecting their patients.

Elizabeth J. Santos, MD, clinical chief, Division of Geriatric Mental Health & Memory Care, and associate professor of psychiatry, neurology & medicine, University of Rochester School of Medicine and Dentistry, Rochester, New York, provided tips to attendees of the American Psychiatric Association (APA) 2024 Annual Meeting, and elaborated on these for this news organization.

Cybercrimes targeting seniors are common. A 2023 University of Michigan National Poll on Healthy Aging found 75% of adults aged 50-80 years experienced a fraud attempt either online or by phone, text, email, or mail in the past 2 years.

The poll found about 30% of respondents reported experiencing financial fraud, which could involve compromising credit cards, hacking bank accounts, or identity theft.

Older age is a risk factor for cybercrime. Seniors may have lower cognitive functioning and/or impaired decision-making. In addition, they are often socially isolated, dependent on others, and have poor health and financial literacy.
 

Romance Scams Common

Romance scams are another common financial fraud. Stephanie Garayalde, MD, a geriatric psychiatrist at the University of Florida, Gainesville, Florida, and another presenter at the APA session, used the example of Mr. L, a 74-year-old outpatient under treatment for depression who was unable to pay his rent.

Mr. L was giving money to his “girlfriend” he met online. Their relationship was totally virtual; she always had constant excuses for not meeting in person. He was funneling increasing funds to pay what he believed were medical bills and to bail her out of various other emergencies.

Once the fraud was discovered, Mr. L not only felt the loneliness of a lost romantic connection but also grappled with feelings of embarrassment and guilt.

“I see older patients who have been scammed who feel ashamed that they haven’t left enough money for their families,” said Dr. Santos.

Another well-known scam targets grandparents. Fraudsters sometimes use an artificial intelligence–generated voice mimicking a young family member and pretend to need money right away for bail or another problem.

In such situations, Dr. Santos advises patients to “hang up and call your family” to verify the call “no matter what the person says or who they sound like.”

Scammers may impersonate government officials to try to get social insurance information. Dr. Santos stresses the importance of never giving out this information. “If someone says they’re from your bank or a government agency like the IRS, hang up and call the bank or agency yourself.”

Evidence suggests this and other cybercrimes are on the rise. The Federal Bureau of Investigation’s Internet Crime Complaint Center received 888,000 complaints in 2023, a 10% increase from 2022, and losses of about $12.5 billion, which is a 22% increase over 2022.

It’s not that uncommon for the same older person to be scammed by numerous people and fall for it again and again, said Dr. Santos.

To mitigate the risk to this vulnerable group, researchers at the University of Central Florida, Orlando, Florida, are developing a scam screener for the elderly that will provide tools to help doctors screen older adults. The screen will focus on identifying factors that make victims most vulnerable, including seniors’ ability to think critically, a necessary skill for guarding against cybercrime.
 

Red Flags

In the meantime, Dr. Santos identified red flags for clinicians. Patients may show deviations in their typical behaviors; for example, they may seem sadder, more subdued, or more withdrawn than usual.

As loneliness and isolation can be a signal of victimization, “ask patients about their connectedness and be suspicious if the connectedness is all virtual,” she said.

Learning about the quality of their relationships is also important. “Instead of asking the superficial question of ‘Do you have friends’, ask ‘How do you talk to your friends? Are you actually getting out and meeting them?’”

If patients report they have never actually seen these so-called friends in-person, it should raise a red flag.

Another clue something may be amiss is “needing to be on their device or be home to get a call at a certain time.” Dr. Santos recalled a patient whose cell phone rang constantly during an evaluation, even after she had changed her phone number several times. “The scammers kept tracking her down,” she said.

Patients who are victims of cybercrime may stop taking their medications, fail to follow up on ordered tests, or miss paying for medical services.

Dr. Santos recommended screening for conditions known to be linked to cybercrime victimization such as depression. One of her patients was attending her memory clinic, but their cognitive issues were due to depression, not dementia.

It is important to identify subtle cognitive impairments. Dr. Santos recommended using the Saint Louis University Mental Status Examination, which she says is easier to use than the Montreal Cognitive Assessment.
 

Avoid Shaming

When managing patients who are potential cybercrime victims, she also suggests doctors be careful about their tone and their attitude. “Don’t shame someone for becoming a victim because it happens to everyone.”

When patients show signs of victimization, physicians could consider asking about their Internet use, social media practices, and general safety surrounding their finances.

They should emphasize the importance of protecting accounts through strong passwords, multifactor authentication when possible, and avoidance of sharing personal information with anyone who calls, emails, or texts.

Clinicians might also consider asking patients to review bills for new or unusual charges, check their bank account statements for withdrawals they didn’t make, and review credit reports for accounts in their name they don’t recognize.

Clinicians should also encourage patients to have a healthcare proxy, power of attorney, and advanced directives and recommend resources that can help victims. These include:

Federal Trade Commission (to report identity theft): https://reportfraud.ftc.gov;  https://www.identitytheft.gov

Federal Bureau of Investigation – Internet Crime and Complaint Center https://www.ic3.gov

National Elder Fraud Hotline (1-833-372-8311) or 1-833-FRAUD-11

http://ovc.ojp.gov/program/stop-elder-fraud/providing-help-restoring-hope

A version of this article appeared on Medscape.com.

Warning letters to primary care physicians (PCPs) regarding overprescription of quetiapine were helpful in reducing overprescribing of this agent, new research suggested.

Investigators analyzed data from an earlier trial that compared prescribing patterns in 5055 PCPs who receive a placebo letter or three warning letters informing them that their prescribing of quetiapine was high and under review by Medicare. Patients in question all had dementia and were either living in nursing homes or in the community.

The intervention reduced quetiapine use among all patients with dementia, with no detectable adverse effects on cognitive function, behavioral symptoms, depression, metabolic diagnoses, hospitalization, or death.

“This study found that overprescribing warning letters to PCPs safely reduced quetiapine prescribing to their patients with dementia,” wrote investigators led by Adam Sacarny, PhD, of the Department of Health Policy and Management, Mailman School of Public Health, Columbia University, New York. 

“This intervention and other[s] like it may be useful for future efforts to promote guideline-concordant care,” they added.

The study was published online in JAMA Network Open.
 

Off-Label Prescribing Common

The off-label use of antipsychotics in patients with dementia is fairly common, the investigators noted, affecting roughly one in seven nursing home residents and a similar number of community-dwelling older adults with dementia.

The agents are often prescribed to treat behavioral symptoms associated with dementia, including agitation and aggression. Although some evidence supports this use, antipsychotics in dementia patients can also cause an increased risk for weight gain, cognitive decline, falls and other injuries, cerebrovascular events, and mortality.

While some professional societies have called for “judicious use of antipsychotics in dementia care,” there is little evidence that reducing antipsychotic use in people with dementia might result in a benefit, investigators wrote.

The researchers analyzed data from a previous trial that focused on quetiapine, which is the most prescribed antipsychotic in the United States and is frequently used for patients with dementia.

In the original study, 2528 PCPs received a placebo letter and 2527 received three warning letters sent by the Centers for Medicare & Medicaid Services (CMS), which identified the highest-volume PCP prescribers of quetiapine.

The warning letters stated that the recipient’s quetiapine prescribing was high relative to their peers and was under review by Medicare. The placebo letter clarified an unrelated regulation. 

The current secondary analysis followed the providers and a cohort of their patients from their first receipt of the letters in 2015 through April 2017. The current evaluation analyzes patients’ outcomes through December 2018, utilizing Medicare fee-for-service claims, Minimum Data Set nursing home assessment, and Medicare enrollment data.
 

Low-Cost, Effective Intervention

While the original study focused on total quetiapine prescribing by study PCPs, the current analysis focused on patients’ total quetiapine use per 90-day period. Additional secondary outcomes included measures of cognitive function and behavioral symptoms, indicators of depression, metabolic diagnoses, indicators of use of hospital and healthcare services, and death.

PCPs in the study had a total of 84,881 patients with dementia living in nursing homes and 261,288 living in the community. At baseline, there were 92,874 patients (mean age, 82 years; 69% female).

The warning letters were associated with reduced quetiapine use among both nursing home patients and community-dwelling patients (adjusted difference, –0.7 days; P = .02 and adjusted difference, −1.5 days; P < .001, respectively).

Among nursing home patients, there were no statistically significant adverse changes in cognitive of behavioral health measures that coincided with reduction in quetiapine use.

Although a higher percentage of treatment vs control patients reported weight loss, the difference was not significant, and rates of metabolic diagnoses were similar in both groups. There were also no significant differences between the groups in emergency department use, inpatient hospital admission, or use of restraints.

Results were similar for patients living in the community.

Additionally, no adverse effects on more severe health endpoints, including rates of hospital use or entry to nursing facilities, were detected. Importantly, the risk for death was statistically significantly lower for patients whose PCPs had received warning letters vs control patients (P = .04).

The analysis “provides evidence that a low-cost letter intervention informed by behavioral science can reduce prescribing of quetiapine to patients with dementia in nursing home and community settings,” the authors wrote.

Researchers did not directly observe the administration of the medication but instead used prescription drug fills as a proxy. Moreover, they could not observe results for patients enrolled in Medicare Advantage, and claims-based and assessment-based outcomes might have been subject to measurement errors and under-ascertainment of diagnoses.

The authors received support from the National Institute on Aging. They reported no relevant financial relationships.

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

Warning letters to primary care physicians (PCPs) regarding overprescription of quetiapine were helpful in reducing overprescribing of this agent, new research suggested.

Investigators analyzed data from an earlier trial that compared prescribing patterns in 5055 PCPs who receive a placebo letter or three warning letters informing them that their prescribing of quetiapine was high and under review by Medicare. Patients in question all had dementia and were either living in nursing homes or in the community.

The intervention reduced quetiapine use among all patients with dementia, with no detectable adverse effects on cognitive function, behavioral symptoms, depression, metabolic diagnoses, hospitalization, or death.

“This study found that overprescribing warning letters to PCPs safely reduced quetiapine prescribing to their patients with dementia,” wrote investigators led by Adam Sacarny, PhD, of the Department of Health Policy and Management, Mailman School of Public Health, Columbia University, New York. 

“This intervention and other[s] like it may be useful for future efforts to promote guideline-concordant care,” they added.

The study was published online in JAMA Network Open.
 

Off-Label Prescribing Common

The off-label use of antipsychotics in patients with dementia is fairly common, the investigators noted, affecting roughly one in seven nursing home residents and a similar number of community-dwelling older adults with dementia.

The agents are often prescribed to treat behavioral symptoms associated with dementia, including agitation and aggression. Although some evidence supports this use, antipsychotics in dementia patients can also cause an increased risk for weight gain, cognitive decline, falls and other injuries, cerebrovascular events, and mortality.

While some professional societies have called for “judicious use of antipsychotics in dementia care,” there is little evidence that reducing antipsychotic use in people with dementia might result in a benefit, investigators wrote.

The researchers analyzed data from a previous trial that focused on quetiapine, which is the most prescribed antipsychotic in the United States and is frequently used for patients with dementia.

In the original study, 2528 PCPs received a placebo letter and 2527 received three warning letters sent by the Centers for Medicare & Medicaid Services (CMS), which identified the highest-volume PCP prescribers of quetiapine.

The warning letters stated that the recipient’s quetiapine prescribing was high relative to their peers and was under review by Medicare. The placebo letter clarified an unrelated regulation. 

The current secondary analysis followed the providers and a cohort of their patients from their first receipt of the letters in 2015 through April 2017. The current evaluation analyzes patients’ outcomes through December 2018, utilizing Medicare fee-for-service claims, Minimum Data Set nursing home assessment, and Medicare enrollment data.
 

Low-Cost, Effective Intervention

While the original study focused on total quetiapine prescribing by study PCPs, the current analysis focused on patients’ total quetiapine use per 90-day period. Additional secondary outcomes included measures of cognitive function and behavioral symptoms, indicators of depression, metabolic diagnoses, indicators of use of hospital and healthcare services, and death.

PCPs in the study had a total of 84,881 patients with dementia living in nursing homes and 261,288 living in the community. At baseline, there were 92,874 patients (mean age, 82 years; 69% female).

The warning letters were associated with reduced quetiapine use among both nursing home patients and community-dwelling patients (adjusted difference, –0.7 days; P = .02 and adjusted difference, −1.5 days; P < .001, respectively).

Among nursing home patients, there were no statistically significant adverse changes in cognitive of behavioral health measures that coincided with reduction in quetiapine use.

Although a higher percentage of treatment vs control patients reported weight loss, the difference was not significant, and rates of metabolic diagnoses were similar in both groups. There were also no significant differences between the groups in emergency department use, inpatient hospital admission, or use of restraints.

Results were similar for patients living in the community.

Additionally, no adverse effects on more severe health endpoints, including rates of hospital use or entry to nursing facilities, were detected. Importantly, the risk for death was statistically significantly lower for patients whose PCPs had received warning letters vs control patients (P = .04).

The analysis “provides evidence that a low-cost letter intervention informed by behavioral science can reduce prescribing of quetiapine to patients with dementia in nursing home and community settings,” the authors wrote.

Researchers did not directly observe the administration of the medication but instead used prescription drug fills as a proxy. Moreover, they could not observe results for patients enrolled in Medicare Advantage, and claims-based and assessment-based outcomes might have been subject to measurement errors and under-ascertainment of diagnoses.

The authors received support from the National Institute on Aging. They reported no relevant financial relationships.

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

Warning letters to primary care physicians (PCPs) regarding overprescription of quetiapine were helpful in reducing overprescribing of this agent, new research suggested.

Investigators analyzed data from an earlier trial that compared prescribing patterns in 5055 PCPs who receive a placebo letter or three warning letters informing them that their prescribing of quetiapine was high and under review by Medicare. Patients in question all had dementia and were either living in nursing homes or in the community.

The intervention reduced quetiapine use among all patients with dementia, with no detectable adverse effects on cognitive function, behavioral symptoms, depression, metabolic diagnoses, hospitalization, or death.

“This study found that overprescribing warning letters to PCPs safely reduced quetiapine prescribing to their patients with dementia,” wrote investigators led by Adam Sacarny, PhD, of the Department of Health Policy and Management, Mailman School of Public Health, Columbia University, New York. 

“This intervention and other[s] like it may be useful for future efforts to promote guideline-concordant care,” they added.

The study was published online in JAMA Network Open.
 

Off-Label Prescribing Common

The off-label use of antipsychotics in patients with dementia is fairly common, the investigators noted, affecting roughly one in seven nursing home residents and a similar number of community-dwelling older adults with dementia.

The agents are often prescribed to treat behavioral symptoms associated with dementia, including agitation and aggression. Although some evidence supports this use, antipsychotics in dementia patients can also cause an increased risk for weight gain, cognitive decline, falls and other injuries, cerebrovascular events, and mortality.

While some professional societies have called for “judicious use of antipsychotics in dementia care,” there is little evidence that reducing antipsychotic use in people with dementia might result in a benefit, investigators wrote.

The researchers analyzed data from a previous trial that focused on quetiapine, which is the most prescribed antipsychotic in the United States and is frequently used for patients with dementia.

In the original study, 2528 PCPs received a placebo letter and 2527 received three warning letters sent by the Centers for Medicare & Medicaid Services (CMS), which identified the highest-volume PCP prescribers of quetiapine.

The warning letters stated that the recipient’s quetiapine prescribing was high relative to their peers and was under review by Medicare. The placebo letter clarified an unrelated regulation. 

The current secondary analysis followed the providers and a cohort of their patients from their first receipt of the letters in 2015 through April 2017. The current evaluation analyzes patients’ outcomes through December 2018, utilizing Medicare fee-for-service claims, Minimum Data Set nursing home assessment, and Medicare enrollment data.
 

Low-Cost, Effective Intervention

While the original study focused on total quetiapine prescribing by study PCPs, the current analysis focused on patients’ total quetiapine use per 90-day period. Additional secondary outcomes included measures of cognitive function and behavioral symptoms, indicators of depression, metabolic diagnoses, indicators of use of hospital and healthcare services, and death.

PCPs in the study had a total of 84,881 patients with dementia living in nursing homes and 261,288 living in the community. At baseline, there were 92,874 patients (mean age, 82 years; 69% female).

The warning letters were associated with reduced quetiapine use among both nursing home patients and community-dwelling patients (adjusted difference, –0.7 days; P = .02 and adjusted difference, −1.5 days; P < .001, respectively).

Among nursing home patients, there were no statistically significant adverse changes in cognitive of behavioral health measures that coincided with reduction in quetiapine use.

Although a higher percentage of treatment vs control patients reported weight loss, the difference was not significant, and rates of metabolic diagnoses were similar in both groups. There were also no significant differences between the groups in emergency department use, inpatient hospital admission, or use of restraints.

Results were similar for patients living in the community.

Additionally, no adverse effects on more severe health endpoints, including rates of hospital use or entry to nursing facilities, were detected. Importantly, the risk for death was statistically significantly lower for patients whose PCPs had received warning letters vs control patients (P = .04).

The analysis “provides evidence that a low-cost letter intervention informed by behavioral science can reduce prescribing of quetiapine to patients with dementia in nursing home and community settings,” the authors wrote.

Researchers did not directly observe the administration of the medication but instead used prescription drug fills as a proxy. Moreover, they could not observe results for patients enrolled in Medicare Advantage, and claims-based and assessment-based outcomes might have been subject to measurement errors and under-ascertainment of diagnoses.

The authors received support from the National Institute on Aging. They reported no relevant financial relationships.

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

Racial discrimination in Black Americans is associated with an increased risk of developing Alzheimer’s disease (AD) in later life, new findings showed.

Researchers found that Black Americans who experience racism in their 40s and 50s are more likely to have increased serum levels of AD biomarkers p-tau181 and neurofilament light (NfL) more than a decade later.

“We know that Black Americans are at an elevated risk of Alzheimer’s disease and other dementias compared to non-Hispanic White Americans, but we don’t fully understand all the factors that contribute to this disproportionate risk,” Michelle Mielke, PhD, co-author and professor of epidemiology and prevention at Wake Forest University School of Medicine, Winston-Salem, North Carolina, said in a press release.

Recent data show AD is twice as prevalent in Black Americans as in Whites, at 18.6% and 10%, respectively. Dr. Mielke said this level of disparity cannot be attributed solely to genetic differences, and evidence suggests that racism and its related stress may play a role.

The findings were published online in Alzheimer’s and Dementia.
 

AD Biomarker Testing

To further explore a possible link between exposure to racism and AD risk, investigators analyzed data from the Family and Community Health Study, a multisite, longitudinal investigation that included more than 800 families in the United States.

Blood samples and information on racial discrimination were collected from 255 middle-aged Black Americans between 2002 and 2005.

Blood samples were tested for serum phosphorylated tau181 (p-Tau181), a marker of AD pathology; NfL, a nonspecific marker of neurodegeneration; and glial fibrillary acidic protein (GFAP), a marker of brain inflammation.

Participants answered questions about racial discrimination, which included whether they have been subjected to disrespectful treatment including racial slurs, harassment from law enforcement, or if they had ever been excluded from social activities because of their race.

The sample included 212 females and 43 males with a mean age of 46. Most participants (70%) lived in urban areas.
 

Stress-Related?

Investigators found no correlation between racial discrimination and increased levels of AD blood biomarkers in 2008 when participants were a mean age of 46 years. However, 11 years later, when participants were roughly 57 years old, investigators found experiencing racism in middle age was significantly correlated with higher levels of both p-Tau181 (r = 0.158; P ≤ .012) and NfL (r = 0.143; P ≤ .023). There was no significant association between reported discrimination and GFAP.

“These findings support the hypothesis that unique life stressors encountered by Black Americans in midlife become biologically embedded and contribute to AD pathology and neurodegeneration later in life,” the authors wrote.

Investigators speculated based on previous research that the stress related to discrimination may be associated with reductions in hippocampal and prefrontal cortex volumes and neurodegeneration in general.

Dr. Mielke also said it’s clear that future studies should focus on racism experienced by Black Americans to further understand their risk for dementia.

“This research can help inform policies and interventions to reduce racial disparities and reduce dementia risk,” she said.

Study limitations include the absence of amyloid biomarkers. Investigators noted that participants had non-detectable levels of amyloid, likely due to the use of serum vs cerebrospinal fluid.

The study was funded by the National Institute on Aging and the National Heart, Lung, and Blood Institute. Mielke reported serving on scientific advisory boards and/or having consulted for Acadia, Biogen, Eisai, LabCorp, Lilly, Merck, PeerView Institute, Roche, Siemens Healthineers, and Sunbird Bio.

A version of this article appeared on Medscape.com.

Racial discrimination in Black Americans is associated with an increased risk of developing Alzheimer’s disease (AD) in later life, new findings showed.

Researchers found that Black Americans who experience racism in their 40s and 50s are more likely to have increased serum levels of AD biomarkers p-tau181 and neurofilament light (NfL) more than a decade later.

“We know that Black Americans are at an elevated risk of Alzheimer’s disease and other dementias compared to non-Hispanic White Americans, but we don’t fully understand all the factors that contribute to this disproportionate risk,” Michelle Mielke, PhD, co-author and professor of epidemiology and prevention at Wake Forest University School of Medicine, Winston-Salem, North Carolina, said in a press release.

Recent data show AD is twice as prevalent in Black Americans as in Whites, at 18.6% and 10%, respectively. Dr. Mielke said this level of disparity cannot be attributed solely to genetic differences, and evidence suggests that racism and its related stress may play a role.

The findings were published online in Alzheimer’s and Dementia.
 

AD Biomarker Testing

To further explore a possible link between exposure to racism and AD risk, investigators analyzed data from the Family and Community Health Study, a multisite, longitudinal investigation that included more than 800 families in the United States.

Blood samples and information on racial discrimination were collected from 255 middle-aged Black Americans between 2002 and 2005.

Blood samples were tested for serum phosphorylated tau181 (p-Tau181), a marker of AD pathology; NfL, a nonspecific marker of neurodegeneration; and glial fibrillary acidic protein (GFAP), a marker of brain inflammation.

Participants answered questions about racial discrimination, which included whether they have been subjected to disrespectful treatment including racial slurs, harassment from law enforcement, or if they had ever been excluded from social activities because of their race.

The sample included 212 females and 43 males with a mean age of 46. Most participants (70%) lived in urban areas.
 

Stress-Related?

Investigators found no correlation between racial discrimination and increased levels of AD blood biomarkers in 2008 when participants were a mean age of 46 years. However, 11 years later, when participants were roughly 57 years old, investigators found experiencing racism in middle age was significantly correlated with higher levels of both p-Tau181 (r = 0.158; P ≤ .012) and NfL (r = 0.143; P ≤ .023). There was no significant association between reported discrimination and GFAP.

“These findings support the hypothesis that unique life stressors encountered by Black Americans in midlife become biologically embedded and contribute to AD pathology and neurodegeneration later in life,” the authors wrote.

Investigators speculated based on previous research that the stress related to discrimination may be associated with reductions in hippocampal and prefrontal cortex volumes and neurodegeneration in general.

Dr. Mielke also said it’s clear that future studies should focus on racism experienced by Black Americans to further understand their risk for dementia.

“This research can help inform policies and interventions to reduce racial disparities and reduce dementia risk,” she said.

Study limitations include the absence of amyloid biomarkers. Investigators noted that participants had non-detectable levels of amyloid, likely due to the use of serum vs cerebrospinal fluid.

The study was funded by the National Institute on Aging and the National Heart, Lung, and Blood Institute. Mielke reported serving on scientific advisory boards and/or having consulted for Acadia, Biogen, Eisai, LabCorp, Lilly, Merck, PeerView Institute, Roche, Siemens Healthineers, and Sunbird Bio.

A version of this article appeared on Medscape.com.

Racial discrimination in Black Americans is associated with an increased risk of developing Alzheimer’s disease (AD) in later life, new findings showed.

Researchers found that Black Americans who experience racism in their 40s and 50s are more likely to have increased serum levels of AD biomarkers p-tau181 and neurofilament light (NfL) more than a decade later.

“We know that Black Americans are at an elevated risk of Alzheimer’s disease and other dementias compared to non-Hispanic White Americans, but we don’t fully understand all the factors that contribute to this disproportionate risk,” Michelle Mielke, PhD, co-author and professor of epidemiology and prevention at Wake Forest University School of Medicine, Winston-Salem, North Carolina, said in a press release.

Recent data show AD is twice as prevalent in Black Americans as in Whites, at 18.6% and 10%, respectively. Dr. Mielke said this level of disparity cannot be attributed solely to genetic differences, and evidence suggests that racism and its related stress may play a role.

The findings were published online in Alzheimer’s and Dementia.
 

AD Biomarker Testing

To further explore a possible link between exposure to racism and AD risk, investigators analyzed data from the Family and Community Health Study, a multisite, longitudinal investigation that included more than 800 families in the United States.

Blood samples and information on racial discrimination were collected from 255 middle-aged Black Americans between 2002 and 2005.

Blood samples were tested for serum phosphorylated tau181 (p-Tau181), a marker of AD pathology; NfL, a nonspecific marker of neurodegeneration; and glial fibrillary acidic protein (GFAP), a marker of brain inflammation.

Participants answered questions about racial discrimination, which included whether they have been subjected to disrespectful treatment including racial slurs, harassment from law enforcement, or if they had ever been excluded from social activities because of their race.

The sample included 212 females and 43 males with a mean age of 46. Most participants (70%) lived in urban areas.
 

Stress-Related?

Investigators found no correlation between racial discrimination and increased levels of AD blood biomarkers in 2008 when participants were a mean age of 46 years. However, 11 years later, when participants were roughly 57 years old, investigators found experiencing racism in middle age was significantly correlated with higher levels of both p-Tau181 (r = 0.158; P ≤ .012) and NfL (r = 0.143; P ≤ .023). There was no significant association between reported discrimination and GFAP.

“These findings support the hypothesis that unique life stressors encountered by Black Americans in midlife become biologically embedded and contribute to AD pathology and neurodegeneration later in life,” the authors wrote.

Investigators speculated based on previous research that the stress related to discrimination may be associated with reductions in hippocampal and prefrontal cortex volumes and neurodegeneration in general.

Dr. Mielke also said it’s clear that future studies should focus on racism experienced by Black Americans to further understand their risk for dementia.

“This research can help inform policies and interventions to reduce racial disparities and reduce dementia risk,” she said.

Study limitations include the absence of amyloid biomarkers. Investigators noted that participants had non-detectable levels of amyloid, likely due to the use of serum vs cerebrospinal fluid.

The study was funded by the National Institute on Aging and the National Heart, Lung, and Blood Institute. Mielke reported serving on scientific advisory boards and/or having consulted for Acadia, Biogen, Eisai, LabCorp, Lilly, Merck, PeerView Institute, Roche, Siemens Healthineers, and Sunbird Bio.

A version of this article appeared on Medscape.com.

Clinicians interested in treating patients with symptoms of mild cognitive impairment or mild dementia should carefully analyze the potential benefits and harms of monoclonal amyloid beta therapy, including likelihood of side effects and overall burden on the patient, according to researchers at the annual meeting of the American Geriatrics Society (AGS). 

Lecanemab (Leqembi) may help some patients by lowering the level of beta-amyloid protein in the brain. Results from a phase 3 trial presented at the conference showed participants with Alzheimer’s disease had a 27% slower progression of the disease compared with placebo.

But clinicians must weigh that advantage against risks and contraindications, according to Esther Oh, MD, PhD, an associate professor in the Division of Geriatric Medicine and Gerontology and co-director of the Johns Hopkins Memory and Alzheimer’s Treatment Center, Johns Hopkins University, Baltimore, Maryland, who spoke during a plenary session. Lecanemab gained accelerated approval by the US Food and Drug Administration in January 2023 and full approval in July 2023.

The results from CLARITY, an 18-month, multicenter, double-blind trial involving 1795 participants aged 50-90 years, showed that the variation between treatment and placebo did not meet the criteria for a minimum clinically important difference for mild cognitive impairment or mild Alzheimer’s disease.

Even more concerning to Dr. Oh was the rate of amyloid-related abnormalities on brain imaging, which can cause brain edema and hemorrhage (12.6% and 17.3%, respectively). Almost 85% of cases were asymptomatic. 

The risk for abnormalities indicates that thrombolytics are contraindicated for patients taking the drug, according to Dr. Oh. 

“Appropriate use recommendations exclude vitamin K antagonists such as warfarin, direct oral anticoagulants and heparin, although aspirin and other antiplatelet agents are allowed,” Dr. Oh said during the presentation.

Blood biomarkers, PET imaging, and levels of amyloid-beta proteins in cerebrospinal fluid are used to determine eligibility for lecanemab. However, tau biomarkers may indicate signs of cognitive impairment decades prior to symptoms. Some evidence indicates that the drug may be more effective in individuals with low tau levels that are evident in earlier stages of disease. Tau can also be determined from cerebrospinal fluid, however, “we do not factor in tau protein as a biomarker for treatment eligibility, but this may become an important biomarker in the future,” Dr. Oh said.

Lecanemab is cost-prohibitive for many patients, with an annual price tag of $26,000. Treatment also requires monthly infusions, a PET, intravenous administration, lab work, multiple MRIs, and potentially an APOE4 serum test.

Medicare covers the majority of services, but patients are responsible for deductibles and copays, an estimated $7000 annually, according to Shari Ling, MD, deputy chief medical officer with the US Centers for Medicare & Medicaid Services, who also spoke during the session. Supplemental or other insurance such as Medicaid are also not included in this estimate.

The Medicare population is growing more complex over time, Dr. Ling said. In 2021, 54% of beneficiaries had five or more comorbidities, which can affect eligibility for lecanemab. 

“Across the healthcare system, we are learning what is necessary for coordination of delivery, for evaluation of people who receive these treatments, and for the care that is not anticipated,” Dr. Ling noted.

Neither speaker reported any financial conflicts of interest.

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

Clinicians interested in treating patients with symptoms of mild cognitive impairment or mild dementia should carefully analyze the potential benefits and harms of monoclonal amyloid beta therapy, including likelihood of side effects and overall burden on the patient, according to researchers at the annual meeting of the American Geriatrics Society (AGS). 

Lecanemab (Leqembi) may help some patients by lowering the level of beta-amyloid protein in the brain. Results from a phase 3 trial presented at the conference showed participants with Alzheimer’s disease had a 27% slower progression of the disease compared with placebo.

But clinicians must weigh that advantage against risks and contraindications, according to Esther Oh, MD, PhD, an associate professor in the Division of Geriatric Medicine and Gerontology and co-director of the Johns Hopkins Memory and Alzheimer’s Treatment Center, Johns Hopkins University, Baltimore, Maryland, who spoke during a plenary session. Lecanemab gained accelerated approval by the US Food and Drug Administration in January 2023 and full approval in July 2023.

The results from CLARITY, an 18-month, multicenter, double-blind trial involving 1795 participants aged 50-90 years, showed that the variation between treatment and placebo did not meet the criteria for a minimum clinically important difference for mild cognitive impairment or mild Alzheimer’s disease.

Even more concerning to Dr. Oh was the rate of amyloid-related abnormalities on brain imaging, which can cause brain edema and hemorrhage (12.6% and 17.3%, respectively). Almost 85% of cases were asymptomatic. 

The risk for abnormalities indicates that thrombolytics are contraindicated for patients taking the drug, according to Dr. Oh. 

“Appropriate use recommendations exclude vitamin K antagonists such as warfarin, direct oral anticoagulants and heparin, although aspirin and other antiplatelet agents are allowed,” Dr. Oh said during the presentation.

Blood biomarkers, PET imaging, and levels of amyloid-beta proteins in cerebrospinal fluid are used to determine eligibility for lecanemab. However, tau biomarkers may indicate signs of cognitive impairment decades prior to symptoms. Some evidence indicates that the drug may be more effective in individuals with low tau levels that are evident in earlier stages of disease. Tau can also be determined from cerebrospinal fluid, however, “we do not factor in tau protein as a biomarker for treatment eligibility, but this may become an important biomarker in the future,” Dr. Oh said.

Lecanemab is cost-prohibitive for many patients, with an annual price tag of $26,000. Treatment also requires monthly infusions, a PET, intravenous administration, lab work, multiple MRIs, and potentially an APOE4 serum test.

Medicare covers the majority of services, but patients are responsible for deductibles and copays, an estimated $7000 annually, according to Shari Ling, MD, deputy chief medical officer with the US Centers for Medicare & Medicaid Services, who also spoke during the session. Supplemental or other insurance such as Medicaid are also not included in this estimate.

The Medicare population is growing more complex over time, Dr. Ling said. In 2021, 54% of beneficiaries had five or more comorbidities, which can affect eligibility for lecanemab. 

“Across the healthcare system, we are learning what is necessary for coordination of delivery, for evaluation of people who receive these treatments, and for the care that is not anticipated,” Dr. Ling noted.

Neither speaker reported any financial conflicts of interest.

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

Clinicians interested in treating patients with symptoms of mild cognitive impairment or mild dementia should carefully analyze the potential benefits and harms of monoclonal amyloid beta therapy, including likelihood of side effects and overall burden on the patient, according to researchers at the annual meeting of the American Geriatrics Society (AGS). 

Lecanemab (Leqembi) may help some patients by lowering the level of beta-amyloid protein in the brain. Results from a phase 3 trial presented at the conference showed participants with Alzheimer’s disease had a 27% slower progression of the disease compared with placebo.

But clinicians must weigh that advantage against risks and contraindications, according to Esther Oh, MD, PhD, an associate professor in the Division of Geriatric Medicine and Gerontology and co-director of the Johns Hopkins Memory and Alzheimer’s Treatment Center, Johns Hopkins University, Baltimore, Maryland, who spoke during a plenary session. Lecanemab gained accelerated approval by the US Food and Drug Administration in January 2023 and full approval in July 2023.

The results from CLARITY, an 18-month, multicenter, double-blind trial involving 1795 participants aged 50-90 years, showed that the variation between treatment and placebo did not meet the criteria for a minimum clinically important difference for mild cognitive impairment or mild Alzheimer’s disease.

Even more concerning to Dr. Oh was the rate of amyloid-related abnormalities on brain imaging, which can cause brain edema and hemorrhage (12.6% and 17.3%, respectively). Almost 85% of cases were asymptomatic. 

The risk for abnormalities indicates that thrombolytics are contraindicated for patients taking the drug, according to Dr. Oh. 

“Appropriate use recommendations exclude vitamin K antagonists such as warfarin, direct oral anticoagulants and heparin, although aspirin and other antiplatelet agents are allowed,” Dr. Oh said during the presentation.

Blood biomarkers, PET imaging, and levels of amyloid-beta proteins in cerebrospinal fluid are used to determine eligibility for lecanemab. However, tau biomarkers may indicate signs of cognitive impairment decades prior to symptoms. Some evidence indicates that the drug may be more effective in individuals with low tau levels that are evident in earlier stages of disease. Tau can also be determined from cerebrospinal fluid, however, “we do not factor in tau protein as a biomarker for treatment eligibility, but this may become an important biomarker in the future,” Dr. Oh said.

Lecanemab is cost-prohibitive for many patients, with an annual price tag of $26,000. Treatment also requires monthly infusions, a PET, intravenous administration, lab work, multiple MRIs, and potentially an APOE4 serum test.

Medicare covers the majority of services, but patients are responsible for deductibles and copays, an estimated $7000 annually, according to Shari Ling, MD, deputy chief medical officer with the US Centers for Medicare & Medicaid Services, who also spoke during the session. Supplemental or other insurance such as Medicaid are also not included in this estimate.

The Medicare population is growing more complex over time, Dr. Ling said. In 2021, 54% of beneficiaries had five or more comorbidities, which can affect eligibility for lecanemab. 

“Across the healthcare system, we are learning what is necessary for coordination of delivery, for evaluation of people who receive these treatments, and for the care that is not anticipated,” Dr. Ling noted.

Neither speaker reported any financial conflicts of interest.

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

In a recent article in the American Journal of Obstetrics & Gynecology, Rebecca C. Thurston, PhD, and Pauline Maki, PhD, leading scientists in the area of menopause’s impact on brain function, presented data from their assessment of 248 late perimenopausal and postmenopausal women who reported hot flashes, also known as vasomotor symptoms (VMS).

Hot flashes are known to be associated with changes in brain white matter, carotid atherosclerosis, brain function, and memory. Dr. Thurston and colleagues objectively measured VMS over 24 hours, using skin conductance monitoring. Plasma concentrations of Alzheimer’s disease biomarkers, including the amyloid beta 42–to–amyloid beta 40 ratio, were assessed. The mean age of study participants was 59 years, and they experienced a mean of five objective VMS daily.

A key finding was that VMS, particularly those occurring during sleep, were associated with a significantly lower amyloid beta 42–to–beta 40 ratio. This finding suggests that nighttime VMS may be a marker of risk for Alzheimer’s disease.

Previous research has found that menopausal hormone therapy is associated with favorable changes in Alzheimer’s disease biomarkers. Likewise, large observational studies have shown a lower incidence of Alzheimer’s disease among women who initiate hormone therapy in their late perimenopausal or early postmenopausal years and continue such therapy long term.

The findings of this important study by Thurston and colleagues provide further evidence to support the tantalizing possibility that agents that reduce nighttime hot flashes (including hormone therapy) may lower the subsequent incidence of Alzheimer’s disease in high-risk women.
 

Dr. Kaunitz is a tenured professor and associate chair in the department of obstetrics and gynecology at the University of Florida College of Medicine–Jacksonville, and medical director and director of menopause and gynecologic ultrasound services at the University of Florida Southside Women’s Health, Jacksonville. He disclosed ties to Sumitomo Pharma America, Mithra, Viatris, Bayer, Merck, Mylan (Viatris), and UpToDate.

A version of this article appeared on Medscape.com.

In a recent article in the American Journal of Obstetrics & Gynecology, Rebecca C. Thurston, PhD, and Pauline Maki, PhD, leading scientists in the area of menopause’s impact on brain function, presented data from their assessment of 248 late perimenopausal and postmenopausal women who reported hot flashes, also known as vasomotor symptoms (VMS).

Hot flashes are known to be associated with changes in brain white matter, carotid atherosclerosis, brain function, and memory. Dr. Thurston and colleagues objectively measured VMS over 24 hours, using skin conductance monitoring. Plasma concentrations of Alzheimer’s disease biomarkers, including the amyloid beta 42–to–amyloid beta 40 ratio, were assessed. The mean age of study participants was 59 years, and they experienced a mean of five objective VMS daily.

A key finding was that VMS, particularly those occurring during sleep, were associated with a significantly lower amyloid beta 42–to–beta 40 ratio. This finding suggests that nighttime VMS may be a marker of risk for Alzheimer’s disease.

Previous research has found that menopausal hormone therapy is associated with favorable changes in Alzheimer’s disease biomarkers. Likewise, large observational studies have shown a lower incidence of Alzheimer’s disease among women who initiate hormone therapy in their late perimenopausal or early postmenopausal years and continue such therapy long term.

The findings of this important study by Thurston and colleagues provide further evidence to support the tantalizing possibility that agents that reduce nighttime hot flashes (including hormone therapy) may lower the subsequent incidence of Alzheimer’s disease in high-risk women.
 

Dr. Kaunitz is a tenured professor and associate chair in the department of obstetrics and gynecology at the University of Florida College of Medicine–Jacksonville, and medical director and director of menopause and gynecologic ultrasound services at the University of Florida Southside Women’s Health, Jacksonville. He disclosed ties to Sumitomo Pharma America, Mithra, Viatris, Bayer, Merck, Mylan (Viatris), and UpToDate.

A version of this article appeared on Medscape.com.

In a recent article in the American Journal of Obstetrics & Gynecology, Rebecca C. Thurston, PhD, and Pauline Maki, PhD, leading scientists in the area of menopause’s impact on brain function, presented data from their assessment of 248 late perimenopausal and postmenopausal women who reported hot flashes, also known as vasomotor symptoms (VMS).

Hot flashes are known to be associated with changes in brain white matter, carotid atherosclerosis, brain function, and memory. Dr. Thurston and colleagues objectively measured VMS over 24 hours, using skin conductance monitoring. Plasma concentrations of Alzheimer’s disease biomarkers, including the amyloid beta 42–to–amyloid beta 40 ratio, were assessed. The mean age of study participants was 59 years, and they experienced a mean of five objective VMS daily.

A key finding was that VMS, particularly those occurring during sleep, were associated with a significantly lower amyloid beta 42–to–beta 40 ratio. This finding suggests that nighttime VMS may be a marker of risk for Alzheimer’s disease.

Previous research has found that menopausal hormone therapy is associated with favorable changes in Alzheimer’s disease biomarkers. Likewise, large observational studies have shown a lower incidence of Alzheimer’s disease among women who initiate hormone therapy in their late perimenopausal or early postmenopausal years and continue such therapy long term.

The findings of this important study by Thurston and colleagues provide further evidence to support the tantalizing possibility that agents that reduce nighttime hot flashes (including hormone therapy) may lower the subsequent incidence of Alzheimer’s disease in high-risk women.
 

Dr. Kaunitz is a tenured professor and associate chair in the department of obstetrics and gynecology at the University of Florida College of Medicine–Jacksonville, and medical director and director of menopause and gynecologic ultrasound services at the University of Florida Southside Women’s Health, Jacksonville. He disclosed ties to Sumitomo Pharma America, Mithra, Viatris, Bayer, Merck, Mylan (Viatris), and UpToDate.

A version of this article appeared on Medscape.com.