Geriatrics

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:

Some vulnerable older patients with untreated metastatic pancreatic cancer can benefit from chemotherapy, but only if they can tolerate enough cycles of treatment, according to results of the randomized phase 2 GIANT study.

METHODOLOGY:

Pancreatic cancer is most often diagnosed in adults aged 65 years or older. Providing cancer treatment for this older, often vulnerable, population comes with significant challenges and can lead to worse survival.

To examine real-world outcomes of older adults with untreated metastatic pancreatic cancer, researchers recruited patients aged 70 years or older and performed a geriatric assessment to identify comorbidities, cognitive issues, and other geriatric abnormalities.

Those who were deemed “fit” (ie, with no geriatric abnormalities) were assigned to receive off-study standard-of-care treatment, whereas those classified as “frail” (ie, with severe abnormalities) received off-study supportive care.

The remaining 176 “vulnerable” patients with mild to moderate geriatric abnormalities completed a geriatric and quality-of-life assessment and were then randomly assigned to receive either dose-reduced 5-fluorouracil (5-FU), leucovorin plus liposomal irinotecan (n = 88) or modified gemcitabine plus nab-paclitaxel (n = 88) every 2 weeks. Ultimately, 79 patients started the 5-FU combination and 75 received gemcitabine plus nab-paclitaxel. Patients were assessed every 8 weeks until disease progression or intolerance.

Overall, patients had a median age of 77 years; 61.9% were aged 75 years or older. About half were female, and 81.5% were White. The majority (87.5%) had a performance status of 0 or 1.

TAKEAWAY:

• Median overall survival was 4.7 months in the gemcitabine plus nab-paclitaxel arm and 4.4 months in the 5-FU combination group, with no significant survival difference observed between the two arms (P = .72).
• When the overall survival analysis was restricted to patients who received at least 4 weeks, or two cycles, of treatment (about 62% of patients), the median overall survival across the two treatment arms reached 8.0 months, in line with expectations for these regimens.
• Patient stratification revealed that those with a performance status of 2 had significantly worse overall survival than those with a status of 0: 1.4 months vs 6.9 months, respectively (hazard ratio [HR], 2.77; P < .001). A similar divide was seen when patients were stratified by physical/functional status and well-being. Age, however, did not significantly influence the results.
• Overall, more than half of patients experienced grade 3 or higher adverse events. Just over 38% of patients received only one to three cycles of therapy, whereas 26% remained on treatment for 12 or more cycles. The adverse event rates were similar between the two regimens, but the toxicity profile was slightly different — the researchers, for instance, observed more peripheral neuropathy with gemcitabine plus nab-paclitaxel and more diarrhea in the 5-FU combination arm.

IN PRACTICE:

• Overall, the “survival outcomes among vulnerable older patients were lower than expected, with high percentage of patients not able to start treatment, or complete one month of therapy due to clinical deterioration,” said study presenter Efrat Dotan, MD, chief, Division of Gastrointestinal Medical Oncology, Fox Chase Cancer Center, Philadelphia. 
• “For vulnerable older adults who can tolerate treatment, these two regimens provide clinicians with options for tailoring therapy based on toxicity profile,” Dr. Dotan added. But “tools are needed to better identify patients who can benefit from treatment.”
• The results underline the need to perform geriatric assessments, as opposed to merely looking at performance status, commented David F. Chang, PhD, MS, MBBS, professor of Surgical Oncology, University of Glasgow, Scotland, who was not involved in the study. 

SOURCE:

The research, presented at the 2024 annual meeting of the American Society of Clinical Oncology, was funded by the National Cancer Institute and the Eastern Cooperative Oncology Group.

LIMITATIONS:

Dr. Chang noted that the study did not reveal which treatment regimen was more effective.

DISCLOSURES:

Dr. Dotan declared relationships with Agenus, Amgen, G1 Therapeutics, Incyte, Olympus, and Taiho Pharmaceutical and institutional relationships with Dragonfly Therapeutics, Gilead Sciences, Ipsen, Kinnate Biopharma, Leap Therapeutics, Lilly, Lutris, NGM Biopharmaceuticals, Relay Therapeutics, and Zymeworks. Dr. Chang declared relationships with Immodulon Therapeutics and Mylan and institutional relationships with AstraZeneca, BMS GmbH & Co. KG, Immodulon Therapeutics, and Merck.

A version of this article appeared on Medscape.com.

TOPLINE:

Some vulnerable older patients with untreated metastatic pancreatic cancer can benefit from chemotherapy, but only if they can tolerate enough cycles of treatment, according to results of the randomized phase 2 GIANT study.

METHODOLOGY:

Pancreatic cancer is most often diagnosed in adults aged 65 years or older. Providing cancer treatment for this older, often vulnerable, population comes with significant challenges and can lead to worse survival.

To examine real-world outcomes of older adults with untreated metastatic pancreatic cancer, researchers recruited patients aged 70 years or older and performed a geriatric assessment to identify comorbidities, cognitive issues, and other geriatric abnormalities.

Those who were deemed “fit” (ie, with no geriatric abnormalities) were assigned to receive off-study standard-of-care treatment, whereas those classified as “frail” (ie, with severe abnormalities) received off-study supportive care.

The remaining 176 “vulnerable” patients with mild to moderate geriatric abnormalities completed a geriatric and quality-of-life assessment and were then randomly assigned to receive either dose-reduced 5-fluorouracil (5-FU), leucovorin plus liposomal irinotecan (n = 88) or modified gemcitabine plus nab-paclitaxel (n = 88) every 2 weeks. Ultimately, 79 patients started the 5-FU combination and 75 received gemcitabine plus nab-paclitaxel. Patients were assessed every 8 weeks until disease progression or intolerance.

Overall, patients had a median age of 77 years; 61.9% were aged 75 years or older. About half were female, and 81.5% were White. The majority (87.5%) had a performance status of 0 or 1.

TAKEAWAY:

• Median overall survival was 4.7 months in the gemcitabine plus nab-paclitaxel arm and 4.4 months in the 5-FU combination group, with no significant survival difference observed between the two arms (P = .72).
• When the overall survival analysis was restricted to patients who received at least 4 weeks, or two cycles, of treatment (about 62% of patients), the median overall survival across the two treatment arms reached 8.0 months, in line with expectations for these regimens.
• Patient stratification revealed that those with a performance status of 2 had significantly worse overall survival than those with a status of 0: 1.4 months vs 6.9 months, respectively (hazard ratio [HR], 2.77; P < .001). A similar divide was seen when patients were stratified by physical/functional status and well-being. Age, however, did not significantly influence the results.
• Overall, more than half of patients experienced grade 3 or higher adverse events. Just over 38% of patients received only one to three cycles of therapy, whereas 26% remained on treatment for 12 or more cycles. The adverse event rates were similar between the two regimens, but the toxicity profile was slightly different — the researchers, for instance, observed more peripheral neuropathy with gemcitabine plus nab-paclitaxel and more diarrhea in the 5-FU combination arm.

IN PRACTICE:

• Overall, the “survival outcomes among vulnerable older patients were lower than expected, with high percentage of patients not able to start treatment, or complete one month of therapy due to clinical deterioration,” said study presenter Efrat Dotan, MD, chief, Division of Gastrointestinal Medical Oncology, Fox Chase Cancer Center, Philadelphia. 
• “For vulnerable older adults who can tolerate treatment, these two regimens provide clinicians with options for tailoring therapy based on toxicity profile,” Dr. Dotan added. But “tools are needed to better identify patients who can benefit from treatment.”
• The results underline the need to perform geriatric assessments, as opposed to merely looking at performance status, commented David F. Chang, PhD, MS, MBBS, professor of Surgical Oncology, University of Glasgow, Scotland, who was not involved in the study. 

SOURCE:

The research, presented at the 2024 annual meeting of the American Society of Clinical Oncology, was funded by the National Cancer Institute and the Eastern Cooperative Oncology Group.

LIMITATIONS:

Dr. Chang noted that the study did not reveal which treatment regimen was more effective.

DISCLOSURES:

Dr. Dotan declared relationships with Agenus, Amgen, G1 Therapeutics, Incyte, Olympus, and Taiho Pharmaceutical and institutional relationships with Dragonfly Therapeutics, Gilead Sciences, Ipsen, Kinnate Biopharma, Leap Therapeutics, Lilly, Lutris, NGM Biopharmaceuticals, Relay Therapeutics, and Zymeworks. Dr. Chang declared relationships with Immodulon Therapeutics and Mylan and institutional relationships with AstraZeneca, BMS GmbH & Co. KG, Immodulon Therapeutics, and Merck.

A version of this article appeared on Medscape.com.

TOPLINE:

Some vulnerable older patients with untreated metastatic pancreatic cancer can benefit from chemotherapy, but only if they can tolerate enough cycles of treatment, according to results of the randomized phase 2 GIANT study.

METHODOLOGY:

Pancreatic cancer is most often diagnosed in adults aged 65 years or older. Providing cancer treatment for this older, often vulnerable, population comes with significant challenges and can lead to worse survival.

To examine real-world outcomes of older adults with untreated metastatic pancreatic cancer, researchers recruited patients aged 70 years or older and performed a geriatric assessment to identify comorbidities, cognitive issues, and other geriatric abnormalities.

Those who were deemed “fit” (ie, with no geriatric abnormalities) were assigned to receive off-study standard-of-care treatment, whereas those classified as “frail” (ie, with severe abnormalities) received off-study supportive care.

The remaining 176 “vulnerable” patients with mild to moderate geriatric abnormalities completed a geriatric and quality-of-life assessment and were then randomly assigned to receive either dose-reduced 5-fluorouracil (5-FU), leucovorin plus liposomal irinotecan (n = 88) or modified gemcitabine plus nab-paclitaxel (n = 88) every 2 weeks. Ultimately, 79 patients started the 5-FU combination and 75 received gemcitabine plus nab-paclitaxel. Patients were assessed every 8 weeks until disease progression or intolerance.

Overall, patients had a median age of 77 years; 61.9% were aged 75 years or older. About half were female, and 81.5% were White. The majority (87.5%) had a performance status of 0 or 1.

TAKEAWAY:

• Median overall survival was 4.7 months in the gemcitabine plus nab-paclitaxel arm and 4.4 months in the 5-FU combination group, with no significant survival difference observed between the two arms (P = .72).
• When the overall survival analysis was restricted to patients who received at least 4 weeks, or two cycles, of treatment (about 62% of patients), the median overall survival across the two treatment arms reached 8.0 months, in line with expectations for these regimens.
• Patient stratification revealed that those with a performance status of 2 had significantly worse overall survival than those with a status of 0: 1.4 months vs 6.9 months, respectively (hazard ratio [HR], 2.77; P < .001). A similar divide was seen when patients were stratified by physical/functional status and well-being. Age, however, did not significantly influence the results.
• Overall, more than half of patients experienced grade 3 or higher adverse events. Just over 38% of patients received only one to three cycles of therapy, whereas 26% remained on treatment for 12 or more cycles. The adverse event rates were similar between the two regimens, but the toxicity profile was slightly different — the researchers, for instance, observed more peripheral neuropathy with gemcitabine plus nab-paclitaxel and more diarrhea in the 5-FU combination arm.

IN PRACTICE:

• Overall, the “survival outcomes among vulnerable older patients were lower than expected, with high percentage of patients not able to start treatment, or complete one month of therapy due to clinical deterioration,” said study presenter Efrat Dotan, MD, chief, Division of Gastrointestinal Medical Oncology, Fox Chase Cancer Center, Philadelphia. 
• “For vulnerable older adults who can tolerate treatment, these two regimens provide clinicians with options for tailoring therapy based on toxicity profile,” Dr. Dotan added. But “tools are needed to better identify patients who can benefit from treatment.”
• The results underline the need to perform geriatric assessments, as opposed to merely looking at performance status, commented David F. Chang, PhD, MS, MBBS, professor of Surgical Oncology, University of Glasgow, Scotland, who was not involved in the study. 

SOURCE:

The research, presented at the 2024 annual meeting of the American Society of Clinical Oncology, was funded by the National Cancer Institute and the Eastern Cooperative Oncology Group.

LIMITATIONS:

Dr. Chang noted that the study did not reveal which treatment regimen was more effective.

DISCLOSURES:

Dr. Dotan declared relationships with Agenus, Amgen, G1 Therapeutics, Incyte, Olympus, and Taiho Pharmaceutical and institutional relationships with Dragonfly Therapeutics, Gilead Sciences, Ipsen, Kinnate Biopharma, Leap Therapeutics, Lilly, Lutris, NGM Biopharmaceuticals, Relay Therapeutics, and Zymeworks. Dr. Chang declared relationships with Immodulon Therapeutics and Mylan and institutional relationships with AstraZeneca, BMS GmbH & Co. KG, Immodulon Therapeutics, and Merck.

A version of this article appeared on Medscape.com.

TOPLINE:

Melatonin supplementation is linked to a reduced risk for developing age-related macular degeneration (AMD) and slowing its progression, suggesting potential as a preventive therapy.

METHODOLOGY:

• Researchers analyzed data from the TriNetX database, covering electronic medical records across the United States from December 2023 to March 2024.
• The retrospective study included patients aged ≥ 50 years, divided into groups based on their history of AMD and melatonin medication codes between November 2008 and November 2023.
• Propensity score matching was used to compare melatonin users and nonusers for the risk for developing any form of AMD or the progression to exudative AMD from the nonexudative form of the condition.

TAKEAWAY:

• Use of melatonin was associated with a 58% reduction in the risk for developing AMD, according to the researchers.
• In people with nonexudative AMD, use of the supplement was linked to a 56% lower risk for progression to exudative AMD.
• The findings were consistent across age groups, suggesting melatonin’s benefits may extend to older populations at higher risk for AMD, the researchers reported.

IN PRACTICE:

“In this cohort study of 121,523 patients with no history of AMD aged ≥ 50 years, taking melatonin was associated with a decreased risk of developing AMD,” the authors of the study wrote. “Likewise, among 66,253 patients with preexisting nonexudative AMD, melatonin supplementation was negatively associated with the rate of progression to exudative AMD.”

Studies in animals and humans have shown melatonin may be a potent antioxidant and anti-inflammatory agent and have both antiangiogenic and mitochondrial-preserving properties, the authors noted. The new findings “provide a rationale for expanding clinical research on the potential therapeutic efficacy of melatonin in preventing AMD development or its progression,” they added. 

SOURCE:

The study was led by Hejin Jeong, Case Western Reserve University School of Medicine, Cleveland, and was published online in JAMA Ophthalmology.

LIMITATIONS:

The study’s reliance on diagnostic codes may have limited the accuracy of identifying AMD progression. Variations in coding practices and the reporting of over-the-counter medications like melatonin could have influenced the results. The study did not control for all modifiable risk factors for AMD, which may have introduced healthy user bias.

DISCLOSURES:

The authors reported various potential conflicts of interest, including receiving personal fees and grants from various pharmaceutical companies. The study was funded by grants from the National Institutes of Health and the Cleveland Eye Bank Foundation.

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:

Melatonin supplementation is linked to a reduced risk for developing age-related macular degeneration (AMD) and slowing its progression, suggesting potential as a preventive therapy.

METHODOLOGY:

• Researchers analyzed data from the TriNetX database, covering electronic medical records across the United States from December 2023 to March 2024.
• The retrospective study included patients aged ≥ 50 years, divided into groups based on their history of AMD and melatonin medication codes between November 2008 and November 2023.
• Propensity score matching was used to compare melatonin users and nonusers for the risk for developing any form of AMD or the progression to exudative AMD from the nonexudative form of the condition.

TAKEAWAY:

• Use of melatonin was associated with a 58% reduction in the risk for developing AMD, according to the researchers.
• In people with nonexudative AMD, use of the supplement was linked to a 56% lower risk for progression to exudative AMD.
• The findings were consistent across age groups, suggesting melatonin’s benefits may extend to older populations at higher risk for AMD, the researchers reported.

IN PRACTICE:

“In this cohort study of 121,523 patients with no history of AMD aged ≥ 50 years, taking melatonin was associated with a decreased risk of developing AMD,” the authors of the study wrote. “Likewise, among 66,253 patients with preexisting nonexudative AMD, melatonin supplementation was negatively associated with the rate of progression to exudative AMD.”

Studies in animals and humans have shown melatonin may be a potent antioxidant and anti-inflammatory agent and have both antiangiogenic and mitochondrial-preserving properties, the authors noted. The new findings “provide a rationale for expanding clinical research on the potential therapeutic efficacy of melatonin in preventing AMD development or its progression,” they added. 

SOURCE:

The study was led by Hejin Jeong, Case Western Reserve University School of Medicine, Cleveland, and was published online in JAMA Ophthalmology.

LIMITATIONS:

The study’s reliance on diagnostic codes may have limited the accuracy of identifying AMD progression. Variations in coding practices and the reporting of over-the-counter medications like melatonin could have influenced the results. The study did not control for all modifiable risk factors for AMD, which may have introduced healthy user bias.

DISCLOSURES:

The authors reported various potential conflicts of interest, including receiving personal fees and grants from various pharmaceutical companies. The study was funded by grants from the National Institutes of Health and the Cleveland Eye Bank Foundation.

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:

Melatonin supplementation is linked to a reduced risk for developing age-related macular degeneration (AMD) and slowing its progression, suggesting potential as a preventive therapy.

METHODOLOGY:

• Researchers analyzed data from the TriNetX database, covering electronic medical records across the United States from December 2023 to March 2024.
• The retrospective study included patients aged ≥ 50 years, divided into groups based on their history of AMD and melatonin medication codes between November 2008 and November 2023.
• Propensity score matching was used to compare melatonin users and nonusers for the risk for developing any form of AMD or the progression to exudative AMD from the nonexudative form of the condition.

TAKEAWAY:

• Use of melatonin was associated with a 58% reduction in the risk for developing AMD, according to the researchers.
• In people with nonexudative AMD, use of the supplement was linked to a 56% lower risk for progression to exudative AMD.
• The findings were consistent across age groups, suggesting melatonin’s benefits may extend to older populations at higher risk for AMD, the researchers reported.

IN PRACTICE:

“In this cohort study of 121,523 patients with no history of AMD aged ≥ 50 years, taking melatonin was associated with a decreased risk of developing AMD,” the authors of the study wrote. “Likewise, among 66,253 patients with preexisting nonexudative AMD, melatonin supplementation was negatively associated with the rate of progression to exudative AMD.”

Studies in animals and humans have shown melatonin may be a potent antioxidant and anti-inflammatory agent and have both antiangiogenic and mitochondrial-preserving properties, the authors noted. The new findings “provide a rationale for expanding clinical research on the potential therapeutic efficacy of melatonin in preventing AMD development or its progression,” they added. 

SOURCE:

The study was led by Hejin Jeong, Case Western Reserve University School of Medicine, Cleveland, and was published online in JAMA Ophthalmology.

LIMITATIONS:

The study’s reliance on diagnostic codes may have limited the accuracy of identifying AMD progression. Variations in coding practices and the reporting of over-the-counter medications like melatonin could have influenced the results. The study did not control for all modifiable risk factors for AMD, which may have introduced healthy user bias.

DISCLOSURES:

The authors reported various potential conflicts of interest, including receiving personal fees and grants from various pharmaceutical companies. The study was funded by grants from the National Institutes of Health and the Cleveland Eye Bank Foundation.

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.

TOPLINE:

Women with low bone density are more likely to report their first fragility hip fracture in their 60s rather than at older ages.

METHODOLOGY:

• Researchers used hip fracture data from the National Health and Nutrition Examination Survey for 2009-2010, 2013-2014, and 2017-2018.
• They included women older than 60 years with a bone mineral density T score ≤ −1 at the femur neck, measured by dual-energy x-ray absorptiometry.
• Fragility fractures are defined as a self-reported hip fracture resulting from a fall from standing height or less.

TAKEAWAY:

• The number of women in their 60s who reported their first hip fracture grew by 50% from 2009 to 2018.
• The opposite was true for women in their 70s and 80s who reported fewer first hip fractures over the study period.
• Reported fragility hip fractures in women overall decreased by half from 2009 to 2018.
• The prevalence of women with osteoporosis (T score ≤ −2.5) grew from 18.1% to 21.3% over 10 years.

IN PRACTICE:

The decrease in fractures overall and in women older than 70 years “may be due to increasing awareness and utilization of measures to decrease falls such as exercise, nutrition, health education, and environmental modifications targeted toward the elderly population,” the authors wrote. The findings also underscore the importance of earlier bone health awareness in primary care to curb the rising trend in younger women, they added.

SOURCE:

The study was led by Avica Atri, MD, of Albert Einstein Medical Center in Philadelphia. She presented the findings at ENDO 2024: The Endocrine Society Annual Meeting.

LIMITATIONS:

The study was retrospective in nature and included self-reported health data.

DISCLOSURES:

The study received no commercial funding. The authors have reported no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Women with low bone density are more likely to report their first fragility hip fracture in their 60s rather than at older ages.

METHODOLOGY:

• Researchers used hip fracture data from the National Health and Nutrition Examination Survey for 2009-2010, 2013-2014, and 2017-2018.
• They included women older than 60 years with a bone mineral density T score ≤ −1 at the femur neck, measured by dual-energy x-ray absorptiometry.
• Fragility fractures are defined as a self-reported hip fracture resulting from a fall from standing height or less.

TAKEAWAY:

• The number of women in their 60s who reported their first hip fracture grew by 50% from 2009 to 2018.
• The opposite was true for women in their 70s and 80s who reported fewer first hip fractures over the study period.
• Reported fragility hip fractures in women overall decreased by half from 2009 to 2018.
• The prevalence of women with osteoporosis (T score ≤ −2.5) grew from 18.1% to 21.3% over 10 years.

IN PRACTICE:

The decrease in fractures overall and in women older than 70 years “may be due to increasing awareness and utilization of measures to decrease falls such as exercise, nutrition, health education, and environmental modifications targeted toward the elderly population,” the authors wrote. The findings also underscore the importance of earlier bone health awareness in primary care to curb the rising trend in younger women, they added.

SOURCE:

The study was led by Avica Atri, MD, of Albert Einstein Medical Center in Philadelphia. She presented the findings at ENDO 2024: The Endocrine Society Annual Meeting.

LIMITATIONS:

The study was retrospective in nature and included self-reported health data.

DISCLOSURES:

The study received no commercial funding. The authors have reported no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Women with low bone density are more likely to report their first fragility hip fracture in their 60s rather than at older ages.

METHODOLOGY:

• Researchers used hip fracture data from the National Health and Nutrition Examination Survey for 2009-2010, 2013-2014, and 2017-2018.
• They included women older than 60 years with a bone mineral density T score ≤ −1 at the femur neck, measured by dual-energy x-ray absorptiometry.
• Fragility fractures are defined as a self-reported hip fracture resulting from a fall from standing height or less.

TAKEAWAY:

• The number of women in their 60s who reported their first hip fracture grew by 50% from 2009 to 2018.
• The opposite was true for women in their 70s and 80s who reported fewer first hip fractures over the study period.
• Reported fragility hip fractures in women overall decreased by half from 2009 to 2018.
• The prevalence of women with osteoporosis (T score ≤ −2.5) grew from 18.1% to 21.3% over 10 years.

IN PRACTICE:

The decrease in fractures overall and in women older than 70 years “may be due to increasing awareness and utilization of measures to decrease falls such as exercise, nutrition, health education, and environmental modifications targeted toward the elderly population,” the authors wrote. The findings also underscore the importance of earlier bone health awareness in primary care to curb the rising trend in younger women, they added.

SOURCE:

The study was led by Avica Atri, MD, of Albert Einstein Medical Center in Philadelphia. She presented the findings at ENDO 2024: The Endocrine Society Annual Meeting.

LIMITATIONS:

The study was retrospective in nature and included self-reported health data.

DISCLOSURES:

The study received no commercial funding. The authors have reported no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

Exercise recommendations typically focus on the duration of physical activity. For example, the World Health Organization advises at least 150 minutes of moderate physical activity per week. A new analysis of data from the Women’s Health Study, published in JAMA Internal Medicine, suggested that step count could also be a useful metric. For some, such a recommendation might be easier to follow.

“It’s not so easy to keep track of how long you’ve been moderately active in a given week,” Cary P. Gross, MD, from the Department of Medicine at Yale University in New Haven, Connecticut, wrote in an editorial. “Counting steps might be easier for some people, especially since most carry a phone that can serve as a pedometer.”
 

The 10,000-Step Recommendation

However, there are no well-founded recommendations for step counts, partly due to a lack of scientific evidence linking steps with mortality and cardiovascular diseases. The often-cited 10,000 steps per day originated from a marketing campaign in Japan in the 1960s.

The research team led by Rikuta Hamaya, MD, from the Division of Preventive Medicine at Brigham and Women’s Hospital in Boston, analyzed data from participants in the Women’s Health Study. This clinical trial in the United States from 1992 to 2004 investigated the use of aspirin and vitamin E for cancer and cardiovascular disease prevention.

The current analysis included 14,399 women who were aged ≥ 62 years and had not developed cardiovascular disease or cancer. Between 2011 and 2015, they measured their physical activity and step count over 7 days using an accelerometer. They were followed-up for an average of 9 years.
 

Risk Reduction With Both Parameters

Moderate physical activity among the participants amounted to a median of 62 minutes per week, with a median daily step count of 5183. Hamaya and his colleagues found that both physical activity parameters were associated with lower mortality and reduced risk for cardiovascular diseases.

Participants who engaged in more than the recommended 150 minutes of moderate-intensity activity per week had a 32% lower mortality risk than those who were the least physically active. Women with > 7000 steps per day had a 42% lower mortality risk than those with the lowest daily step count.

Women in the top three quartiles of physical activity outlived those in the lowest quartile by an average of 2.22 months (time) or 2.36 months (steps), according to Hamaya and his team. The survival advantage was independent of body mass index.

For the endpoint of cardiovascular diseases (heart attack, stroke, and cardiovascular mortality), the researchers observed similar results as for mortality.
 

More Ways to Reach the Goal

Dr. Hamaya emphasized the importance of offering multiple ways to meet exercise recommendations: “For some, especially younger people, physical activity includes sports like tennis, soccer, walking, or jogging. All these can be tracked well with step counting. But for others, activity means cycling or swimming, which is easier to measure by duration.”

For Dr. Gross, the new findings provide a basis for using step counts to set physical activity goals — both in individual patient counseling and in formal guidelines. However, he stressed that further studies are necessary.

“The results need to be replicated in various populations, not just among men and younger people but also among ethnic minorities and lower-income populations, who often have less time and space for structured physical activity.”
 

This story was translated from Medscape German edition 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.

Exercise recommendations typically focus on the duration of physical activity. For example, the World Health Organization advises at least 150 minutes of moderate physical activity per week. A new analysis of data from the Women’s Health Study, published in JAMA Internal Medicine, suggested that step count could also be a useful metric. For some, such a recommendation might be easier to follow.

“It’s not so easy to keep track of how long you’ve been moderately active in a given week,” Cary P. Gross, MD, from the Department of Medicine at Yale University in New Haven, Connecticut, wrote in an editorial. “Counting steps might be easier for some people, especially since most carry a phone that can serve as a pedometer.”
 

The 10,000-Step Recommendation

However, there are no well-founded recommendations for step counts, partly due to a lack of scientific evidence linking steps with mortality and cardiovascular diseases. The often-cited 10,000 steps per day originated from a marketing campaign in Japan in the 1960s.

The research team led by Rikuta Hamaya, MD, from the Division of Preventive Medicine at Brigham and Women’s Hospital in Boston, analyzed data from participants in the Women’s Health Study. This clinical trial in the United States from 1992 to 2004 investigated the use of aspirin and vitamin E for cancer and cardiovascular disease prevention.

The current analysis included 14,399 women who were aged ≥ 62 years and had not developed cardiovascular disease or cancer. Between 2011 and 2015, they measured their physical activity and step count over 7 days using an accelerometer. They were followed-up for an average of 9 years.
 

Risk Reduction With Both Parameters

Moderate physical activity among the participants amounted to a median of 62 minutes per week, with a median daily step count of 5183. Hamaya and his colleagues found that both physical activity parameters were associated with lower mortality and reduced risk for cardiovascular diseases.

Participants who engaged in more than the recommended 150 minutes of moderate-intensity activity per week had a 32% lower mortality risk than those who were the least physically active. Women with > 7000 steps per day had a 42% lower mortality risk than those with the lowest daily step count.

Women in the top three quartiles of physical activity outlived those in the lowest quartile by an average of 2.22 months (time) or 2.36 months (steps), according to Hamaya and his team. The survival advantage was independent of body mass index.

For the endpoint of cardiovascular diseases (heart attack, stroke, and cardiovascular mortality), the researchers observed similar results as for mortality.
 

More Ways to Reach the Goal

Dr. Hamaya emphasized the importance of offering multiple ways to meet exercise recommendations: “For some, especially younger people, physical activity includes sports like tennis, soccer, walking, or jogging. All these can be tracked well with step counting. But for others, activity means cycling or swimming, which is easier to measure by duration.”

For Dr. Gross, the new findings provide a basis for using step counts to set physical activity goals — both in individual patient counseling and in formal guidelines. However, he stressed that further studies are necessary.

“The results need to be replicated in various populations, not just among men and younger people but also among ethnic minorities and lower-income populations, who often have less time and space for structured physical activity.”
 

This story was translated from Medscape German edition 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.

Exercise recommendations typically focus on the duration of physical activity. For example, the World Health Organization advises at least 150 minutes of moderate physical activity per week. A new analysis of data from the Women’s Health Study, published in JAMA Internal Medicine, suggested that step count could also be a useful metric. For some, such a recommendation might be easier to follow.

“It’s not so easy to keep track of how long you’ve been moderately active in a given week,” Cary P. Gross, MD, from the Department of Medicine at Yale University in New Haven, Connecticut, wrote in an editorial. “Counting steps might be easier for some people, especially since most carry a phone that can serve as a pedometer.”
 

The 10,000-Step Recommendation

However, there are no well-founded recommendations for step counts, partly due to a lack of scientific evidence linking steps with mortality and cardiovascular diseases. The often-cited 10,000 steps per day originated from a marketing campaign in Japan in the 1960s.

The research team led by Rikuta Hamaya, MD, from the Division of Preventive Medicine at Brigham and Women’s Hospital in Boston, analyzed data from participants in the Women’s Health Study. This clinical trial in the United States from 1992 to 2004 investigated the use of aspirin and vitamin E for cancer and cardiovascular disease prevention.

The current analysis included 14,399 women who were aged ≥ 62 years and had not developed cardiovascular disease or cancer. Between 2011 and 2015, they measured their physical activity and step count over 7 days using an accelerometer. They were followed-up for an average of 9 years.
 

Risk Reduction With Both Parameters

Moderate physical activity among the participants amounted to a median of 62 minutes per week, with a median daily step count of 5183. Hamaya and his colleagues found that both physical activity parameters were associated with lower mortality and reduced risk for cardiovascular diseases.

Participants who engaged in more than the recommended 150 minutes of moderate-intensity activity per week had a 32% lower mortality risk than those who were the least physically active. Women with > 7000 steps per day had a 42% lower mortality risk than those with the lowest daily step count.

Women in the top three quartiles of physical activity outlived those in the lowest quartile by an average of 2.22 months (time) or 2.36 months (steps), according to Hamaya and his team. The survival advantage was independent of body mass index.

For the endpoint of cardiovascular diseases (heart attack, stroke, and cardiovascular mortality), the researchers observed similar results as for mortality.
 

More Ways to Reach the Goal

Dr. Hamaya emphasized the importance of offering multiple ways to meet exercise recommendations: “For some, especially younger people, physical activity includes sports like tennis, soccer, walking, or jogging. All these can be tracked well with step counting. But for others, activity means cycling or swimming, which is easier to measure by duration.”

For Dr. Gross, the new findings provide a basis for using step counts to set physical activity goals — both in individual patient counseling and in formal guidelines. However, he stressed that further studies are necessary.

“The results need to be replicated in various populations, not just among men and younger people but also among ethnic minorities and lower-income populations, who often have less time and space for structured physical activity.”
 

This story was translated from Medscape German edition 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.

Exercise interventions are recommended to help prevent falls and fall-related morbidity in community-dwelling adults aged 65 years and older who are at increased risk of falls, according to a new recommendation statement from the U.S. Preventive Services Task Force (USPSTF) (JAMA. 2024 Jun 4. doi: 10.1001/jama.2024.8481).

Falls remain the leading cause of injury-related morbidity and mortality among older adults in the United States, with approximately 27% of community-dwelling individuals aged 65 years and older reporting at least one fall in the past year, wrote lead author Wanda K. Nicholson, MD, of George Washington University, Washington, and colleagues.

The task force concluded with moderate certainty that exercise interventions yielded a moderate benefit in fall reduction among older adults at risk (grade B recommendation).

The decision to offer multifactorial fall prevention interventions to older adults at risk for falls should be individualized based on assessment of potential risks and benefits of these interventions, including circumstances of prior falls, presence of comorbid medical conditions, and the patient’s values and preferences (grade C recommendation), the authors wrote.

The exercise intervention could include individual or group activity, although most of the studies in the systematic review involved group exercise, the authors noted.

The recommendation was based on data from a systematic evidence review published in JAMA (2024 Jun 4. doi: 10.1001/jama.2024.4166). The task force reviewed data from 83 randomized trials published between January 1, 2016, and May 8, 2023, deemed fair to good quality that examined six types of fall prevention interventions in a total of 48,839 individuals. Of these, 28 studies involved multifactorial interventions and 27 involved exercise interventions.

Overall, multifactorial interventions and exercise interventions were associated with a significant reduction in falls (incidence rate ratio 0.84 and 0.85, respectively).

Exercise interventions were significantly associated with reduced individual risk of one or more falls and injurious falls, but not with reduced individual risk of injurious falls. However, multifactorial interventions were not significantly associated with reductions in risk of one or more falls, injurious falls, fall-related fractures, individual risk of injurious falls, or individual risk of fall-related fractures.

Although teasing out the specific exercise components that are most effective for fall prevention is challenging, the most commonly studied components associated with reduced risk of falls included gait training, balance training, and functional training, followed by strength and resistance training, the task force noted.

Duration of exercise interventions in the reviewed studies ranged from 2 to 30 months and the most common frequency of sessions was 2 to 3 per week.

Based on these findings, the task force found that exercise had the most consistent benefits for reduced risk across several fall-related outcomes. Although individuals in the studies of multifactorial interventions were at increased risk for falls, the multistep process of interventions to address an individual’s multiple risk factors limited their effectiveness, in part because of logistical challenges and inconsistent adherence, the authors wrote.

The results of the review were limited by several factors, including the focus on studies with a primary or secondary aim of fall prevention, the fact that the recommendation does not apply to many subgroups of older adults, and the lack of data on health outcomes unrelated to falls that were associated with the interventions, the authors noted.

The new recommendation is consistent with and replaces the 2018 USPSTF recommendation on interventions for fall prevention in community-dwelling older adults, but without the recommendation against vitamin D supplementation as a fall prevention intervention. The new recommendation does not address vitamin D use; evidence will be examined in a separate recommendation, the task force wrote.
 

How to Get Older Adults Moving

“The biggest obstacle to exercise is patient inertia and choice to engage in other sedentary activities,” David B. Reuben, MD, and David A. Ganz, MD, both of the University of California, Los Angeles, wrote in an accompanying editorial (JAMA. 2024 Jun 4. doi: 10.1001/jama.2024.9063).

“Given the demonstrated benefits of exercise for cardiovascular disease, cognitive function, and favorable associations with all-cause, cardiovascular, and cancer mortality, specific fall prevention exercise recommendations need to be considered in the context of universal exercise recommendations, including aerobic and muscle strengthening exercise,” the authors wrote. However, maintaining regular exercise is a challenge for many older adults, and more research is needed on factors that drive exercise initiation and adherence in this population, they said.

Multifactorial fall assessments in particular take time, and more fall prevention programs are needed that include multifactorial assessments and interventions, the editorialists said. “Even if primary care clinicians faithfully implement the USPSTF recommendations, a significant reduction in falls and their resulting injuries is still far off,” in part, because of the need for more programs and policies, and the need to improve access to exercise programs and provide insurance coverage for them, they noted.

“Above all, older persons need to be active participants in exercise and reduction of risk factors for falls,” the editorialists concluded.

The research for the recommendation was funded by the Agency for Healthcare Research and Quality (AHRQ). The authors had no financial conflicts to disclose. Dr. Ganz disclosed serving as an author of the 2022 World Guidelines for Falls Prevention and Management for Older Adults.

Exercise interventions are recommended to help prevent falls and fall-related morbidity in community-dwelling adults aged 65 years and older who are at increased risk of falls, according to a new recommendation statement from the U.S. Preventive Services Task Force (USPSTF) (JAMA. 2024 Jun 4. doi: 10.1001/jama.2024.8481).

Falls remain the leading cause of injury-related morbidity and mortality among older adults in the United States, with approximately 27% of community-dwelling individuals aged 65 years and older reporting at least one fall in the past year, wrote lead author Wanda K. Nicholson, MD, of George Washington University, Washington, and colleagues.

The task force concluded with moderate certainty that exercise interventions yielded a moderate benefit in fall reduction among older adults at risk (grade B recommendation).

The decision to offer multifactorial fall prevention interventions to older adults at risk for falls should be individualized based on assessment of potential risks and benefits of these interventions, including circumstances of prior falls, presence of comorbid medical conditions, and the patient’s values and preferences (grade C recommendation), the authors wrote.

The exercise intervention could include individual or group activity, although most of the studies in the systematic review involved group exercise, the authors noted.

The recommendation was based on data from a systematic evidence review published in JAMA (2024 Jun 4. doi: 10.1001/jama.2024.4166). The task force reviewed data from 83 randomized trials published between January 1, 2016, and May 8, 2023, deemed fair to good quality that examined six types of fall prevention interventions in a total of 48,839 individuals. Of these, 28 studies involved multifactorial interventions and 27 involved exercise interventions.

Overall, multifactorial interventions and exercise interventions were associated with a significant reduction in falls (incidence rate ratio 0.84 and 0.85, respectively).

Exercise interventions were significantly associated with reduced individual risk of one or more falls and injurious falls, but not with reduced individual risk of injurious falls. However, multifactorial interventions were not significantly associated with reductions in risk of one or more falls, injurious falls, fall-related fractures, individual risk of injurious falls, or individual risk of fall-related fractures.

Although teasing out the specific exercise components that are most effective for fall prevention is challenging, the most commonly studied components associated with reduced risk of falls included gait training, balance training, and functional training, followed by strength and resistance training, the task force noted.

Duration of exercise interventions in the reviewed studies ranged from 2 to 30 months and the most common frequency of sessions was 2 to 3 per week.

Based on these findings, the task force found that exercise had the most consistent benefits for reduced risk across several fall-related outcomes. Although individuals in the studies of multifactorial interventions were at increased risk for falls, the multistep process of interventions to address an individual’s multiple risk factors limited their effectiveness, in part because of logistical challenges and inconsistent adherence, the authors wrote.

The results of the review were limited by several factors, including the focus on studies with a primary or secondary aim of fall prevention, the fact that the recommendation does not apply to many subgroups of older adults, and the lack of data on health outcomes unrelated to falls that were associated with the interventions, the authors noted.

The new recommendation is consistent with and replaces the 2018 USPSTF recommendation on interventions for fall prevention in community-dwelling older adults, but without the recommendation against vitamin D supplementation as a fall prevention intervention. The new recommendation does not address vitamin D use; evidence will be examined in a separate recommendation, the task force wrote.
 

How to Get Older Adults Moving

“The biggest obstacle to exercise is patient inertia and choice to engage in other sedentary activities,” David B. Reuben, MD, and David A. Ganz, MD, both of the University of California, Los Angeles, wrote in an accompanying editorial (JAMA. 2024 Jun 4. doi: 10.1001/jama.2024.9063).

“Given the demonstrated benefits of exercise for cardiovascular disease, cognitive function, and favorable associations with all-cause, cardiovascular, and cancer mortality, specific fall prevention exercise recommendations need to be considered in the context of universal exercise recommendations, including aerobic and muscle strengthening exercise,” the authors wrote. However, maintaining regular exercise is a challenge for many older adults, and more research is needed on factors that drive exercise initiation and adherence in this population, they said.

Multifactorial fall assessments in particular take time, and more fall prevention programs are needed that include multifactorial assessments and interventions, the editorialists said. “Even if primary care clinicians faithfully implement the USPSTF recommendations, a significant reduction in falls and their resulting injuries is still far off,” in part, because of the need for more programs and policies, and the need to improve access to exercise programs and provide insurance coverage for them, they noted.

“Above all, older persons need to be active participants in exercise and reduction of risk factors for falls,” the editorialists concluded.

The research for the recommendation was funded by the Agency for Healthcare Research and Quality (AHRQ). The authors had no financial conflicts to disclose. Dr. Ganz disclosed serving as an author of the 2022 World Guidelines for Falls Prevention and Management for Older Adults.

Exercise interventions are recommended to help prevent falls and fall-related morbidity in community-dwelling adults aged 65 years and older who are at increased risk of falls, according to a new recommendation statement from the U.S. Preventive Services Task Force (USPSTF) (JAMA. 2024 Jun 4. doi: 10.1001/jama.2024.8481).

Falls remain the leading cause of injury-related morbidity and mortality among older adults in the United States, with approximately 27% of community-dwelling individuals aged 65 years and older reporting at least one fall in the past year, wrote lead author Wanda K. Nicholson, MD, of George Washington University, Washington, and colleagues.

The task force concluded with moderate certainty that exercise interventions yielded a moderate benefit in fall reduction among older adults at risk (grade B recommendation).

The decision to offer multifactorial fall prevention interventions to older adults at risk for falls should be individualized based on assessment of potential risks and benefits of these interventions, including circumstances of prior falls, presence of comorbid medical conditions, and the patient’s values and preferences (grade C recommendation), the authors wrote.

The exercise intervention could include individual or group activity, although most of the studies in the systematic review involved group exercise, the authors noted.

The recommendation was based on data from a systematic evidence review published in JAMA (2024 Jun 4. doi: 10.1001/jama.2024.4166). The task force reviewed data from 83 randomized trials published between January 1, 2016, and May 8, 2023, deemed fair to good quality that examined six types of fall prevention interventions in a total of 48,839 individuals. Of these, 28 studies involved multifactorial interventions and 27 involved exercise interventions.

Overall, multifactorial interventions and exercise interventions were associated with a significant reduction in falls (incidence rate ratio 0.84 and 0.85, respectively).

Exercise interventions were significantly associated with reduced individual risk of one or more falls and injurious falls, but not with reduced individual risk of injurious falls. However, multifactorial interventions were not significantly associated with reductions in risk of one or more falls, injurious falls, fall-related fractures, individual risk of injurious falls, or individual risk of fall-related fractures.

Although teasing out the specific exercise components that are most effective for fall prevention is challenging, the most commonly studied components associated with reduced risk of falls included gait training, balance training, and functional training, followed by strength and resistance training, the task force noted.

Duration of exercise interventions in the reviewed studies ranged from 2 to 30 months and the most common frequency of sessions was 2 to 3 per week.

Based on these findings, the task force found that exercise had the most consistent benefits for reduced risk across several fall-related outcomes. Although individuals in the studies of multifactorial interventions were at increased risk for falls, the multistep process of interventions to address an individual’s multiple risk factors limited their effectiveness, in part because of logistical challenges and inconsistent adherence, the authors wrote.

The results of the review were limited by several factors, including the focus on studies with a primary or secondary aim of fall prevention, the fact that the recommendation does not apply to many subgroups of older adults, and the lack of data on health outcomes unrelated to falls that were associated with the interventions, the authors noted.

The new recommendation is consistent with and replaces the 2018 USPSTF recommendation on interventions for fall prevention in community-dwelling older adults, but without the recommendation against vitamin D supplementation as a fall prevention intervention. The new recommendation does not address vitamin D use; evidence will be examined in a separate recommendation, the task force wrote.
 

How to Get Older Adults Moving

“The biggest obstacle to exercise is patient inertia and choice to engage in other sedentary activities,” David B. Reuben, MD, and David A. Ganz, MD, both of the University of California, Los Angeles, wrote in an accompanying editorial (JAMA. 2024 Jun 4. doi: 10.1001/jama.2024.9063).

“Given the demonstrated benefits of exercise for cardiovascular disease, cognitive function, and favorable associations with all-cause, cardiovascular, and cancer mortality, specific fall prevention exercise recommendations need to be considered in the context of universal exercise recommendations, including aerobic and muscle strengthening exercise,” the authors wrote. However, maintaining regular exercise is a challenge for many older adults, and more research is needed on factors that drive exercise initiation and adherence in this population, they said.

Multifactorial fall assessments in particular take time, and more fall prevention programs are needed that include multifactorial assessments and interventions, the editorialists said. “Even if primary care clinicians faithfully implement the USPSTF recommendations, a significant reduction in falls and their resulting injuries is still far off,” in part, because of the need for more programs and policies, and the need to improve access to exercise programs and provide insurance coverage for them, they noted.

“Above all, older persons need to be active participants in exercise and reduction of risk factors for falls,” the editorialists concluded.

The research for the recommendation was funded by the Agency for Healthcare Research and Quality (AHRQ). The authors had no financial conflicts to disclose. Dr. Ganz disclosed serving as an author of the 2022 World Guidelines for Falls Prevention and Management for Older Adults.

NASHVILLE, TENNESSEE — Individuals with multiple sclerosis are living longer, healthier lives. More than half of patients with MS are 55 years or older, and the incidence of late-onset MS is rising.

This can lead to complex treatment decisions, according to Amy Perrin Ross, APN, MSN, CNRN, MSCN, who is the neuroscience program coordinator at Loyola Medical Center in Maywood, Illinois.

“Age was ranked as the second most important factor affecting treatment decisions in a recent survey of MS specialists,” said Ms. Ross, during a presentation at the annual meeting of the Consortium of Multiple Sclerosis Centers. But there is little evidence to support treatment decisions, since there are few older patients enrolled in clinical trials. The average age is around 30-34 years.
 

MS in Older Patients

Aging is associated with immune system changes. There is a decline in inflammatory activity and an accompanying 17% reduction in the relapse rate with every 5 years of advancing age, and the majority of relapses occur within 30 years of onset. The bad news is that patients have reduced capacity to recover from relapses as they age.

“When I’m talking to patients about pros and cons [of treatment], I do mention that, yes, your relapse rate might be less, but as we age, we have less of an ability to completely recover,” said Ms. Ross.

The efficacy of disease-modifying therapies (DMTs) goes down with advancing age. One meta-analyis of 38 randomized trials and 13 therapies found that benefit with respect to disease progression generally disappeared by the age of 53. “Age is an essential modifier of drug efficacy,” said Ms. Ross.

On the other hand, another meta-analysis found that success in treating relapses was similar across age groups. “So it seems that we can successfully treat our patients’ relapses: There was no significant association between age and reductions in annualized relapse rate,” she said, though she noted that clinical trial populations are likely to be dissimilar to aging patients, many of whom have gone years without experiencing a relapse.

Aging can also lead to differences in potential adverse effects of DMTs. Patients with MS experience faster immunosenescence, in which normal changes to the innate and adaptive immune system are accelerated. This can lead to greater risk of infection, and other adverse events can include post-administration reactions and changes to serum IgG levels.

Other conditions that should be monitored for include progressive multifocal leukoencephalopathy, and malignancies are more prevalent among people with MS than the general population, although it is unclear if this is due to the use of DMTs or other factors, or even just coincidence, said Ms. Ross. “Those are all things to keep in mind as we’re pushing forward with therapy for patients,” she said.

Comorbidities that occur with aging can also affect treatment outcomes, and could tip the balance against use of DMTs in some situations.
 

What Does the Literature Say?

There has been a range of retrospective studies looking at the results of discontinuation of DMTs with advancing age, and the results have been mixed. Some factors are associated with greater likelihood of disease reactivation, including younger age, female sex, shorter duration without a relapse, MRI activity, and degree of disability.

A study of a French registry including patients aged 50 years and older who went off DMTs found that 100% of patients who discontinued therapy were on older injectable DMTs, and 34.9% of that group restarted therapy over a mean follow-up of 7 years. The risk of relapse or disability progression was similar between the groups, but discontinuers who started with Expanded Disability Status Scale (EDSS) scores lower than 6.0 were more likely to reach an EDSS score of 6.0.

The DISCOMS study compared 259 patients randomized to continue DMTs versus discontinuation of DMTs. “What they found was that noninferiority was not shown. Disease activity, such as relapses and new lesions, [occurred in] 12% of the discontinuers and 5% of the continuers,” said Ms. Ross.

One option to balance risk and benefit is DMT de-escalation, with the aim to match disease therapy with disease activity over time. A 2023 survey of 224 neurologists to identify characteristics in older patients that would prompt de-escalation. The most common reasons were overall safety or comorbidity concerns (62% endorsed), high risk of infection (59%), low disease activity or stable disease (50%), concerns about efficacy (41%), high disability (37%), and patient choice (36%). About 7% reported that they generally do not de-escalate.

The preferred de-escalation therapies included glatiramer acetate (29%), fumarates (27%), teriflunomide (23%), and interferon betas (21%).

Ms. Ross noted that the study was likely conducted around the height of the COVID-19 pandemic. “So I wonder if some of these results might be a little bit different [than if it was conducted at a different time],” she said.
 

Other Concerns and Options

During the Q&A session, one audience member asked if physicians should consider low-efficacy medications in older patients with the idea that they at least get a little bit of protection.

Patricia Coyle, MD, who also presented during the session, framed her response around whether the patient had relapsing or progressive MS. “If somebody has had relapsing MS and has never transitioned to progressive MS, and they’re 70, maybe they don’t need to be on any DMT. If there’s no longer a focal inflammatory relapsing phase, if we could feel confident on that possibility, then maybe they don’t need to be on a relapsing DMT,” said Dr. Coyle, who is director of the MS Comprehensive Care Center at Stony Brook University Medical Center in Stony Brook, New York.

Alternatively, if a patient has progressive MS, she said she would recommend discontinuing treatment if she believes the patient is being harmed by it, to focus instead on health and wellness.

Another questioner wondered what to do with a 70-year-old patient who has had no infections, has normal IgG, but insists on continuing high-efficacy B-cell therapy. Dr. Coyle responded that she would tell the patient that she believes it isn’t offering any benefit, but if the patient insisted, she would continue: “I’m not living with MS the way they are. If they tell me, ‘I believe it’s helping me and I want to stay on it,’ then so long as I don’t think I’m overtly harming them, I’m going to treat them.”

Ms. Ross agreed, and suggested that ceding to the patient’s will is an important consideration. “I think sometimes what we’re doing, if we’re not causing harm, what we’re doing is bolstering these people’s ability to continue to have hope, and that in my mind is a big part of managing their disease,” she said.

Ms. Ross has financial relationships with Alexion Pharmaceuticals, Amgen/Horizon, ArgenX, Banner, Bristol Myers Squibb, EMD Serono, Roche, Sandoz, TG Therapeutics, UCB, and Viatris. Dr. Coyle has consulted for Accordant, Amgen, Bristol Myers Squibb, EMD Serono, Genentech, GlaxoSmithKline, Horizon Therapeutics, LabCorp, Eli Lilly, Mylan, Novartis, and Sanofi Genzyme. She has received research funding from Celgene, CorEvitas, Genentech/Roche, NINDS, and Sanofi Genzyme.
 

NASHVILLE, TENNESSEE — Individuals with multiple sclerosis are living longer, healthier lives. More than half of patients with MS are 55 years or older, and the incidence of late-onset MS is rising.

This can lead to complex treatment decisions, according to Amy Perrin Ross, APN, MSN, CNRN, MSCN, who is the neuroscience program coordinator at Loyola Medical Center in Maywood, Illinois.

“Age was ranked as the second most important factor affecting treatment decisions in a recent survey of MS specialists,” said Ms. Ross, during a presentation at the annual meeting of the Consortium of Multiple Sclerosis Centers. But there is little evidence to support treatment decisions, since there are few older patients enrolled in clinical trials. The average age is around 30-34 years.
 

MS in Older Patients

Aging is associated with immune system changes. There is a decline in inflammatory activity and an accompanying 17% reduction in the relapse rate with every 5 years of advancing age, and the majority of relapses occur within 30 years of onset. The bad news is that patients have reduced capacity to recover from relapses as they age.

“When I’m talking to patients about pros and cons [of treatment], I do mention that, yes, your relapse rate might be less, but as we age, we have less of an ability to completely recover,” said Ms. Ross.

The efficacy of disease-modifying therapies (DMTs) goes down with advancing age. One meta-analyis of 38 randomized trials and 13 therapies found that benefit with respect to disease progression generally disappeared by the age of 53. “Age is an essential modifier of drug efficacy,” said Ms. Ross.

On the other hand, another meta-analysis found that success in treating relapses was similar across age groups. “So it seems that we can successfully treat our patients’ relapses: There was no significant association between age and reductions in annualized relapse rate,” she said, though she noted that clinical trial populations are likely to be dissimilar to aging patients, many of whom have gone years without experiencing a relapse.

Aging can also lead to differences in potential adverse effects of DMTs. Patients with MS experience faster immunosenescence, in which normal changes to the innate and adaptive immune system are accelerated. This can lead to greater risk of infection, and other adverse events can include post-administration reactions and changes to serum IgG levels.

Other conditions that should be monitored for include progressive multifocal leukoencephalopathy, and malignancies are more prevalent among people with MS than the general population, although it is unclear if this is due to the use of DMTs or other factors, or even just coincidence, said Ms. Ross. “Those are all things to keep in mind as we’re pushing forward with therapy for patients,” she said.

Comorbidities that occur with aging can also affect treatment outcomes, and could tip the balance against use of DMTs in some situations.
 

What Does the Literature Say?

There has been a range of retrospective studies looking at the results of discontinuation of DMTs with advancing age, and the results have been mixed. Some factors are associated with greater likelihood of disease reactivation, including younger age, female sex, shorter duration without a relapse, MRI activity, and degree of disability.

A study of a French registry including patients aged 50 years and older who went off DMTs found that 100% of patients who discontinued therapy were on older injectable DMTs, and 34.9% of that group restarted therapy over a mean follow-up of 7 years. The risk of relapse or disability progression was similar between the groups, but discontinuers who started with Expanded Disability Status Scale (EDSS) scores lower than 6.0 were more likely to reach an EDSS score of 6.0.

The DISCOMS study compared 259 patients randomized to continue DMTs versus discontinuation of DMTs. “What they found was that noninferiority was not shown. Disease activity, such as relapses and new lesions, [occurred in] 12% of the discontinuers and 5% of the continuers,” said Ms. Ross.

One option to balance risk and benefit is DMT de-escalation, with the aim to match disease therapy with disease activity over time. A 2023 survey of 224 neurologists to identify characteristics in older patients that would prompt de-escalation. The most common reasons were overall safety or comorbidity concerns (62% endorsed), high risk of infection (59%), low disease activity or stable disease (50%), concerns about efficacy (41%), high disability (37%), and patient choice (36%). About 7% reported that they generally do not de-escalate.

The preferred de-escalation therapies included glatiramer acetate (29%), fumarates (27%), teriflunomide (23%), and interferon betas (21%).

Ms. Ross noted that the study was likely conducted around the height of the COVID-19 pandemic. “So I wonder if some of these results might be a little bit different [than if it was conducted at a different time],” she said.
 

Other Concerns and Options

During the Q&A session, one audience member asked if physicians should consider low-efficacy medications in older patients with the idea that they at least get a little bit of protection.

Patricia Coyle, MD, who also presented during the session, framed her response around whether the patient had relapsing or progressive MS. “If somebody has had relapsing MS and has never transitioned to progressive MS, and they’re 70, maybe they don’t need to be on any DMT. If there’s no longer a focal inflammatory relapsing phase, if we could feel confident on that possibility, then maybe they don’t need to be on a relapsing DMT,” said Dr. Coyle, who is director of the MS Comprehensive Care Center at Stony Brook University Medical Center in Stony Brook, New York.

Alternatively, if a patient has progressive MS, she said she would recommend discontinuing treatment if she believes the patient is being harmed by it, to focus instead on health and wellness.

Another questioner wondered what to do with a 70-year-old patient who has had no infections, has normal IgG, but insists on continuing high-efficacy B-cell therapy. Dr. Coyle responded that she would tell the patient that she believes it isn’t offering any benefit, but if the patient insisted, she would continue: “I’m not living with MS the way they are. If they tell me, ‘I believe it’s helping me and I want to stay on it,’ then so long as I don’t think I’m overtly harming them, I’m going to treat them.”

Ms. Ross agreed, and suggested that ceding to the patient’s will is an important consideration. “I think sometimes what we’re doing, if we’re not causing harm, what we’re doing is bolstering these people’s ability to continue to have hope, and that in my mind is a big part of managing their disease,” she said.

Ms. Ross has financial relationships with Alexion Pharmaceuticals, Amgen/Horizon, ArgenX, Banner, Bristol Myers Squibb, EMD Serono, Roche, Sandoz, TG Therapeutics, UCB, and Viatris. Dr. Coyle has consulted for Accordant, Amgen, Bristol Myers Squibb, EMD Serono, Genentech, GlaxoSmithKline, Horizon Therapeutics, LabCorp, Eli Lilly, Mylan, Novartis, and Sanofi Genzyme. She has received research funding from Celgene, CorEvitas, Genentech/Roche, NINDS, and Sanofi Genzyme.
 

NASHVILLE, TENNESSEE — Individuals with multiple sclerosis are living longer, healthier lives. More than half of patients with MS are 55 years or older, and the incidence of late-onset MS is rising.

This can lead to complex treatment decisions, according to Amy Perrin Ross, APN, MSN, CNRN, MSCN, who is the neuroscience program coordinator at Loyola Medical Center in Maywood, Illinois.

“Age was ranked as the second most important factor affecting treatment decisions in a recent survey of MS specialists,” said Ms. Ross, during a presentation at the annual meeting of the Consortium of Multiple Sclerosis Centers. But there is little evidence to support treatment decisions, since there are few older patients enrolled in clinical trials. The average age is around 30-34 years.
 

MS in Older Patients

Aging is associated with immune system changes. There is a decline in inflammatory activity and an accompanying 17% reduction in the relapse rate with every 5 years of advancing age, and the majority of relapses occur within 30 years of onset. The bad news is that patients have reduced capacity to recover from relapses as they age.

“When I’m talking to patients about pros and cons [of treatment], I do mention that, yes, your relapse rate might be less, but as we age, we have less of an ability to completely recover,” said Ms. Ross.

The efficacy of disease-modifying therapies (DMTs) goes down with advancing age. One meta-analyis of 38 randomized trials and 13 therapies found that benefit with respect to disease progression generally disappeared by the age of 53. “Age is an essential modifier of drug efficacy,” said Ms. Ross.

On the other hand, another meta-analysis found that success in treating relapses was similar across age groups. “So it seems that we can successfully treat our patients’ relapses: There was no significant association between age and reductions in annualized relapse rate,” she said, though she noted that clinical trial populations are likely to be dissimilar to aging patients, many of whom have gone years without experiencing a relapse.

Aging can also lead to differences in potential adverse effects of DMTs. Patients with MS experience faster immunosenescence, in which normal changes to the innate and adaptive immune system are accelerated. This can lead to greater risk of infection, and other adverse events can include post-administration reactions and changes to serum IgG levels.

Other conditions that should be monitored for include progressive multifocal leukoencephalopathy, and malignancies are more prevalent among people with MS than the general population, although it is unclear if this is due to the use of DMTs or other factors, or even just coincidence, said Ms. Ross. “Those are all things to keep in mind as we’re pushing forward with therapy for patients,” she said.

Comorbidities that occur with aging can also affect treatment outcomes, and could tip the balance against use of DMTs in some situations.
 

What Does the Literature Say?

There has been a range of retrospective studies looking at the results of discontinuation of DMTs with advancing age, and the results have been mixed. Some factors are associated with greater likelihood of disease reactivation, including younger age, female sex, shorter duration without a relapse, MRI activity, and degree of disability.

A study of a French registry including patients aged 50 years and older who went off DMTs found that 100% of patients who discontinued therapy were on older injectable DMTs, and 34.9% of that group restarted therapy over a mean follow-up of 7 years. The risk of relapse or disability progression was similar between the groups, but discontinuers who started with Expanded Disability Status Scale (EDSS) scores lower than 6.0 were more likely to reach an EDSS score of 6.0.

The DISCOMS study compared 259 patients randomized to continue DMTs versus discontinuation of DMTs. “What they found was that noninferiority was not shown. Disease activity, such as relapses and new lesions, [occurred in] 12% of the discontinuers and 5% of the continuers,” said Ms. Ross.

One option to balance risk and benefit is DMT de-escalation, with the aim to match disease therapy with disease activity over time. A 2023 survey of 224 neurologists to identify characteristics in older patients that would prompt de-escalation. The most common reasons were overall safety or comorbidity concerns (62% endorsed), high risk of infection (59%), low disease activity or stable disease (50%), concerns about efficacy (41%), high disability (37%), and patient choice (36%). About 7% reported that they generally do not de-escalate.

The preferred de-escalation therapies included glatiramer acetate (29%), fumarates (27%), teriflunomide (23%), and interferon betas (21%).

Ms. Ross noted that the study was likely conducted around the height of the COVID-19 pandemic. “So I wonder if some of these results might be a little bit different [than if it was conducted at a different time],” she said.
 

Other Concerns and Options

During the Q&A session, one audience member asked if physicians should consider low-efficacy medications in older patients with the idea that they at least get a little bit of protection.

Patricia Coyle, MD, who also presented during the session, framed her response around whether the patient had relapsing or progressive MS. “If somebody has had relapsing MS and has never transitioned to progressive MS, and they’re 70, maybe they don’t need to be on any DMT. If there’s no longer a focal inflammatory relapsing phase, if we could feel confident on that possibility, then maybe they don’t need to be on a relapsing DMT,” said Dr. Coyle, who is director of the MS Comprehensive Care Center at Stony Brook University Medical Center in Stony Brook, New York.

Alternatively, if a patient has progressive MS, she said she would recommend discontinuing treatment if she believes the patient is being harmed by it, to focus instead on health and wellness.

Another questioner wondered what to do with a 70-year-old patient who has had no infections, has normal IgG, but insists on continuing high-efficacy B-cell therapy. Dr. Coyle responded that she would tell the patient that she believes it isn’t offering any benefit, but if the patient insisted, she would continue: “I’m not living with MS the way they are. If they tell me, ‘I believe it’s helping me and I want to stay on it,’ then so long as I don’t think I’m overtly harming them, I’m going to treat them.”

Ms. Ross agreed, and suggested that ceding to the patient’s will is an important consideration. “I think sometimes what we’re doing, if we’re not causing harm, what we’re doing is bolstering these people’s ability to continue to have hope, and that in my mind is a big part of managing their disease,” she said.

Ms. Ross has financial relationships with Alexion Pharmaceuticals, Amgen/Horizon, ArgenX, Banner, Bristol Myers Squibb, EMD Serono, Roche, Sandoz, TG Therapeutics, UCB, and Viatris. Dr. Coyle has consulted for Accordant, Amgen, Bristol Myers Squibb, EMD Serono, Genentech, GlaxoSmithKline, Horizon Therapeutics, LabCorp, Eli Lilly, Mylan, Novartis, and Sanofi Genzyme. She has received research funding from Celgene, CorEvitas, Genentech/Roche, NINDS, and Sanofi Genzyme.
 

Patients at least 75 years old saw a reduced risk of overall cardiovascular incidence with statin therapy without increased risk of severe adverse effects in a study published in Annals of Internal Medicine.

“Of note, the benefits and safety of statin therapy were consistently found in adults aged 85 years or older,” wrote the authors, led by Wanchun Xu, a PhD student with the Department of Family Medicine and Primary Care, Li Ka Shing Faculty of Medicine, The University of Hong Kong, in the Special Administrative Region, China.

Geriatrician Jerry H. Gurwitz, MD, the Dr. John Meyers Professor in Primary Care Medicine at UMass Chan Medical School in Boston, said he found the results of this trial “remarkable,” but is awaiting the results of the much-anticipated randomized, controlled PREVENTABLE trial years from now for more definitive evidence.
 

Little Consensus on Statins for This Age Group

Prescribing statins for primary prevention of CVD in the most senior patient groups has been controversial. There is little consensus as patients in this age group have been underrepresented in randomized controlled trials.

Major guidelines for use of statins in the primary prevention of CVD, including the US Preventive Services Task Force, exclude specific guidance for statin use in patients older than 75, citing insufficient evidence.

Ms. Xu and colleagues used territory-wide electronic health records in a sequential target trial emulation comparing matched cohorts that did or did not start statins. There were 42,680 matched person-trials in the group of patients aged 75-84 years and 5,390 matched person-trials in the 85 and older group. The average follow-up was 5.3 years and people with CVDs at baseline, such as coronary heart disease, were excluded. Patients who met indications for statin initiation from January 2008 to December 2015 were included.

Risk Reduction Seen in Both Senior Groups

Of the 42,680 matched person-trials in the 75-84 age group, 9676 developed cardiovascular disease; of the 5390 in the 85-plus group, 1600 developed CVD.

In the younger cohort, the 5-year reduced risk for overall CVD incidence when statin therapy was initiated was 1.20% (95% CI, 0.57%-1.82%) in the intention-to-treat (ITT) analysis; 5.00% (95% CI, 1.11%-8.89%) in the per protocol (PP) analysis.

Reduced risk for overall CVD incidence in the 85-and-older group when statins were initiated was 4.44% in the ITT analysis (95% CI, 1.40%-7.48%); and 12.50% in the PP analysis (95% CI, 4.33%-20.66%). There was no significantly increased risk for liver dysfunction or myopathies in either age group, the authors stated.

One of the biggest strengths of the study is the use of population-based data over a long period. One of the limitations was that the researchers were not able to measure lifestyle factors such as diet and physical activity in their analysis.

Dr. Gurwitz, who has done drug research in older adults for decades, said “the results are very compelling,” and in the oldest group “almost too compelling. Wow.”

Numbers Needed to Treat Are Strikingly Low

He noted that the authors thoroughly acknowledge limitations of the trial. But he also pointed to the impressive number needed to treat reported by the researchers.

The authors stated: “[O]n the basis of the estimated absolute risk reduction in the PP analysis, the number needed to treat [NNT] to prevent 1 CVD event in 5 years was 20 (95% CI, 11-90) in those aged 75-84 years and 8 (95% CI, 5-23) in those aged 85 years or older.”

For perspective, he said, “Sometimes you’re seeing numbers needed to treat for vaccinations of 400 to prevent one hospitalization. They are using real-world information and they are seeing this remarkable effect. If it’s that good in the real world, it’s going to be even better in a clinical trial. That’s why I have some reservations about whether it’s really that good.”

Dr. Gurwitz said, “I’m not ready to start an 87-year-old on statin therapy who hasn’t been on it before for primary prevention, despite the results of this very well done study.” He will await the findings of PREVENTABLE, which aims to enroll 20,000 people at least 75 years old to look at statin use. But in the meantime, he will discuss the Xu et al. results and other evidence with patients if they request statins and may prescribe them as part of shared decision making.

He said the question of whether to use statins in primary prevention is similar to the question of whether to use aspirin as primary prevention for CVD in older adults.

Originally, “Most of us thought, yes, it’s probably a good thing,” he said, but now “there have been a lot of deprescribing efforts to get older people off of aspirin.

“In the United States, believe it or not, 48% of people 75 and older are on statins already,” Dr. Gurwitz said. “Maybe that’s good,” he said, but added physicians won’t know for sure until PREVENTABLE results are in.

“If I didn’t already know the PREVENTABLE trial was going on, and it was never going to happen, I would find this [Xu et al. study] very influential,” Dr. Gurwitz said. “I’m willing to wait.”

The study was funded by the Health and Medical Research Fund, Health Bureau, the Government of Hong Kong Special Administrative Region, China, and the National Natural Science Foundation of China. Coauthors reported grants from the Kerry Group Kuok Foundation, the Malaysian College of Family Physicians, and the International Association of Chinese Nephrologists in Hong Kong. Dr. Gurwitz reported no relevant financial relationships.

Patients at least 75 years old saw a reduced risk of overall cardiovascular incidence with statin therapy without increased risk of severe adverse effects in a study published in Annals of Internal Medicine.

“Of note, the benefits and safety of statin therapy were consistently found in adults aged 85 years or older,” wrote the authors, led by Wanchun Xu, a PhD student with the Department of Family Medicine and Primary Care, Li Ka Shing Faculty of Medicine, The University of Hong Kong, in the Special Administrative Region, China.

Geriatrician Jerry H. Gurwitz, MD, the Dr. John Meyers Professor in Primary Care Medicine at UMass Chan Medical School in Boston, said he found the results of this trial “remarkable,” but is awaiting the results of the much-anticipated randomized, controlled PREVENTABLE trial years from now for more definitive evidence.
 

Little Consensus on Statins for This Age Group

Prescribing statins for primary prevention of CVD in the most senior patient groups has been controversial. There is little consensus as patients in this age group have been underrepresented in randomized controlled trials.

Major guidelines for use of statins in the primary prevention of CVD, including the US Preventive Services Task Force, exclude specific guidance for statin use in patients older than 75, citing insufficient evidence.

Ms. Xu and colleagues used territory-wide electronic health records in a sequential target trial emulation comparing matched cohorts that did or did not start statins. There were 42,680 matched person-trials in the group of patients aged 75-84 years and 5,390 matched person-trials in the 85 and older group. The average follow-up was 5.3 years and people with CVDs at baseline, such as coronary heart disease, were excluded. Patients who met indications for statin initiation from January 2008 to December 2015 were included.

Risk Reduction Seen in Both Senior Groups

Of the 42,680 matched person-trials in the 75-84 age group, 9676 developed cardiovascular disease; of the 5390 in the 85-plus group, 1600 developed CVD.

In the younger cohort, the 5-year reduced risk for overall CVD incidence when statin therapy was initiated was 1.20% (95% CI, 0.57%-1.82%) in the intention-to-treat (ITT) analysis; 5.00% (95% CI, 1.11%-8.89%) in the per protocol (PP) analysis.

Reduced risk for overall CVD incidence in the 85-and-older group when statins were initiated was 4.44% in the ITT analysis (95% CI, 1.40%-7.48%); and 12.50% in the PP analysis (95% CI, 4.33%-20.66%). There was no significantly increased risk for liver dysfunction or myopathies in either age group, the authors stated.

One of the biggest strengths of the study is the use of population-based data over a long period. One of the limitations was that the researchers were not able to measure lifestyle factors such as diet and physical activity in their analysis.

Dr. Gurwitz, who has done drug research in older adults for decades, said “the results are very compelling,” and in the oldest group “almost too compelling. Wow.”

Numbers Needed to Treat Are Strikingly Low

He noted that the authors thoroughly acknowledge limitations of the trial. But he also pointed to the impressive number needed to treat reported by the researchers.

The authors stated: “[O]n the basis of the estimated absolute risk reduction in the PP analysis, the number needed to treat [NNT] to prevent 1 CVD event in 5 years was 20 (95% CI, 11-90) in those aged 75-84 years and 8 (95% CI, 5-23) in those aged 85 years or older.”

For perspective, he said, “Sometimes you’re seeing numbers needed to treat for vaccinations of 400 to prevent one hospitalization. They are using real-world information and they are seeing this remarkable effect. If it’s that good in the real world, it’s going to be even better in a clinical trial. That’s why I have some reservations about whether it’s really that good.”

Dr. Gurwitz said, “I’m not ready to start an 87-year-old on statin therapy who hasn’t been on it before for primary prevention, despite the results of this very well done study.” He will await the findings of PREVENTABLE, which aims to enroll 20,000 people at least 75 years old to look at statin use. But in the meantime, he will discuss the Xu et al. results and other evidence with patients if they request statins and may prescribe them as part of shared decision making.

He said the question of whether to use statins in primary prevention is similar to the question of whether to use aspirin as primary prevention for CVD in older adults.

Originally, “Most of us thought, yes, it’s probably a good thing,” he said, but now “there have been a lot of deprescribing efforts to get older people off of aspirin.

“In the United States, believe it or not, 48% of people 75 and older are on statins already,” Dr. Gurwitz said. “Maybe that’s good,” he said, but added physicians won’t know for sure until PREVENTABLE results are in.

“If I didn’t already know the PREVENTABLE trial was going on, and it was never going to happen, I would find this [Xu et al. study] very influential,” Dr. Gurwitz said. “I’m willing to wait.”

The study was funded by the Health and Medical Research Fund, Health Bureau, the Government of Hong Kong Special Administrative Region, China, and the National Natural Science Foundation of China. Coauthors reported grants from the Kerry Group Kuok Foundation, the Malaysian College of Family Physicians, and the International Association of Chinese Nephrologists in Hong Kong. Dr. Gurwitz reported no relevant financial relationships.

Patients at least 75 years old saw a reduced risk of overall cardiovascular incidence with statin therapy without increased risk of severe adverse effects in a study published in Annals of Internal Medicine.

“Of note, the benefits and safety of statin therapy were consistently found in adults aged 85 years or older,” wrote the authors, led by Wanchun Xu, a PhD student with the Department of Family Medicine and Primary Care, Li Ka Shing Faculty of Medicine, The University of Hong Kong, in the Special Administrative Region, China.

Geriatrician Jerry H. Gurwitz, MD, the Dr. John Meyers Professor in Primary Care Medicine at UMass Chan Medical School in Boston, said he found the results of this trial “remarkable,” but is awaiting the results of the much-anticipated randomized, controlled PREVENTABLE trial years from now for more definitive evidence.
 

Little Consensus on Statins for This Age Group

Prescribing statins for primary prevention of CVD in the most senior patient groups has been controversial. There is little consensus as patients in this age group have been underrepresented in randomized controlled trials.

Major guidelines for use of statins in the primary prevention of CVD, including the US Preventive Services Task Force, exclude specific guidance for statin use in patients older than 75, citing insufficient evidence.

Ms. Xu and colleagues used territory-wide electronic health records in a sequential target trial emulation comparing matched cohorts that did or did not start statins. There were 42,680 matched person-trials in the group of patients aged 75-84 years and 5,390 matched person-trials in the 85 and older group. The average follow-up was 5.3 years and people with CVDs at baseline, such as coronary heart disease, were excluded. Patients who met indications for statin initiation from January 2008 to December 2015 were included.

Risk Reduction Seen in Both Senior Groups

Of the 42,680 matched person-trials in the 75-84 age group, 9676 developed cardiovascular disease; of the 5390 in the 85-plus group, 1600 developed CVD.

In the younger cohort, the 5-year reduced risk for overall CVD incidence when statin therapy was initiated was 1.20% (95% CI, 0.57%-1.82%) in the intention-to-treat (ITT) analysis; 5.00% (95% CI, 1.11%-8.89%) in the per protocol (PP) analysis.

Reduced risk for overall CVD incidence in the 85-and-older group when statins were initiated was 4.44% in the ITT analysis (95% CI, 1.40%-7.48%); and 12.50% in the PP analysis (95% CI, 4.33%-20.66%). There was no significantly increased risk for liver dysfunction or myopathies in either age group, the authors stated.

One of the biggest strengths of the study is the use of population-based data over a long period. One of the limitations was that the researchers were not able to measure lifestyle factors such as diet and physical activity in their analysis.

Dr. Gurwitz, who has done drug research in older adults for decades, said “the results are very compelling,” and in the oldest group “almost too compelling. Wow.”

Numbers Needed to Treat Are Strikingly Low

He noted that the authors thoroughly acknowledge limitations of the trial. But he also pointed to the impressive number needed to treat reported by the researchers.

The authors stated: “[O]n the basis of the estimated absolute risk reduction in the PP analysis, the number needed to treat [NNT] to prevent 1 CVD event in 5 years was 20 (95% CI, 11-90) in those aged 75-84 years and 8 (95% CI, 5-23) in those aged 85 years or older.”

For perspective, he said, “Sometimes you’re seeing numbers needed to treat for vaccinations of 400 to prevent one hospitalization. They are using real-world information and they are seeing this remarkable effect. If it’s that good in the real world, it’s going to be even better in a clinical trial. That’s why I have some reservations about whether it’s really that good.”

Dr. Gurwitz said, “I’m not ready to start an 87-year-old on statin therapy who hasn’t been on it before for primary prevention, despite the results of this very well done study.” He will await the findings of PREVENTABLE, which aims to enroll 20,000 people at least 75 years old to look at statin use. But in the meantime, he will discuss the Xu et al. results and other evidence with patients if they request statins and may prescribe them as part of shared decision making.

He said the question of whether to use statins in primary prevention is similar to the question of whether to use aspirin as primary prevention for CVD in older adults.

Originally, “Most of us thought, yes, it’s probably a good thing,” he said, but now “there have been a lot of deprescribing efforts to get older people off of aspirin.

“In the United States, believe it or not, 48% of people 75 and older are on statins already,” Dr. Gurwitz said. “Maybe that’s good,” he said, but added physicians won’t know for sure until PREVENTABLE results are in.

“If I didn’t already know the PREVENTABLE trial was going on, and it was never going to happen, I would find this [Xu et al. study] very influential,” Dr. Gurwitz said. “I’m willing to wait.”

The study was funded by the Health and Medical Research Fund, Health Bureau, the Government of Hong Kong Special Administrative Region, China, and the National Natural Science Foundation of China. Coauthors reported grants from the Kerry Group Kuok Foundation, the Malaysian College of Family Physicians, and the International Association of Chinese Nephrologists in Hong Kong. Dr. Gurwitz reported no relevant financial relationships.

According to a US cross-sectional study, every fifth hospital patient with a respiratory syncytial virus (RSV) infection develops an acute cardiovascular event. For patients with a preexisting cardiovascular condition, an acute cardiovascular event occurs in every third patient, as shown by data published in JAMA Internal Medicine.

RSV attacks the respiratory tract, especially the mucous membranes of the upper airways and the ciliated epithelium of the trachea and bronchi. It is not the first respiratory virus with devastating consequences for the cardiovascular system.

“In the COVID-19 pandemic, we painfully learned that patients with preexisting cardiovascular conditions have significantly higher mortality rates and that cardiovascular causes are essential in COVID-19 mortality,” said Stephan Baldus, MD, director of Clinic III for Internal Medicine at the Heart Center of the University Hospital Cologne in Cologne, Germany.

“A direct link between the virus and the development of acute coronary events has also been demonstrated for influenza. Studies have shown that in the early days of an influenza infection, the rates of heart attacks and subsequent deaths increase significantly,” Dr. Baldus added. “And now, this study shows that patients with cardiovascular diseases have a critically increased risk for an acute cardiovascular event during an RSV infection.”
 

RSV Surveillance

Rebecca C. Woodruff, PhD, of the Centers for Disease Control and Prevention in Atlanta, and her colleagues analyzed data from an RSV surveillance program involving hospitals in 12 US states. The data covered hospitalized adults aged 50 years and older from five RSV seasons (from 2014/2015 to 2017/2018 and 2022/2023).

The 6248 patients were hospitalized for various reasons. They had a mean age of 73 years, and 60% of them were women. RSV infection was detected through a physician-ordered test within 14 days of admission. Slightly more than half (56.4%) of the patients had a preexisting cardiovascular condition that did not necessitate hospital treatment.

The researchers reported that more than a fifth (22.4%) of the patients with RSV had an acute cardiovascular event. Acute heart failure was most common (15.8%), but there were also acute ischemic heart disease in 7.5%, hypertensive crisis in 1.3%, ventricular tachycardia in 1.1%, and cardiogenic shock in 0.6%.
 

Acute Cardiovascular Events

Among the study population, 8.5% had no documented cardiovascular preexisting conditions. However, the risk was particularly elevated in patients with cardiovascular preexisting conditions. Overall, 33.0% of them had an acute cardiovascular event during the RSV infection.

Patients with acute cardiovascular events were almost twice as likely to have a severe course as those without acute cardiovascular events. The researchers considered treatment in the intensive care unit, the need for invasive mechanical ventilation, or the patient’s death in the hospital as severe outcomes.

Of all hospitalized patients with RSV, 18.6% required intensive care unit treatment, and 4.9% died during hospitalization. Compared with those without acute cardiovascular events, those with acute cardiovascular events had a significantly higher risk for intensive care treatment (25.8% vs 16.5%) and death in the hospital (8.1% vs 4.0%).

Although the analysis is not a prospective controlled study, according to Dr. Baldus, the results strongly suggest that RSV has cardiovascular effects. “When one in five hospitalized patients develops a cardiovascular event, that’s very suggestive,” he said.
 

More Testing Needed?

The results add to the evidence that RSV infections in older patients are associated with considerable morbidity and mortality. Unlike for COVID-19 and influenza, however, there is hardly any surveillance for RSV infections. RSV testing in hospitals is rare. Many doctors opt against testing for RSV because they are not aware of the importance of RSV as a pathogen in adults, but also because the diagnosis of RSV has no therapeutic consequences, wrote Dr. Woodruff and her colleagues.

Because there is no targeted therapy for an RSV infection, the detection of RSV can only be used as a marker for a risk for the development of an acute cardiovascular event, according to Dr. Baldus. Even considering the new study data, he emphasized, “Not every patient with a cardiovascular preexisting condition needs to be tested for RSV.”

The crucial factor is the clinical presentation. “If there is a clinical indication of pulmonary impairment (shortness of breath, tachypnea, subfebrile temperatures, or a diminished general condition) it would be desirable to perform an RSV test. This is especially true for patients requiring intensive care who need respiratory support,” said Dr. Baldus.
 

Benefits of Vaccination

The results highlight the basic epidemiology of potential cardiovascular complications of RSV infections, but before RSV vaccination became available, wrote Dr. Woodruff and her colleagues.

In 2023, the first RSV vaccine for adults aged 60 years and older was approved. “Here, a door to additional possibilities opens,” said Dr. Baldus. Although there are currently no official vaccination recommendations from Germany’s Standing Vaccination Commission, medical societies of oncologists and pulmonologists recommend vaccination against RSV. “Given the relevance of cardiovascular diseases for the prognosis of patients, but also for the occurrence of an acute cardiovascular event upon detection of RSV, the corresponding recommendation is expected to come,” said Dr. Baldus.

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

According to a US cross-sectional study, every fifth hospital patient with a respiratory syncytial virus (RSV) infection develops an acute cardiovascular event. For patients with a preexisting cardiovascular condition, an acute cardiovascular event occurs in every third patient, as shown by data published in JAMA Internal Medicine.

RSV attacks the respiratory tract, especially the mucous membranes of the upper airways and the ciliated epithelium of the trachea and bronchi. It is not the first respiratory virus with devastating consequences for the cardiovascular system.

“In the COVID-19 pandemic, we painfully learned that patients with preexisting cardiovascular conditions have significantly higher mortality rates and that cardiovascular causes are essential in COVID-19 mortality,” said Stephan Baldus, MD, director of Clinic III for Internal Medicine at the Heart Center of the University Hospital Cologne in Cologne, Germany.

“A direct link between the virus and the development of acute coronary events has also been demonstrated for influenza. Studies have shown that in the early days of an influenza infection, the rates of heart attacks and subsequent deaths increase significantly,” Dr. Baldus added. “And now, this study shows that patients with cardiovascular diseases have a critically increased risk for an acute cardiovascular event during an RSV infection.”
 

RSV Surveillance

Rebecca C. Woodruff, PhD, of the Centers for Disease Control and Prevention in Atlanta, and her colleagues analyzed data from an RSV surveillance program involving hospitals in 12 US states. The data covered hospitalized adults aged 50 years and older from five RSV seasons (from 2014/2015 to 2017/2018 and 2022/2023).

The 6248 patients were hospitalized for various reasons. They had a mean age of 73 years, and 60% of them were women. RSV infection was detected through a physician-ordered test within 14 days of admission. Slightly more than half (56.4%) of the patients had a preexisting cardiovascular condition that did not necessitate hospital treatment.

The researchers reported that more than a fifth (22.4%) of the patients with RSV had an acute cardiovascular event. Acute heart failure was most common (15.8%), but there were also acute ischemic heart disease in 7.5%, hypertensive crisis in 1.3%, ventricular tachycardia in 1.1%, and cardiogenic shock in 0.6%.
 

Acute Cardiovascular Events

Among the study population, 8.5% had no documented cardiovascular preexisting conditions. However, the risk was particularly elevated in patients with cardiovascular preexisting conditions. Overall, 33.0% of them had an acute cardiovascular event during the RSV infection.

Patients with acute cardiovascular events were almost twice as likely to have a severe course as those without acute cardiovascular events. The researchers considered treatment in the intensive care unit, the need for invasive mechanical ventilation, or the patient’s death in the hospital as severe outcomes.

Of all hospitalized patients with RSV, 18.6% required intensive care unit treatment, and 4.9% died during hospitalization. Compared with those without acute cardiovascular events, those with acute cardiovascular events had a significantly higher risk for intensive care treatment (25.8% vs 16.5%) and death in the hospital (8.1% vs 4.0%).

Although the analysis is not a prospective controlled study, according to Dr. Baldus, the results strongly suggest that RSV has cardiovascular effects. “When one in five hospitalized patients develops a cardiovascular event, that’s very suggestive,” he said.
 

More Testing Needed?

The results add to the evidence that RSV infections in older patients are associated with considerable morbidity and mortality. Unlike for COVID-19 and influenza, however, there is hardly any surveillance for RSV infections. RSV testing in hospitals is rare. Many doctors opt against testing for RSV because they are not aware of the importance of RSV as a pathogen in adults, but also because the diagnosis of RSV has no therapeutic consequences, wrote Dr. Woodruff and her colleagues.

Because there is no targeted therapy for an RSV infection, the detection of RSV can only be used as a marker for a risk for the development of an acute cardiovascular event, according to Dr. Baldus. Even considering the new study data, he emphasized, “Not every patient with a cardiovascular preexisting condition needs to be tested for RSV.”

The crucial factor is the clinical presentation. “If there is a clinical indication of pulmonary impairment (shortness of breath, tachypnea, subfebrile temperatures, or a diminished general condition) it would be desirable to perform an RSV test. This is especially true for patients requiring intensive care who need respiratory support,” said Dr. Baldus.
 

Benefits of Vaccination

The results highlight the basic epidemiology of potential cardiovascular complications of RSV infections, but before RSV vaccination became available, wrote Dr. Woodruff and her colleagues.

In 2023, the first RSV vaccine for adults aged 60 years and older was approved. “Here, a door to additional possibilities opens,” said Dr. Baldus. Although there are currently no official vaccination recommendations from Germany’s Standing Vaccination Commission, medical societies of oncologists and pulmonologists recommend vaccination against RSV. “Given the relevance of cardiovascular diseases for the prognosis of patients, but also for the occurrence of an acute cardiovascular event upon detection of RSV, the corresponding recommendation is expected to come,” said Dr. Baldus.

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

According to a US cross-sectional study, every fifth hospital patient with a respiratory syncytial virus (RSV) infection develops an acute cardiovascular event. For patients with a preexisting cardiovascular condition, an acute cardiovascular event occurs in every third patient, as shown by data published in JAMA Internal Medicine.

RSV attacks the respiratory tract, especially the mucous membranes of the upper airways and the ciliated epithelium of the trachea and bronchi. It is not the first respiratory virus with devastating consequences for the cardiovascular system.

“In the COVID-19 pandemic, we painfully learned that patients with preexisting cardiovascular conditions have significantly higher mortality rates and that cardiovascular causes are essential in COVID-19 mortality,” said Stephan Baldus, MD, director of Clinic III for Internal Medicine at the Heart Center of the University Hospital Cologne in Cologne, Germany.

“A direct link between the virus and the development of acute coronary events has also been demonstrated for influenza. Studies have shown that in the early days of an influenza infection, the rates of heart attacks and subsequent deaths increase significantly,” Dr. Baldus added. “And now, this study shows that patients with cardiovascular diseases have a critically increased risk for an acute cardiovascular event during an RSV infection.”
 

RSV Surveillance

Rebecca C. Woodruff, PhD, of the Centers for Disease Control and Prevention in Atlanta, and her colleagues analyzed data from an RSV surveillance program involving hospitals in 12 US states. The data covered hospitalized adults aged 50 years and older from five RSV seasons (from 2014/2015 to 2017/2018 and 2022/2023).

The 6248 patients were hospitalized for various reasons. They had a mean age of 73 years, and 60% of them were women. RSV infection was detected through a physician-ordered test within 14 days of admission. Slightly more than half (56.4%) of the patients had a preexisting cardiovascular condition that did not necessitate hospital treatment.

The researchers reported that more than a fifth (22.4%) of the patients with RSV had an acute cardiovascular event. Acute heart failure was most common (15.8%), but there were also acute ischemic heart disease in 7.5%, hypertensive crisis in 1.3%, ventricular tachycardia in 1.1%, and cardiogenic shock in 0.6%.
 

Acute Cardiovascular Events

Among the study population, 8.5% had no documented cardiovascular preexisting conditions. However, the risk was particularly elevated in patients with cardiovascular preexisting conditions. Overall, 33.0% of them had an acute cardiovascular event during the RSV infection.

Patients with acute cardiovascular events were almost twice as likely to have a severe course as those without acute cardiovascular events. The researchers considered treatment in the intensive care unit, the need for invasive mechanical ventilation, or the patient’s death in the hospital as severe outcomes.

Of all hospitalized patients with RSV, 18.6% required intensive care unit treatment, and 4.9% died during hospitalization. Compared with those without acute cardiovascular events, those with acute cardiovascular events had a significantly higher risk for intensive care treatment (25.8% vs 16.5%) and death in the hospital (8.1% vs 4.0%).

Although the analysis is not a prospective controlled study, according to Dr. Baldus, the results strongly suggest that RSV has cardiovascular effects. “When one in five hospitalized patients develops a cardiovascular event, that’s very suggestive,” he said.
 

More Testing Needed?

The results add to the evidence that RSV infections in older patients are associated with considerable morbidity and mortality. Unlike for COVID-19 and influenza, however, there is hardly any surveillance for RSV infections. RSV testing in hospitals is rare. Many doctors opt against testing for RSV because they are not aware of the importance of RSV as a pathogen in adults, but also because the diagnosis of RSV has no therapeutic consequences, wrote Dr. Woodruff and her colleagues.

Because there is no targeted therapy for an RSV infection, the detection of RSV can only be used as a marker for a risk for the development of an acute cardiovascular event, according to Dr. Baldus. Even considering the new study data, he emphasized, “Not every patient with a cardiovascular preexisting condition needs to be tested for RSV.”

The crucial factor is the clinical presentation. “If there is a clinical indication of pulmonary impairment (shortness of breath, tachypnea, subfebrile temperatures, or a diminished general condition) it would be desirable to perform an RSV test. This is especially true for patients requiring intensive care who need respiratory support,” said Dr. Baldus.
 

Benefits of Vaccination

The results highlight the basic epidemiology of potential cardiovascular complications of RSV infections, but before RSV vaccination became available, wrote Dr. Woodruff and her colleagues.

In 2023, the first RSV vaccine for adults aged 60 years and older was approved. “Here, a door to additional possibilities opens,” said Dr. Baldus. Although there are currently no official vaccination recommendations from Germany’s Standing Vaccination Commission, medical societies of oncologists and pulmonologists recommend vaccination against RSV. “Given the relevance of cardiovascular diseases for the prognosis of patients, but also for the occurrence of an acute cardiovascular event upon detection of RSV, the corresponding recommendation is expected to come,” said Dr. Baldus.

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