Geriatrics

Rates of underdiagnosed dementia are higher in US states that require clinicians to report a dementia diagnosis to their department of motor vehicles (DMV), new research suggests.

Investigators found that primary care physicians (PCPs) in states with clinician reporting mandates had a 59% higher probability of underdiagnosing dementia compared with their counterparts in states that require patients to self-report or that have no reporting mandates.

“Our findings in this cross-sectional study raise concerns about potential adverse effects of mandatory clinician reporting for dementia diagnosis and underscore the need for careful consideration of the effect of such policies,” wrote the investigators, led by Soeren Mattke, MD, DSc, director of the USC Brain Health Observatory and research professor of economics at the University of Southern California, Los Angeles. 

The study was published online in JAMA Network Open.
 

Lack of Guidance 

As the US population ages, the number of older drivers is increasing, with 55.8 million drivers 65 years old or older. Approximately 7 million people in this age group have dementia — an estimate that is expected to increase to nearly 12 million by 2040.

The aging population raises a “critical policy question” about how to ensure road safety. Although the American Medical Association’s Code of Ethics outlines a physician’s obligation to identify drivers with medical impairments that impede safe driving, guidance restricting cognitively impaired drivers from driving is lacking.

In addition, evidence as to whether cognitive impairment indeed poses a threat to driving safety is mixed and has led to a lack of uniform policies with respect to reporting dementia. 

Four states explicitly require clinicians to report dementia diagnoses to the DMV, which will then determine the patient’s fitness to drive, whereas 14 states require people with dementia to self-report. The remaining states have no explicit reporting requirements.

The issue of mandatory reporting is controversial, the researchers noted. On the one hand, physicians could protect patients and others by reporting potentially unsafe drivers.

On the other hand, evidence of an association with lower accident risks in patients with dementia is sparse and mandatory reporting may adversely affect physician-patient relationships. Empirical evidence for unintended consequences of reporting laws is lacking.

To examine the potential link between dementia underdiagnosis and mandatory reporting policies, the investigators analyzed the 100% data from the Medicare fee-for-service program and Medicare Advantage plans from 2017 to 2019, which included 223,036 PCPs with a panel of 25 or more Medicare patients.

The researchers examined dementia diagnosis rates in the patient panel of PCPs, rather than neurologists or gerontologists, regardless of who documented the diagnosis. Dr. Mattke said that it is possible that the diagnosis was established after referral to a specialist.

Each physician’s expected number of dementia cases was estimated using a predictive model based on patient characteristics. The researchers then compared the estimate with observed dementia diagnoses, thereby identifying clinicians who underdiagnosed dementia after sampling errors were accounted for.
 

‘Heavy-Handed Interference’

The researchers adjusted for several covariates potentially associated with a clinician’s probability of underdiagnosing dementia. These included sex, office location, practice specialty, racial/ethnic composition of the patient panel, and percentage of patients dually eligible for Medicare and Medicaid. The table shows PCP characteristics.

167934_table_web.jpg

“Our study is the first to provide empirical evidence for the potential adverse effects of reporting policies,” the researchers noted. “Although we found that some clinicians underdiagnosed dementia regardless of state mandates, the key finding of this study reveals that primary care clinicians who practice in states with clinician reporting mandates were 59% more likely to do so…compared with those states with no reporting requirements…or driver self-reporting requirements.”

The investigators suggested that one potential explanation for underdiagnosis is patient resistance to cognitive testing. If patients were aware that the clinician was obligated by law to report their dementia diagnosis to the DMV, “they might be more inclined to conceal their symptoms or refuse further assessments, in addition to the general stigma and resistance to a formal assessment after a positive dementia screening result.”

“The findings suggest that policymakers might want to rethink those physician reporting mandates, since we also could not find conclusive evidence that they improve road safety,” Dr. Mattke said. “Maybe patients and their physicians can arrive at a sensible approach to determine driving fitness without such heavy-handed interference.”

However, he cautioned that the findings are not definitive and further study is needed before firm recommendations either for or against mandatory reporting. 

In addition, the researchers noted several study limitations. One is that dementia underdiagnosis may also be associated with factors not captured in their model, including physician-patient relationships, health literacy, or language barriers.

However, Dr. Mattke noted, “ my sense is that those unobservable factors are not systematically related to state reporting policies and having omitted them would therefore not bias our results.”

Experts Weigh In 

Commenting on the research, Morgan Daven, MA, the Alzheimer’s Association vice president of health systems, said that dementia is widely and significantly underdiagnosed, and not only in the states with dementia reporting mandates. Many factors may contribute to underdiagnosis, and although the study shows an association between reporting mandates and underdiagnosis, it does not demonstrate causation. 

That said, Mr. Daven added, “fear and stigma related to dementia may inhibit the clinician, the patient, and their family from pursuing detection and diagnosis for dementia. As a society, we need to address dementia fear and stigma for all parties.” 

He noted that useful tools include healthcare policies, workforce training, public awareness and education, and public policies to mitigate fear and stigma and their negative effects on diagnosis, care, support, and communication. 

A potential study limitation is that it relied only on diagnoses by PCPs. Mr. Daven noted that the diagnosis of Alzheimer’ disease — the most common cause of dementia — is confirmation of amyloid buildup via a biomarker test, using PET or cerebrospinal fluid analysis. 

“Both of these tests are extremely limited in their use and accessibility in a primary care setting. Inclusion of diagnoses by dementia specialists would provide a more complete picture,” he said. 

Mr. Daven added that the Alzheimer’s Association encourages families to proactively discuss driving and other disease-related safety concerns as soon as possible. The Alzheimer’s Association Dementia and Driving webpage offers tips and strategies to discuss driving concerns with a family member. 

In an accompanying editorial, Donald Redelmeier, MD, MS(HSR), and Vidhi Bhatt, BSc, both of the Department of Medicine, University of Toronto, differentiate the mandate for physicians to warn patients with dementia about traffic safety from the mandate for reporting child maltreatment, gunshot victims, or communicable diseases. They noted that mandated warnings “are not easy, can engender patient dissatisfaction, and need to be handled with tact.”

Yet, they pointed out, “breaking bad news is what practicing medicine entails.” They emphasized that, regardless of government mandates, “counseling patients for more road safety is an essential skill for clinicians in diverse states who hope to help their patients avoid becoming more traffic statistics.”

Research reported in this publication was supported by Genentech, a member of the Roche Group, and a grant from the National Institute on Aging of the National Institutes of Health. Dr. Mattke reported receiving grants from Genentech for a research contract with USC during the conduct of the study; personal fees from Eisai, Biogen, C2N, Novo Nordisk, Novartis, and Roche Genentech; and serving on the Senscio Systems board of directors, ALZpath scientific advisory board, AiCure scientific advisory board, and Boston Millennia Partners scientific advisory board outside the submitted work. The other authors’ disclosures are listed on the original paper. The editorial was supported by the Canada Research Chair in Medical Decision Sciences, the Canadian Institutes of Health Research, Kimel-Schatzky Traumatic Brain Injury Research Fund, and the Graduate Diploma Program in Health Research at the University of Toronto. The editorial authors report no other relevant financial relationships. 
 

A version of this article appeared on Medscape.com.

Rates of underdiagnosed dementia are higher in US states that require clinicians to report a dementia diagnosis to their department of motor vehicles (DMV), new research suggests.

Investigators found that primary care physicians (PCPs) in states with clinician reporting mandates had a 59% higher probability of underdiagnosing dementia compared with their counterparts in states that require patients to self-report or that have no reporting mandates.

“Our findings in this cross-sectional study raise concerns about potential adverse effects of mandatory clinician reporting for dementia diagnosis and underscore the need for careful consideration of the effect of such policies,” wrote the investigators, led by Soeren Mattke, MD, DSc, director of the USC Brain Health Observatory and research professor of economics at the University of Southern California, Los Angeles. 

The study was published online in JAMA Network Open.
 

Lack of Guidance 

As the US population ages, the number of older drivers is increasing, with 55.8 million drivers 65 years old or older. Approximately 7 million people in this age group have dementia — an estimate that is expected to increase to nearly 12 million by 2040.

The aging population raises a “critical policy question” about how to ensure road safety. Although the American Medical Association’s Code of Ethics outlines a physician’s obligation to identify drivers with medical impairments that impede safe driving, guidance restricting cognitively impaired drivers from driving is lacking.

In addition, evidence as to whether cognitive impairment indeed poses a threat to driving safety is mixed and has led to a lack of uniform policies with respect to reporting dementia. 

Four states explicitly require clinicians to report dementia diagnoses to the DMV, which will then determine the patient’s fitness to drive, whereas 14 states require people with dementia to self-report. The remaining states have no explicit reporting requirements.

The issue of mandatory reporting is controversial, the researchers noted. On the one hand, physicians could protect patients and others by reporting potentially unsafe drivers.

On the other hand, evidence of an association with lower accident risks in patients with dementia is sparse and mandatory reporting may adversely affect physician-patient relationships. Empirical evidence for unintended consequences of reporting laws is lacking.

To examine the potential link between dementia underdiagnosis and mandatory reporting policies, the investigators analyzed the 100% data from the Medicare fee-for-service program and Medicare Advantage plans from 2017 to 2019, which included 223,036 PCPs with a panel of 25 or more Medicare patients.

The researchers examined dementia diagnosis rates in the patient panel of PCPs, rather than neurologists or gerontologists, regardless of who documented the diagnosis. Dr. Mattke said that it is possible that the diagnosis was established after referral to a specialist.

Each physician’s expected number of dementia cases was estimated using a predictive model based on patient characteristics. The researchers then compared the estimate with observed dementia diagnoses, thereby identifying clinicians who underdiagnosed dementia after sampling errors were accounted for.
 

‘Heavy-Handed Interference’

The researchers adjusted for several covariates potentially associated with a clinician’s probability of underdiagnosing dementia. These included sex, office location, practice specialty, racial/ethnic composition of the patient panel, and percentage of patients dually eligible for Medicare and Medicaid. The table shows PCP characteristics.

167934_table_web.jpg

“Our study is the first to provide empirical evidence for the potential adverse effects of reporting policies,” the researchers noted. “Although we found that some clinicians underdiagnosed dementia regardless of state mandates, the key finding of this study reveals that primary care clinicians who practice in states with clinician reporting mandates were 59% more likely to do so…compared with those states with no reporting requirements…or driver self-reporting requirements.”

The investigators suggested that one potential explanation for underdiagnosis is patient resistance to cognitive testing. If patients were aware that the clinician was obligated by law to report their dementia diagnosis to the DMV, “they might be more inclined to conceal their symptoms or refuse further assessments, in addition to the general stigma and resistance to a formal assessment after a positive dementia screening result.”

“The findings suggest that policymakers might want to rethink those physician reporting mandates, since we also could not find conclusive evidence that they improve road safety,” Dr. Mattke said. “Maybe patients and their physicians can arrive at a sensible approach to determine driving fitness without such heavy-handed interference.”

However, he cautioned that the findings are not definitive and further study is needed before firm recommendations either for or against mandatory reporting. 

In addition, the researchers noted several study limitations. One is that dementia underdiagnosis may also be associated with factors not captured in their model, including physician-patient relationships, health literacy, or language barriers.

However, Dr. Mattke noted, “ my sense is that those unobservable factors are not systematically related to state reporting policies and having omitted them would therefore not bias our results.”

Experts Weigh In 

Commenting on the research, Morgan Daven, MA, the Alzheimer’s Association vice president of health systems, said that dementia is widely and significantly underdiagnosed, and not only in the states with dementia reporting mandates. Many factors may contribute to underdiagnosis, and although the study shows an association between reporting mandates and underdiagnosis, it does not demonstrate causation. 

That said, Mr. Daven added, “fear and stigma related to dementia may inhibit the clinician, the patient, and their family from pursuing detection and diagnosis for dementia. As a society, we need to address dementia fear and stigma for all parties.” 

He noted that useful tools include healthcare policies, workforce training, public awareness and education, and public policies to mitigate fear and stigma and their negative effects on diagnosis, care, support, and communication. 

A potential study limitation is that it relied only on diagnoses by PCPs. Mr. Daven noted that the diagnosis of Alzheimer’ disease — the most common cause of dementia — is confirmation of amyloid buildup via a biomarker test, using PET or cerebrospinal fluid analysis. 

“Both of these tests are extremely limited in their use and accessibility in a primary care setting. Inclusion of diagnoses by dementia specialists would provide a more complete picture,” he said. 

Mr. Daven added that the Alzheimer’s Association encourages families to proactively discuss driving and other disease-related safety concerns as soon as possible. The Alzheimer’s Association Dementia and Driving webpage offers tips and strategies to discuss driving concerns with a family member. 

In an accompanying editorial, Donald Redelmeier, MD, MS(HSR), and Vidhi Bhatt, BSc, both of the Department of Medicine, University of Toronto, differentiate the mandate for physicians to warn patients with dementia about traffic safety from the mandate for reporting child maltreatment, gunshot victims, or communicable diseases. They noted that mandated warnings “are not easy, can engender patient dissatisfaction, and need to be handled with tact.”

Yet, they pointed out, “breaking bad news is what practicing medicine entails.” They emphasized that, regardless of government mandates, “counseling patients for more road safety is an essential skill for clinicians in diverse states who hope to help their patients avoid becoming more traffic statistics.”

Research reported in this publication was supported by Genentech, a member of the Roche Group, and a grant from the National Institute on Aging of the National Institutes of Health. Dr. Mattke reported receiving grants from Genentech for a research contract with USC during the conduct of the study; personal fees from Eisai, Biogen, C2N, Novo Nordisk, Novartis, and Roche Genentech; and serving on the Senscio Systems board of directors, ALZpath scientific advisory board, AiCure scientific advisory board, and Boston Millennia Partners scientific advisory board outside the submitted work. The other authors’ disclosures are listed on the original paper. The editorial was supported by the Canada Research Chair in Medical Decision Sciences, the Canadian Institutes of Health Research, Kimel-Schatzky Traumatic Brain Injury Research Fund, and the Graduate Diploma Program in Health Research at the University of Toronto. The editorial authors report no other relevant financial relationships. 
 

A version of this article appeared on Medscape.com.

Rates of underdiagnosed dementia are higher in US states that require clinicians to report a dementia diagnosis to their department of motor vehicles (DMV), new research suggests.

Investigators found that primary care physicians (PCPs) in states with clinician reporting mandates had a 59% higher probability of underdiagnosing dementia compared with their counterparts in states that require patients to self-report or that have no reporting mandates.

“Our findings in this cross-sectional study raise concerns about potential adverse effects of mandatory clinician reporting for dementia diagnosis and underscore the need for careful consideration of the effect of such policies,” wrote the investigators, led by Soeren Mattke, MD, DSc, director of the USC Brain Health Observatory and research professor of economics at the University of Southern California, Los Angeles. 

The study was published online in JAMA Network Open.
 

Lack of Guidance 

As the US population ages, the number of older drivers is increasing, with 55.8 million drivers 65 years old or older. Approximately 7 million people in this age group have dementia — an estimate that is expected to increase to nearly 12 million by 2040.

The aging population raises a “critical policy question” about how to ensure road safety. Although the American Medical Association’s Code of Ethics outlines a physician’s obligation to identify drivers with medical impairments that impede safe driving, guidance restricting cognitively impaired drivers from driving is lacking.

In addition, evidence as to whether cognitive impairment indeed poses a threat to driving safety is mixed and has led to a lack of uniform policies with respect to reporting dementia. 

Four states explicitly require clinicians to report dementia diagnoses to the DMV, which will then determine the patient’s fitness to drive, whereas 14 states require people with dementia to self-report. The remaining states have no explicit reporting requirements.

The issue of mandatory reporting is controversial, the researchers noted. On the one hand, physicians could protect patients and others by reporting potentially unsafe drivers.

On the other hand, evidence of an association with lower accident risks in patients with dementia is sparse and mandatory reporting may adversely affect physician-patient relationships. Empirical evidence for unintended consequences of reporting laws is lacking.

To examine the potential link between dementia underdiagnosis and mandatory reporting policies, the investigators analyzed the 100% data from the Medicare fee-for-service program and Medicare Advantage plans from 2017 to 2019, which included 223,036 PCPs with a panel of 25 or more Medicare patients.

The researchers examined dementia diagnosis rates in the patient panel of PCPs, rather than neurologists or gerontologists, regardless of who documented the diagnosis. Dr. Mattke said that it is possible that the diagnosis was established after referral to a specialist.

Each physician’s expected number of dementia cases was estimated using a predictive model based on patient characteristics. The researchers then compared the estimate with observed dementia diagnoses, thereby identifying clinicians who underdiagnosed dementia after sampling errors were accounted for.
 

‘Heavy-Handed Interference’

The researchers adjusted for several covariates potentially associated with a clinician’s probability of underdiagnosing dementia. These included sex, office location, practice specialty, racial/ethnic composition of the patient panel, and percentage of patients dually eligible for Medicare and Medicaid. The table shows PCP characteristics.

167934_table_web.jpg

“Our study is the first to provide empirical evidence for the potential adverse effects of reporting policies,” the researchers noted. “Although we found that some clinicians underdiagnosed dementia regardless of state mandates, the key finding of this study reveals that primary care clinicians who practice in states with clinician reporting mandates were 59% more likely to do so…compared with those states with no reporting requirements…or driver self-reporting requirements.”

The investigators suggested that one potential explanation for underdiagnosis is patient resistance to cognitive testing. If patients were aware that the clinician was obligated by law to report their dementia diagnosis to the DMV, “they might be more inclined to conceal their symptoms or refuse further assessments, in addition to the general stigma and resistance to a formal assessment after a positive dementia screening result.”

“The findings suggest that policymakers might want to rethink those physician reporting mandates, since we also could not find conclusive evidence that they improve road safety,” Dr. Mattke said. “Maybe patients and their physicians can arrive at a sensible approach to determine driving fitness without such heavy-handed interference.”

However, he cautioned that the findings are not definitive and further study is needed before firm recommendations either for or against mandatory reporting. 

In addition, the researchers noted several study limitations. One is that dementia underdiagnosis may also be associated with factors not captured in their model, including physician-patient relationships, health literacy, or language barriers.

However, Dr. Mattke noted, “ my sense is that those unobservable factors are not systematically related to state reporting policies and having omitted them would therefore not bias our results.”

Experts Weigh In 

Commenting on the research, Morgan Daven, MA, the Alzheimer’s Association vice president of health systems, said that dementia is widely and significantly underdiagnosed, and not only in the states with dementia reporting mandates. Many factors may contribute to underdiagnosis, and although the study shows an association between reporting mandates and underdiagnosis, it does not demonstrate causation. 

That said, Mr. Daven added, “fear and stigma related to dementia may inhibit the clinician, the patient, and their family from pursuing detection and diagnosis for dementia. As a society, we need to address dementia fear and stigma for all parties.” 

He noted that useful tools include healthcare policies, workforce training, public awareness and education, and public policies to mitigate fear and stigma and their negative effects on diagnosis, care, support, and communication. 

A potential study limitation is that it relied only on diagnoses by PCPs. Mr. Daven noted that the diagnosis of Alzheimer’ disease — the most common cause of dementia — is confirmation of amyloid buildup via a biomarker test, using PET or cerebrospinal fluid analysis. 

“Both of these tests are extremely limited in their use and accessibility in a primary care setting. Inclusion of diagnoses by dementia specialists would provide a more complete picture,” he said. 

Mr. Daven added that the Alzheimer’s Association encourages families to proactively discuss driving and other disease-related safety concerns as soon as possible. The Alzheimer’s Association Dementia and Driving webpage offers tips and strategies to discuss driving concerns with a family member. 

In an accompanying editorial, Donald Redelmeier, MD, MS(HSR), and Vidhi Bhatt, BSc, both of the Department of Medicine, University of Toronto, differentiate the mandate for physicians to warn patients with dementia about traffic safety from the mandate for reporting child maltreatment, gunshot victims, or communicable diseases. They noted that mandated warnings “are not easy, can engender patient dissatisfaction, and need to be handled with tact.”

Yet, they pointed out, “breaking bad news is what practicing medicine entails.” They emphasized that, regardless of government mandates, “counseling patients for more road safety is an essential skill for clinicians in diverse states who hope to help their patients avoid becoming more traffic statistics.”

Research reported in this publication was supported by Genentech, a member of the Roche Group, and a grant from the National Institute on Aging of the National Institutes of Health. Dr. Mattke reported receiving grants from Genentech for a research contract with USC during the conduct of the study; personal fees from Eisai, Biogen, C2N, Novo Nordisk, Novartis, and Roche Genentech; and serving on the Senscio Systems board of directors, ALZpath scientific advisory board, AiCure scientific advisory board, and Boston Millennia Partners scientific advisory board outside the submitted work. The other authors’ disclosures are listed on the original paper. The editorial was supported by the Canada Research Chair in Medical Decision Sciences, the Canadian Institutes of Health Research, Kimel-Schatzky Traumatic Brain Injury Research Fund, and the Graduate Diploma Program in Health Research at the University of Toronto. The editorial authors report no other relevant financial relationships. 
 

A version of this article appeared on Medscape.com.

DENVER — Treatment with AXS-05, a combination of dextromethorphan and bupropion, demonstrated rapid, sustained, and clinically meaningful improvement in agitation related to Alzheimer’s disease and was generally well tolerated in the phase 3 ACCORD trial. 

More than half of participants in the open-label extension period of the randomized clinical trial responded to the medication, which was associated with a 3.6-fold lower risk for relapse compared with placebo. 

“The positive efficacy and favorable safety results with AXS-05 support its potential to fulfill a high unmet need for the treatment of Alzheimer’s disease agitation,” said Anton P. Porsteinsson, MD, director of the Alzheimer’s Disease Care, Research and Education Program, University of Rochester, New York. 

The findings were presented at the 2024 annual meeting of the American Academy of Neurology. 
 

Common and Disruptive

Agitation is reported in up to 70% of patients with Alzheimer’s disease and is characterized by emotional distress, aggressive behaviors, disruptive irritability, and disinhibition. Alzheimer’s disease-related agitation has been associated with increased caregiver burden, decreased functioning, accelerated cognitive decline, earlier nursing home placement, and increased mortality.

A previous phase 2/3 study of AXS-05 showed that the investigative agent led to rapid and significantly improvement in Alzheimer’s disease agitation, as measured by the Cohen-Mansfield Agitation Inventory (CMAI) total score, compared with placebo. 

ACCORD was a phase 3, randomized, double-blind, placebo-controlled withdrawal trial evaluating the efficacy and safety of AXS-05 in patients with Alzheimer’s disease agitation. 

In the open-label period, 178 adults with probable Alzheimer’s disease and clinically significant agitation received AXS-05 (titrated to 45 mg dextromethorphan/105 mg bupropion twice daily) for up to 9 weeks.

A total of 108 (61%) patients had a sustained response, with 30% or more improvement from baseline in the CMAI total score and improvement on the Patient Global Impression of Change that were both maintained for 4 or more consecutive weeks. These patients entered the double-blind phase and were randomly allocated to receive twice-daily AXS-05 or placebo for up to 26 weeks.

In the double-blind period, AXS-05 “substantially and statistically” increased the time to relapse of agitation symptoms compared with placebo (hazard ratio [HR], 0.275; P = .014).

“The risk of relapse was 3.6-fold lower with AXS-05 compared with placebo,” Dr. Porsteinsson reported. 

AXS-05 was also associated with a significantly lower relapse rate compared with placebo (7.5% vs 25.9%; P = .018).

Rates of discontinuation in the double-blind period owing to adverse events (AEs) were low (0% for AXS-05 and 1.9% for placebo). Three serious AEs were reported: one in the AXS-05 group (fecaloma), which was not related to study medication, and two in the placebo group (cardiac arrest, femur fracture).

Falls were reported in four participants in the AXS-05 group, none of which were related to study medication or associated with serious AEs, and in two participants in the placebo group, one of which was associated with femur fracture.

One death was reported in the placebo group. There was no evidence of cognitive decline with AXS-05, and treatment was not associated with sedation. 
 

Promising Agent 

Commenting on this research, Glen R. Finney, MD, director of the Geisinger Memory and Cognition Clinic in Wilkes-Barre, Pennsylvania, said the data “look promising as a safe way to help address acute agitation and reduce agitation reoccurrence.

“Agitation is a common, distressing, and sometimes safety issue for people fighting Alzheimer’s disease, and there’s very little evidence for efficacy and significant side effect issues for current medical management of agitation in Alzheimer’s disease,” said Dr. Finney, who was not part of the study.

He noted that first-line strategies for addressing agitation involve behavioral and environmental interventions. 

“See if there’s a reason for the agitation and address that. Look for triggers for agitation and avoid those. Find places, things, and interactions that help people with Alzheimer’s disease avoid agitation: familiar locations, music, simple engaging activities. Reassurance, redirection, and distraction can help de-escalate agitation. Provide a safe environment that reduces safety risks,” Dr. Finney explained. 

The next step, when medically appropriate, is trying acetylcholinesterase inhibitors such as donepezil, rivastigmine, and galantamine, and then adding memantine, a weak N-methyl-D-aspartate receptor antagonist. 

“These medications can help reduce the risk of agitation,” Dr. Finney said. 

“Beyond that, the evidence becomes weaker for any specific treatments, and that is where treatments with emerging evidence of efficacy and safety like dextromethorphan-bupropion become important,” Dr. Finney added. 

Last May, the US Food and Drug Administration (FDA) approved the antipsychotic brexpiprazole (Rexulti) for Alzheimer’s disease-related agitation, making it the first FDA-approved drug for this indication. 

The drug includes a boxed warning for medications in this class that older patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk for death.

“There’s certainly a need to have multiple options for treating agitation in individuals with Alzheimer’s disease,” said Rebecca Edelmayer, PhD, senior director of scientific engagement for the Alzheimer’s Association. 

Dr. Edelmayer, who was not part of the study, noted that in the ACCORD study, AXS-05 “significantly delayed the relapse or prevented the relapse with Alzheimer’s disease agitation compared with the placebo group and it was generally well tolerated, but it will be important to make sure that there’s more thorough review of the data overall to be sure that it’s both safe and effective.”

The study was funded by Axsome Therapeutics, the manufacturer of AXS-05. Dr. Porsteinsson has disclosed no relevant conflicts of interest. Dr. Finney and Dr. Edelmayer have no relevant disclosures.

A version of this article appeared on Medscape.com.

DENVER — Treatment with AXS-05, a combination of dextromethorphan and bupropion, demonstrated rapid, sustained, and clinically meaningful improvement in agitation related to Alzheimer’s disease and was generally well tolerated in the phase 3 ACCORD trial. 

More than half of participants in the open-label extension period of the randomized clinical trial responded to the medication, which was associated with a 3.6-fold lower risk for relapse compared with placebo. 

“The positive efficacy and favorable safety results with AXS-05 support its potential to fulfill a high unmet need for the treatment of Alzheimer’s disease agitation,” said Anton P. Porsteinsson, MD, director of the Alzheimer’s Disease Care, Research and Education Program, University of Rochester, New York. 

The findings were presented at the 2024 annual meeting of the American Academy of Neurology. 
 

Common and Disruptive

Agitation is reported in up to 70% of patients with Alzheimer’s disease and is characterized by emotional distress, aggressive behaviors, disruptive irritability, and disinhibition. Alzheimer’s disease-related agitation has been associated with increased caregiver burden, decreased functioning, accelerated cognitive decline, earlier nursing home placement, and increased mortality.

A previous phase 2/3 study of AXS-05 showed that the investigative agent led to rapid and significantly improvement in Alzheimer’s disease agitation, as measured by the Cohen-Mansfield Agitation Inventory (CMAI) total score, compared with placebo. 

ACCORD was a phase 3, randomized, double-blind, placebo-controlled withdrawal trial evaluating the efficacy and safety of AXS-05 in patients with Alzheimer’s disease agitation. 

In the open-label period, 178 adults with probable Alzheimer’s disease and clinically significant agitation received AXS-05 (titrated to 45 mg dextromethorphan/105 mg bupropion twice daily) for up to 9 weeks.

A total of 108 (61%) patients had a sustained response, with 30% or more improvement from baseline in the CMAI total score and improvement on the Patient Global Impression of Change that were both maintained for 4 or more consecutive weeks. These patients entered the double-blind phase and were randomly allocated to receive twice-daily AXS-05 or placebo for up to 26 weeks.

In the double-blind period, AXS-05 “substantially and statistically” increased the time to relapse of agitation symptoms compared with placebo (hazard ratio [HR], 0.275; P = .014).

“The risk of relapse was 3.6-fold lower with AXS-05 compared with placebo,” Dr. Porsteinsson reported. 

AXS-05 was also associated with a significantly lower relapse rate compared with placebo (7.5% vs 25.9%; P = .018).

Rates of discontinuation in the double-blind period owing to adverse events (AEs) were low (0% for AXS-05 and 1.9% for placebo). Three serious AEs were reported: one in the AXS-05 group (fecaloma), which was not related to study medication, and two in the placebo group (cardiac arrest, femur fracture).

Falls were reported in four participants in the AXS-05 group, none of which were related to study medication or associated with serious AEs, and in two participants in the placebo group, one of which was associated with femur fracture.

One death was reported in the placebo group. There was no evidence of cognitive decline with AXS-05, and treatment was not associated with sedation. 
 

Promising Agent 

Commenting on this research, Glen R. Finney, MD, director of the Geisinger Memory and Cognition Clinic in Wilkes-Barre, Pennsylvania, said the data “look promising as a safe way to help address acute agitation and reduce agitation reoccurrence.

“Agitation is a common, distressing, and sometimes safety issue for people fighting Alzheimer’s disease, and there’s very little evidence for efficacy and significant side effect issues for current medical management of agitation in Alzheimer’s disease,” said Dr. Finney, who was not part of the study.

He noted that first-line strategies for addressing agitation involve behavioral and environmental interventions. 

“See if there’s a reason for the agitation and address that. Look for triggers for agitation and avoid those. Find places, things, and interactions that help people with Alzheimer’s disease avoid agitation: familiar locations, music, simple engaging activities. Reassurance, redirection, and distraction can help de-escalate agitation. Provide a safe environment that reduces safety risks,” Dr. Finney explained. 

The next step, when medically appropriate, is trying acetylcholinesterase inhibitors such as donepezil, rivastigmine, and galantamine, and then adding memantine, a weak N-methyl-D-aspartate receptor antagonist. 

“These medications can help reduce the risk of agitation,” Dr. Finney said. 

“Beyond that, the evidence becomes weaker for any specific treatments, and that is where treatments with emerging evidence of efficacy and safety like dextromethorphan-bupropion become important,” Dr. Finney added. 

Last May, the US Food and Drug Administration (FDA) approved the antipsychotic brexpiprazole (Rexulti) for Alzheimer’s disease-related agitation, making it the first FDA-approved drug for this indication. 

The drug includes a boxed warning for medications in this class that older patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk for death.

“There’s certainly a need to have multiple options for treating agitation in individuals with Alzheimer’s disease,” said Rebecca Edelmayer, PhD, senior director of scientific engagement for the Alzheimer’s Association. 

Dr. Edelmayer, who was not part of the study, noted that in the ACCORD study, AXS-05 “significantly delayed the relapse or prevented the relapse with Alzheimer’s disease agitation compared with the placebo group and it was generally well tolerated, but it will be important to make sure that there’s more thorough review of the data overall to be sure that it’s both safe and effective.”

The study was funded by Axsome Therapeutics, the manufacturer of AXS-05. Dr. Porsteinsson has disclosed no relevant conflicts of interest. Dr. Finney and Dr. Edelmayer have no relevant disclosures.

A version of this article appeared on Medscape.com.

DENVER — Treatment with AXS-05, a combination of dextromethorphan and bupropion, demonstrated rapid, sustained, and clinically meaningful improvement in agitation related to Alzheimer’s disease and was generally well tolerated in the phase 3 ACCORD trial. 

More than half of participants in the open-label extension period of the randomized clinical trial responded to the medication, which was associated with a 3.6-fold lower risk for relapse compared with placebo. 

“The positive efficacy and favorable safety results with AXS-05 support its potential to fulfill a high unmet need for the treatment of Alzheimer’s disease agitation,” said Anton P. Porsteinsson, MD, director of the Alzheimer’s Disease Care, Research and Education Program, University of Rochester, New York. 

The findings were presented at the 2024 annual meeting of the American Academy of Neurology. 
 

Common and Disruptive

Agitation is reported in up to 70% of patients with Alzheimer’s disease and is characterized by emotional distress, aggressive behaviors, disruptive irritability, and disinhibition. Alzheimer’s disease-related agitation has been associated with increased caregiver burden, decreased functioning, accelerated cognitive decline, earlier nursing home placement, and increased mortality.

A previous phase 2/3 study of AXS-05 showed that the investigative agent led to rapid and significantly improvement in Alzheimer’s disease agitation, as measured by the Cohen-Mansfield Agitation Inventory (CMAI) total score, compared with placebo. 

ACCORD was a phase 3, randomized, double-blind, placebo-controlled withdrawal trial evaluating the efficacy and safety of AXS-05 in patients with Alzheimer’s disease agitation. 

In the open-label period, 178 adults with probable Alzheimer’s disease and clinically significant agitation received AXS-05 (titrated to 45 mg dextromethorphan/105 mg bupropion twice daily) for up to 9 weeks.

A total of 108 (61%) patients had a sustained response, with 30% or more improvement from baseline in the CMAI total score and improvement on the Patient Global Impression of Change that were both maintained for 4 or more consecutive weeks. These patients entered the double-blind phase and were randomly allocated to receive twice-daily AXS-05 or placebo for up to 26 weeks.

In the double-blind period, AXS-05 “substantially and statistically” increased the time to relapse of agitation symptoms compared with placebo (hazard ratio [HR], 0.275; P = .014).

“The risk of relapse was 3.6-fold lower with AXS-05 compared with placebo,” Dr. Porsteinsson reported. 

AXS-05 was also associated with a significantly lower relapse rate compared with placebo (7.5% vs 25.9%; P = .018).

Rates of discontinuation in the double-blind period owing to adverse events (AEs) were low (0% for AXS-05 and 1.9% for placebo). Three serious AEs were reported: one in the AXS-05 group (fecaloma), which was not related to study medication, and two in the placebo group (cardiac arrest, femur fracture).

Falls were reported in four participants in the AXS-05 group, none of which were related to study medication or associated with serious AEs, and in two participants in the placebo group, one of which was associated with femur fracture.

One death was reported in the placebo group. There was no evidence of cognitive decline with AXS-05, and treatment was not associated with sedation. 
 

Promising Agent 

Commenting on this research, Glen R. Finney, MD, director of the Geisinger Memory and Cognition Clinic in Wilkes-Barre, Pennsylvania, said the data “look promising as a safe way to help address acute agitation and reduce agitation reoccurrence.

“Agitation is a common, distressing, and sometimes safety issue for people fighting Alzheimer’s disease, and there’s very little evidence for efficacy and significant side effect issues for current medical management of agitation in Alzheimer’s disease,” said Dr. Finney, who was not part of the study.

He noted that first-line strategies for addressing agitation involve behavioral and environmental interventions. 

“See if there’s a reason for the agitation and address that. Look for triggers for agitation and avoid those. Find places, things, and interactions that help people with Alzheimer’s disease avoid agitation: familiar locations, music, simple engaging activities. Reassurance, redirection, and distraction can help de-escalate agitation. Provide a safe environment that reduces safety risks,” Dr. Finney explained. 

The next step, when medically appropriate, is trying acetylcholinesterase inhibitors such as donepezil, rivastigmine, and galantamine, and then adding memantine, a weak N-methyl-D-aspartate receptor antagonist. 

“These medications can help reduce the risk of agitation,” Dr. Finney said. 

“Beyond that, the evidence becomes weaker for any specific treatments, and that is where treatments with emerging evidence of efficacy and safety like dextromethorphan-bupropion become important,” Dr. Finney added. 

Last May, the US Food and Drug Administration (FDA) approved the antipsychotic brexpiprazole (Rexulti) for Alzheimer’s disease-related agitation, making it the first FDA-approved drug for this indication. 

The drug includes a boxed warning for medications in this class that older patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk for death.

“There’s certainly a need to have multiple options for treating agitation in individuals with Alzheimer’s disease,” said Rebecca Edelmayer, PhD, senior director of scientific engagement for the Alzheimer’s Association. 

Dr. Edelmayer, who was not part of the study, noted that in the ACCORD study, AXS-05 “significantly delayed the relapse or prevented the relapse with Alzheimer’s disease agitation compared with the placebo group and it was generally well tolerated, but it will be important to make sure that there’s more thorough review of the data overall to be sure that it’s both safe and effective.”

The study was funded by Axsome Therapeutics, the manufacturer of AXS-05. Dr. Porsteinsson has disclosed no relevant conflicts of interest. Dr. Finney and Dr. Edelmayer have no relevant disclosures.

A version of this article appeared on Medscape.com.

Caring for older adults was one of the most rewarding parts of my years practicing as a clinical cardiologist. I appreciated their wisdom, humor, and, very often, their respect and appreciation for physicians. It was always upsetting to see them suffer a mild fall or episode of atrial fibrillation and recognize that it could have major health ramifications.

Life expectancy has improved dramatically, but longer lifespans also mean more opportunity for illness, pain, chronic disease, and dependence on others. Having successfully helped older adults live longer, the question now becomes, how can we, as physicians, add more life to those years? How can we increase their “healthspans”?

That is not just a question for geriatric care. With fewer than two practicing geriatricians for every 10,000 older individuals, it is obvious that geriatricians cannot shoulder this responsibility alone. Almost all primary care physicians and subspecialists should prepare to care for older individuals and help them age healthfully.

Susan Friedman, MD, a board-certified geriatrics and lifestyle medicine clinician at the University of Rochester School of Medicine and Dentistry, Rochester, New York, reviewed the literature on the connection between lifestyle and healthy aging and concluded that the integration of lifestyle medicine into medical care for older adults is key to compressing morbidity. The pillars of lifestyle medicine — optimal nutrition, physical activity, stress management, restorative sleep, positive social connections, and avoidance of risky substances — both individually or as a sum are associated with less chronic disease, improved engagement in life, better physical and cognitive function, less frailty, and less sarcopenia. Framing discussions with patients around the six pillars of lifestyle medicine can be an effective strategy.
 

Optimal Nutrition

For a variety of reasons, older adults, especially those living alone, often lose the desire to prepare a nourishing meal. Older adults require different protein intake than younger patients to offset age-related sarcopenia, but helping them select healthy sources of protein is imperative. Both adequate protein consumption and eating patterns high in vegetables, legumes, fruit, and nuts and low in saturated fat, red meat, and processed meat can lower the risk of developing frailty.

Asking a patient to share a 24-hour food recall, and based upon that, resourcing nutritional guidance, a lifestyle medicine program or specialist, and insurance or community resources for food-as-medicine services, is a good first step.
 

Physical Activity

Increasing general physical activity can be a tough ask for many older adults, and joint pain is a common reason they demur. Messaging around targeted exercises to mitigate falls, improve muscle strength, and reduce joint pain may be more appealing. Contemporary research demonstrates that exercise, particularly open-skill exercise that requires quick decisions (such as table tennis) can be powerful. Maintaining cognition, mood enhancement, and independence may also be motivating messages.

The first step is curiosity: What does your patient like to do? Referral to a physical therapist or an exercise specialist to provide stepwise guidance along with resourcing community opportunities can then follow.
 

Restorative Sleep

“I’m old. I don’t need as much sleep.” We’ve probably all heard older patients say this. But the National Sleep Foundation’s report on sleep health and aging indicates that the need to sleep does not decrease with age. The ability to sleep, however, may decline. Assessing and treating disordered sleep is another example of how each lifestyle medicine pillar, such as nutrition and physical activity, is multidimensional and interacts to support the functional integrity of older patients. It’s hard to feel motivated to go for a walk if you lack adequate sleep.
 

Stress Management

Exploring stress with patients can be very revealing. Do they experience stress that energizes and has a positive effect? How much of their day is spent in negatively impactful distress? Chronic stress has been shown to affect immune function in older individuals. Start conversations with your older patients to normalize the importance of stress as a health measure.
 

Positive Social Connections

Loneliness puts individuals at higher risk for heart disease, stroke, and dementia and even increases the risk for premature death by up to 60%. Yet, clinicians and patients rarely discuss social connections during medical appointments. Tools such as the UCLA Loneliness Scale exist for health practitioners to assess and identify patients at risk for loneliness, as do resources to integrate social care into the delivery of healthcare.
 

Avoidance of Risky Substances

Alcohol assessments are not just for younger patients. One study found that 5.6 million adults ages 65 or older engaged in binge drinking in the past month. Because of body changes, the negative effects of alcohol may be greater on older adults, including interactions between alcohol and commonly prescribed medications. 

Conducting a lifestyle assessment is an important way to engage with older patients and allows clinicians to identify opportunities to improve health behaviors, understand obstacles, and support patients to make lifestyle changes. It may uncover ways to remove some of the pill and treatment burdens that older adults often experience. The American College of Lifestyle Medicine (ACLM) offers clinical practice resources to support clinicians as well as “Lifestyle Medicine and Food as Medicine Essentials,” a 5.5-hour complimentary CE/CME course on food and lifestyle medicine that introduces clinicians to the therapeutic use of lifestyle medicine. ACLM also offers members interest groups focused on geriatrics, fitness, and mental health, which may be beneficial to clinicians treating older adults.

By engaging with older patients on their lifestyle behaviors, we can ensure that we are doing all we can to help them live longer — and live better.

Dr. Collings is director of lifestyle medicine, Silicon Valley Medical Development, and past president, American College of Lifestyle Medicine, Mountain View, California. She has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Caring for older adults was one of the most rewarding parts of my years practicing as a clinical cardiologist. I appreciated their wisdom, humor, and, very often, their respect and appreciation for physicians. It was always upsetting to see them suffer a mild fall or episode of atrial fibrillation and recognize that it could have major health ramifications.

Life expectancy has improved dramatically, but longer lifespans also mean more opportunity for illness, pain, chronic disease, and dependence on others. Having successfully helped older adults live longer, the question now becomes, how can we, as physicians, add more life to those years? How can we increase their “healthspans”?

That is not just a question for geriatric care. With fewer than two practicing geriatricians for every 10,000 older individuals, it is obvious that geriatricians cannot shoulder this responsibility alone. Almost all primary care physicians and subspecialists should prepare to care for older individuals and help them age healthfully.

Susan Friedman, MD, a board-certified geriatrics and lifestyle medicine clinician at the University of Rochester School of Medicine and Dentistry, Rochester, New York, reviewed the literature on the connection between lifestyle and healthy aging and concluded that the integration of lifestyle medicine into medical care for older adults is key to compressing morbidity. The pillars of lifestyle medicine — optimal nutrition, physical activity, stress management, restorative sleep, positive social connections, and avoidance of risky substances — both individually or as a sum are associated with less chronic disease, improved engagement in life, better physical and cognitive function, less frailty, and less sarcopenia. Framing discussions with patients around the six pillars of lifestyle medicine can be an effective strategy.
 

Optimal Nutrition

For a variety of reasons, older adults, especially those living alone, often lose the desire to prepare a nourishing meal. Older adults require different protein intake than younger patients to offset age-related sarcopenia, but helping them select healthy sources of protein is imperative. Both adequate protein consumption and eating patterns high in vegetables, legumes, fruit, and nuts and low in saturated fat, red meat, and processed meat can lower the risk of developing frailty.

Asking a patient to share a 24-hour food recall, and based upon that, resourcing nutritional guidance, a lifestyle medicine program or specialist, and insurance or community resources for food-as-medicine services, is a good first step.
 

Physical Activity

Increasing general physical activity can be a tough ask for many older adults, and joint pain is a common reason they demur. Messaging around targeted exercises to mitigate falls, improve muscle strength, and reduce joint pain may be more appealing. Contemporary research demonstrates that exercise, particularly open-skill exercise that requires quick decisions (such as table tennis) can be powerful. Maintaining cognition, mood enhancement, and independence may also be motivating messages.

The first step is curiosity: What does your patient like to do? Referral to a physical therapist or an exercise specialist to provide stepwise guidance along with resourcing community opportunities can then follow.
 

Restorative Sleep

“I’m old. I don’t need as much sleep.” We’ve probably all heard older patients say this. But the National Sleep Foundation’s report on sleep health and aging indicates that the need to sleep does not decrease with age. The ability to sleep, however, may decline. Assessing and treating disordered sleep is another example of how each lifestyle medicine pillar, such as nutrition and physical activity, is multidimensional and interacts to support the functional integrity of older patients. It’s hard to feel motivated to go for a walk if you lack adequate sleep.
 

Stress Management

Exploring stress with patients can be very revealing. Do they experience stress that energizes and has a positive effect? How much of their day is spent in negatively impactful distress? Chronic stress has been shown to affect immune function in older individuals. Start conversations with your older patients to normalize the importance of stress as a health measure.
 

Positive Social Connections

Loneliness puts individuals at higher risk for heart disease, stroke, and dementia and even increases the risk for premature death by up to 60%. Yet, clinicians and patients rarely discuss social connections during medical appointments. Tools such as the UCLA Loneliness Scale exist for health practitioners to assess and identify patients at risk for loneliness, as do resources to integrate social care into the delivery of healthcare.
 

Avoidance of Risky Substances

Alcohol assessments are not just for younger patients. One study found that 5.6 million adults ages 65 or older engaged in binge drinking in the past month. Because of body changes, the negative effects of alcohol may be greater on older adults, including interactions between alcohol and commonly prescribed medications. 

Conducting a lifestyle assessment is an important way to engage with older patients and allows clinicians to identify opportunities to improve health behaviors, understand obstacles, and support patients to make lifestyle changes. It may uncover ways to remove some of the pill and treatment burdens that older adults often experience. The American College of Lifestyle Medicine (ACLM) offers clinical practice resources to support clinicians as well as “Lifestyle Medicine and Food as Medicine Essentials,” a 5.5-hour complimentary CE/CME course on food and lifestyle medicine that introduces clinicians to the therapeutic use of lifestyle medicine. ACLM also offers members interest groups focused on geriatrics, fitness, and mental health, which may be beneficial to clinicians treating older adults.

By engaging with older patients on their lifestyle behaviors, we can ensure that we are doing all we can to help them live longer — and live better.

Dr. Collings is director of lifestyle medicine, Silicon Valley Medical Development, and past president, American College of Lifestyle Medicine, Mountain View, California. She has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Caring for older adults was one of the most rewarding parts of my years practicing as a clinical cardiologist. I appreciated their wisdom, humor, and, very often, their respect and appreciation for physicians. It was always upsetting to see them suffer a mild fall or episode of atrial fibrillation and recognize that it could have major health ramifications.

Life expectancy has improved dramatically, but longer lifespans also mean more opportunity for illness, pain, chronic disease, and dependence on others. Having successfully helped older adults live longer, the question now becomes, how can we, as physicians, add more life to those years? How can we increase their “healthspans”?

That is not just a question for geriatric care. With fewer than two practicing geriatricians for every 10,000 older individuals, it is obvious that geriatricians cannot shoulder this responsibility alone. Almost all primary care physicians and subspecialists should prepare to care for older individuals and help them age healthfully.

Susan Friedman, MD, a board-certified geriatrics and lifestyle medicine clinician at the University of Rochester School of Medicine and Dentistry, Rochester, New York, reviewed the literature on the connection between lifestyle and healthy aging and concluded that the integration of lifestyle medicine into medical care for older adults is key to compressing morbidity. The pillars of lifestyle medicine — optimal nutrition, physical activity, stress management, restorative sleep, positive social connections, and avoidance of risky substances — both individually or as a sum are associated with less chronic disease, improved engagement in life, better physical and cognitive function, less frailty, and less sarcopenia. Framing discussions with patients around the six pillars of lifestyle medicine can be an effective strategy.
 

Optimal Nutrition

For a variety of reasons, older adults, especially those living alone, often lose the desire to prepare a nourishing meal. Older adults require different protein intake than younger patients to offset age-related sarcopenia, but helping them select healthy sources of protein is imperative. Both adequate protein consumption and eating patterns high in vegetables, legumes, fruit, and nuts and low in saturated fat, red meat, and processed meat can lower the risk of developing frailty.

Asking a patient to share a 24-hour food recall, and based upon that, resourcing nutritional guidance, a lifestyle medicine program or specialist, and insurance or community resources for food-as-medicine services, is a good first step.
 

Physical Activity

Increasing general physical activity can be a tough ask for many older adults, and joint pain is a common reason they demur. Messaging around targeted exercises to mitigate falls, improve muscle strength, and reduce joint pain may be more appealing. Contemporary research demonstrates that exercise, particularly open-skill exercise that requires quick decisions (such as table tennis) can be powerful. Maintaining cognition, mood enhancement, and independence may also be motivating messages.

The first step is curiosity: What does your patient like to do? Referral to a physical therapist or an exercise specialist to provide stepwise guidance along with resourcing community opportunities can then follow.
 

Restorative Sleep

“I’m old. I don’t need as much sleep.” We’ve probably all heard older patients say this. But the National Sleep Foundation’s report on sleep health and aging indicates that the need to sleep does not decrease with age. The ability to sleep, however, may decline. Assessing and treating disordered sleep is another example of how each lifestyle medicine pillar, such as nutrition and physical activity, is multidimensional and interacts to support the functional integrity of older patients. It’s hard to feel motivated to go for a walk if you lack adequate sleep.
 

Stress Management

Exploring stress with patients can be very revealing. Do they experience stress that energizes and has a positive effect? How much of their day is spent in negatively impactful distress? Chronic stress has been shown to affect immune function in older individuals. Start conversations with your older patients to normalize the importance of stress as a health measure.
 

Positive Social Connections

Loneliness puts individuals at higher risk for heart disease, stroke, and dementia and even increases the risk for premature death by up to 60%. Yet, clinicians and patients rarely discuss social connections during medical appointments. Tools such as the UCLA Loneliness Scale exist for health practitioners to assess and identify patients at risk for loneliness, as do resources to integrate social care into the delivery of healthcare.
 

Avoidance of Risky Substances

Alcohol assessments are not just for younger patients. One study found that 5.6 million adults ages 65 or older engaged in binge drinking in the past month. Because of body changes, the negative effects of alcohol may be greater on older adults, including interactions between alcohol and commonly prescribed medications. 

Conducting a lifestyle assessment is an important way to engage with older patients and allows clinicians to identify opportunities to improve health behaviors, understand obstacles, and support patients to make lifestyle changes. It may uncover ways to remove some of the pill and treatment burdens that older adults often experience. The American College of Lifestyle Medicine (ACLM) offers clinical practice resources to support clinicians as well as “Lifestyle Medicine and Food as Medicine Essentials,” a 5.5-hour complimentary CE/CME course on food and lifestyle medicine that introduces clinicians to the therapeutic use of lifestyle medicine. ACLM also offers members interest groups focused on geriatrics, fitness, and mental health, which may be beneficial to clinicians treating older adults.

By engaging with older patients on their lifestyle behaviors, we can ensure that we are doing all we can to help them live longer — and live better.

Dr. Collings is director of lifestyle medicine, Silicon Valley Medical Development, and past president, American College of Lifestyle Medicine, Mountain View, California. She has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Antipsychotic use in older adults with dementia is associated with a significant increased risk for stroke, myocardial infarction, heart failure, pneumonia, fracture, acute kidney injury, and a range of other health problems compared with nonuse, new research showed.

The adverse events are far broader and pose more severe health risks than previously reported, investigators noted, and suggested greater caution is needed when prescribing antipsychotics to treat psychological symptoms of dementia.

The matched cohort study used patient registry data on nearly 174,000 people with dementia and compared those who were prescribed an antipsychotic on or after their dementia diagnosis with those who had not received a prescription for the drugs.

Any antipsychotic use was associated with double the risk for pneumonia, a 1.7-fold increased risk for acute kidney injury, and 1.6-fold higher odds of venous thromboembolism compared to nonuse.

Investigators found an increased risk for all outcomes studied, except for ventricular arrythmia, and risk was highest for most within the first week of treatment.

“Any potential benefits of antipsychotic treatment therefore need to be weighed against the risk of serious harm across multiple outcomes. Although there may be times when an antipsychotic prescription is the least bad option, clinicians should actively consider the risks, considering patients’ pre-existing comorbidities and living support,” lead investigator Pearl Mok, research fellow at the Centre for Pharmacoepidemiology and Drug Safety, The University of Manchester, Manchester, England, and colleagues wrote.

The findings were published online in The BMJ.
 

High Risk

Depression, aggression, anxiety, psychosis, and other behavioral and psychological symptoms are common in people with dementia. Despite earlier reports of increased risk for stroke and mortality with antipsychotic use, the drugs are frequently prescribed to treat these symptoms.

While some preliminary studies identified other adverse outcomes from antipsychotic use, results are limited and inconsistent.

Investigators used primary and secondary care data from the Clinical Practice Research Datalink in England. A total of 173,910 adults (63% women) had a dementia diagnosis between January 1998 and May 2018.

Of the total cohort, 35,339 patients were prescribed an antipsychotic on, or after, a dementia diagnosis. Each was matched with up to 15 patients with dementia with no history of antipsychotic use following diagnosis.

Almost 80% of antipsychotic prescriptions were for risperidone, quetiapine, haloperidol, and olanzapine.

Any antipsychotic use was associated with significantly higher risks for pneumonia (hazard ratio [HR], 2.03; 95% CI, 1.96-2.10), acute kidney injury (HR, 1.57; 95% CI, 1.48-1.66), stroke (HR, 1.54; 95% CI, 1.46-1.63), venous thromboembolism (HR, 1.52; 95% CI, 1.38-1.67), fracture (HR, 1.36; 95% CI, 1.30-1.44), myocardial infarction (HR, 1.22; 95% CI, 1.12-1.34), and heart failure (HR, 1.16; 95% CI, 1.09-1.24).

The risk for all conditions was highest within the first 3 months of treatment, with a cumulative incidence of pneumonia among antipsychotic users of 4.48% vs 1.49% among nonusers. At 1 year, this increased to 10.41% for users vs 5.63% for nonusers.

“Given the higher risks of adverse events in the early days after drug initiation, clinical examinations should be taken before, and clinical reviews conducted shortly after, the start of treatment,” the authors wrote. “Our study reaffirms that these drugs should only be prescribed for the shortest period possible.”
 

‘Serious Harms’

In an accompanying editorial, Raya Elfadel Kheirbek, MD, and Cristina LaFont, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, said the findings “highlight the need for careful justification of antipsychotic use in dementia care, including a comprehensive assessment of the benefits weighed against a broader range of serious harms than previously acknowledged.”

“Using antipsychotics for the management of dementia-related behaviors requires nuanced decision-making after careful assessment, informed by a personalized approach,” they continued. “Dr. Mok and colleagues call for a critical re-evaluation of antipsychotic use in this clinical setting.”

While the findings add to and expand what was already known, “we need to be clear that they don’t show antipsychotics cause all the adverse outcomes reported,” Masud Husain, DPhil, professor of neurology, University of Oxford, England, said in a statement.

While investigators attempted to use matched controls with dementia who had not received antipsychotics, “the people who were prescribed the drugs may simply have been more vulnerable to some of the conditions that occurred more frequently in them, such as pneumonia and cardiovascular disorders,” said Dr. Husain, who was not part of the research.

Although the study was not designed to explore reverse causality, the findings are important for clinicians who prescribe antipsychotics for patients with dementia, Robert Howard, professor of old age psychiatry, at the University of College London, London, England said in a statement.

“Initiation of these drugs in people with dementia should only ever be under specialist supervision, with involvement of patients and family members in informed discussion and review,” said Dr. Howard, who was not involved in the study.

The study was funded by the National Institute for Health and Care Research. Dr. Mok reported no relevant conflicts. Other authors’ disclosures are included in the original article. Dr. Hussain, Dr. Howard, Dr. Kheirbek, and Dr. LeFon reported no relevant conflicts.

A version of this article appeared on Medscape.com.

Antipsychotic use in older adults with dementia is associated with a significant increased risk for stroke, myocardial infarction, heart failure, pneumonia, fracture, acute kidney injury, and a range of other health problems compared with nonuse, new research showed.

The adverse events are far broader and pose more severe health risks than previously reported, investigators noted, and suggested greater caution is needed when prescribing antipsychotics to treat psychological symptoms of dementia.

The matched cohort study used patient registry data on nearly 174,000 people with dementia and compared those who were prescribed an antipsychotic on or after their dementia diagnosis with those who had not received a prescription for the drugs.

Any antipsychotic use was associated with double the risk for pneumonia, a 1.7-fold increased risk for acute kidney injury, and 1.6-fold higher odds of venous thromboembolism compared to nonuse.

Investigators found an increased risk for all outcomes studied, except for ventricular arrythmia, and risk was highest for most within the first week of treatment.

“Any potential benefits of antipsychotic treatment therefore need to be weighed against the risk of serious harm across multiple outcomes. Although there may be times when an antipsychotic prescription is the least bad option, clinicians should actively consider the risks, considering patients’ pre-existing comorbidities and living support,” lead investigator Pearl Mok, research fellow at the Centre for Pharmacoepidemiology and Drug Safety, The University of Manchester, Manchester, England, and colleagues wrote.

The findings were published online in The BMJ.
 

High Risk

Depression, aggression, anxiety, psychosis, and other behavioral and psychological symptoms are common in people with dementia. Despite earlier reports of increased risk for stroke and mortality with antipsychotic use, the drugs are frequently prescribed to treat these symptoms.

While some preliminary studies identified other adverse outcomes from antipsychotic use, results are limited and inconsistent.

Investigators used primary and secondary care data from the Clinical Practice Research Datalink in England. A total of 173,910 adults (63% women) had a dementia diagnosis between January 1998 and May 2018.

Of the total cohort, 35,339 patients were prescribed an antipsychotic on, or after, a dementia diagnosis. Each was matched with up to 15 patients with dementia with no history of antipsychotic use following diagnosis.

Almost 80% of antipsychotic prescriptions were for risperidone, quetiapine, haloperidol, and olanzapine.

Any antipsychotic use was associated with significantly higher risks for pneumonia (hazard ratio [HR], 2.03; 95% CI, 1.96-2.10), acute kidney injury (HR, 1.57; 95% CI, 1.48-1.66), stroke (HR, 1.54; 95% CI, 1.46-1.63), venous thromboembolism (HR, 1.52; 95% CI, 1.38-1.67), fracture (HR, 1.36; 95% CI, 1.30-1.44), myocardial infarction (HR, 1.22; 95% CI, 1.12-1.34), and heart failure (HR, 1.16; 95% CI, 1.09-1.24).

The risk for all conditions was highest within the first 3 months of treatment, with a cumulative incidence of pneumonia among antipsychotic users of 4.48% vs 1.49% among nonusers. At 1 year, this increased to 10.41% for users vs 5.63% for nonusers.

“Given the higher risks of adverse events in the early days after drug initiation, clinical examinations should be taken before, and clinical reviews conducted shortly after, the start of treatment,” the authors wrote. “Our study reaffirms that these drugs should only be prescribed for the shortest period possible.”
 

‘Serious Harms’

In an accompanying editorial, Raya Elfadel Kheirbek, MD, and Cristina LaFont, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, said the findings “highlight the need for careful justification of antipsychotic use in dementia care, including a comprehensive assessment of the benefits weighed against a broader range of serious harms than previously acknowledged.”

“Using antipsychotics for the management of dementia-related behaviors requires nuanced decision-making after careful assessment, informed by a personalized approach,” they continued. “Dr. Mok and colleagues call for a critical re-evaluation of antipsychotic use in this clinical setting.”

While the findings add to and expand what was already known, “we need to be clear that they don’t show antipsychotics cause all the adverse outcomes reported,” Masud Husain, DPhil, professor of neurology, University of Oxford, England, said in a statement.

While investigators attempted to use matched controls with dementia who had not received antipsychotics, “the people who were prescribed the drugs may simply have been more vulnerable to some of the conditions that occurred more frequently in them, such as pneumonia and cardiovascular disorders,” said Dr. Husain, who was not part of the research.

Although the study was not designed to explore reverse causality, the findings are important for clinicians who prescribe antipsychotics for patients with dementia, Robert Howard, professor of old age psychiatry, at the University of College London, London, England said in a statement.

“Initiation of these drugs in people with dementia should only ever be under specialist supervision, with involvement of patients and family members in informed discussion and review,” said Dr. Howard, who was not involved in the study.

The study was funded by the National Institute for Health and Care Research. Dr. Mok reported no relevant conflicts. Other authors’ disclosures are included in the original article. Dr. Hussain, Dr. Howard, Dr. Kheirbek, and Dr. LeFon reported no relevant conflicts.

A version of this article appeared on Medscape.com.

Antipsychotic use in older adults with dementia is associated with a significant increased risk for stroke, myocardial infarction, heart failure, pneumonia, fracture, acute kidney injury, and a range of other health problems compared with nonuse, new research showed.

The adverse events are far broader and pose more severe health risks than previously reported, investigators noted, and suggested greater caution is needed when prescribing antipsychotics to treat psychological symptoms of dementia.

The matched cohort study used patient registry data on nearly 174,000 people with dementia and compared those who were prescribed an antipsychotic on or after their dementia diagnosis with those who had not received a prescription for the drugs.

Any antipsychotic use was associated with double the risk for pneumonia, a 1.7-fold increased risk for acute kidney injury, and 1.6-fold higher odds of venous thromboembolism compared to nonuse.

Investigators found an increased risk for all outcomes studied, except for ventricular arrythmia, and risk was highest for most within the first week of treatment.

“Any potential benefits of antipsychotic treatment therefore need to be weighed against the risk of serious harm across multiple outcomes. Although there may be times when an antipsychotic prescription is the least bad option, clinicians should actively consider the risks, considering patients’ pre-existing comorbidities and living support,” lead investigator Pearl Mok, research fellow at the Centre for Pharmacoepidemiology and Drug Safety, The University of Manchester, Manchester, England, and colleagues wrote.

The findings were published online in The BMJ.
 

High Risk

Depression, aggression, anxiety, psychosis, and other behavioral and psychological symptoms are common in people with dementia. Despite earlier reports of increased risk for stroke and mortality with antipsychotic use, the drugs are frequently prescribed to treat these symptoms.

While some preliminary studies identified other adverse outcomes from antipsychotic use, results are limited and inconsistent.

Investigators used primary and secondary care data from the Clinical Practice Research Datalink in England. A total of 173,910 adults (63% women) had a dementia diagnosis between January 1998 and May 2018.

Of the total cohort, 35,339 patients were prescribed an antipsychotic on, or after, a dementia diagnosis. Each was matched with up to 15 patients with dementia with no history of antipsychotic use following diagnosis.

Almost 80% of antipsychotic prescriptions were for risperidone, quetiapine, haloperidol, and olanzapine.

Any antipsychotic use was associated with significantly higher risks for pneumonia (hazard ratio [HR], 2.03; 95% CI, 1.96-2.10), acute kidney injury (HR, 1.57; 95% CI, 1.48-1.66), stroke (HR, 1.54; 95% CI, 1.46-1.63), venous thromboembolism (HR, 1.52; 95% CI, 1.38-1.67), fracture (HR, 1.36; 95% CI, 1.30-1.44), myocardial infarction (HR, 1.22; 95% CI, 1.12-1.34), and heart failure (HR, 1.16; 95% CI, 1.09-1.24).

The risk for all conditions was highest within the first 3 months of treatment, with a cumulative incidence of pneumonia among antipsychotic users of 4.48% vs 1.49% among nonusers. At 1 year, this increased to 10.41% for users vs 5.63% for nonusers.

“Given the higher risks of adverse events in the early days after drug initiation, clinical examinations should be taken before, and clinical reviews conducted shortly after, the start of treatment,” the authors wrote. “Our study reaffirms that these drugs should only be prescribed for the shortest period possible.”
 

‘Serious Harms’

In an accompanying editorial, Raya Elfadel Kheirbek, MD, and Cristina LaFont, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, said the findings “highlight the need for careful justification of antipsychotic use in dementia care, including a comprehensive assessment of the benefits weighed against a broader range of serious harms than previously acknowledged.”

“Using antipsychotics for the management of dementia-related behaviors requires nuanced decision-making after careful assessment, informed by a personalized approach,” they continued. “Dr. Mok and colleagues call for a critical re-evaluation of antipsychotic use in this clinical setting.”

While the findings add to and expand what was already known, “we need to be clear that they don’t show antipsychotics cause all the adverse outcomes reported,” Masud Husain, DPhil, professor of neurology, University of Oxford, England, said in a statement.

While investigators attempted to use matched controls with dementia who had not received antipsychotics, “the people who were prescribed the drugs may simply have been more vulnerable to some of the conditions that occurred more frequently in them, such as pneumonia and cardiovascular disorders,” said Dr. Husain, who was not part of the research.

Although the study was not designed to explore reverse causality, the findings are important for clinicians who prescribe antipsychotics for patients with dementia, Robert Howard, professor of old age psychiatry, at the University of College London, London, England said in a statement.

“Initiation of these drugs in people with dementia should only ever be under specialist supervision, with involvement of patients and family members in informed discussion and review,” said Dr. Howard, who was not involved in the study.

The study was funded by the National Institute for Health and Care Research. Dr. Mok reported no relevant conflicts. Other authors’ disclosures are included in the original article. Dr. Hussain, Dr. Howard, Dr. Kheirbek, and Dr. LeFon reported no relevant conflicts.

A version of this article appeared on Medscape.com.

FROM BMJ

The lifetime risk of atrial fibrillation (AF) increased from 2000 to 2022 from one in four to one in three, a Danish population-based study of temporal trends found.

Heart failure was the most frequent complication linked to this arrhythmia, with a lifetime risk of two in five, twice that of stroke, according to investigators led by Nicklas Vinter, MD, PhD, a postdoctoral researcher at the Danish Center for Health Service Research in the Department of Clinical Medicine at Aalborg University, Denmark.

Published in BMJ, the study found the lifetime risks of post-AF stroke, ischemic stroke, and myocardial infarction improved only modestly over time and remained high, with virtually no improvement in the lifetime risk of heart failure.

Vinter_Nicklas_Denmark_web.jpg

The Study

The cohort consisted of 3.5 million individuals (51.7% women) who did not have AF as of age 45 or older. These individuals were followed until incident AF, migration, death, or end of follow-up, whichever came first.

All 362,721 individuals with incident AF (53.6% men) but no prevalent complication were further followed over two time periods (2000-2010 and 2011-2020) until incident heart failure, stroke, or myocardial infarction.

Among the findings:

• Lifetime AF risk increased from 24.2% in 2000-2010 to 30.9% in 2011-2022, for a difference of 6.7% (95% confidence interval [CI], 6.5%-6.8%).
• Lifetime AF risk rose across all subgroups over time, with a larger increase in men and individuals with heart failure, myocardial infarction, stroke, diabetes, and chronic kidney disease.
• Lifetime risk of heart failure was 42.9% in 2000-2010 and 42.1% in 2011-2022, for a difference of −0.8% (95% CI, −3.8% to 2.2%).
• The lifetime risks of post-AF stroke and of myocardial infarction decreased slightly between the two periods, from 22.4% to 19.9% for stroke (difference −2.5%, 95% CI, −4.2% to −0.7%) and from 13.7% to 9.8% for myocardial infarction (−3.9%, 95% CI, −5.3% to −2.4%). No differential decrease between men and women emerged.

“Our novel quantification of the long-term downstream consequences of atrial fibrillation highlights the critical need for treatments to further decrease stroke risk as well as for heart failure prevention strategies among patients with atrial fibrillation,” the Danish researchers wrote.

Offering an outsider’s perspective, John P. Higgins, MD, MBA, MPhil, a sports cardiologist at McGovern Medical School at The University of Texas Health Science Center at Houston, said, “Think of atrial fibrillation as a barometer of underlying stress on the heart. When blood pressure is high, or a patient has underlying asymptomatic coronary artery disease or heart failure, they are more likely to have episodes of atrial fibrillation.”

Higgins_John_P_TX_web.jpg

Wu_Jianhua_UK_web.JPG

FROM BMJ

The lifetime risk of atrial fibrillation (AF) increased from 2000 to 2022 from one in four to one in three, a Danish population-based study of temporal trends found.

Heart failure was the most frequent complication linked to this arrhythmia, with a lifetime risk of two in five, twice that of stroke, according to investigators led by Nicklas Vinter, MD, PhD, a postdoctoral researcher at the Danish Center for Health Service Research in the Department of Clinical Medicine at Aalborg University, Denmark.

Published in BMJ, the study found the lifetime risks of post-AF stroke, ischemic stroke, and myocardial infarction improved only modestly over time and remained high, with virtually no improvement in the lifetime risk of heart failure.

Vinter_Nicklas_Denmark_web.jpg

The Study

The cohort consisted of 3.5 million individuals (51.7% women) who did not have AF as of age 45 or older. These individuals were followed until incident AF, migration, death, or end of follow-up, whichever came first.

All 362,721 individuals with incident AF (53.6% men) but no prevalent complication were further followed over two time periods (2000-2010 and 2011-2020) until incident heart failure, stroke, or myocardial infarction.

Among the findings:

• Lifetime AF risk increased from 24.2% in 2000-2010 to 30.9% in 2011-2022, for a difference of 6.7% (95% confidence interval [CI], 6.5%-6.8%).
• Lifetime AF risk rose across all subgroups over time, with a larger increase in men and individuals with heart failure, myocardial infarction, stroke, diabetes, and chronic kidney disease.
• Lifetime risk of heart failure was 42.9% in 2000-2010 and 42.1% in 2011-2022, for a difference of −0.8% (95% CI, −3.8% to 2.2%).
• The lifetime risks of post-AF stroke and of myocardial infarction decreased slightly between the two periods, from 22.4% to 19.9% for stroke (difference −2.5%, 95% CI, −4.2% to −0.7%) and from 13.7% to 9.8% for myocardial infarction (−3.9%, 95% CI, −5.3% to −2.4%). No differential decrease between men and women emerged.

“Our novel quantification of the long-term downstream consequences of atrial fibrillation highlights the critical need for treatments to further decrease stroke risk as well as for heart failure prevention strategies among patients with atrial fibrillation,” the Danish researchers wrote.

Offering an outsider’s perspective, John P. Higgins, MD, MBA, MPhil, a sports cardiologist at McGovern Medical School at The University of Texas Health Science Center at Houston, said, “Think of atrial fibrillation as a barometer of underlying stress on the heart. When blood pressure is high, or a patient has underlying asymptomatic coronary artery disease or heart failure, they are more likely to have episodes of atrial fibrillation.”

Higgins_John_P_TX_web.jpg

Wu_Jianhua_UK_web.JPG

FROM BMJ

The lifetime risk of atrial fibrillation (AF) increased from 2000 to 2022 from one in four to one in three, a Danish population-based study of temporal trends found.

Heart failure was the most frequent complication linked to this arrhythmia, with a lifetime risk of two in five, twice that of stroke, according to investigators led by Nicklas Vinter, MD, PhD, a postdoctoral researcher at the Danish Center for Health Service Research in the Department of Clinical Medicine at Aalborg University, Denmark.

Published in BMJ, the study found the lifetime risks of post-AF stroke, ischemic stroke, and myocardial infarction improved only modestly over time and remained high, with virtually no improvement in the lifetime risk of heart failure.

Vinter_Nicklas_Denmark_web.jpg

The Study

The cohort consisted of 3.5 million individuals (51.7% women) who did not have AF as of age 45 or older. These individuals were followed until incident AF, migration, death, or end of follow-up, whichever came first.

All 362,721 individuals with incident AF (53.6% men) but no prevalent complication were further followed over two time periods (2000-2010 and 2011-2020) until incident heart failure, stroke, or myocardial infarction.

Among the findings:

• Lifetime AF risk increased from 24.2% in 2000-2010 to 30.9% in 2011-2022, for a difference of 6.7% (95% confidence interval [CI], 6.5%-6.8%).
• Lifetime AF risk rose across all subgroups over time, with a larger increase in men and individuals with heart failure, myocardial infarction, stroke, diabetes, and chronic kidney disease.
• Lifetime risk of heart failure was 42.9% in 2000-2010 and 42.1% in 2011-2022, for a difference of −0.8% (95% CI, −3.8% to 2.2%).
• The lifetime risks of post-AF stroke and of myocardial infarction decreased slightly between the two periods, from 22.4% to 19.9% for stroke (difference −2.5%, 95% CI, −4.2% to −0.7%) and from 13.7% to 9.8% for myocardial infarction (−3.9%, 95% CI, −5.3% to −2.4%). No differential decrease between men and women emerged.

“Our novel quantification of the long-term downstream consequences of atrial fibrillation highlights the critical need for treatments to further decrease stroke risk as well as for heart failure prevention strategies among patients with atrial fibrillation,” the Danish researchers wrote.

Offering an outsider’s perspective, John P. Higgins, MD, MBA, MPhil, a sports cardiologist at McGovern Medical School at The University of Texas Health Science Center at Houston, said, “Think of atrial fibrillation as a barometer of underlying stress on the heart. When blood pressure is high, or a patient has underlying asymptomatic coronary artery disease or heart failure, they are more likely to have episodes of atrial fibrillation.”

Higgins_John_P_TX_web.jpg

Wu_Jianhua_UK_web.JPG

DENVER — Upon entry into the open-label extension (OLE) of the pivotal trial that led to approval of lecanemab for Alzheimer’s disease, placebo patients failed to show any appreciable catch up to the benefit achieved in the experimental arm, according to a first report of 6-month OLE data.

Due to the steady disease progression observed after the switch of placebo to active therapy, the message of these data is that “early initiation of lecanemab is important,” according to Michael Irizarry, MD, the senior vice president of clinical research at Eisai Ltd, which markets lecanemab.

The 6-month OLE data along with data from a tau PET substudy were presented by Dr. Irizarry at the 2024 annual meeting of the American Academy of Neurology.

From the start of the OLE through the 6-month follow-up, the downward trajectory of cognitive function, as measured with the Clinical Dementia Rating – Sum of Boxes (CDR-SB), has been parallel for the lecanemab-start and switch arms. As a result, the degree of separation between active and placebo groups over the course of the OLE has remained unchanged from the end of the randomized trial.

This does not rule out any benefit in the switch arm, according to Dr. Irizarry. Although there was no discernible change in the trajectory of decline among placebo patients after they were switched to lecanemab, Dr. Irizarry postulated that this might overlook the greater likely decline over time with no treatment.

“There was no placebo group in the OLE to compare with those on active treatment,” he pointed out. He then juxtaposed data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Over the same 6-month timeframe, these data show a hypothetical separation of the curves if no treatment had been received.

The 6-month OLE data provide a preliminary look at outcomes in a planned 4-year follow-up. At the end of the randomized CLARITY trial, the mean decline from the baseline CDR-SB score of 3.2, was 1.21 in the lecanemab group, translating into a 38% decline, and 1.66 in the placebo group, translating into about a 50% decline. Over the 6 months of OLE, there has been a further mean CDR-SB reduction of approximately 0.6 in both arms, suggesting a further 18% decline from baseline.
 

Additional Data

In the pivotal CLARITY trial, which was published a few months prior to regulatory approval early last year, 1785 patients were randomized to 10 mg/kg lecanemab or placebo infused every 2 weeks. At the end of 18 months, the superiority of lecanemab for the primary endpoint of adverse change in CDR-SB was highly significant (P < .001) as were the differences in key secondary endpoints, such as Alzheimer’s Disease Composite Score (P < .001).

Of those who participated in CLARITY, 1385 patients entered the OLE. Placebo patients were switched to lecanemab which is being maintained in all patients on the trial schedule of 10 mg/kg administered by intravenous infusion every 2 weeks.

In addition to the overall OLE 6-month data, which has not raised any new safety signals, Dr. Irizarry provided a new look at the PET TAU substudy with a focus on patients who entered the study with a low relative tau burden. Of the three classifications, which also included medium and high tau, as measured with positron-emission tomography (PET), the low tau group represented 41.2% of the 342 tau PET substudy participants. With only 2.9% entering the study with a high tau burden, almost all the others fell in the medium stratification.

Due to the potential for a lower therapeutic response, “patients with low Tau are often excluded from trials,” Dr. Irizarry said. But the sizable proportion of low tau patients has permitted an assessment of relative response with lecanemab, which turned out to be substantial.

“Consistent rates of clinical stability or improvements were observed regardless of baseline tau levels with the highest rates of improvements observed for the low tau group after 24 months of follow-up,” Dr. Irizarry reported.

In previously reported results from the tau PET substudy, lecanemab was shown to slow tau spread at least numerically in every section of the brain evaluated, including the frontal, cingulate, parietal, and whole cortical gray matter areas. The reductions reached significance for the medial temporal (P = .0024), meta temporal (P = .012), and temporal (P = .16) portions.

When most recently evaluated in the OLE, the CDR-SB score declined 38% less among those treated with lecanemab than those treated with placebo in the subgroup enrolled in the tau PET substudy.

Relative to those with intermediate or high tau, patients in the low tau had an even greater reduction in cognitive decline than those with higher tau burdens. Although Dr. Irizarry cautioned that greater baseline CDR-SB scores exaggerated the treatment effect in the low tau group, the message is that “a lecanemab treatment effect is seen even when baseline tau levels are low.”

Now, with the recent market withdrawal of aducanumab, another anti-amyloid monoclonal antibody that was previously approved for Alzheimer’s disease, lecanemab is the only therapy currently available for the goal of changing disease progression, not just modifying symptoms.
 

Looking Long Term

Both sets of data provide important messages for clinicians, according to Marcelo Matiello, MD, a physician investigator at Mass General Hospital and associate professor of neurology at Harvard Medical School, Boston.

“Clinicians are really looking for more data because this remains a relatively new drug,” he said. Both sets of findings presented by Dr. Irizarry “look good but the follow-up is still short, so I think everyone is still looking closely at long-term safety and efficacy.”

The need for continuous indefinite therapy is one concern that Dr. Matiello expressed. As moderator of the session in which these data were presented, Dr. Matiello specifically asked Dr. Irizarry if there are plans to explore whether periods without treatment might be a means to reduce the cost and burden of frequent infusions while preserving cognitive gains.

In response, Dr. Irizarry said that earlier studies showed rapid progression when lecanemab was stopped. On this basis, he thinks therapy must be maintained, but he did say that there are plans to look at less frequent dosing, such as once per month. He also said that a subcutaneous formulation in development might also reduce the burden of prolonged treatment.

Dr. Irizarry is an employee of Eisai Ltd., which manufacturers lecanemab. Dr. Matiello reports no potential conflicts of interest.

DENVER — Upon entry into the open-label extension (OLE) of the pivotal trial that led to approval of lecanemab for Alzheimer’s disease, placebo patients failed to show any appreciable catch up to the benefit achieved in the experimental arm, according to a first report of 6-month OLE data.

Due to the steady disease progression observed after the switch of placebo to active therapy, the message of these data is that “early initiation of lecanemab is important,” according to Michael Irizarry, MD, the senior vice president of clinical research at Eisai Ltd, which markets lecanemab.

The 6-month OLE data along with data from a tau PET substudy were presented by Dr. Irizarry at the 2024 annual meeting of the American Academy of Neurology.

From the start of the OLE through the 6-month follow-up, the downward trajectory of cognitive function, as measured with the Clinical Dementia Rating – Sum of Boxes (CDR-SB), has been parallel for the lecanemab-start and switch arms. As a result, the degree of separation between active and placebo groups over the course of the OLE has remained unchanged from the end of the randomized trial.

This does not rule out any benefit in the switch arm, according to Dr. Irizarry. Although there was no discernible change in the trajectory of decline among placebo patients after they were switched to lecanemab, Dr. Irizarry postulated that this might overlook the greater likely decline over time with no treatment.

“There was no placebo group in the OLE to compare with those on active treatment,” he pointed out. He then juxtaposed data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Over the same 6-month timeframe, these data show a hypothetical separation of the curves if no treatment had been received.

The 6-month OLE data provide a preliminary look at outcomes in a planned 4-year follow-up. At the end of the randomized CLARITY trial, the mean decline from the baseline CDR-SB score of 3.2, was 1.21 in the lecanemab group, translating into a 38% decline, and 1.66 in the placebo group, translating into about a 50% decline. Over the 6 months of OLE, there has been a further mean CDR-SB reduction of approximately 0.6 in both arms, suggesting a further 18% decline from baseline.
 

Additional Data

In the pivotal CLARITY trial, which was published a few months prior to regulatory approval early last year, 1785 patients were randomized to 10 mg/kg lecanemab or placebo infused every 2 weeks. At the end of 18 months, the superiority of lecanemab for the primary endpoint of adverse change in CDR-SB was highly significant (P < .001) as were the differences in key secondary endpoints, such as Alzheimer’s Disease Composite Score (P < .001).

Of those who participated in CLARITY, 1385 patients entered the OLE. Placebo patients were switched to lecanemab which is being maintained in all patients on the trial schedule of 10 mg/kg administered by intravenous infusion every 2 weeks.

In addition to the overall OLE 6-month data, which has not raised any new safety signals, Dr. Irizarry provided a new look at the PET TAU substudy with a focus on patients who entered the study with a low relative tau burden. Of the three classifications, which also included medium and high tau, as measured with positron-emission tomography (PET), the low tau group represented 41.2% of the 342 tau PET substudy participants. With only 2.9% entering the study with a high tau burden, almost all the others fell in the medium stratification.

Due to the potential for a lower therapeutic response, “patients with low Tau are often excluded from trials,” Dr. Irizarry said. But the sizable proportion of low tau patients has permitted an assessment of relative response with lecanemab, which turned out to be substantial.

“Consistent rates of clinical stability or improvements were observed regardless of baseline tau levels with the highest rates of improvements observed for the low tau group after 24 months of follow-up,” Dr. Irizarry reported.

In previously reported results from the tau PET substudy, lecanemab was shown to slow tau spread at least numerically in every section of the brain evaluated, including the frontal, cingulate, parietal, and whole cortical gray matter areas. The reductions reached significance for the medial temporal (P = .0024), meta temporal (P = .012), and temporal (P = .16) portions.

When most recently evaluated in the OLE, the CDR-SB score declined 38% less among those treated with lecanemab than those treated with placebo in the subgroup enrolled in the tau PET substudy.

Relative to those with intermediate or high tau, patients in the low tau had an even greater reduction in cognitive decline than those with higher tau burdens. Although Dr. Irizarry cautioned that greater baseline CDR-SB scores exaggerated the treatment effect in the low tau group, the message is that “a lecanemab treatment effect is seen even when baseline tau levels are low.”

Now, with the recent market withdrawal of aducanumab, another anti-amyloid monoclonal antibody that was previously approved for Alzheimer’s disease, lecanemab is the only therapy currently available for the goal of changing disease progression, not just modifying symptoms.
 

Looking Long Term

Both sets of data provide important messages for clinicians, according to Marcelo Matiello, MD, a physician investigator at Mass General Hospital and associate professor of neurology at Harvard Medical School, Boston.

“Clinicians are really looking for more data because this remains a relatively new drug,” he said. Both sets of findings presented by Dr. Irizarry “look good but the follow-up is still short, so I think everyone is still looking closely at long-term safety and efficacy.”

The need for continuous indefinite therapy is one concern that Dr. Matiello expressed. As moderator of the session in which these data were presented, Dr. Matiello specifically asked Dr. Irizarry if there are plans to explore whether periods without treatment might be a means to reduce the cost and burden of frequent infusions while preserving cognitive gains.

In response, Dr. Irizarry said that earlier studies showed rapid progression when lecanemab was stopped. On this basis, he thinks therapy must be maintained, but he did say that there are plans to look at less frequent dosing, such as once per month. He also said that a subcutaneous formulation in development might also reduce the burden of prolonged treatment.

Dr. Irizarry is an employee of Eisai Ltd., which manufacturers lecanemab. Dr. Matiello reports no potential conflicts of interest.

DENVER — Upon entry into the open-label extension (OLE) of the pivotal trial that led to approval of lecanemab for Alzheimer’s disease, placebo patients failed to show any appreciable catch up to the benefit achieved in the experimental arm, according to a first report of 6-month OLE data.

Due to the steady disease progression observed after the switch of placebo to active therapy, the message of these data is that “early initiation of lecanemab is important,” according to Michael Irizarry, MD, the senior vice president of clinical research at Eisai Ltd, which markets lecanemab.

The 6-month OLE data along with data from a tau PET substudy were presented by Dr. Irizarry at the 2024 annual meeting of the American Academy of Neurology.

From the start of the OLE through the 6-month follow-up, the downward trajectory of cognitive function, as measured with the Clinical Dementia Rating – Sum of Boxes (CDR-SB), has been parallel for the lecanemab-start and switch arms. As a result, the degree of separation between active and placebo groups over the course of the OLE has remained unchanged from the end of the randomized trial.

This does not rule out any benefit in the switch arm, according to Dr. Irizarry. Although there was no discernible change in the trajectory of decline among placebo patients after they were switched to lecanemab, Dr. Irizarry postulated that this might overlook the greater likely decline over time with no treatment.

“There was no placebo group in the OLE to compare with those on active treatment,” he pointed out. He then juxtaposed data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Over the same 6-month timeframe, these data show a hypothetical separation of the curves if no treatment had been received.

The 6-month OLE data provide a preliminary look at outcomes in a planned 4-year follow-up. At the end of the randomized CLARITY trial, the mean decline from the baseline CDR-SB score of 3.2, was 1.21 in the lecanemab group, translating into a 38% decline, and 1.66 in the placebo group, translating into about a 50% decline. Over the 6 months of OLE, there has been a further mean CDR-SB reduction of approximately 0.6 in both arms, suggesting a further 18% decline from baseline.
 

Additional Data

In the pivotal CLARITY trial, which was published a few months prior to regulatory approval early last year, 1785 patients were randomized to 10 mg/kg lecanemab or placebo infused every 2 weeks. At the end of 18 months, the superiority of lecanemab for the primary endpoint of adverse change in CDR-SB was highly significant (P < .001) as were the differences in key secondary endpoints, such as Alzheimer’s Disease Composite Score (P < .001).

Of those who participated in CLARITY, 1385 patients entered the OLE. Placebo patients were switched to lecanemab which is being maintained in all patients on the trial schedule of 10 mg/kg administered by intravenous infusion every 2 weeks.

In addition to the overall OLE 6-month data, which has not raised any new safety signals, Dr. Irizarry provided a new look at the PET TAU substudy with a focus on patients who entered the study with a low relative tau burden. Of the three classifications, which also included medium and high tau, as measured with positron-emission tomography (PET), the low tau group represented 41.2% of the 342 tau PET substudy participants. With only 2.9% entering the study with a high tau burden, almost all the others fell in the medium stratification.

Due to the potential for a lower therapeutic response, “patients with low Tau are often excluded from trials,” Dr. Irizarry said. But the sizable proportion of low tau patients has permitted an assessment of relative response with lecanemab, which turned out to be substantial.

“Consistent rates of clinical stability or improvements were observed regardless of baseline tau levels with the highest rates of improvements observed for the low tau group after 24 months of follow-up,” Dr. Irizarry reported.

In previously reported results from the tau PET substudy, lecanemab was shown to slow tau spread at least numerically in every section of the brain evaluated, including the frontal, cingulate, parietal, and whole cortical gray matter areas. The reductions reached significance for the medial temporal (P = .0024), meta temporal (P = .012), and temporal (P = .16) portions.

When most recently evaluated in the OLE, the CDR-SB score declined 38% less among those treated with lecanemab than those treated with placebo in the subgroup enrolled in the tau PET substudy.

Relative to those with intermediate or high tau, patients in the low tau had an even greater reduction in cognitive decline than those with higher tau burdens. Although Dr. Irizarry cautioned that greater baseline CDR-SB scores exaggerated the treatment effect in the low tau group, the message is that “a lecanemab treatment effect is seen even when baseline tau levels are low.”

Now, with the recent market withdrawal of aducanumab, another anti-amyloid monoclonal antibody that was previously approved for Alzheimer’s disease, lecanemab is the only therapy currently available for the goal of changing disease progression, not just modifying symptoms.
 

Looking Long Term

Both sets of data provide important messages for clinicians, according to Marcelo Matiello, MD, a physician investigator at Mass General Hospital and associate professor of neurology at Harvard Medical School, Boston.

“Clinicians are really looking for more data because this remains a relatively new drug,” he said. Both sets of findings presented by Dr. Irizarry “look good but the follow-up is still short, so I think everyone is still looking closely at long-term safety and efficacy.”

The need for continuous indefinite therapy is one concern that Dr. Matiello expressed. As moderator of the session in which these data were presented, Dr. Matiello specifically asked Dr. Irizarry if there are plans to explore whether periods without treatment might be a means to reduce the cost and burden of frequent infusions while preserving cognitive gains.

In response, Dr. Irizarry said that earlier studies showed rapid progression when lecanemab was stopped. On this basis, he thinks therapy must be maintained, but he did say that there are plans to look at less frequent dosing, such as once per month. He also said that a subcutaneous formulation in development might also reduce the burden of prolonged treatment.

Dr. Irizarry is an employee of Eisai Ltd., which manufacturers lecanemab. Dr. Matiello reports no potential conflicts of interest.

Large-scale salt substitution holds promise for reducing mortality with no elevated risk of serious harms, especially for older people at increased cardiovascular disease (CVD) risk, a systematic review and meta-analysis by Australian researchers suggested.

The study, published in Annals of Internal Medicine, adds more evidence that broad adoption of potassium-rich salt substitutes for food preparation could have a significant effect on population health.

Although the supporting evidence was of low certainty, the analysis of 16 international randomized controlled trials of various interventions with 35,321 participants found salt substitution to be associated with an absolute reduction of 5 in 1000 in all-cause mortality (confidence interval, –3 to –7) and 3 in 1000 in CVD mortality (CI, –1 to –5).

Led by Hannah Greenwood, BPsychSc, a cardiovascular researcher at the Institute for Evidence-Based Healthcare at Bond University in Gold Coast, Queensland, the investigators also found very low certainty evidence of an absolute reduction of 8 in 1000 in major adverse cardiovascular events (CI, 0 to –15), with a 1 in 1000 decrease in more serious adverse events (CI, 4 to –2) in the same population.

Seven of the 16 studies were conducted in China and Taiwan and seven were conducted in populations of older age (mean age 62 years) and/or at higher cardiovascular risk.

With most of the data deriving from populations of older age at higher-than-average CV risk and/or eating an Asian diet, the findings’ generalizability to populations following a Western diet and/or at average CVD risk is limited, the researchers acknowledged.

“We are less certain about the effects in Western, younger, and healthy population groups,” corresponding author Loai Albarqouni, MD, MSc, PhD, assistant professor at the Institute for Evidence-Based Healthcare, said in an interview. “While we saw small, clinically meaningful reductions in cardiovascular deaths and events, effectiveness should be better established before salt substitutes are recommended more broadly, though they are promising.”

In addition, he said, since the longest follow-up of substitute use was 10 years, “we can’t speak to benefits or harms beyond this time frame.”

Albarqouni_Loai_AUSTRALIA_web.jpg

Laing_Emma_GA_web.jpg

Miranda_J_Jaime_AUSTRALIA_web.jpg

Large-scale salt substitution holds promise for reducing mortality with no elevated risk of serious harms, especially for older people at increased cardiovascular disease (CVD) risk, a systematic review and meta-analysis by Australian researchers suggested.

The study, published in Annals of Internal Medicine, adds more evidence that broad adoption of potassium-rich salt substitutes for food preparation could have a significant effect on population health.

Although the supporting evidence was of low certainty, the analysis of 16 international randomized controlled trials of various interventions with 35,321 participants found salt substitution to be associated with an absolute reduction of 5 in 1000 in all-cause mortality (confidence interval, –3 to –7) and 3 in 1000 in CVD mortality (CI, –1 to –5).

Led by Hannah Greenwood, BPsychSc, a cardiovascular researcher at the Institute for Evidence-Based Healthcare at Bond University in Gold Coast, Queensland, the investigators also found very low certainty evidence of an absolute reduction of 8 in 1000 in major adverse cardiovascular events (CI, 0 to –15), with a 1 in 1000 decrease in more serious adverse events (CI, 4 to –2) in the same population.

Seven of the 16 studies were conducted in China and Taiwan and seven were conducted in populations of older age (mean age 62 years) and/or at higher cardiovascular risk.

With most of the data deriving from populations of older age at higher-than-average CV risk and/or eating an Asian diet, the findings’ generalizability to populations following a Western diet and/or at average CVD risk is limited, the researchers acknowledged.

“We are less certain about the effects in Western, younger, and healthy population groups,” corresponding author Loai Albarqouni, MD, MSc, PhD, assistant professor at the Institute for Evidence-Based Healthcare, said in an interview. “While we saw small, clinically meaningful reductions in cardiovascular deaths and events, effectiveness should be better established before salt substitutes are recommended more broadly, though they are promising.”

In addition, he said, since the longest follow-up of substitute use was 10 years, “we can’t speak to benefits or harms beyond this time frame.”

Albarqouni_Loai_AUSTRALIA_web.jpg

Laing_Emma_GA_web.jpg

Miranda_J_Jaime_AUSTRALIA_web.jpg

Large-scale salt substitution holds promise for reducing mortality with no elevated risk of serious harms, especially for older people at increased cardiovascular disease (CVD) risk, a systematic review and meta-analysis by Australian researchers suggested.

The study, published in Annals of Internal Medicine, adds more evidence that broad adoption of potassium-rich salt substitutes for food preparation could have a significant effect on population health.

Although the supporting evidence was of low certainty, the analysis of 16 international randomized controlled trials of various interventions with 35,321 participants found salt substitution to be associated with an absolute reduction of 5 in 1000 in all-cause mortality (confidence interval, –3 to –7) and 3 in 1000 in CVD mortality (CI, –1 to –5).

Led by Hannah Greenwood, BPsychSc, a cardiovascular researcher at the Institute for Evidence-Based Healthcare at Bond University in Gold Coast, Queensland, the investigators also found very low certainty evidence of an absolute reduction of 8 in 1000 in major adverse cardiovascular events (CI, 0 to –15), with a 1 in 1000 decrease in more serious adverse events (CI, 4 to –2) in the same population.

Seven of the 16 studies were conducted in China and Taiwan and seven were conducted in populations of older age (mean age 62 years) and/or at higher cardiovascular risk.

With most of the data deriving from populations of older age at higher-than-average CV risk and/or eating an Asian diet, the findings’ generalizability to populations following a Western diet and/or at average CVD risk is limited, the researchers acknowledged.

“We are less certain about the effects in Western, younger, and healthy population groups,” corresponding author Loai Albarqouni, MD, MSc, PhD, assistant professor at the Institute for Evidence-Based Healthcare, said in an interview. “While we saw small, clinically meaningful reductions in cardiovascular deaths and events, effectiveness should be better established before salt substitutes are recommended more broadly, though they are promising.”

In addition, he said, since the longest follow-up of substitute use was 10 years, “we can’t speak to benefits or harms beyond this time frame.”

Albarqouni_Loai_AUSTRALIA_web.jpg

Laing_Emma_GA_web.jpg

Miranda_J_Jaime_AUSTRALIA_web.jpg

Hormone Therapy (HT) is a good option for most women over age 65, despite entrenched fears about HT safety, according to findings from a new study published in Menopause.

The study, led by Seo H. Baik, PhD, of Lister Hill National Center for Biomedical Communications, National Library of Medicine, in Bethesda, Maryland, and colleagues is based on the health records of 10 million senior women on Medicare from 2007 to 2020. It concludes there are important health benefits with HT beyond age 65 and the effects of using HT after age 65 vary by type of therapy, route of administration, and dose.
 

Controversial Since Women’s Health Initiative

Use of HT after age 65 has been controversial in light of the findings of the Women’s Health Initiative (WHI) study in 2002. Since that study, many women have decided against HT, especially after age 65, because of fears of increased risks for cancers and heart disease.

Baik et al. concluded that, compared with never using or stopping use of HT before the age of 65 years, the use of estrogen alone beyond age 65 years was associated with the following significant risk reductions: mortality (19%); breast cancer (16%); lung cancer (13%); colorectal cancer (12%); congestive heart failure (5%); venous thromboembolism (5%); atrial fibrillation (4%); acute myocardial infarction (11%); and dementia (2%).

The authors further found that estrogen plus progestin was associated with significant risk reductions in endometrial cancer (45%); ovarian cancer (21%); ischemic heart disease (5%); congestive heart failure (5%); and venous thromboembolism (5%).

Estrogen plus progesterone, however, was linked with risk reduction only in congestive heart failure (4%).

Reassuring Results

“These results should provide additional reassurance to women about hormone therapy,” said Lisa C, Larkin, MD, president of The Menopause Society. “This data is largely consistent with the WHI data as we understand it today — that for the majority of women with symptoms transitioning through menopause, hormone therapy is the most effective treatment and has benefits that outweigh risks.”

There may be some exceptions, she noted, particularly in older women with high risk for cardiovascular disease and stroke. Among those women, she explained, the risks of HT may outweigh the benefits and it may be appropriate to stop hormone therapy.

“In these older women with specific risk factors, the discussion of continuing or stopping HT is nuanced and complex and must involve shared decision-making,” she said.

Elevated Breast Cancer Risk Can be Mitigated

With a therapy combining estrogen and progestogen, both estrogen plus progestin and estrogen plus progesterone were associated with a 10%-19% increased risk of breast cancer, but the authors say that risk can be mitigated using low doses of transdermal or vaginal estrogen plus progestin.

“In general, risk reductions appear to be greater with low rather than medium or high doses, vaginal or transdermal rather than oral preparations, and with E2 (estradiol) rather than conjugated estrogen,” the authors write.

The authors report that over 14 years of follow-up (from 2007 to 2020), the proportion of senior women taking any HT-containing estrogen dropped by half, from 11.4% to 5.5%. E2 has largely replaced conjugated estrogen (CEE); and vaginal administration largely replaced oral.

Controversy Remains

Even with these results, hormone use will remain controversial, Dr. Larkin said, without enormous efforts to educate. Menopausal HT therapy in young 50-year-old women having symptoms is still controversial — despite the large body of evidence supporting safety and benefit in the majority of women, she said.

“For the last 25 years we have completely neglected education of clinicians about menopause and the data on hormone therapy,” she said. “As a result, most of the clinicians practicing do not understand the data and remain very negative about hormones even in younger women. The decades of lack of education of clinicians about menopause is one of the major reasons far too many young, healthy, 50-year-old women with symptoms are not getting the care they need [hormone therapy] at menopause.” Instead, she says, women are told to take supplements because some providers think hormone therapy is too dangerous.

Lauren Streicher, MD, a clinical professor of obstetrics and gynecology at Northwestern University’s Feinberg School of Medicine, and founding director of the Northwestern Medical Center for Sexual Medicine and Menopause, both in Chicago, says, “In the WHI, 70% of the women were over the age of 65 when they initiated therapy, which partially accounts for the negative outcomes. In addition, in WHI, everyone was taking oral [HT]. This (current) data is very reassuring — and validating — for women who would like to continue taking HT.”

Dr. Streicher says women who would like to start HT after 65 should be counseled on individual risks and after cardiac health is evaluated. But, she notes, this study did not address that.

‘Best Time to Stop HT is When You Die’

She says in her practice she will counsel women who are on HT and would like to continue after age 65 the way she always has: “If someone is taking HT and has no specific reason to stop, there is no reason to stop at some arbitrary age or time and that if they do, they will lose many of the benefits,” particularly bone, cognitive, cardiovascular, and vulvovaginal benefits, she explained. “The best time to stop HT is when you die,” Dr. Streicher said, “And, given the reduction in mortality in women who take HT, that will be at a much older age than women who don’t take HT.”

So will these new data be convincing?

“It will convince the already convinced — menopause experts who follow the data. It is the rare menopause expert that tells women to stop HT,” Dr. Streicher said.

However, she said, “The overwhelming majority of clinicians in the US currently do not prescribe HT. Sadly, I don’t think this will change much.”

The authors report no relevant financial relationships. Dr. Larkin consults for several women’s health companies including Mayne Pharma, Astellas, Johnson & Johnson, Grail, Pfizer, and Solv Wellness. Dr. Streicher reports no relevant financial relationships.

Hormone Therapy (HT) is a good option for most women over age 65, despite entrenched fears about HT safety, according to findings from a new study published in Menopause.

The study, led by Seo H. Baik, PhD, of Lister Hill National Center for Biomedical Communications, National Library of Medicine, in Bethesda, Maryland, and colleagues is based on the health records of 10 million senior women on Medicare from 2007 to 2020. It concludes there are important health benefits with HT beyond age 65 and the effects of using HT after age 65 vary by type of therapy, route of administration, and dose.
 

Controversial Since Women’s Health Initiative

Use of HT after age 65 has been controversial in light of the findings of the Women’s Health Initiative (WHI) study in 2002. Since that study, many women have decided against HT, especially after age 65, because of fears of increased risks for cancers and heart disease.

Baik et al. concluded that, compared with never using or stopping use of HT before the age of 65 years, the use of estrogen alone beyond age 65 years was associated with the following significant risk reductions: mortality (19%); breast cancer (16%); lung cancer (13%); colorectal cancer (12%); congestive heart failure (5%); venous thromboembolism (5%); atrial fibrillation (4%); acute myocardial infarction (11%); and dementia (2%).

The authors further found that estrogen plus progestin was associated with significant risk reductions in endometrial cancer (45%); ovarian cancer (21%); ischemic heart disease (5%); congestive heart failure (5%); and venous thromboembolism (5%).

Estrogen plus progesterone, however, was linked with risk reduction only in congestive heart failure (4%).

Reassuring Results

“These results should provide additional reassurance to women about hormone therapy,” said Lisa C, Larkin, MD, president of The Menopause Society. “This data is largely consistent with the WHI data as we understand it today — that for the majority of women with symptoms transitioning through menopause, hormone therapy is the most effective treatment and has benefits that outweigh risks.”

There may be some exceptions, she noted, particularly in older women with high risk for cardiovascular disease and stroke. Among those women, she explained, the risks of HT may outweigh the benefits and it may be appropriate to stop hormone therapy.

“In these older women with specific risk factors, the discussion of continuing or stopping HT is nuanced and complex and must involve shared decision-making,” she said.

Elevated Breast Cancer Risk Can be Mitigated

With a therapy combining estrogen and progestogen, both estrogen plus progestin and estrogen plus progesterone were associated with a 10%-19% increased risk of breast cancer, but the authors say that risk can be mitigated using low doses of transdermal or vaginal estrogen plus progestin.

“In general, risk reductions appear to be greater with low rather than medium or high doses, vaginal or transdermal rather than oral preparations, and with E2 (estradiol) rather than conjugated estrogen,” the authors write.

The authors report that over 14 years of follow-up (from 2007 to 2020), the proportion of senior women taking any HT-containing estrogen dropped by half, from 11.4% to 5.5%. E2 has largely replaced conjugated estrogen (CEE); and vaginal administration largely replaced oral.

Controversy Remains

Even with these results, hormone use will remain controversial, Dr. Larkin said, without enormous efforts to educate. Menopausal HT therapy in young 50-year-old women having symptoms is still controversial — despite the large body of evidence supporting safety and benefit in the majority of women, she said.

“For the last 25 years we have completely neglected education of clinicians about menopause and the data on hormone therapy,” she said. “As a result, most of the clinicians practicing do not understand the data and remain very negative about hormones even in younger women. The decades of lack of education of clinicians about menopause is one of the major reasons far too many young, healthy, 50-year-old women with symptoms are not getting the care they need [hormone therapy] at menopause.” Instead, she says, women are told to take supplements because some providers think hormone therapy is too dangerous.

Lauren Streicher, MD, a clinical professor of obstetrics and gynecology at Northwestern University’s Feinberg School of Medicine, and founding director of the Northwestern Medical Center for Sexual Medicine and Menopause, both in Chicago, says, “In the WHI, 70% of the women were over the age of 65 when they initiated therapy, which partially accounts for the negative outcomes. In addition, in WHI, everyone was taking oral [HT]. This (current) data is very reassuring — and validating — for women who would like to continue taking HT.”

Dr. Streicher says women who would like to start HT after 65 should be counseled on individual risks and after cardiac health is evaluated. But, she notes, this study did not address that.

‘Best Time to Stop HT is When You Die’

She says in her practice she will counsel women who are on HT and would like to continue after age 65 the way she always has: “If someone is taking HT and has no specific reason to stop, there is no reason to stop at some arbitrary age or time and that if they do, they will lose many of the benefits,” particularly bone, cognitive, cardiovascular, and vulvovaginal benefits, she explained. “The best time to stop HT is when you die,” Dr. Streicher said, “And, given the reduction in mortality in women who take HT, that will be at a much older age than women who don’t take HT.”

So will these new data be convincing?

“It will convince the already convinced — menopause experts who follow the data. It is the rare menopause expert that tells women to stop HT,” Dr. Streicher said.

However, she said, “The overwhelming majority of clinicians in the US currently do not prescribe HT. Sadly, I don’t think this will change much.”

The authors report no relevant financial relationships. Dr. Larkin consults for several women’s health companies including Mayne Pharma, Astellas, Johnson & Johnson, Grail, Pfizer, and Solv Wellness. Dr. Streicher reports no relevant financial relationships.

Hormone Therapy (HT) is a good option for most women over age 65, despite entrenched fears about HT safety, according to findings from a new study published in Menopause.

The study, led by Seo H. Baik, PhD, of Lister Hill National Center for Biomedical Communications, National Library of Medicine, in Bethesda, Maryland, and colleagues is based on the health records of 10 million senior women on Medicare from 2007 to 2020. It concludes there are important health benefits with HT beyond age 65 and the effects of using HT after age 65 vary by type of therapy, route of administration, and dose.
 

Controversial Since Women’s Health Initiative

Use of HT after age 65 has been controversial in light of the findings of the Women’s Health Initiative (WHI) study in 2002. Since that study, many women have decided against HT, especially after age 65, because of fears of increased risks for cancers and heart disease.

Baik et al. concluded that, compared with never using or stopping use of HT before the age of 65 years, the use of estrogen alone beyond age 65 years was associated with the following significant risk reductions: mortality (19%); breast cancer (16%); lung cancer (13%); colorectal cancer (12%); congestive heart failure (5%); venous thromboembolism (5%); atrial fibrillation (4%); acute myocardial infarction (11%); and dementia (2%).

The authors further found that estrogen plus progestin was associated with significant risk reductions in endometrial cancer (45%); ovarian cancer (21%); ischemic heart disease (5%); congestive heart failure (5%); and venous thromboembolism (5%).

Estrogen plus progesterone, however, was linked with risk reduction only in congestive heart failure (4%).

Reassuring Results

“These results should provide additional reassurance to women about hormone therapy,” said Lisa C, Larkin, MD, president of The Menopause Society. “This data is largely consistent with the WHI data as we understand it today — that for the majority of women with symptoms transitioning through menopause, hormone therapy is the most effective treatment and has benefits that outweigh risks.”

There may be some exceptions, she noted, particularly in older women with high risk for cardiovascular disease and stroke. Among those women, she explained, the risks of HT may outweigh the benefits and it may be appropriate to stop hormone therapy.

“In these older women with specific risk factors, the discussion of continuing or stopping HT is nuanced and complex and must involve shared decision-making,” she said.

Elevated Breast Cancer Risk Can be Mitigated

With a therapy combining estrogen and progestogen, both estrogen plus progestin and estrogen plus progesterone were associated with a 10%-19% increased risk of breast cancer, but the authors say that risk can be mitigated using low doses of transdermal or vaginal estrogen plus progestin.

“In general, risk reductions appear to be greater with low rather than medium or high doses, vaginal or transdermal rather than oral preparations, and with E2 (estradiol) rather than conjugated estrogen,” the authors write.

The authors report that over 14 years of follow-up (from 2007 to 2020), the proportion of senior women taking any HT-containing estrogen dropped by half, from 11.4% to 5.5%. E2 has largely replaced conjugated estrogen (CEE); and vaginal administration largely replaced oral.

Controversy Remains

Even with these results, hormone use will remain controversial, Dr. Larkin said, without enormous efforts to educate. Menopausal HT therapy in young 50-year-old women having symptoms is still controversial — despite the large body of evidence supporting safety and benefit in the majority of women, she said.

“For the last 25 years we have completely neglected education of clinicians about menopause and the data on hormone therapy,” she said. “As a result, most of the clinicians practicing do not understand the data and remain very negative about hormones even in younger women. The decades of lack of education of clinicians about menopause is one of the major reasons far too many young, healthy, 50-year-old women with symptoms are not getting the care they need [hormone therapy] at menopause.” Instead, she says, women are told to take supplements because some providers think hormone therapy is too dangerous.

Lauren Streicher, MD, a clinical professor of obstetrics and gynecology at Northwestern University’s Feinberg School of Medicine, and founding director of the Northwestern Medical Center for Sexual Medicine and Menopause, both in Chicago, says, “In the WHI, 70% of the women were over the age of 65 when they initiated therapy, which partially accounts for the negative outcomes. In addition, in WHI, everyone was taking oral [HT]. This (current) data is very reassuring — and validating — for women who would like to continue taking HT.”

Dr. Streicher says women who would like to start HT after 65 should be counseled on individual risks and after cardiac health is evaluated. But, she notes, this study did not address that.

‘Best Time to Stop HT is When You Die’

She says in her practice she will counsel women who are on HT and would like to continue after age 65 the way she always has: “If someone is taking HT and has no specific reason to stop, there is no reason to stop at some arbitrary age or time and that if they do, they will lose many of the benefits,” particularly bone, cognitive, cardiovascular, and vulvovaginal benefits, she explained. “The best time to stop HT is when you die,” Dr. Streicher said, “And, given the reduction in mortality in women who take HT, that will be at a much older age than women who don’t take HT.”

So will these new data be convincing?

“It will convince the already convinced — menopause experts who follow the data. It is the rare menopause expert that tells women to stop HT,” Dr. Streicher said.

However, she said, “The overwhelming majority of clinicians in the US currently do not prescribe HT. Sadly, I don’t think this will change much.”

The authors report no relevant financial relationships. Dr. Larkin consults for several women’s health companies including Mayne Pharma, Astellas, Johnson & Johnson, Grail, Pfizer, and Solv Wellness. Dr. Streicher reports no relevant financial relationships.

Among adults with type 2 diabetes (T2D) older than 65 years, a body mass index (BMI) in the moderate overweight category (26-28) appears to offer better protection from cardiovascular death than does a BMI in the “normal” range, new data suggested.

On the other hand, the study findings also suggest that the “normal” range of 23-25 is optimal for middle-aged adults with T2D.

The findings reflect a previously demonstrated phenomenon called the “obesity paradox,” in which older people with overweight may have better outcomes than leaner people due to factors such as bone loss, frailty, and nutritional deficits, study lead author Shaoyong Xu, of Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, China, told this news organization.

“In this era of population growth and aging, the question arises as to whether obesity or overweight can be beneficial in improving survival rates for older individuals with diabetes. This topic holds significant relevance due to the potential implications it has on weight management strategies for older adults. If overweight does not pose an increased risk of cardiovascular mortality, it may suggest that older individuals are not necessarily required to strive for weight loss to achieve so-called normal values.”

Moreover, Dr. Xu added, “inappropriate weight loss and being underweight could potentially elevate the risk of cardiovascular events, myocardial infarction, cerebral infarction, and all-cause mortality.”

Thus, he said, “while there are general guidelines recommending a BMI below 25, our findings suggest that personalized BMI targets may be more beneficial, particularly for different age groups and individuals with specific health conditions.”

Asked to comment, Ian J. Neeland, MD, director of cardiovascular prevention, University Hospitals Harrington Heart & Vascular Institute, Case Western Reserve University, Cleveland, Ohio, pointed out that older people who are underweight or in lower weight categories may be more likely to smoke or have undiagnosed cancer, or that “their BMI is not so much reflective of fat mass as of low muscle mass, or sarcopenia, and that is definitely a risk factor for adverse outcomes and risks. ... And those who have slightly higher BMIs may be maintaining muscle mass, even though they’re older, and therefore they have less risk.”

However, Dr. Neeland disagreed with the authors’ conclusions regarding “optimal” BMI. “Just because you have different risk categories based on BMI doesn’t mean that’s ‘optimal’ BMI. The way I would interpret this paper is that there’s an association of mildly overweight with better outcomes in adults who are over 65 with type 2 diabetes. We need to try to understand the mechanisms underlying that observation.”

Dr. Neeland advised that for an older person with T2D who has low muscle mass and frailty, “I wouldn’t recommend necessarily targeted weight loss in that person. But I would potentially recommend weight loss in addition to resistance training, muscle building, and endurance training, and therefore reducing fat mass. The goal would be not so much weight loss but reduction of body fat and maintaining and improving muscle health.”
 

U-Shaped Relationship Found Between Age, BMI, and Cardiovascular Disease (CVD) Risk

The data come from the UK Biobank, a population-based prospective cohort study of adults in the United Kingdom. A total of 22,874 participants with baseline T2D were included in the current study. Baseline surveys were conducted between 2006 and 2010, and follow-up was a median of 12.52 years. During that time, 891 people died of CVD.

Hazard ratios were adjusted for baseline variables including age, sex, smoking history, alcohol consumption, level of physical exercise, and history of CVDs.

Compared with people with BMI a < 25 in the group who were aged 65 years or younger, those with a BMI of 25.0-29.9 had a 13% higher risk for cardiovascular death. However, among those older than 65 years, a BMI between 25.0 and 29.9 was associated with an 18% lower risk.

A U-shaped relationship was found between BMI and the risk for cardiovascular death, with an optimal BMI cutoff of 24.0 in the under-65 group and a 27.0 cutoff in the older group. Ranges of 23.0-25.0 in the under-65 group and 26.0-28 in the older group were associated with the lowest cardiovascular risk.

In contrast, there was a linear relationship between both waist circumference and waist-to-height ratio and the risk for cardiovascular death, making those more direct measures of adiposity, Dr. Xu told this news organization.

“For clinicians, our data underscores the importance of considering age when assessing BMI targets for cardiovascular health. Personalized treatment plans that account for age-specific BMI cutoffs and other risk factors may enhance patient outcomes and reduce CVD mortality,” Dr. Xu said.

However, he added, “while these findings suggest an optimal BMI range, it is crucial to acknowledge that these cutoff points may vary based on gender, race, and other factors. Our future studies will validate these findings in different populations and attempt to explain the mechanism by which the optimal nodal values exist in people with diabetes at different ages.”

Dr. Neeland cautioned, “I think more work needs to be done in terms of not just identifying the risk differences but understanding why and how to better risk stratify individuals and do personalized medicine. I think that’s important, but you have to have good data to support the strategies you’re going to use. These data are observational, and they’re a good start, but they wouldn’t directly impact practice at this point.”

The data will be presented at the European Congress on Obesity taking place May 12-15 in Venice, Italy.

The authors declared no competing interests. Study funding came from several sources, including the Young Talents Project of Hubei Provincial Health Commission, China, Hubei Provincial Natural Science Foundation of China, the Science and Technology Research Key Project of the Education Department of Hubei Province China, and the Sanuo Diabetes Charity Foundation, China, and the Xiangyang Science and Technology Plan Project, China. Dr. Neeland is a speaker and/or consultant for Boehringer Ingelheim, Novo Nordisk, Bayer, and Eli Lilly and Company.
 

A version of this article appeared on Medscape.com.

Among adults with type 2 diabetes (T2D) older than 65 years, a body mass index (BMI) in the moderate overweight category (26-28) appears to offer better protection from cardiovascular death than does a BMI in the “normal” range, new data suggested.

On the other hand, the study findings also suggest that the “normal” range of 23-25 is optimal for middle-aged adults with T2D.

The findings reflect a previously demonstrated phenomenon called the “obesity paradox,” in which older people with overweight may have better outcomes than leaner people due to factors such as bone loss, frailty, and nutritional deficits, study lead author Shaoyong Xu, of Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, China, told this news organization.

“In this era of population growth and aging, the question arises as to whether obesity or overweight can be beneficial in improving survival rates for older individuals with diabetes. This topic holds significant relevance due to the potential implications it has on weight management strategies for older adults. If overweight does not pose an increased risk of cardiovascular mortality, it may suggest that older individuals are not necessarily required to strive for weight loss to achieve so-called normal values.”

Moreover, Dr. Xu added, “inappropriate weight loss and being underweight could potentially elevate the risk of cardiovascular events, myocardial infarction, cerebral infarction, and all-cause mortality.”

Thus, he said, “while there are general guidelines recommending a BMI below 25, our findings suggest that personalized BMI targets may be more beneficial, particularly for different age groups and individuals with specific health conditions.”

Asked to comment, Ian J. Neeland, MD, director of cardiovascular prevention, University Hospitals Harrington Heart & Vascular Institute, Case Western Reserve University, Cleveland, Ohio, pointed out that older people who are underweight or in lower weight categories may be more likely to smoke or have undiagnosed cancer, or that “their BMI is not so much reflective of fat mass as of low muscle mass, or sarcopenia, and that is definitely a risk factor for adverse outcomes and risks. ... And those who have slightly higher BMIs may be maintaining muscle mass, even though they’re older, and therefore they have less risk.”

However, Dr. Neeland disagreed with the authors’ conclusions regarding “optimal” BMI. “Just because you have different risk categories based on BMI doesn’t mean that’s ‘optimal’ BMI. The way I would interpret this paper is that there’s an association of mildly overweight with better outcomes in adults who are over 65 with type 2 diabetes. We need to try to understand the mechanisms underlying that observation.”

Dr. Neeland advised that for an older person with T2D who has low muscle mass and frailty, “I wouldn’t recommend necessarily targeted weight loss in that person. But I would potentially recommend weight loss in addition to resistance training, muscle building, and endurance training, and therefore reducing fat mass. The goal would be not so much weight loss but reduction of body fat and maintaining and improving muscle health.”
 

U-Shaped Relationship Found Between Age, BMI, and Cardiovascular Disease (CVD) Risk

The data come from the UK Biobank, a population-based prospective cohort study of adults in the United Kingdom. A total of 22,874 participants with baseline T2D were included in the current study. Baseline surveys were conducted between 2006 and 2010, and follow-up was a median of 12.52 years. During that time, 891 people died of CVD.

Hazard ratios were adjusted for baseline variables including age, sex, smoking history, alcohol consumption, level of physical exercise, and history of CVDs.

Compared with people with BMI a < 25 in the group who were aged 65 years or younger, those with a BMI of 25.0-29.9 had a 13% higher risk for cardiovascular death. However, among those older than 65 years, a BMI between 25.0 and 29.9 was associated with an 18% lower risk.

A U-shaped relationship was found between BMI and the risk for cardiovascular death, with an optimal BMI cutoff of 24.0 in the under-65 group and a 27.0 cutoff in the older group. Ranges of 23.0-25.0 in the under-65 group and 26.0-28 in the older group were associated with the lowest cardiovascular risk.

In contrast, there was a linear relationship between both waist circumference and waist-to-height ratio and the risk for cardiovascular death, making those more direct measures of adiposity, Dr. Xu told this news organization.

“For clinicians, our data underscores the importance of considering age when assessing BMI targets for cardiovascular health. Personalized treatment plans that account for age-specific BMI cutoffs and other risk factors may enhance patient outcomes and reduce CVD mortality,” Dr. Xu said.

However, he added, “while these findings suggest an optimal BMI range, it is crucial to acknowledge that these cutoff points may vary based on gender, race, and other factors. Our future studies will validate these findings in different populations and attempt to explain the mechanism by which the optimal nodal values exist in people with diabetes at different ages.”

Dr. Neeland cautioned, “I think more work needs to be done in terms of not just identifying the risk differences but understanding why and how to better risk stratify individuals and do personalized medicine. I think that’s important, but you have to have good data to support the strategies you’re going to use. These data are observational, and they’re a good start, but they wouldn’t directly impact practice at this point.”

The data will be presented at the European Congress on Obesity taking place May 12-15 in Venice, Italy.

The authors declared no competing interests. Study funding came from several sources, including the Young Talents Project of Hubei Provincial Health Commission, China, Hubei Provincial Natural Science Foundation of China, the Science and Technology Research Key Project of the Education Department of Hubei Province China, and the Sanuo Diabetes Charity Foundation, China, and the Xiangyang Science and Technology Plan Project, China. Dr. Neeland is a speaker and/or consultant for Boehringer Ingelheim, Novo Nordisk, Bayer, and Eli Lilly and Company.
 

A version of this article appeared on Medscape.com.

Among adults with type 2 diabetes (T2D) older than 65 years, a body mass index (BMI) in the moderate overweight category (26-28) appears to offer better protection from cardiovascular death than does a BMI in the “normal” range, new data suggested.

On the other hand, the study findings also suggest that the “normal” range of 23-25 is optimal for middle-aged adults with T2D.

The findings reflect a previously demonstrated phenomenon called the “obesity paradox,” in which older people with overweight may have better outcomes than leaner people due to factors such as bone loss, frailty, and nutritional deficits, study lead author Shaoyong Xu, of Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, China, told this news organization.

“In this era of population growth and aging, the question arises as to whether obesity or overweight can be beneficial in improving survival rates for older individuals with diabetes. This topic holds significant relevance due to the potential implications it has on weight management strategies for older adults. If overweight does not pose an increased risk of cardiovascular mortality, it may suggest that older individuals are not necessarily required to strive for weight loss to achieve so-called normal values.”

Moreover, Dr. Xu added, “inappropriate weight loss and being underweight could potentially elevate the risk of cardiovascular events, myocardial infarction, cerebral infarction, and all-cause mortality.”

Thus, he said, “while there are general guidelines recommending a BMI below 25, our findings suggest that personalized BMI targets may be more beneficial, particularly for different age groups and individuals with specific health conditions.”

Asked to comment, Ian J. Neeland, MD, director of cardiovascular prevention, University Hospitals Harrington Heart & Vascular Institute, Case Western Reserve University, Cleveland, Ohio, pointed out that older people who are underweight or in lower weight categories may be more likely to smoke or have undiagnosed cancer, or that “their BMI is not so much reflective of fat mass as of low muscle mass, or sarcopenia, and that is definitely a risk factor for adverse outcomes and risks. ... And those who have slightly higher BMIs may be maintaining muscle mass, even though they’re older, and therefore they have less risk.”

However, Dr. Neeland disagreed with the authors’ conclusions regarding “optimal” BMI. “Just because you have different risk categories based on BMI doesn’t mean that’s ‘optimal’ BMI. The way I would interpret this paper is that there’s an association of mildly overweight with better outcomes in adults who are over 65 with type 2 diabetes. We need to try to understand the mechanisms underlying that observation.”

Dr. Neeland advised that for an older person with T2D who has low muscle mass and frailty, “I wouldn’t recommend necessarily targeted weight loss in that person. But I would potentially recommend weight loss in addition to resistance training, muscle building, and endurance training, and therefore reducing fat mass. The goal would be not so much weight loss but reduction of body fat and maintaining and improving muscle health.”
 

U-Shaped Relationship Found Between Age, BMI, and Cardiovascular Disease (CVD) Risk

The data come from the UK Biobank, a population-based prospective cohort study of adults in the United Kingdom. A total of 22,874 participants with baseline T2D were included in the current study. Baseline surveys were conducted between 2006 and 2010, and follow-up was a median of 12.52 years. During that time, 891 people died of CVD.

Hazard ratios were adjusted for baseline variables including age, sex, smoking history, alcohol consumption, level of physical exercise, and history of CVDs.

Compared with people with BMI a < 25 in the group who were aged 65 years or younger, those with a BMI of 25.0-29.9 had a 13% higher risk for cardiovascular death. However, among those older than 65 years, a BMI between 25.0 and 29.9 was associated with an 18% lower risk.

A U-shaped relationship was found between BMI and the risk for cardiovascular death, with an optimal BMI cutoff of 24.0 in the under-65 group and a 27.0 cutoff in the older group. Ranges of 23.0-25.0 in the under-65 group and 26.0-28 in the older group were associated with the lowest cardiovascular risk.

In contrast, there was a linear relationship between both waist circumference and waist-to-height ratio and the risk for cardiovascular death, making those more direct measures of adiposity, Dr. Xu told this news organization.

“For clinicians, our data underscores the importance of considering age when assessing BMI targets for cardiovascular health. Personalized treatment plans that account for age-specific BMI cutoffs and other risk factors may enhance patient outcomes and reduce CVD mortality,” Dr. Xu said.

However, he added, “while these findings suggest an optimal BMI range, it is crucial to acknowledge that these cutoff points may vary based on gender, race, and other factors. Our future studies will validate these findings in different populations and attempt to explain the mechanism by which the optimal nodal values exist in people with diabetes at different ages.”

Dr. Neeland cautioned, “I think more work needs to be done in terms of not just identifying the risk differences but understanding why and how to better risk stratify individuals and do personalized medicine. I think that’s important, but you have to have good data to support the strategies you’re going to use. These data are observational, and they’re a good start, but they wouldn’t directly impact practice at this point.”

The data will be presented at the European Congress on Obesity taking place May 12-15 in Venice, Italy.

The authors declared no competing interests. Study funding came from several sources, including the Young Talents Project of Hubei Provincial Health Commission, China, Hubei Provincial Natural Science Foundation of China, the Science and Technology Research Key Project of the Education Department of Hubei Province China, and the Sanuo Diabetes Charity Foundation, China, and the Xiangyang Science and Technology Plan Project, China. Dr. Neeland is a speaker and/or consultant for Boehringer Ingelheim, Novo Nordisk, Bayer, and Eli Lilly and Company.
 

A version of this article appeared on Medscape.com.

TOPLINE: 

The geriatric emergency medication safety recommendations (GEMS-Rx) is the first expert consensus-based list identifying high-risk medication classes that should not be prescribed to older patients visiting the emergency department (ED).

METHODOLOGY:

• Around half of the geriatric patients presenting to the ED get discharged with new prescriptions. Some of the newly prescribed drugs may not be appropriate for use in individuals aged ≥ 65 years, thereby increasing the risk for unfavorable adverse events.
• The American Geriatrics Society (AGS)  has already established guidelines to identify potentially inappropriate medications in older adults; however, the criteria are centered on chronic conditions and long-term medication use and are unsuitable for managing ED prescriptions.
• In this study, the GEMS-Rx high-risk prescription list was prepared with a panel of 10 ED physicians with expertise in geriatrics and quality measurement and a pharmacist with expertise in geriatric pharmacotherapy and emergency medicine.
• They reviewed over 30 medication classes from the 2019 AGS Beers Criteria that were deemed inappropriate for use in older patients. Despite their not being included in the Beers list, the use of short- and long-acting opioids was also discussed.
• After three rounds of review and discussion, the panelists ranked each class of medication on a 5-point Likert scale, with a score of 1 indicating the lowest and 5 indicating the greatest need for avoiding a drug in an ED prescription.

TAKEAWAY:

• The first round suggested that first-generation antihistamines, metoclopramide, short-acting opioids, antipsychotics, barbiturates, skeletal muscle relaxants, and benzodiazepines should be avoided, with mean Likert scores ranging from 3.7 to 4.6.
• Although nonbenzodiazepine and benzodiazepine receptor agonist hypnotics (“Z-drugs”) were not initially considered owing to their low frequency of prescription in ED settings, the panelists finally included “Z” drugs and sulfonylureas in the GEMS-Rx list after the second and third rounds.
• The final list of high-risk medications to be avoided in ED settings that were prioritized included benzodiazepines, skeletal muscle relaxants, barbiturates, first-generation antipsychotics, first-generation antihistamines, “Z” drugs, metoclopramide, and sulfonylureas.
• However, seizure disorders, benzodiazepine withdrawal, ethanol withdrawal, severe generalized anxiety disorder, end-of-life care, allergic reactions, and ED visits for prescription refilling were deemed exceptional cases in which these high-risk medications could be prescribed.

IN PRACTICE:

“By combining expert consensus and evidence-based criteria, this list can serve as a resource to guide prescribing decisions and mitigate potential risks associated with medications at this crucial care transition. The incorporation of this emergency medicine-specific geriatric prescription list in a national quality measure has the potential to improve patient safety and enhance the quality of care for the millions of older adults who seek care in EDs each year,” the authors said.

SOURCE:

This study was led by Rachel M. Skains, MD, MSPH, Department of Emergency Medicine, University of Alabama at Birmingham, and published online in Annals of Emergency Medicine.

LIMITATIONS:

The GEMS-Rx list was prepared by physicians and pharmacists and may not have fully captured data regarding individual patient preferences, comorbidities, or other contextual factors. During the meetings, the panelists’ identities were not concealed from one another, which may have affected the conversations owing to response and social desirability bias. Furthermore, this list may not be generalizable to other settings because it was produced and intended for usage in US EDs.

DISCLOSURES:

This work was supported by the American College of Emergency Physicians. Some of the authors, including the lead author, declared being supported by various funding agencies. Few authors also declared serving in leadership positions for several sources.

A version of this article appeared on Medscape.com.

TOPLINE: 

The geriatric emergency medication safety recommendations (GEMS-Rx) is the first expert consensus-based list identifying high-risk medication classes that should not be prescribed to older patients visiting the emergency department (ED).

METHODOLOGY:

• Around half of the geriatric patients presenting to the ED get discharged with new prescriptions. Some of the newly prescribed drugs may not be appropriate for use in individuals aged ≥ 65 years, thereby increasing the risk for unfavorable adverse events.
• The American Geriatrics Society (AGS)  has already established guidelines to identify potentially inappropriate medications in older adults; however, the criteria are centered on chronic conditions and long-term medication use and are unsuitable for managing ED prescriptions.
• In this study, the GEMS-Rx high-risk prescription list was prepared with a panel of 10 ED physicians with expertise in geriatrics and quality measurement and a pharmacist with expertise in geriatric pharmacotherapy and emergency medicine.
• They reviewed over 30 medication classes from the 2019 AGS Beers Criteria that were deemed inappropriate for use in older patients. Despite their not being included in the Beers list, the use of short- and long-acting opioids was also discussed.
• After three rounds of review and discussion, the panelists ranked each class of medication on a 5-point Likert scale, with a score of 1 indicating the lowest and 5 indicating the greatest need for avoiding a drug in an ED prescription.

TAKEAWAY:

• The first round suggested that first-generation antihistamines, metoclopramide, short-acting opioids, antipsychotics, barbiturates, skeletal muscle relaxants, and benzodiazepines should be avoided, with mean Likert scores ranging from 3.7 to 4.6.
• Although nonbenzodiazepine and benzodiazepine receptor agonist hypnotics (“Z-drugs”) were not initially considered owing to their low frequency of prescription in ED settings, the panelists finally included “Z” drugs and sulfonylureas in the GEMS-Rx list after the second and third rounds.
• The final list of high-risk medications to be avoided in ED settings that were prioritized included benzodiazepines, skeletal muscle relaxants, barbiturates, first-generation antipsychotics, first-generation antihistamines, “Z” drugs, metoclopramide, and sulfonylureas.
• However, seizure disorders, benzodiazepine withdrawal, ethanol withdrawal, severe generalized anxiety disorder, end-of-life care, allergic reactions, and ED visits for prescription refilling were deemed exceptional cases in which these high-risk medications could be prescribed.

IN PRACTICE:

“By combining expert consensus and evidence-based criteria, this list can serve as a resource to guide prescribing decisions and mitigate potential risks associated with medications at this crucial care transition. The incorporation of this emergency medicine-specific geriatric prescription list in a national quality measure has the potential to improve patient safety and enhance the quality of care for the millions of older adults who seek care in EDs each year,” the authors said.

SOURCE:

This study was led by Rachel M. Skains, MD, MSPH, Department of Emergency Medicine, University of Alabama at Birmingham, and published online in Annals of Emergency Medicine.

LIMITATIONS:

The GEMS-Rx list was prepared by physicians and pharmacists and may not have fully captured data regarding individual patient preferences, comorbidities, or other contextual factors. During the meetings, the panelists’ identities were not concealed from one another, which may have affected the conversations owing to response and social desirability bias. Furthermore, this list may not be generalizable to other settings because it was produced and intended for usage in US EDs.

DISCLOSURES:

This work was supported by the American College of Emergency Physicians. Some of the authors, including the lead author, declared being supported by various funding agencies. Few authors also declared serving in leadership positions for several sources.

A version of this article appeared on Medscape.com.

TOPLINE: 

The geriatric emergency medication safety recommendations (GEMS-Rx) is the first expert consensus-based list identifying high-risk medication classes that should not be prescribed to older patients visiting the emergency department (ED).

METHODOLOGY:

• Around half of the geriatric patients presenting to the ED get discharged with new prescriptions. Some of the newly prescribed drugs may not be appropriate for use in individuals aged ≥ 65 years, thereby increasing the risk for unfavorable adverse events.
• The American Geriatrics Society (AGS)  has already established guidelines to identify potentially inappropriate medications in older adults; however, the criteria are centered on chronic conditions and long-term medication use and are unsuitable for managing ED prescriptions.
• In this study, the GEMS-Rx high-risk prescription list was prepared with a panel of 10 ED physicians with expertise in geriatrics and quality measurement and a pharmacist with expertise in geriatric pharmacotherapy and emergency medicine.
• They reviewed over 30 medication classes from the 2019 AGS Beers Criteria that were deemed inappropriate for use in older patients. Despite their not being included in the Beers list, the use of short- and long-acting opioids was also discussed.
• After three rounds of review and discussion, the panelists ranked each class of medication on a 5-point Likert scale, with a score of 1 indicating the lowest and 5 indicating the greatest need for avoiding a drug in an ED prescription.

TAKEAWAY:

• The first round suggested that first-generation antihistamines, metoclopramide, short-acting opioids, antipsychotics, barbiturates, skeletal muscle relaxants, and benzodiazepines should be avoided, with mean Likert scores ranging from 3.7 to 4.6.
• Although nonbenzodiazepine and benzodiazepine receptor agonist hypnotics (“Z-drugs”) were not initially considered owing to their low frequency of prescription in ED settings, the panelists finally included “Z” drugs and sulfonylureas in the GEMS-Rx list after the second and third rounds.
• The final list of high-risk medications to be avoided in ED settings that were prioritized included benzodiazepines, skeletal muscle relaxants, barbiturates, first-generation antipsychotics, first-generation antihistamines, “Z” drugs, metoclopramide, and sulfonylureas.
• However, seizure disorders, benzodiazepine withdrawal, ethanol withdrawal, severe generalized anxiety disorder, end-of-life care, allergic reactions, and ED visits for prescription refilling were deemed exceptional cases in which these high-risk medications could be prescribed.

IN PRACTICE:

“By combining expert consensus and evidence-based criteria, this list can serve as a resource to guide prescribing decisions and mitigate potential risks associated with medications at this crucial care transition. The incorporation of this emergency medicine-specific geriatric prescription list in a national quality measure has the potential to improve patient safety and enhance the quality of care for the millions of older adults who seek care in EDs each year,” the authors said.

SOURCE:

This study was led by Rachel M. Skains, MD, MSPH, Department of Emergency Medicine, University of Alabama at Birmingham, and published online in Annals of Emergency Medicine.

LIMITATIONS:

The GEMS-Rx list was prepared by physicians and pharmacists and may not have fully captured data regarding individual patient preferences, comorbidities, or other contextual factors. During the meetings, the panelists’ identities were not concealed from one another, which may have affected the conversations owing to response and social desirability bias. Furthermore, this list may not be generalizable to other settings because it was produced and intended for usage in US EDs.

DISCLOSURES:

This work was supported by the American College of Emergency Physicians. Some of the authors, including the lead author, declared being supported by various funding agencies. Few authors also declared serving in leadership positions for several sources.

A version of this article appeared on Medscape.com.