Geriatrics

TOPLINE:

In the first year of the COVID-19 pandemic, there was a significant drop in working memory and executive function in older individuals. This was attributed to an increase in known dementia risk factors, including increased alcohol use and a more sedentary lifestyle. This trend persisted into the second year of the pandemic, after social restrictions had eased.

METHODOLOGY:

• In total, 3,140 participants (54% women; mean age, 68 years) in the PROTECT study, a longitudinal aging study in the United Kingdom, completed annual cognitive assessments and self-reported questionnaires related to mental health and lifestyle.
• Investigators analyzed cognition across three time periods: during the year before the pandemic (March 2019 to February 2020), during pandemic year 1 (March 2020 to February 2021), and pandemic year 2 (March 2021 to February 2022).
• Investigators conducted a subanalysis on those with mild cognitive impairment and those with a history of COVID-19 (n = 752).

TAKEAWAY:

• During the first year of the pandemic, when there were societal lockdowns totaling 6 months, significant worsening of executive function and working memory was seen across the entire cohort (effect sizes, 0.15 and 0.51, respectively), in people with mild cognitive impairment (effect sizes, 0.13 and 0.40, respectively), and in those with a previous history of COVID-19 (effect sizes, 0.24 and 0.46, respectively).
• Worsening of working memory was sustained across the whole cohort in the second year of the pandemic after lockdowns were lifted (effect size, 0.47).
• Even after investigators removed data on people with mild cognitive impairment and COVID-19, the decline in executive function (effect size, 0.15; P < .0001) and working memory (effect size, 0.53; P < .0001) persisted.
• Cognitive decline was significantly associated with known risk factors for dementia, such as reduced exercise (P = .0049) and increased alcohol use (P = .049), across the whole cohort, as well as depression (P = .011) in those with a history of COVID-19 and loneliness (P = .0038) in those with mild cognitive impairment.

IN PRACTICE:

Investigators noted that these data add to existing knowledge of long-standing health consequences of COVID-19, especially for older people with memory problems. “On the positive note, there is evidence that lifestyle changes and improved health management can positively influence mental functioning,” study coauthor Dag Aarsland, MD, PhD, professor of old age psychiatry at the Institute of Psychiatry, Psychology & Neuroscience of King’s College London, said in a press release. “The current study underlines the importance of careful monitoring of people at risk during major events such as the pandemic.”

SOURCE:

The study was led by Anne Corbett, PhD, of University of Exeter, and was published online in The Lancet Healthy Longevity. The research was funded by the National Institute for Health and Care Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London and the NIHR Exeter Biomedical Research Centre.

LIMITATIONS:

The study relied on self-reported data. In addition, the PROTECT cohort is self-selected and may skew toward participants with higher education levels.

DISCLOSURES:

Dr. Corbett reported receiving funding from the NIHR and grants from Synexus, reMYND, and Novo Nordisk. Other disclosures are noted in the original article.
 

A version of this article appeared on Medscape.com.

TOPLINE:

In the first year of the COVID-19 pandemic, there was a significant drop in working memory and executive function in older individuals. This was attributed to an increase in known dementia risk factors, including increased alcohol use and a more sedentary lifestyle. This trend persisted into the second year of the pandemic, after social restrictions had eased.

METHODOLOGY:

• In total, 3,140 participants (54% women; mean age, 68 years) in the PROTECT study, a longitudinal aging study in the United Kingdom, completed annual cognitive assessments and self-reported questionnaires related to mental health and lifestyle.
• Investigators analyzed cognition across three time periods: during the year before the pandemic (March 2019 to February 2020), during pandemic year 1 (March 2020 to February 2021), and pandemic year 2 (March 2021 to February 2022).
• Investigators conducted a subanalysis on those with mild cognitive impairment and those with a history of COVID-19 (n = 752).

TAKEAWAY:

• During the first year of the pandemic, when there were societal lockdowns totaling 6 months, significant worsening of executive function and working memory was seen across the entire cohort (effect sizes, 0.15 and 0.51, respectively), in people with mild cognitive impairment (effect sizes, 0.13 and 0.40, respectively), and in those with a previous history of COVID-19 (effect sizes, 0.24 and 0.46, respectively).
• Worsening of working memory was sustained across the whole cohort in the second year of the pandemic after lockdowns were lifted (effect size, 0.47).
• Even after investigators removed data on people with mild cognitive impairment and COVID-19, the decline in executive function (effect size, 0.15; P < .0001) and working memory (effect size, 0.53; P < .0001) persisted.
• Cognitive decline was significantly associated with known risk factors for dementia, such as reduced exercise (P = .0049) and increased alcohol use (P = .049), across the whole cohort, as well as depression (P = .011) in those with a history of COVID-19 and loneliness (P = .0038) in those with mild cognitive impairment.

IN PRACTICE:

Investigators noted that these data add to existing knowledge of long-standing health consequences of COVID-19, especially for older people with memory problems. “On the positive note, there is evidence that lifestyle changes and improved health management can positively influence mental functioning,” study coauthor Dag Aarsland, MD, PhD, professor of old age psychiatry at the Institute of Psychiatry, Psychology & Neuroscience of King’s College London, said in a press release. “The current study underlines the importance of careful monitoring of people at risk during major events such as the pandemic.”

SOURCE:

The study was led by Anne Corbett, PhD, of University of Exeter, and was published online in The Lancet Healthy Longevity. The research was funded by the National Institute for Health and Care Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London and the NIHR Exeter Biomedical Research Centre.

LIMITATIONS:

The study relied on self-reported data. In addition, the PROTECT cohort is self-selected and may skew toward participants with higher education levels.

DISCLOSURES:

Dr. Corbett reported receiving funding from the NIHR and grants from Synexus, reMYND, and Novo Nordisk. Other disclosures are noted in the original article.
 

A version of this article appeared on Medscape.com.

TOPLINE:

In the first year of the COVID-19 pandemic, there was a significant drop in working memory and executive function in older individuals. This was attributed to an increase in known dementia risk factors, including increased alcohol use and a more sedentary lifestyle. This trend persisted into the second year of the pandemic, after social restrictions had eased.

METHODOLOGY:

• In total, 3,140 participants (54% women; mean age, 68 years) in the PROTECT study, a longitudinal aging study in the United Kingdom, completed annual cognitive assessments and self-reported questionnaires related to mental health and lifestyle.
• Investigators analyzed cognition across three time periods: during the year before the pandemic (March 2019 to February 2020), during pandemic year 1 (March 2020 to February 2021), and pandemic year 2 (March 2021 to February 2022).
• Investigators conducted a subanalysis on those with mild cognitive impairment and those with a history of COVID-19 (n = 752).

TAKEAWAY:

• During the first year of the pandemic, when there were societal lockdowns totaling 6 months, significant worsening of executive function and working memory was seen across the entire cohort (effect sizes, 0.15 and 0.51, respectively), in people with mild cognitive impairment (effect sizes, 0.13 and 0.40, respectively), and in those with a previous history of COVID-19 (effect sizes, 0.24 and 0.46, respectively).
• Worsening of working memory was sustained across the whole cohort in the second year of the pandemic after lockdowns were lifted (effect size, 0.47).
• Even after investigators removed data on people with mild cognitive impairment and COVID-19, the decline in executive function (effect size, 0.15; P < .0001) and working memory (effect size, 0.53; P < .0001) persisted.
• Cognitive decline was significantly associated with known risk factors for dementia, such as reduced exercise (P = .0049) and increased alcohol use (P = .049), across the whole cohort, as well as depression (P = .011) in those with a history of COVID-19 and loneliness (P = .0038) in those with mild cognitive impairment.

IN PRACTICE:

Investigators noted that these data add to existing knowledge of long-standing health consequences of COVID-19, especially for older people with memory problems. “On the positive note, there is evidence that lifestyle changes and improved health management can positively influence mental functioning,” study coauthor Dag Aarsland, MD, PhD, professor of old age psychiatry at the Institute of Psychiatry, Psychology & Neuroscience of King’s College London, said in a press release. “The current study underlines the importance of careful monitoring of people at risk during major events such as the pandemic.”

SOURCE:

The study was led by Anne Corbett, PhD, of University of Exeter, and was published online in The Lancet Healthy Longevity. The research was funded by the National Institute for Health and Care Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London and the NIHR Exeter Biomedical Research Centre.

LIMITATIONS:

The study relied on self-reported data. In addition, the PROTECT cohort is self-selected and may skew toward participants with higher education levels.

DISCLOSURES:

Dr. Corbett reported receiving funding from the NIHR and grants from Synexus, reMYND, and Novo Nordisk. Other disclosures are noted in the original article.
 

A version of this article appeared on Medscape.com.

Recorded October 13, 2023. This transcript has been edited for clarity.

Kathrin LaFaver, MD: I’ll be talking today with Dr. Meredith Wicklund, senior associate consultant and behavioral neurologist specialist at Mayo Clinic in Arizona. Welcome, Meredith.

Meredith Wicklund, MD: Thank you.
 

Lecanemab data

Dr. LaFaver: I’m very excited about our topic. We’ll be talking about monoclonal antibody therapy against amyloid in Alzheimer’s disease – which has really been a hot topic, especially this year with the FDA approval of lecanemab – and associated questions. Could you give us a brief overview of why there has been so much research interest in this topic of anti-amyloid antibodies?

Dr. Wicklund: The pathologic component of what defines something as Alzheimer’s disease is, by definition, presence of amyloid plaques and tau tangles. When it was first discovered in the 1980s that the component of the plaques was actually the amyloid protein – beta amyloid specifically – interest went right from there to developing therapies to directly target the pathology that is Alzheimer’s disease.

Dr. LaFaver: Lecanemab is the first FDA-approved disease-modifying antibody in that realm. Could you review the study data, especially as it applies to both of us in daily neurology clinic?

Dr. Wicklund: The study data from a phase 3 trial did show, for the primary outcome, that there was a 27% slowing of decline compared with individuals on placebo. It’s important to point out that this was slowing of decline. It was not stabilizing decline. It was not improving decline.

I think it’s important that we inform our patients that really, even with this therapy, there’s no prospect of stabilizing or restoring cognition or function. We do progress at a slower rate compared with individuals not on this treatment, which, given that this medication is for individuals in mild disease who have relatively preserved functional status, that can be potentially very meaningful to families.

The overall benefit was small. It essentially amounts to half a point on an 18-point scale, which is statistically significant. How much clinical meaningfulness that actually leads to is unclear. Finding clinical meaningfulness cannot be defined by a particular test. It really can only be defined on the individual level, what is meaningful to them.
 

Recommended tests

Dr. LaFaver: It is my understanding that, to qualify for lecanemab use, one needs to have a biomarker-supported diagnosis of Alzheimer’s disease, either via an amyloid PET scan or CSF biomarkers. What would your recommendation be for a neurologist in practice to go about these requirements?

Dr. Wicklund: Since this medication is directly targeting the amyloid pathology, and it does convey a potential risk, we want to make sure that the actual pathology is present in the individuals before we treat them and potentially expose them to risk. The best way of doing that is through either an amyloid PET scan or spinal fluid testing of beta amyloid and tau.

There are several plasma-based biomarkers in development. However, I would avoid using those currently. There are still many unknowns in terms of what exactly is the right species of tau that we should be looking at, the right mechanism of the lab test, how minority status may influence it, and how different comorbidities may influence it.

I would recommend, at this time, sticking with amyloid PET or CSF testing. Given that amyloid PET is not widely available in many community practices, generally only available at academic centers, and is quite costly, many insurances do not cover it – although Medicare has a proposal to potentially start covering it – I generally go with spinal fluid testing, which is more widely available. There are several labs across the country that can process that testing in a reliable way.
 

Amyloid-related imaging abnormalities

Dr. LaFaver: That’s very helpful to know. There’s been a large amount of buzz just these past couple of weeks about the blood biomarker coming up. I think, as you point out, this wasn’t the marker used in the clinical studies and there are still unknowns. Maybe it’s not quite time for clinical use, unfortunately.

We also have learned that there are significant potential risks involved. One issue that’s really been a focus is ARIA – amyloid-related imaging abnormalities. Could you speak a bit about that and requirements for monitoring?

Dr. Wicklund: ARIA essentially amounts to either vasogenic edema, microhemorrhages, or superficial siderosis that develops as a result of treatment. It relates to activation of the immune system with these passive monoclonal antibodies that’s going to occur with targeting against the plaques. In the parenchyma, it will cause edema. If you have amyloid in the walls of the blood vessels, it can cause microhemorrhages.

While the term “ARIA” implies an imaging-related abnormality, and it largely is purely an imaging finding, it’s not solely an imaging-related finding. It can cause symptoms, including very serious symptoms.

Overall, with lecanemab, the incidence of ARIA within the treatment group in the phase 3 study, combined between both ARIA-E (edema/effusion) and ARIA-H (hemorrhage), was 21.5%, with about 17% being ARIA-H and about 12.5% being ARIA-E. Of course, they can occur at the same time.

Overall, in terms of people in the clinical trials, for most it was purely an imaging-related finding. About 3% developed symptomatic ARIA. Some of those were very serious symptoms, including things like seizures and need to be hospitalized. A couple of deaths have been attributed to ARIA as well.

Patients on anticoagulation

Dr. LaFaver: Along those lines, any additional words to say for people who might be on anticoagulation or might require medications for a stroke, for example?

Dr. Wicklund: While individuals on anticoagulation were allowed in the clinical trials, the current, published appropriate-use guideline is recommending against its use, as several of the serious adverse effects, including the deaths, were for the most part attributed to anticoagulation use.

When it comes to acute stroke treatment, one must carefully consider use of tPA, as two of the three deaths were tPA associated in the clinical trials. It shouldn’t necessarily be an absolute contraindication, but it can make the clinical picture very muddy. If an individual is on lecanemab and comes to the ER with acute stroke-like symptoms, it’s more likely that they’re going to be having an ARIA side effect rather than an acute stroke.

A general recommendation would be to obtain an acute head CT with a CTA, and if there is a large vessel occlusion, proceed to thrombectomy. However, if there isn’t a large vessel occlusion, if you have the ability to get a rapid MRI with diffusion-weighted imaging to screen for acute stroke changes or tissue flair with acute edema changes suggestive of ARIA, that would be preferred before proceeding with thrombolysis. These are all relative contraindications and are going to depend on what’s available near you.
 

Donanemab approval pending

Dr. LaFaver: This will be an issue because the population we’re talking about is definitely at risk for stroke as well as Alzheimer’s disease. Where do you see this field going as far as amyloid antibody therapy is concerned, with another agent, donanemab, possibly getting FDA approval later this year as well?

Dr. Wicklund: We’re anticipating that donanemab will get FDA approval in the next coming months. Donanemab also targets the amyloid in the brain, although lecanemab and donanemab target different aspects of the production of the amyloid plaque. They were both shown to have roughly equal efficacy in their phase 3 clinical trials. Donanemab has the benefit of being a once-monthly infusion as opposed to twice-monthly infusions with lecanemab. It does have a slightly higher risk for ARIA compared with lecanemab.

Those are just some things to take into consideration when talking with your patients. In terms of where we’re going from here, we’re moving even earlier in terms of disease state. The lecanemab and donanemab phase 3 trials were done in individuals with mild cognitive impairment or mild dementia due to Alzheimer’s disease. They should not be used in individuals with moderate or more advanced Alzheimer’s disease.

There are ongoing, large, national, multicenter clinical trials of both lecanemab and donanemab in a preclinical state of Alzheimer’s disease. These individuals have evidence of amyloidosis, either through PET imaging or through CSF, but are clinically asymptomatic and do not yet have any signs of cognitive impairment or functional decline. We look forward to those results in the next few years. Hopefully, they’ll be able to show even greater benefit when moving into these early disease states in terms of delaying or even preventing cognitive decline.

Dr. LaFaver: That’s definitely very interesting to hear about. Where can people go for more information?

Dr. Wicklund: There’s a guideline on the use of lecanemab through the American Academy of Neurology. I encourage you to look at that. Also, look at the appropriate-use recommendations that were published this year in The Journal of Prevention of Alzheimer’s Disease.

Dr. LaFaver: Wonderful. With that being said, thank you so much for talking to me. I learned a lot. Thanks, everyone, for listening.
 

Dr. LaFaver is a neurologist at Saratoga Hospital Medical Group, Saratoga Springs, N.Y. She disclosed having no relevant financial relationships. Dr. Wicklund is senior associate consultant in the department of Neurology at Mayo Clinic, Phoenix, Ariz. She disclosed having no relevant financial relationships.

A version of this article appeared on Medscape.com.

Recorded October 13, 2023. This transcript has been edited for clarity.

Kathrin LaFaver, MD: I’ll be talking today with Dr. Meredith Wicklund, senior associate consultant and behavioral neurologist specialist at Mayo Clinic in Arizona. Welcome, Meredith.

Meredith Wicklund, MD: Thank you.
 

Lecanemab data

Dr. LaFaver: I’m very excited about our topic. We’ll be talking about monoclonal antibody therapy against amyloid in Alzheimer’s disease – which has really been a hot topic, especially this year with the FDA approval of lecanemab – and associated questions. Could you give us a brief overview of why there has been so much research interest in this topic of anti-amyloid antibodies?

Dr. Wicklund: The pathologic component of what defines something as Alzheimer’s disease is, by definition, presence of amyloid plaques and tau tangles. When it was first discovered in the 1980s that the component of the plaques was actually the amyloid protein – beta amyloid specifically – interest went right from there to developing therapies to directly target the pathology that is Alzheimer’s disease.

Dr. LaFaver: Lecanemab is the first FDA-approved disease-modifying antibody in that realm. Could you review the study data, especially as it applies to both of us in daily neurology clinic?

Dr. Wicklund: The study data from a phase 3 trial did show, for the primary outcome, that there was a 27% slowing of decline compared with individuals on placebo. It’s important to point out that this was slowing of decline. It was not stabilizing decline. It was not improving decline.

I think it’s important that we inform our patients that really, even with this therapy, there’s no prospect of stabilizing or restoring cognition or function. We do progress at a slower rate compared with individuals not on this treatment, which, given that this medication is for individuals in mild disease who have relatively preserved functional status, that can be potentially very meaningful to families.

The overall benefit was small. It essentially amounts to half a point on an 18-point scale, which is statistically significant. How much clinical meaningfulness that actually leads to is unclear. Finding clinical meaningfulness cannot be defined by a particular test. It really can only be defined on the individual level, what is meaningful to them.
 

Recommended tests

Dr. LaFaver: It is my understanding that, to qualify for lecanemab use, one needs to have a biomarker-supported diagnosis of Alzheimer’s disease, either via an amyloid PET scan or CSF biomarkers. What would your recommendation be for a neurologist in practice to go about these requirements?

Dr. Wicklund: Since this medication is directly targeting the amyloid pathology, and it does convey a potential risk, we want to make sure that the actual pathology is present in the individuals before we treat them and potentially expose them to risk. The best way of doing that is through either an amyloid PET scan or spinal fluid testing of beta amyloid and tau.

There are several plasma-based biomarkers in development. However, I would avoid using those currently. There are still many unknowns in terms of what exactly is the right species of tau that we should be looking at, the right mechanism of the lab test, how minority status may influence it, and how different comorbidities may influence it.

I would recommend, at this time, sticking with amyloid PET or CSF testing. Given that amyloid PET is not widely available in many community practices, generally only available at academic centers, and is quite costly, many insurances do not cover it – although Medicare has a proposal to potentially start covering it – I generally go with spinal fluid testing, which is more widely available. There are several labs across the country that can process that testing in a reliable way.
 

Amyloid-related imaging abnormalities

Dr. LaFaver: That’s very helpful to know. There’s been a large amount of buzz just these past couple of weeks about the blood biomarker coming up. I think, as you point out, this wasn’t the marker used in the clinical studies and there are still unknowns. Maybe it’s not quite time for clinical use, unfortunately.

We also have learned that there are significant potential risks involved. One issue that’s really been a focus is ARIA – amyloid-related imaging abnormalities. Could you speak a bit about that and requirements for monitoring?

Dr. Wicklund: ARIA essentially amounts to either vasogenic edema, microhemorrhages, or superficial siderosis that develops as a result of treatment. It relates to activation of the immune system with these passive monoclonal antibodies that’s going to occur with targeting against the plaques. In the parenchyma, it will cause edema. If you have amyloid in the walls of the blood vessels, it can cause microhemorrhages.

While the term “ARIA” implies an imaging-related abnormality, and it largely is purely an imaging finding, it’s not solely an imaging-related finding. It can cause symptoms, including very serious symptoms.

Overall, with lecanemab, the incidence of ARIA within the treatment group in the phase 3 study, combined between both ARIA-E (edema/effusion) and ARIA-H (hemorrhage), was 21.5%, with about 17% being ARIA-H and about 12.5% being ARIA-E. Of course, they can occur at the same time.

Overall, in terms of people in the clinical trials, for most it was purely an imaging-related finding. About 3% developed symptomatic ARIA. Some of those were very serious symptoms, including things like seizures and need to be hospitalized. A couple of deaths have been attributed to ARIA as well.

Patients on anticoagulation

Dr. LaFaver: Along those lines, any additional words to say for people who might be on anticoagulation or might require medications for a stroke, for example?

Dr. Wicklund: While individuals on anticoagulation were allowed in the clinical trials, the current, published appropriate-use guideline is recommending against its use, as several of the serious adverse effects, including the deaths, were for the most part attributed to anticoagulation use.

When it comes to acute stroke treatment, one must carefully consider use of tPA, as two of the three deaths were tPA associated in the clinical trials. It shouldn’t necessarily be an absolute contraindication, but it can make the clinical picture very muddy. If an individual is on lecanemab and comes to the ER with acute stroke-like symptoms, it’s more likely that they’re going to be having an ARIA side effect rather than an acute stroke.

A general recommendation would be to obtain an acute head CT with a CTA, and if there is a large vessel occlusion, proceed to thrombectomy. However, if there isn’t a large vessel occlusion, if you have the ability to get a rapid MRI with diffusion-weighted imaging to screen for acute stroke changes or tissue flair with acute edema changes suggestive of ARIA, that would be preferred before proceeding with thrombolysis. These are all relative contraindications and are going to depend on what’s available near you.
 

Donanemab approval pending

Dr. LaFaver: This will be an issue because the population we’re talking about is definitely at risk for stroke as well as Alzheimer’s disease. Where do you see this field going as far as amyloid antibody therapy is concerned, with another agent, donanemab, possibly getting FDA approval later this year as well?

Dr. Wicklund: We’re anticipating that donanemab will get FDA approval in the next coming months. Donanemab also targets the amyloid in the brain, although lecanemab and donanemab target different aspects of the production of the amyloid plaque. They were both shown to have roughly equal efficacy in their phase 3 clinical trials. Donanemab has the benefit of being a once-monthly infusion as opposed to twice-monthly infusions with lecanemab. It does have a slightly higher risk for ARIA compared with lecanemab.

Those are just some things to take into consideration when talking with your patients. In terms of where we’re going from here, we’re moving even earlier in terms of disease state. The lecanemab and donanemab phase 3 trials were done in individuals with mild cognitive impairment or mild dementia due to Alzheimer’s disease. They should not be used in individuals with moderate or more advanced Alzheimer’s disease.

There are ongoing, large, national, multicenter clinical trials of both lecanemab and donanemab in a preclinical state of Alzheimer’s disease. These individuals have evidence of amyloidosis, either through PET imaging or through CSF, but are clinically asymptomatic and do not yet have any signs of cognitive impairment or functional decline. We look forward to those results in the next few years. Hopefully, they’ll be able to show even greater benefit when moving into these early disease states in terms of delaying or even preventing cognitive decline.

Dr. LaFaver: That’s definitely very interesting to hear about. Where can people go for more information?

Dr. Wicklund: There’s a guideline on the use of lecanemab through the American Academy of Neurology. I encourage you to look at that. Also, look at the appropriate-use recommendations that were published this year in The Journal of Prevention of Alzheimer’s Disease.

Dr. LaFaver: Wonderful. With that being said, thank you so much for talking to me. I learned a lot. Thanks, everyone, for listening.
 

Dr. LaFaver is a neurologist at Saratoga Hospital Medical Group, Saratoga Springs, N.Y. She disclosed having no relevant financial relationships. Dr. Wicklund is senior associate consultant in the department of Neurology at Mayo Clinic, Phoenix, Ariz. She disclosed having no relevant financial relationships.

A version of this article appeared on Medscape.com.

Recorded October 13, 2023. This transcript has been edited for clarity.

Kathrin LaFaver, MD: I’ll be talking today with Dr. Meredith Wicklund, senior associate consultant and behavioral neurologist specialist at Mayo Clinic in Arizona. Welcome, Meredith.

Meredith Wicklund, MD: Thank you.
 

Lecanemab data

Dr. LaFaver: I’m very excited about our topic. We’ll be talking about monoclonal antibody therapy against amyloid in Alzheimer’s disease – which has really been a hot topic, especially this year with the FDA approval of lecanemab – and associated questions. Could you give us a brief overview of why there has been so much research interest in this topic of anti-amyloid antibodies?

Dr. Wicklund: The pathologic component of what defines something as Alzheimer’s disease is, by definition, presence of amyloid plaques and tau tangles. When it was first discovered in the 1980s that the component of the plaques was actually the amyloid protein – beta amyloid specifically – interest went right from there to developing therapies to directly target the pathology that is Alzheimer’s disease.

Dr. LaFaver: Lecanemab is the first FDA-approved disease-modifying antibody in that realm. Could you review the study data, especially as it applies to both of us in daily neurology clinic?

Dr. Wicklund: The study data from a phase 3 trial did show, for the primary outcome, that there was a 27% slowing of decline compared with individuals on placebo. It’s important to point out that this was slowing of decline. It was not stabilizing decline. It was not improving decline.

I think it’s important that we inform our patients that really, even with this therapy, there’s no prospect of stabilizing or restoring cognition or function. We do progress at a slower rate compared with individuals not on this treatment, which, given that this medication is for individuals in mild disease who have relatively preserved functional status, that can be potentially very meaningful to families.

The overall benefit was small. It essentially amounts to half a point on an 18-point scale, which is statistically significant. How much clinical meaningfulness that actually leads to is unclear. Finding clinical meaningfulness cannot be defined by a particular test. It really can only be defined on the individual level, what is meaningful to them.
 

Recommended tests

Dr. LaFaver: It is my understanding that, to qualify for lecanemab use, one needs to have a biomarker-supported diagnosis of Alzheimer’s disease, either via an amyloid PET scan or CSF biomarkers. What would your recommendation be for a neurologist in practice to go about these requirements?

Dr. Wicklund: Since this medication is directly targeting the amyloid pathology, and it does convey a potential risk, we want to make sure that the actual pathology is present in the individuals before we treat them and potentially expose them to risk. The best way of doing that is through either an amyloid PET scan or spinal fluid testing of beta amyloid and tau.

There are several plasma-based biomarkers in development. However, I would avoid using those currently. There are still many unknowns in terms of what exactly is the right species of tau that we should be looking at, the right mechanism of the lab test, how minority status may influence it, and how different comorbidities may influence it.

I would recommend, at this time, sticking with amyloid PET or CSF testing. Given that amyloid PET is not widely available in many community practices, generally only available at academic centers, and is quite costly, many insurances do not cover it – although Medicare has a proposal to potentially start covering it – I generally go with spinal fluid testing, which is more widely available. There are several labs across the country that can process that testing in a reliable way.
 

Amyloid-related imaging abnormalities

Dr. LaFaver: That’s very helpful to know. There’s been a large amount of buzz just these past couple of weeks about the blood biomarker coming up. I think, as you point out, this wasn’t the marker used in the clinical studies and there are still unknowns. Maybe it’s not quite time for clinical use, unfortunately.

We also have learned that there are significant potential risks involved. One issue that’s really been a focus is ARIA – amyloid-related imaging abnormalities. Could you speak a bit about that and requirements for monitoring?

Dr. Wicklund: ARIA essentially amounts to either vasogenic edema, microhemorrhages, or superficial siderosis that develops as a result of treatment. It relates to activation of the immune system with these passive monoclonal antibodies that’s going to occur with targeting against the plaques. In the parenchyma, it will cause edema. If you have amyloid in the walls of the blood vessels, it can cause microhemorrhages.

While the term “ARIA” implies an imaging-related abnormality, and it largely is purely an imaging finding, it’s not solely an imaging-related finding. It can cause symptoms, including very serious symptoms.

Overall, with lecanemab, the incidence of ARIA within the treatment group in the phase 3 study, combined between both ARIA-E (edema/effusion) and ARIA-H (hemorrhage), was 21.5%, with about 17% being ARIA-H and about 12.5% being ARIA-E. Of course, they can occur at the same time.

Overall, in terms of people in the clinical trials, for most it was purely an imaging-related finding. About 3% developed symptomatic ARIA. Some of those were very serious symptoms, including things like seizures and need to be hospitalized. A couple of deaths have been attributed to ARIA as well.

Patients on anticoagulation

Dr. LaFaver: Along those lines, any additional words to say for people who might be on anticoagulation or might require medications for a stroke, for example?

Dr. Wicklund: While individuals on anticoagulation were allowed in the clinical trials, the current, published appropriate-use guideline is recommending against its use, as several of the serious adverse effects, including the deaths, were for the most part attributed to anticoagulation use.

When it comes to acute stroke treatment, one must carefully consider use of tPA, as two of the three deaths were tPA associated in the clinical trials. It shouldn’t necessarily be an absolute contraindication, but it can make the clinical picture very muddy. If an individual is on lecanemab and comes to the ER with acute stroke-like symptoms, it’s more likely that they’re going to be having an ARIA side effect rather than an acute stroke.

A general recommendation would be to obtain an acute head CT with a CTA, and if there is a large vessel occlusion, proceed to thrombectomy. However, if there isn’t a large vessel occlusion, if you have the ability to get a rapid MRI with diffusion-weighted imaging to screen for acute stroke changes or tissue flair with acute edema changes suggestive of ARIA, that would be preferred before proceeding with thrombolysis. These are all relative contraindications and are going to depend on what’s available near you.
 

Donanemab approval pending

Dr. LaFaver: This will be an issue because the population we’re talking about is definitely at risk for stroke as well as Alzheimer’s disease. Where do you see this field going as far as amyloid antibody therapy is concerned, with another agent, donanemab, possibly getting FDA approval later this year as well?

Dr. Wicklund: We’re anticipating that donanemab will get FDA approval in the next coming months. Donanemab also targets the amyloid in the brain, although lecanemab and donanemab target different aspects of the production of the amyloid plaque. They were both shown to have roughly equal efficacy in their phase 3 clinical trials. Donanemab has the benefit of being a once-monthly infusion as opposed to twice-monthly infusions with lecanemab. It does have a slightly higher risk for ARIA compared with lecanemab.

Those are just some things to take into consideration when talking with your patients. In terms of where we’re going from here, we’re moving even earlier in terms of disease state. The lecanemab and donanemab phase 3 trials were done in individuals with mild cognitive impairment or mild dementia due to Alzheimer’s disease. They should not be used in individuals with moderate or more advanced Alzheimer’s disease.

There are ongoing, large, national, multicenter clinical trials of both lecanemab and donanemab in a preclinical state of Alzheimer’s disease. These individuals have evidence of amyloidosis, either through PET imaging or through CSF, but are clinically asymptomatic and do not yet have any signs of cognitive impairment or functional decline. We look forward to those results in the next few years. Hopefully, they’ll be able to show even greater benefit when moving into these early disease states in terms of delaying or even preventing cognitive decline.

Dr. LaFaver: That’s definitely very interesting to hear about. Where can people go for more information?

Dr. Wicklund: There’s a guideline on the use of lecanemab through the American Academy of Neurology. I encourage you to look at that. Also, look at the appropriate-use recommendations that were published this year in The Journal of Prevention of Alzheimer’s Disease.

Dr. LaFaver: Wonderful. With that being said, thank you so much for talking to me. I learned a lot. Thanks, everyone, for listening.
 

Dr. LaFaver is a neurologist at Saratoga Hospital Medical Group, Saratoga Springs, N.Y. She disclosed having no relevant financial relationships. Dr. Wicklund is senior associate consultant in the department of Neurology at Mayo Clinic, Phoenix, Ariz. She disclosed having no relevant financial relationships.

A version of this article appeared on Medscape.com.

A novel approach aimed at enhancing everyday memory may lead older adults to feel more confident that they can accurately recollect phone numbers, names, and other information, according to findings from a small randomized controlled trial that were presented at the annual meeting of the Gerontological Society of America.

The tool, called Everyday Memory and Metacognitive Intervention (EMMI), trains people to be more mindful of memories, like where they parked their car, by repeating information at increasing intervals and self-testing.

EMMI “is a very important approach, focused on everyday memory,” said George W. Rebok, PhD, professor emeritus in the department of mental health at Johns Hopkins University, Baltimore, who was not involved with the study. “Many times, when we do memory interventions, we only focus on improving objective memories,” such as recalling major life events or one-time occurrences.

Everyday memory was defined as recalling basic facts including names, phone numbers, and daily appointments. The research, led by Ann Pearman, MD, associate director of adult psychology at Case Western Reserve University School of Medicine at MetroHealth Medical Center, Cleveland, Ohio, expanded on previous work she conducted with colleagues. That study found that EMMI may help improve confidence in the ability to recollect information and functional independence among older adults.

The current study was of 62 of the same participants in the earlier research, with one group that received EMMI (n = 30) and another that underwent traditional memory strategy training ([MSC]; n = 32). Both groups underwent four 3-hour virtual training sessions in their designated intervention over 2 weeks.

“One of the most important parts of the study is the [training] period,” when participants build new habits to help recall their everyday memories, Dr. Pearman said.

For 7 weeks, participants reported errors in everyday memories on a smartphone and submitted diary entries for each. Dr. Rebok that said tracking can help identify patterns or circumstances under which a person is likely to experience a memory lapse.

The study found mixed results when comparing EMMI with MSC, with the latter group demonstrating greater improvements in associative memory, such as pairing of a name to a face, highlighting the effectiveness of traditional MCS.

However, participants who underwent EMMI reported an increase in self-confidence that they were able to remember things, compared with those in the MSC group (4.92, confidence interval 95%, P = .30).

The EMMI intervention also was not uniformly effective in reducing memory errors across all participants in the group, which is to be expected, experts note. “In memory training, as with any kind of cognitive training, one size doesn’t fit all,” Dr. Rebok said.

“The mixed findings may highlight the need for a holistic approach to memory improvement and brain health, especially in older adults,” said Krystal L. Culler, DBH, founder of the Virtual Brain Health Center in Cleveland, who was not involved with the study.

EMMI could potentially be part of a broader strategy that includes lifestyle factors like sleep hygiene, physical exercise, diet, and social engagement to support optimal memory care, Dr. Culler said.

Patients who noticed some change in their memory and who are interested in making some positive changes in their daily cognitive functioning may benefit most from EMMI, according to Dr. Pearman.

“Making proactive decisions about memory challenges [patients] in their thinking and doing in everyday life,” she said.

Dr. Pearman shared that she and her colleagues are now looking into a combined EMMI and traditional memory strategy training to maximize the benefits of both interventions.

The study was supported by the Retirement Research Foundation (2018-2019); and the National Institute of Diabetes and Digestive and Kidney Diseases (P30DK111024) from the Georgia Center for Diabetes Translation Research. The study authors report no relevant conflicts. Dr. Culler and Dr. Rebok report no relevant financial relationships.

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

A novel approach aimed at enhancing everyday memory may lead older adults to feel more confident that they can accurately recollect phone numbers, names, and other information, according to findings from a small randomized controlled trial that were presented at the annual meeting of the Gerontological Society of America.

The tool, called Everyday Memory and Metacognitive Intervention (EMMI), trains people to be more mindful of memories, like where they parked their car, by repeating information at increasing intervals and self-testing.

EMMI “is a very important approach, focused on everyday memory,” said George W. Rebok, PhD, professor emeritus in the department of mental health at Johns Hopkins University, Baltimore, who was not involved with the study. “Many times, when we do memory interventions, we only focus on improving objective memories,” such as recalling major life events or one-time occurrences.

Everyday memory was defined as recalling basic facts including names, phone numbers, and daily appointments. The research, led by Ann Pearman, MD, associate director of adult psychology at Case Western Reserve University School of Medicine at MetroHealth Medical Center, Cleveland, Ohio, expanded on previous work she conducted with colleagues. That study found that EMMI may help improve confidence in the ability to recollect information and functional independence among older adults.

The current study was of 62 of the same participants in the earlier research, with one group that received EMMI (n = 30) and another that underwent traditional memory strategy training ([MSC]; n = 32). Both groups underwent four 3-hour virtual training sessions in their designated intervention over 2 weeks.

“One of the most important parts of the study is the [training] period,” when participants build new habits to help recall their everyday memories, Dr. Pearman said.

For 7 weeks, participants reported errors in everyday memories on a smartphone and submitted diary entries for each. Dr. Rebok that said tracking can help identify patterns or circumstances under which a person is likely to experience a memory lapse.

The study found mixed results when comparing EMMI with MSC, with the latter group demonstrating greater improvements in associative memory, such as pairing of a name to a face, highlighting the effectiveness of traditional MCS.

However, participants who underwent EMMI reported an increase in self-confidence that they were able to remember things, compared with those in the MSC group (4.92, confidence interval 95%, P = .30).

The EMMI intervention also was not uniformly effective in reducing memory errors across all participants in the group, which is to be expected, experts note. “In memory training, as with any kind of cognitive training, one size doesn’t fit all,” Dr. Rebok said.

“The mixed findings may highlight the need for a holistic approach to memory improvement and brain health, especially in older adults,” said Krystal L. Culler, DBH, founder of the Virtual Brain Health Center in Cleveland, who was not involved with the study.

EMMI could potentially be part of a broader strategy that includes lifestyle factors like sleep hygiene, physical exercise, diet, and social engagement to support optimal memory care, Dr. Culler said.

Patients who noticed some change in their memory and who are interested in making some positive changes in their daily cognitive functioning may benefit most from EMMI, according to Dr. Pearman.

“Making proactive decisions about memory challenges [patients] in their thinking and doing in everyday life,” she said.

Dr. Pearman shared that she and her colleagues are now looking into a combined EMMI and traditional memory strategy training to maximize the benefits of both interventions.

The study was supported by the Retirement Research Foundation (2018-2019); and the National Institute of Diabetes and Digestive and Kidney Diseases (P30DK111024) from the Georgia Center for Diabetes Translation Research. The study authors report no relevant conflicts. Dr. Culler and Dr. Rebok report no relevant financial relationships.

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

A novel approach aimed at enhancing everyday memory may lead older adults to feel more confident that they can accurately recollect phone numbers, names, and other information, according to findings from a small randomized controlled trial that were presented at the annual meeting of the Gerontological Society of America.

The tool, called Everyday Memory and Metacognitive Intervention (EMMI), trains people to be more mindful of memories, like where they parked their car, by repeating information at increasing intervals and self-testing.

EMMI “is a very important approach, focused on everyday memory,” said George W. Rebok, PhD, professor emeritus in the department of mental health at Johns Hopkins University, Baltimore, who was not involved with the study. “Many times, when we do memory interventions, we only focus on improving objective memories,” such as recalling major life events or one-time occurrences.

Everyday memory was defined as recalling basic facts including names, phone numbers, and daily appointments. The research, led by Ann Pearman, MD, associate director of adult psychology at Case Western Reserve University School of Medicine at MetroHealth Medical Center, Cleveland, Ohio, expanded on previous work she conducted with colleagues. That study found that EMMI may help improve confidence in the ability to recollect information and functional independence among older adults.

The current study was of 62 of the same participants in the earlier research, with one group that received EMMI (n = 30) and another that underwent traditional memory strategy training ([MSC]; n = 32). Both groups underwent four 3-hour virtual training sessions in their designated intervention over 2 weeks.

“One of the most important parts of the study is the [training] period,” when participants build new habits to help recall their everyday memories, Dr. Pearman said.

For 7 weeks, participants reported errors in everyday memories on a smartphone and submitted diary entries for each. Dr. Rebok that said tracking can help identify patterns or circumstances under which a person is likely to experience a memory lapse.

The study found mixed results when comparing EMMI with MSC, with the latter group demonstrating greater improvements in associative memory, such as pairing of a name to a face, highlighting the effectiveness of traditional MCS.

However, participants who underwent EMMI reported an increase in self-confidence that they were able to remember things, compared with those in the MSC group (4.92, confidence interval 95%, P = .30).

The EMMI intervention also was not uniformly effective in reducing memory errors across all participants in the group, which is to be expected, experts note. “In memory training, as with any kind of cognitive training, one size doesn’t fit all,” Dr. Rebok said.

“The mixed findings may highlight the need for a holistic approach to memory improvement and brain health, especially in older adults,” said Krystal L. Culler, DBH, founder of the Virtual Brain Health Center in Cleveland, who was not involved with the study.

EMMI could potentially be part of a broader strategy that includes lifestyle factors like sleep hygiene, physical exercise, diet, and social engagement to support optimal memory care, Dr. Culler said.

Patients who noticed some change in their memory and who are interested in making some positive changes in their daily cognitive functioning may benefit most from EMMI, according to Dr. Pearman.

“Making proactive decisions about memory challenges [patients] in their thinking and doing in everyday life,” she said.

Dr. Pearman shared that she and her colleagues are now looking into a combined EMMI and traditional memory strategy training to maximize the benefits of both interventions.

The study was supported by the Retirement Research Foundation (2018-2019); and the National Institute of Diabetes and Digestive and Kidney Diseases (P30DK111024) from the Georgia Center for Diabetes Translation Research. The study authors report no relevant conflicts. Dr. Culler and Dr. Rebok report no relevant financial relationships.

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

Glucagon-like peptide 1 (GLP-1) agonists may help clinicians manage uncontrolled type 2 diabetes in some older patients without the need for additional glucose-controlling medications, according to a study presented Nov. 8 at the annual meeting of the Gerontological Society of America.

The study analyzed charts of 30 adults aged 65-84 years who were seen in clinic from January 2022 to February 2023 and were started on GLP-1 or GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) agonists. Participants had uncontrolled type 2 diabetes with initial A1c levels ranging from 9.6% to 12.6% and a body mass index between 27 and 48.2. The patients also received education about their conditions as well as counseling on diet and lifestyle modifications.

All participants experienced a reduction in A1c to a range of 5.8% to 7.7%, and a moderate reduction in BMI to between 23 and 39.8 within the year.

“The reduction in BMI that we saw in our patients even though they were still in the category of obesity produces a substantial benefit in the management [of type 2 diabetes],” because weight loss helps to control the condition, said Anna Pendrey, MD, assistant professor of clinical family medicine and geriatrics at Indiana University, Indianapolis, and sole author of the study.

In some cases, the addition of a GLP-1 agonist or GLP-1/GIP agonist allowed for clinicians to deprescribe other medications such as insulin and sulfonylureas, which can cause hypoglycemia in older adults, Dr. Pendrey said.

Approximately 11% of U.S. adults have type 2 diabetes, a percentage that is likely to grow given the prevalence of childhood obesity, according to the Centers for Disease Control and Prevention. Dr. Pendrey highlighted the increased incidence of newly diagnosed diabetes in individuals aged 65-79 years.

Previous studies have shown that GLP-1 agonists have the potential to aid in weight reduction, glucose control, and the prevention of major adverse cardiovascular events in these patients.

The new study is one of many post hoc analyses that mark another step forward in addressing the complex challenges associated with diabetes in older adults, according to Rodolfo Galindo, MD, director of the Comprehensive Diabetes Center at the University of Miami Health System in Florida.

“I believe this is important because unfortunately many of our older adults have both diabetes and obesity,” Dr. Galindo, who was not involved with the research, told this news organization. “You can induce remission of type 2 diabetes through weight loss that GLP-1s can cause.”

The treatment paradigm has shifted away from focusing only on lowering glucose levels as the primary means to prevent complications from diabetes, Dr. Galindo said.

Indeed, weight loss can modify diseases and prevent other complications associated with type 2 diabetes, Dr. Pendrey said.

“Weight loss and diabetes mellitus control also produces cardiovascular protection that is significant for patients with diabetes, so this group of patients in my opinion are the ones that benefit the most from GLP-1s,” she said.

Side effects of GLP-1 agonists can include nausea and vomiting, which could lead to dehydration. GLP-1s can also increase the risk for pancreatitis. For older adults, weight loss from the drug could cause sarcopenia, or loss of muscle mass, Dr. Galindo said.

“This is the reason why patients in treatment with GLP-1s have to be in close contact with their providers,” Dr. Pendrey said.

This study was independently supported. Dr. Pendrey and Dr. Galindo report no relevant conflicts.

A version of this article appeared on Medscape.com.

Glucagon-like peptide 1 (GLP-1) agonists may help clinicians manage uncontrolled type 2 diabetes in some older patients without the need for additional glucose-controlling medications, according to a study presented Nov. 8 at the annual meeting of the Gerontological Society of America.

The study analyzed charts of 30 adults aged 65-84 years who were seen in clinic from January 2022 to February 2023 and were started on GLP-1 or GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) agonists. Participants had uncontrolled type 2 diabetes with initial A1c levels ranging from 9.6% to 12.6% and a body mass index between 27 and 48.2. The patients also received education about their conditions as well as counseling on diet and lifestyle modifications.

All participants experienced a reduction in A1c to a range of 5.8% to 7.7%, and a moderate reduction in BMI to between 23 and 39.8 within the year.

“The reduction in BMI that we saw in our patients even though they were still in the category of obesity produces a substantial benefit in the management [of type 2 diabetes],” because weight loss helps to control the condition, said Anna Pendrey, MD, assistant professor of clinical family medicine and geriatrics at Indiana University, Indianapolis, and sole author of the study.

In some cases, the addition of a GLP-1 agonist or GLP-1/GIP agonist allowed for clinicians to deprescribe other medications such as insulin and sulfonylureas, which can cause hypoglycemia in older adults, Dr. Pendrey said.

Approximately 11% of U.S. adults have type 2 diabetes, a percentage that is likely to grow given the prevalence of childhood obesity, according to the Centers for Disease Control and Prevention. Dr. Pendrey highlighted the increased incidence of newly diagnosed diabetes in individuals aged 65-79 years.

Previous studies have shown that GLP-1 agonists have the potential to aid in weight reduction, glucose control, and the prevention of major adverse cardiovascular events in these patients.

The new study is one of many post hoc analyses that mark another step forward in addressing the complex challenges associated with diabetes in older adults, according to Rodolfo Galindo, MD, director of the Comprehensive Diabetes Center at the University of Miami Health System in Florida.

“I believe this is important because unfortunately many of our older adults have both diabetes and obesity,” Dr. Galindo, who was not involved with the research, told this news organization. “You can induce remission of type 2 diabetes through weight loss that GLP-1s can cause.”

The treatment paradigm has shifted away from focusing only on lowering glucose levels as the primary means to prevent complications from diabetes, Dr. Galindo said.

Indeed, weight loss can modify diseases and prevent other complications associated with type 2 diabetes, Dr. Pendrey said.

“Weight loss and diabetes mellitus control also produces cardiovascular protection that is significant for patients with diabetes, so this group of patients in my opinion are the ones that benefit the most from GLP-1s,” she said.

Side effects of GLP-1 agonists can include nausea and vomiting, which could lead to dehydration. GLP-1s can also increase the risk for pancreatitis. For older adults, weight loss from the drug could cause sarcopenia, or loss of muscle mass, Dr. Galindo said.

“This is the reason why patients in treatment with GLP-1s have to be in close contact with their providers,” Dr. Pendrey said.

This study was independently supported. Dr. Pendrey and Dr. Galindo report no relevant conflicts.

A version of this article appeared on Medscape.com.

Glucagon-like peptide 1 (GLP-1) agonists may help clinicians manage uncontrolled type 2 diabetes in some older patients without the need for additional glucose-controlling medications, according to a study presented Nov. 8 at the annual meeting of the Gerontological Society of America.

The study analyzed charts of 30 adults aged 65-84 years who were seen in clinic from January 2022 to February 2023 and were started on GLP-1 or GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) agonists. Participants had uncontrolled type 2 diabetes with initial A1c levels ranging from 9.6% to 12.6% and a body mass index between 27 and 48.2. The patients also received education about their conditions as well as counseling on diet and lifestyle modifications.

All participants experienced a reduction in A1c to a range of 5.8% to 7.7%, and a moderate reduction in BMI to between 23 and 39.8 within the year.

“The reduction in BMI that we saw in our patients even though they were still in the category of obesity produces a substantial benefit in the management [of type 2 diabetes],” because weight loss helps to control the condition, said Anna Pendrey, MD, assistant professor of clinical family medicine and geriatrics at Indiana University, Indianapolis, and sole author of the study.

In some cases, the addition of a GLP-1 agonist or GLP-1/GIP agonist allowed for clinicians to deprescribe other medications such as insulin and sulfonylureas, which can cause hypoglycemia in older adults, Dr. Pendrey said.

Approximately 11% of U.S. adults have type 2 diabetes, a percentage that is likely to grow given the prevalence of childhood obesity, according to the Centers for Disease Control and Prevention. Dr. Pendrey highlighted the increased incidence of newly diagnosed diabetes in individuals aged 65-79 years.

Previous studies have shown that GLP-1 agonists have the potential to aid in weight reduction, glucose control, and the prevention of major adverse cardiovascular events in these patients.

The new study is one of many post hoc analyses that mark another step forward in addressing the complex challenges associated with diabetes in older adults, according to Rodolfo Galindo, MD, director of the Comprehensive Diabetes Center at the University of Miami Health System in Florida.

“I believe this is important because unfortunately many of our older adults have both diabetes and obesity,” Dr. Galindo, who was not involved with the research, told this news organization. “You can induce remission of type 2 diabetes through weight loss that GLP-1s can cause.”

The treatment paradigm has shifted away from focusing only on lowering glucose levels as the primary means to prevent complications from diabetes, Dr. Galindo said.

Indeed, weight loss can modify diseases and prevent other complications associated with type 2 diabetes, Dr. Pendrey said.

“Weight loss and diabetes mellitus control also produces cardiovascular protection that is significant for patients with diabetes, so this group of patients in my opinion are the ones that benefit the most from GLP-1s,” she said.

Side effects of GLP-1 agonists can include nausea and vomiting, which could lead to dehydration. GLP-1s can also increase the risk for pancreatitis. For older adults, weight loss from the drug could cause sarcopenia, or loss of muscle mass, Dr. Galindo said.

“This is the reason why patients in treatment with GLP-1s have to be in close contact with their providers,” Dr. Pendrey said.

This study was independently supported. Dr. Pendrey and Dr. Galindo report no relevant conflicts.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

Today we are going to talk about the American Geriatrics Society 2023 updated Beers Criteria guidance for medication use in older adults. These criteria have been updated and revised approximately every 5 years since 1991 and serve to alert us to medications for which the risk-benefit ratio is not as good in older adults as in the rest of the population.

These are important criteria because medications are metabolized differently in older adults and have different effects compared with younger patients. For the sake of these criteria, older adults are 65 years of age or older. That said, we know that everyone from 65 to 100 is not the same. As people age, they develop more comorbidities, they become more frail, and they are more sensitive to the effects and side effects of drugs.

The guidance covers potentially inappropriate medications for older adults. The word “potentially” is important because this is guidance. As clinicians, we make decisions involving individuals. This guidance should be used with judgment, integrating the clinical context of the individual patient.

There is a lot in this guidance. I am going to try to cover what I feel are the most important points.

Aspirin. Since the risk for major bleeding increases with age, for primary prevention of atherosclerotic cardiovascular disease, the harm can be greater than the benefit in older adults, so aspirin should not be used for primary prevention. Aspirin remains indicated for secondary prevention in individuals with established cardiovascular disease.

Warfarin. For treatment of atrial fibrillation or venous thromboembolism (deep vein thrombosis or pulmonary embolism), warfarin should be avoided if possible. Warfarin has a higher risk for major bleeding, particularly intracranial bleeding, than direct oral anticoagulants (DOACs); therefore the latter are preferred. Rivaroxaban should be avoided, as it has a higher risk for major bleeding in older adults than the other DOACs. Apixaban is preferred over dabigatran. If a patient is well controlled on warfarin, you can consider continuing that treatment.

Antipsychotics. These include first- and second-generation antipsychotics such as aripiprazole, haloperidol, olanzapine, quetiapine, risperidone, and others. The guidance says to avoid these agents except for FDA-approved indications such as schizophrenia, bipolar disorder, and adjuvant treatment of depression. Use of these antipsychotics can increase risk for stroke, heart attack, and mortality. Essentially, the guidance says do not use these medications lightly for the treatment of agitated dementia. For those of us with older patients, this can get tricky because agitated dementia is a difficult issue for which there are no good effective medications. The Beers guidance recognizes this in saying that these medications should be avoided unless behavioral interventions have failed. So, there are times where you may need to use these medicines, but use them judiciously.

For patients with dementia, anticholinergics, antipsychotics, and benzodiazepines should be avoided if possible.

Benzodiazepines. Benzodiazepines should also be avoided because older adults have increased sensitivity to their effects due to slower metabolism and clearance of these medications, which can lead to a much longer half-life and higher serum level. In older adults, benzodiazepines increase the risk for cognitive impairment, delirium, falls, fractures, and even motor accidents. The same concerns affect the group of non-benzodiazepine sleeping medicines known as “Z-drugs.”

Nonsteroidal anti-inflammatory drugs (NSAIDs). Used frequently in our practices, NSAIDs are nevertheless on the list. As we think through the risk-benefit ratio of using NSAIDs in older adults, we often underappreciate the risks of these agents. Upper gastrointestinal ulcers with bleeding occur in approximately 1% of patients treated for 3-6 months with an NSAID and in 2%-4% of patients treated for a year. NSAIDs also increase the risk for renal impairment and cardiovascular disease.

Other medications to avoid (if possible). These include:

Sulfonylureas, due to a high risk for hypoglycemia. A short-acting sulfonylurea, such as glipizide, should be used if one is needed.

Proton pump inhibitors should not be used long-term if it can be avoided.

Digoxin should not be first-line treatment for atrial fibrillation or heart failure. Decreased renal clearance in older adults can lead to toxic levels of digoxin, particularly during acute illnesses. Avoid doses > 0.125 mg/day.

Nitrofurantoin should be avoided when the patient’s creatinine clearance is < 30 or for long-term suppressive therapy.

Avoid combining medications that have high anticholinergic side effects, such as scopolamine, diphenhydramine, oxybutynin, cyclobenzaprine, and others.

It is always important to understand the benefits and the risks of the drugs we prescribe. It is also important to remember that older adults are a particularly vulnerable population. The Beers criteria provide important guidance, which we can then use to make decisions about medicines for individual patients.

Dr. Skolnik is a professor in the department of family medicine at Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, and associate director in the department of family medicine at Abington (Pa.) Jefferson Health. He disclosed ties with AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, GSK, Merck, Sanofi, Sanofi Pasteur, and Teva.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

Today we are going to talk about the American Geriatrics Society 2023 updated Beers Criteria guidance for medication use in older adults. These criteria have been updated and revised approximately every 5 years since 1991 and serve to alert us to medications for which the risk-benefit ratio is not as good in older adults as in the rest of the population.

These are important criteria because medications are metabolized differently in older adults and have different effects compared with younger patients. For the sake of these criteria, older adults are 65 years of age or older. That said, we know that everyone from 65 to 100 is not the same. As people age, they develop more comorbidities, they become more frail, and they are more sensitive to the effects and side effects of drugs.

The guidance covers potentially inappropriate medications for older adults. The word “potentially” is important because this is guidance. As clinicians, we make decisions involving individuals. This guidance should be used with judgment, integrating the clinical context of the individual patient.

There is a lot in this guidance. I am going to try to cover what I feel are the most important points.

Aspirin. Since the risk for major bleeding increases with age, for primary prevention of atherosclerotic cardiovascular disease, the harm can be greater than the benefit in older adults, so aspirin should not be used for primary prevention. Aspirin remains indicated for secondary prevention in individuals with established cardiovascular disease.

Warfarin. For treatment of atrial fibrillation or venous thromboembolism (deep vein thrombosis or pulmonary embolism), warfarin should be avoided if possible. Warfarin has a higher risk for major bleeding, particularly intracranial bleeding, than direct oral anticoagulants (DOACs); therefore the latter are preferred. Rivaroxaban should be avoided, as it has a higher risk for major bleeding in older adults than the other DOACs. Apixaban is preferred over dabigatran. If a patient is well controlled on warfarin, you can consider continuing that treatment.

Antipsychotics. These include first- and second-generation antipsychotics such as aripiprazole, haloperidol, olanzapine, quetiapine, risperidone, and others. The guidance says to avoid these agents except for FDA-approved indications such as schizophrenia, bipolar disorder, and adjuvant treatment of depression. Use of these antipsychotics can increase risk for stroke, heart attack, and mortality. Essentially, the guidance says do not use these medications lightly for the treatment of agitated dementia. For those of us with older patients, this can get tricky because agitated dementia is a difficult issue for which there are no good effective medications. The Beers guidance recognizes this in saying that these medications should be avoided unless behavioral interventions have failed. So, there are times where you may need to use these medicines, but use them judiciously.

For patients with dementia, anticholinergics, antipsychotics, and benzodiazepines should be avoided if possible.

Benzodiazepines. Benzodiazepines should also be avoided because older adults have increased sensitivity to their effects due to slower metabolism and clearance of these medications, which can lead to a much longer half-life and higher serum level. In older adults, benzodiazepines increase the risk for cognitive impairment, delirium, falls, fractures, and even motor accidents. The same concerns affect the group of non-benzodiazepine sleeping medicines known as “Z-drugs.”

Nonsteroidal anti-inflammatory drugs (NSAIDs). Used frequently in our practices, NSAIDs are nevertheless on the list. As we think through the risk-benefit ratio of using NSAIDs in older adults, we often underappreciate the risks of these agents. Upper gastrointestinal ulcers with bleeding occur in approximately 1% of patients treated for 3-6 months with an NSAID and in 2%-4% of patients treated for a year. NSAIDs also increase the risk for renal impairment and cardiovascular disease.

Other medications to avoid (if possible). These include:

Sulfonylureas, due to a high risk for hypoglycemia. A short-acting sulfonylurea, such as glipizide, should be used if one is needed.

Proton pump inhibitors should not be used long-term if it can be avoided.

Digoxin should not be first-line treatment for atrial fibrillation or heart failure. Decreased renal clearance in older adults can lead to toxic levels of digoxin, particularly during acute illnesses. Avoid doses > 0.125 mg/day.

Nitrofurantoin should be avoided when the patient’s creatinine clearance is < 30 or for long-term suppressive therapy.

Avoid combining medications that have high anticholinergic side effects, such as scopolamine, diphenhydramine, oxybutynin, cyclobenzaprine, and others.

It is always important to understand the benefits and the risks of the drugs we prescribe. It is also important to remember that older adults are a particularly vulnerable population. The Beers criteria provide important guidance, which we can then use to make decisions about medicines for individual patients.

Dr. Skolnik is a professor in the department of family medicine at Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, and associate director in the department of family medicine at Abington (Pa.) Jefferson Health. He disclosed ties with AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, GSK, Merck, Sanofi, Sanofi Pasteur, and Teva.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

Today we are going to talk about the American Geriatrics Society 2023 updated Beers Criteria guidance for medication use in older adults. These criteria have been updated and revised approximately every 5 years since 1991 and serve to alert us to medications for which the risk-benefit ratio is not as good in older adults as in the rest of the population.

These are important criteria because medications are metabolized differently in older adults and have different effects compared with younger patients. For the sake of these criteria, older adults are 65 years of age or older. That said, we know that everyone from 65 to 100 is not the same. As people age, they develop more comorbidities, they become more frail, and they are more sensitive to the effects and side effects of drugs.

The guidance covers potentially inappropriate medications for older adults. The word “potentially” is important because this is guidance. As clinicians, we make decisions involving individuals. This guidance should be used with judgment, integrating the clinical context of the individual patient.

There is a lot in this guidance. I am going to try to cover what I feel are the most important points.

Aspirin. Since the risk for major bleeding increases with age, for primary prevention of atherosclerotic cardiovascular disease, the harm can be greater than the benefit in older adults, so aspirin should not be used for primary prevention. Aspirin remains indicated for secondary prevention in individuals with established cardiovascular disease.

Warfarin. For treatment of atrial fibrillation or venous thromboembolism (deep vein thrombosis or pulmonary embolism), warfarin should be avoided if possible. Warfarin has a higher risk for major bleeding, particularly intracranial bleeding, than direct oral anticoagulants (DOACs); therefore the latter are preferred. Rivaroxaban should be avoided, as it has a higher risk for major bleeding in older adults than the other DOACs. Apixaban is preferred over dabigatran. If a patient is well controlled on warfarin, you can consider continuing that treatment.

Antipsychotics. These include first- and second-generation antipsychotics such as aripiprazole, haloperidol, olanzapine, quetiapine, risperidone, and others. The guidance says to avoid these agents except for FDA-approved indications such as schizophrenia, bipolar disorder, and adjuvant treatment of depression. Use of these antipsychotics can increase risk for stroke, heart attack, and mortality. Essentially, the guidance says do not use these medications lightly for the treatment of agitated dementia. For those of us with older patients, this can get tricky because agitated dementia is a difficult issue for which there are no good effective medications. The Beers guidance recognizes this in saying that these medications should be avoided unless behavioral interventions have failed. So, there are times where you may need to use these medicines, but use them judiciously.

For patients with dementia, anticholinergics, antipsychotics, and benzodiazepines should be avoided if possible.

Benzodiazepines. Benzodiazepines should also be avoided because older adults have increased sensitivity to their effects due to slower metabolism and clearance of these medications, which can lead to a much longer half-life and higher serum level. In older adults, benzodiazepines increase the risk for cognitive impairment, delirium, falls, fractures, and even motor accidents. The same concerns affect the group of non-benzodiazepine sleeping medicines known as “Z-drugs.”

Nonsteroidal anti-inflammatory drugs (NSAIDs). Used frequently in our practices, NSAIDs are nevertheless on the list. As we think through the risk-benefit ratio of using NSAIDs in older adults, we often underappreciate the risks of these agents. Upper gastrointestinal ulcers with bleeding occur in approximately 1% of patients treated for 3-6 months with an NSAID and in 2%-4% of patients treated for a year. NSAIDs also increase the risk for renal impairment and cardiovascular disease.

Other medications to avoid (if possible). These include:

Sulfonylureas, due to a high risk for hypoglycemia. A short-acting sulfonylurea, such as glipizide, should be used if one is needed.

Proton pump inhibitors should not be used long-term if it can be avoided.

Digoxin should not be first-line treatment for atrial fibrillation or heart failure. Decreased renal clearance in older adults can lead to toxic levels of digoxin, particularly during acute illnesses. Avoid doses > 0.125 mg/day.

Nitrofurantoin should be avoided when the patient’s creatinine clearance is < 30 or for long-term suppressive therapy.

Avoid combining medications that have high anticholinergic side effects, such as scopolamine, diphenhydramine, oxybutynin, cyclobenzaprine, and others.

It is always important to understand the benefits and the risks of the drugs we prescribe. It is also important to remember that older adults are a particularly vulnerable population. The Beers criteria provide important guidance, which we can then use to make decisions about medicines for individual patients.

Dr. Skolnik is a professor in the department of family medicine at Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, and associate director in the department of family medicine at Abington (Pa.) Jefferson Health. He disclosed ties with AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, GSK, Merck, Sanofi, Sanofi Pasteur, and Teva.

A version of this article appeared on Medscape.com.

TOPLINE:

Strength training at any point in life is associated with a lower risk of knee pain and osteoarthritis, contrary to persistent assumptions of adverse effects.

METHODOLOGY:

• Researchers reviewed data on strength training and knee pain from 2,607 adults. They used the Historical Physical Activity Survey Instrument to assess the impact of strength training during four periods (ages 12-18 years, 19-34 years, 35-49 years, and 50 years and older).
• The participants were enrolled in the Osteoarthritis Initiative, a multicenter, prospective, longitudinal study; 44% were male, the average age was 64.3 years, and the mean body mass index was 28.5 kg/m².
• Strength training was defined as those exposed and not exposed, as well as divided into low, medium, and high tertiles for those exposed. A total of 818 individuals were exposed to strength training, and 1,789 were not exposed to strength training.
• The primary outcomes were frequent knee pain, radiographic OA (ROA), and symptomatic radiographic OA (SOA).

TAKEAWAY:

• The study is the first to examine the effect of strength training on knee health in a community population sample not selected for a history of elite weight lifting.
• Overall, strength training at any point in life was associated with lower incidence of frequent knee pain, ROA, and SOA, compared with no strength training (odds ratios, 0.82, 0.83, and 0.77, respectively).
• When separated by tertiles, only the high-exposure group had significantly reduced odds of frequent knee pain, ROA, and SOA, with odds ratios of 0.74, 0.70, and 0.69, respectively. A dose-response relationship appeared for all three conditions, with the lowest odds ratios in the highest strength training exposure groups.
• Findings were similar for different age ranges, but the association between strength training and less frequent knee pain, less ROA, and less SOA was strongest in the older age groups.

IN PRACTICE:

“Our findings support the idea that the medical community should proactively encourage more people to participate in strength training to help reduce their risk of osteoarthritis and other chronic conditions,” the researchers write.

SOURCE:

The study, with first author Grace H. Lo, MD, of Baylor College of Medicine, Houston, and colleagues, was published in Arthritis and Rheumatology.

LIMITATIONS:

The observational design and self-selected study population of strength training participants might bias the results, including participants’ recall of their activity level levels and changes in exercise trends over time. More research is needed to explore associations between strength training and knee OA among those who started strength training at a younger age.

DISCLOSURES:

The study was funded in part by the VA Health Services Research and Development Center for Innovations in Quality, Effectiveness, and Safety at the Michael E. DeBakey VA Medical Center, Houston, and by donations to the Tupper Research Fund at Tufts Medical Center. The Osteoarthritis Initiative is supported by the National Institutes of Health; private funding partners include Merck Research Laboratories, Novartis, GlaxoSmithKline, and Pfizer. Three authors report having financial relationships with multiple pharmaceutical companies.

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

TOPLINE:

Strength training at any point in life is associated with a lower risk of knee pain and osteoarthritis, contrary to persistent assumptions of adverse effects.

METHODOLOGY:

• Researchers reviewed data on strength training and knee pain from 2,607 adults. They used the Historical Physical Activity Survey Instrument to assess the impact of strength training during four periods (ages 12-18 years, 19-34 years, 35-49 years, and 50 years and older).
• The participants were enrolled in the Osteoarthritis Initiative, a multicenter, prospective, longitudinal study; 44% were male, the average age was 64.3 years, and the mean body mass index was 28.5 kg/m².
• Strength training was defined as those exposed and not exposed, as well as divided into low, medium, and high tertiles for those exposed. A total of 818 individuals were exposed to strength training, and 1,789 were not exposed to strength training.
• The primary outcomes were frequent knee pain, radiographic OA (ROA), and symptomatic radiographic OA (SOA).

TAKEAWAY:

• The study is the first to examine the effect of strength training on knee health in a community population sample not selected for a history of elite weight lifting.
• Overall, strength training at any point in life was associated with lower incidence of frequent knee pain, ROA, and SOA, compared with no strength training (odds ratios, 0.82, 0.83, and 0.77, respectively).
• When separated by tertiles, only the high-exposure group had significantly reduced odds of frequent knee pain, ROA, and SOA, with odds ratios of 0.74, 0.70, and 0.69, respectively. A dose-response relationship appeared for all three conditions, with the lowest odds ratios in the highest strength training exposure groups.
• Findings were similar for different age ranges, but the association between strength training and less frequent knee pain, less ROA, and less SOA was strongest in the older age groups.

IN PRACTICE:

“Our findings support the idea that the medical community should proactively encourage more people to participate in strength training to help reduce their risk of osteoarthritis and other chronic conditions,” the researchers write.

SOURCE:

The study, with first author Grace H. Lo, MD, of Baylor College of Medicine, Houston, and colleagues, was published in Arthritis and Rheumatology.

LIMITATIONS:

The observational design and self-selected study population of strength training participants might bias the results, including participants’ recall of their activity level levels and changes in exercise trends over time. More research is needed to explore associations between strength training and knee OA among those who started strength training at a younger age.

DISCLOSURES:

The study was funded in part by the VA Health Services Research and Development Center for Innovations in Quality, Effectiveness, and Safety at the Michael E. DeBakey VA Medical Center, Houston, and by donations to the Tupper Research Fund at Tufts Medical Center. The Osteoarthritis Initiative is supported by the National Institutes of Health; private funding partners include Merck Research Laboratories, Novartis, GlaxoSmithKline, and Pfizer. Three authors report having financial relationships with multiple pharmaceutical companies.

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

TOPLINE:

Strength training at any point in life is associated with a lower risk of knee pain and osteoarthritis, contrary to persistent assumptions of adverse effects.

METHODOLOGY:

• Researchers reviewed data on strength training and knee pain from 2,607 adults. They used the Historical Physical Activity Survey Instrument to assess the impact of strength training during four periods (ages 12-18 years, 19-34 years, 35-49 years, and 50 years and older).
• The participants were enrolled in the Osteoarthritis Initiative, a multicenter, prospective, longitudinal study; 44% were male, the average age was 64.3 years, and the mean body mass index was 28.5 kg/m².
• Strength training was defined as those exposed and not exposed, as well as divided into low, medium, and high tertiles for those exposed. A total of 818 individuals were exposed to strength training, and 1,789 were not exposed to strength training.
• The primary outcomes were frequent knee pain, radiographic OA (ROA), and symptomatic radiographic OA (SOA).

TAKEAWAY:

• The study is the first to examine the effect of strength training on knee health in a community population sample not selected for a history of elite weight lifting.
• Overall, strength training at any point in life was associated with lower incidence of frequent knee pain, ROA, and SOA, compared with no strength training (odds ratios, 0.82, 0.83, and 0.77, respectively).
• When separated by tertiles, only the high-exposure group had significantly reduced odds of frequent knee pain, ROA, and SOA, with odds ratios of 0.74, 0.70, and 0.69, respectively. A dose-response relationship appeared for all three conditions, with the lowest odds ratios in the highest strength training exposure groups.
• Findings were similar for different age ranges, but the association between strength training and less frequent knee pain, less ROA, and less SOA was strongest in the older age groups.

IN PRACTICE:

“Our findings support the idea that the medical community should proactively encourage more people to participate in strength training to help reduce their risk of osteoarthritis and other chronic conditions,” the researchers write.

SOURCE:

The study, with first author Grace H. Lo, MD, of Baylor College of Medicine, Houston, and colleagues, was published in Arthritis and Rheumatology.

LIMITATIONS:

The observational design and self-selected study population of strength training participants might bias the results, including participants’ recall of their activity level levels and changes in exercise trends over time. More research is needed to explore associations between strength training and knee OA among those who started strength training at a younger age.

DISCLOSURES:

The study was funded in part by the VA Health Services Research and Development Center for Innovations in Quality, Effectiveness, and Safety at the Michael E. DeBakey VA Medical Center, Houston, and by donations to the Tupper Research Fund at Tufts Medical Center. The Osteoarthritis Initiative is supported by the National Institutes of Health; private funding partners include Merck Research Laboratories, Novartis, GlaxoSmithKline, and Pfizer. Three authors report having financial relationships with multiple pharmaceutical companies.

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

TOPLINE:

New research suggests terminating metformin may raise the risk for dementia in older adults with type 2 diabetes, providing more evidence of metformin’s potential neuroprotective effects.

METHODOLOGY:

• Researchers evaluated the association between discontinuing metformin for reasons unrelated to kidney dysfunction and dementia incidence.
• The cohort included 12,220 Kaiser Permanente Northern California members who stopped metformin early (with normal kidney function) and 29,126 routine metformin users.
• The cohort of early terminators was 46% women with an average age of 59 years at the start of metformin prescription. The cohort continuing metformin was 47% women, with a start age of 61 years.

TAKEAWAY:

• Adults who stopped metformin early were 21% more likely to be diagnosed with dementia during follow up (hazard ratio, 1.21; 95% confidence interval, 1.12-1.30), compared with routine metformin users.
• This association was largely independent of changes in A1c level and insulin usage.

IN PRACTICE:

The findings “corroborate the largely consistent evidence from other observational studies showing an association between metformin use and lower dementia incidence [and] may have important implications for clinical treatment of adults with diabetes,” the authors write.

SOURCE:

The study, with first author Scott Zimmerman, MPH, University of California, San Francisco, was published online  in JAMA Network Open.

LIMITATIONS:

Dementia diagnosis was obtained based on medical records. Factors such as race, ethnicity, or time on metformin were not evaluated. Information on the exact reason for stopping metformin was not available.

DISCLOSURES:

The study was funded by grants from the National Institutes of Health, National Institute on Aging. Mr. Zimmerman owns stock in AbbVie, Gilead Sciences, CRISPR Therapeutics, and Abbott Laboratories. Disclosure for the other study authors can be found with the original article.

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

TOPLINE:

New research suggests terminating metformin may raise the risk for dementia in older adults with type 2 diabetes, providing more evidence of metformin’s potential neuroprotective effects.

METHODOLOGY:

• Researchers evaluated the association between discontinuing metformin for reasons unrelated to kidney dysfunction and dementia incidence.
• The cohort included 12,220 Kaiser Permanente Northern California members who stopped metformin early (with normal kidney function) and 29,126 routine metformin users.
• The cohort of early terminators was 46% women with an average age of 59 years at the start of metformin prescription. The cohort continuing metformin was 47% women, with a start age of 61 years.

TAKEAWAY:

• Adults who stopped metformin early were 21% more likely to be diagnosed with dementia during follow up (hazard ratio, 1.21; 95% confidence interval, 1.12-1.30), compared with routine metformin users.
• This association was largely independent of changes in A1c level and insulin usage.

IN PRACTICE:

The findings “corroborate the largely consistent evidence from other observational studies showing an association between metformin use and lower dementia incidence [and] may have important implications for clinical treatment of adults with diabetes,” the authors write.

SOURCE:

The study, with first author Scott Zimmerman, MPH, University of California, San Francisco, was published online  in JAMA Network Open.

LIMITATIONS:

Dementia diagnosis was obtained based on medical records. Factors such as race, ethnicity, or time on metformin were not evaluated. Information on the exact reason for stopping metformin was not available.

DISCLOSURES:

The study was funded by grants from the National Institutes of Health, National Institute on Aging. Mr. Zimmerman owns stock in AbbVie, Gilead Sciences, CRISPR Therapeutics, and Abbott Laboratories. Disclosure for the other study authors can be found with the original article.

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

TOPLINE:

New research suggests terminating metformin may raise the risk for dementia in older adults with type 2 diabetes, providing more evidence of metformin’s potential neuroprotective effects.

METHODOLOGY:

• Researchers evaluated the association between discontinuing metformin for reasons unrelated to kidney dysfunction and dementia incidence.
• The cohort included 12,220 Kaiser Permanente Northern California members who stopped metformin early (with normal kidney function) and 29,126 routine metformin users.
• The cohort of early terminators was 46% women with an average age of 59 years at the start of metformin prescription. The cohort continuing metformin was 47% women, with a start age of 61 years.

TAKEAWAY:

• Adults who stopped metformin early were 21% more likely to be diagnosed with dementia during follow up (hazard ratio, 1.21; 95% confidence interval, 1.12-1.30), compared with routine metformin users.
• This association was largely independent of changes in A1c level and insulin usage.

IN PRACTICE:

The findings “corroborate the largely consistent evidence from other observational studies showing an association between metformin use and lower dementia incidence [and] may have important implications for clinical treatment of adults with diabetes,” the authors write.

SOURCE:

The study, with first author Scott Zimmerman, MPH, University of California, San Francisco, was published online  in JAMA Network Open.

LIMITATIONS:

Dementia diagnosis was obtained based on medical records. Factors such as race, ethnicity, or time on metformin were not evaluated. Information on the exact reason for stopping metformin was not available.

DISCLOSURES:

The study was funded by grants from the National Institutes of Health, National Institute on Aging. Mr. Zimmerman owns stock in AbbVie, Gilead Sciences, CRISPR Therapeutics, and Abbott Laboratories. Disclosure for the other study authors can be found with the original article.

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

TOPLINE:

Detection rates of mild cognitive impairment (MCI) in primary care are extremely low, with only about 8% of expected cases diagnosed on average, a finding that points to an urgent need to improve early detection in primary care.

METHODOLOGY:

• Researchers estimated MCI detection rates among 226,756 primary care clinicians and 54,597 practices that had at least 25 patients enrolled in Medicare between 2017 and 2019. 
• They compared the expected number of MCI cases, based on a predictive model, to actual diagnosed cases as documented in claims and encounter data.
• They accounted for uncertainty in these estimates to determine whether detection rates are within the expected range or significantly higher or lower.

TAKEAWAY:

• More than 25% of clinicians and practices did not have a single patient with diagnosed MCI; the average detection rate was 0.01 for both clinicians and practices.
• The modeled expected MCI detection rate, however, was much higher (average 0.19 for clinicians and 0.20 for practices).
• Average detection rates for clinicians and practices was 0.08, with more than 99% of clinicians and practices underdiagnosing MCI; clinicians practicing geriatric medicine had higher detection rates than others.

IN PRACTICE:

The findings are “concerning not only because patients might not get identified for a disease-modifying AD treatment in time, but also because numerous causes of MCI – such as hypothyroidism and medication side effects – are reversible, and the condition itself can be stabilized by lifestyle modification interventions,” the authors write.

SOURCE:

The study was published online in the Journal of Prevention of Alzheimer’s Disease. The first author was Ying Liu, PhD, of the University of Southern California, Los Angeles.

LIMITATIONS:

The predictive model based on demographic information has only moderate accuracy. Expected prevalence of MCI was based on cognitive test scores, which is not the same as a true clinical diagnosis.

DISCLOSURES:

The study was partially funded by a contract from Genentech to the University of Southern California. Coauthors Soeren Mattke and Christopher Wallick have disclosed relationships with Genentech.

A version of this article appeared on Medscape.com.

TOPLINE:

Detection rates of mild cognitive impairment (MCI) in primary care are extremely low, with only about 8% of expected cases diagnosed on average, a finding that points to an urgent need to improve early detection in primary care.

METHODOLOGY:

• Researchers estimated MCI detection rates among 226,756 primary care clinicians and 54,597 practices that had at least 25 patients enrolled in Medicare between 2017 and 2019. 
• They compared the expected number of MCI cases, based on a predictive model, to actual diagnosed cases as documented in claims and encounter data.
• They accounted for uncertainty in these estimates to determine whether detection rates are within the expected range or significantly higher or lower.

TAKEAWAY:

• More than 25% of clinicians and practices did not have a single patient with diagnosed MCI; the average detection rate was 0.01 for both clinicians and practices.
• The modeled expected MCI detection rate, however, was much higher (average 0.19 for clinicians and 0.20 for practices).
• Average detection rates for clinicians and practices was 0.08, with more than 99% of clinicians and practices underdiagnosing MCI; clinicians practicing geriatric medicine had higher detection rates than others.

IN PRACTICE:

The findings are “concerning not only because patients might not get identified for a disease-modifying AD treatment in time, but also because numerous causes of MCI – such as hypothyroidism and medication side effects – are reversible, and the condition itself can be stabilized by lifestyle modification interventions,” the authors write.

SOURCE:

The study was published online in the Journal of Prevention of Alzheimer’s Disease. The first author was Ying Liu, PhD, of the University of Southern California, Los Angeles.

LIMITATIONS:

The predictive model based on demographic information has only moderate accuracy. Expected prevalence of MCI was based on cognitive test scores, which is not the same as a true clinical diagnosis.

DISCLOSURES:

The study was partially funded by a contract from Genentech to the University of Southern California. Coauthors Soeren Mattke and Christopher Wallick have disclosed relationships with Genentech.

A version of this article appeared on Medscape.com.

TOPLINE:

Detection rates of mild cognitive impairment (MCI) in primary care are extremely low, with only about 8% of expected cases diagnosed on average, a finding that points to an urgent need to improve early detection in primary care.

METHODOLOGY:

• Researchers estimated MCI detection rates among 226,756 primary care clinicians and 54,597 practices that had at least 25 patients enrolled in Medicare between 2017 and 2019. 
• They compared the expected number of MCI cases, based on a predictive model, to actual diagnosed cases as documented in claims and encounter data.
• They accounted for uncertainty in these estimates to determine whether detection rates are within the expected range or significantly higher or lower.

TAKEAWAY:

• More than 25% of clinicians and practices did not have a single patient with diagnosed MCI; the average detection rate was 0.01 for both clinicians and practices.
• The modeled expected MCI detection rate, however, was much higher (average 0.19 for clinicians and 0.20 for practices).
• Average detection rates for clinicians and practices was 0.08, with more than 99% of clinicians and practices underdiagnosing MCI; clinicians practicing geriatric medicine had higher detection rates than others.

IN PRACTICE:

The findings are “concerning not only because patients might not get identified for a disease-modifying AD treatment in time, but also because numerous causes of MCI – such as hypothyroidism and medication side effects – are reversible, and the condition itself can be stabilized by lifestyle modification interventions,” the authors write.

SOURCE:

The study was published online in the Journal of Prevention of Alzheimer’s Disease. The first author was Ying Liu, PhD, of the University of Southern California, Los Angeles.

LIMITATIONS:

The predictive model based on demographic information has only moderate accuracy. Expected prevalence of MCI was based on cognitive test scores, which is not the same as a true clinical diagnosis.

DISCLOSURES:

The study was partially funded by a contract from Genentech to the University of Southern California. Coauthors Soeren Mattke and Christopher Wallick have disclosed relationships with Genentech.

A version of this article appeared on Medscape.com.

BARCELONA – Intermittent benzodiazepine use significantly reduces the risk for falls, fractures, and mortality in older adults compared with chronic use of these medications, results of a large-scale study show.

Investigators matched more than 57,000 chronic benzodiazepine users with nearly 114,000 intermittent users and found that, at 1 year, chronic users had an 8% increased risk for emergency department visits and/or hospitalizations for falls.

Chronic users also had a 25% increased risk for hip fracture, a 4% raised risk for ED visits and/or hospitalizations for any reason, and a 23% increased risk for death.

Study investigator Simon J.C. Davies, MD, PhD, MSc, Centre for Addiction & Mental Health, Toronto, said that the research shows that, where possible, patients older than 65 years with anxiety or insomnia who are taking benzodiazepines should not stay on these medications continuously.

However, he acknowledged that, “in practical terms, there will be some who can’t change or do not want to change” their treatment.

The findings were presented at the annual meeting of the European College of Neuropsychopharmacology.
 

Wide range of adverse outcomes

The authors noted that benzodiazepines are used to treat anxiety and insomnia but are associated with a range of adverse outcomes, including falls, fractures, cognitive impairment, and mortality as well as tolerance and dose escalation.

“These risks are especially relevant in older adults,” they added, noting that some guidelines recommend avoiding the drugs in this population, whereas other suggest short-term benzodiazepine use for a maximum of 4 weeks.

Despite this, “benzodiazepines are widely prescribed in older adults.” One study showed that almost 15% of adults aged 65 years or older received at least one benzodiazepine prescription.

Moreover, chronic use is more common in older versus younger patients.

Benzodiazepine use among older adults “used to be higher,” Dr. Davies said in an interview, at around 20%, but the “numbers have come down,” partly because of the introduction of benzodiazepine-like sleep medications but also because of educational efforts.

“There are certainly campaigns in Ontario to educate physicians,” Dr. Davies said, “but I think more broadly people are aware of the activity of these drugs, and the tolerance and other issues.”

To compare the risk associated with chronic versus intermittent use of benzodiazepines in older adults, the team performed a population-based cohort study using linked health care databases in Ontario.

They focused on adults aged 65 years or older with a first benzodiazepine prescription after at least 1 year without taking the drugs.

Chronic benzodiazepine use was defined as 120 days of prescriptions over the first 180 days after the index prescription. Patients who met these criteria were matched with intermittent users in a 2:1 ratio by age and sex.

Patients were then propensity matched using 24 variables, including health system use in the year prior to the index prescription, clinical diagnoses, prior psychiatric health system use, falls, and income level.

The team identified 57,072 chronic benzodiazepine users and 312,468 intermittent users, of whom, 57,041 and 113,839, respectively, were propensity matched.

As expected, chronic users were prescribed benzodiazepines for more days than were the intermittent users over both the initial 180-day exposure period, at 141 days versus 33 days, and again during a further 180-day follow-up period, at 181 days versus 19 days.

Over the follow-up period, the daily lorazepam dose-equivalents of chronic users four times that of intermittent users.

Hospitalizations and/or ED visits for falls were higher among patients in the chronic benzodiazepine group, at 4.6% versus 3.2% in those who took the drugs intermittently.

After adjusting for benzodiazepine dose, the team found that chronic benzodiazepine use was associated with a significant increase in the risk for falls leading to hospital presentation over the 360-day study period, compared with intermittent use (hazard ratio, 1.08; P = .0124).
 

Sex differences

In addition, chronic use was linked to a significantly increased risk for hip fracture (HR, 1.25; P = .0095), and long-term care admission (HR, 1.32; P < .0001).

There was also a significant increase in ED visits and/or hospitalizations for any reason with chronic benzodiazepine use versus intermittent use (HR, 1.04; P = .0007), and an increase in the risk for death (HR, 1.23; P < .0001).

A nonsignificant increased risk for wrist fracture was also associated with chronic use of benzodiazepines (HR, 1.02; P = .8683).

Further analysis revealed some sex differences. For instance, men had a marked increase in the risk for hip fracture with chronic use (HR, 1.50; P = .0154), whereas the risk was not significant in women (HR, 1.16; P = .1332). In addition, mortality risk associated with chronic use was higher in men than in women (HR, 1.39; P < .0001 vs. HR, 1.10; P = .2245).

The decision to discontinue chronic benzodiazepine use can be challenging, said Dr. Davies. “If you’re advising people to stop, what happens to the treatment of their anxiety?”

He said that there are many other treatment options for anxiety that don’t come with tolerance or risk for addiction.

“My position would be that intermittent use is perfectly acceptable while you bide your time to explore other treatments. They may be pharmacological; they may, of course, be lifestyle changes, psychotherapies, and so on,” said Dr. Davies.

If, however, patients feel that chronic benzodiazepine use is their only option, this research informs that decision by quantifying the risks.

“We’ve always known that there was a problem, but there haven’t been high-quality epidemiological studies like this that allowed us to say what the numbers are,” said Dr. Davies.
 

Confirmatory research

In a comment, Christoph U. Correll, MD, professor of psychiatry at Hofstra University, Hempstead, N.Y., noted that the risk associated with benzodiazepine use, especially in older people, has been demonstrated repeatedly.

“In that context, it is not surprising that less continuous exposure to an established risk factor attenuates the risk for these adverse outcomes,” he said.

Dr. Correll, who was not involved in the study pointed out there is nevertheless a “risk of residual confounding by indication.”

In other words, “people with intermittent benzodiazepine use may have less severe underlying illness and better healthy lifestyle behaviors than those requiring chronic benzodiazepine administration.”

Also commenting on the research, Christian Vinkers, MD, PhD, psychiatrist and professor of stress and resilience, Amsterdam University Medical Centre, said that it confirms “once again that long-term benzodiazepine use should not be encouraged.”

“The risk of falls, as well as cognitive side effects and impaired driving skills, with the risk of road accidents, make chronic overuse of benzodiazepines a public health issue. Of course, there is a small group of patients who should have access to long-term use, but it is reasonable to assume that this group is currently too large,” he added.

The study was funded through a grant from the University of Toronto Department of Psychiatry Excellence Funds. No relevant financial relationships were declared.

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

BARCELONA – Intermittent benzodiazepine use significantly reduces the risk for falls, fractures, and mortality in older adults compared with chronic use of these medications, results of a large-scale study show.

Investigators matched more than 57,000 chronic benzodiazepine users with nearly 114,000 intermittent users and found that, at 1 year, chronic users had an 8% increased risk for emergency department visits and/or hospitalizations for falls.

Chronic users also had a 25% increased risk for hip fracture, a 4% raised risk for ED visits and/or hospitalizations for any reason, and a 23% increased risk for death.

Study investigator Simon J.C. Davies, MD, PhD, MSc, Centre for Addiction & Mental Health, Toronto, said that the research shows that, where possible, patients older than 65 years with anxiety or insomnia who are taking benzodiazepines should not stay on these medications continuously.

However, he acknowledged that, “in practical terms, there will be some who can’t change or do not want to change” their treatment.

The findings were presented at the annual meeting of the European College of Neuropsychopharmacology.
 

Wide range of adverse outcomes

The authors noted that benzodiazepines are used to treat anxiety and insomnia but are associated with a range of adverse outcomes, including falls, fractures, cognitive impairment, and mortality as well as tolerance and dose escalation.

“These risks are especially relevant in older adults,” they added, noting that some guidelines recommend avoiding the drugs in this population, whereas other suggest short-term benzodiazepine use for a maximum of 4 weeks.

Despite this, “benzodiazepines are widely prescribed in older adults.” One study showed that almost 15% of adults aged 65 years or older received at least one benzodiazepine prescription.

Moreover, chronic use is more common in older versus younger patients.

Benzodiazepine use among older adults “used to be higher,” Dr. Davies said in an interview, at around 20%, but the “numbers have come down,” partly because of the introduction of benzodiazepine-like sleep medications but also because of educational efforts.

“There are certainly campaigns in Ontario to educate physicians,” Dr. Davies said, “but I think more broadly people are aware of the activity of these drugs, and the tolerance and other issues.”

To compare the risk associated with chronic versus intermittent use of benzodiazepines in older adults, the team performed a population-based cohort study using linked health care databases in Ontario.

They focused on adults aged 65 years or older with a first benzodiazepine prescription after at least 1 year without taking the drugs.

Chronic benzodiazepine use was defined as 120 days of prescriptions over the first 180 days after the index prescription. Patients who met these criteria were matched with intermittent users in a 2:1 ratio by age and sex.

Patients were then propensity matched using 24 variables, including health system use in the year prior to the index prescription, clinical diagnoses, prior psychiatric health system use, falls, and income level.

The team identified 57,072 chronic benzodiazepine users and 312,468 intermittent users, of whom, 57,041 and 113,839, respectively, were propensity matched.

As expected, chronic users were prescribed benzodiazepines for more days than were the intermittent users over both the initial 180-day exposure period, at 141 days versus 33 days, and again during a further 180-day follow-up period, at 181 days versus 19 days.

Over the follow-up period, the daily lorazepam dose-equivalents of chronic users four times that of intermittent users.

Hospitalizations and/or ED visits for falls were higher among patients in the chronic benzodiazepine group, at 4.6% versus 3.2% in those who took the drugs intermittently.

After adjusting for benzodiazepine dose, the team found that chronic benzodiazepine use was associated with a significant increase in the risk for falls leading to hospital presentation over the 360-day study period, compared with intermittent use (hazard ratio, 1.08; P = .0124).
 

Sex differences

In addition, chronic use was linked to a significantly increased risk for hip fracture (HR, 1.25; P = .0095), and long-term care admission (HR, 1.32; P < .0001).

There was also a significant increase in ED visits and/or hospitalizations for any reason with chronic benzodiazepine use versus intermittent use (HR, 1.04; P = .0007), and an increase in the risk for death (HR, 1.23; P < .0001).

A nonsignificant increased risk for wrist fracture was also associated with chronic use of benzodiazepines (HR, 1.02; P = .8683).

Further analysis revealed some sex differences. For instance, men had a marked increase in the risk for hip fracture with chronic use (HR, 1.50; P = .0154), whereas the risk was not significant in women (HR, 1.16; P = .1332). In addition, mortality risk associated with chronic use was higher in men than in women (HR, 1.39; P < .0001 vs. HR, 1.10; P = .2245).

The decision to discontinue chronic benzodiazepine use can be challenging, said Dr. Davies. “If you’re advising people to stop, what happens to the treatment of their anxiety?”

He said that there are many other treatment options for anxiety that don’t come with tolerance or risk for addiction.

“My position would be that intermittent use is perfectly acceptable while you bide your time to explore other treatments. They may be pharmacological; they may, of course, be lifestyle changes, psychotherapies, and so on,” said Dr. Davies.

If, however, patients feel that chronic benzodiazepine use is their only option, this research informs that decision by quantifying the risks.

“We’ve always known that there was a problem, but there haven’t been high-quality epidemiological studies like this that allowed us to say what the numbers are,” said Dr. Davies.
 

Confirmatory research

In a comment, Christoph U. Correll, MD, professor of psychiatry at Hofstra University, Hempstead, N.Y., noted that the risk associated with benzodiazepine use, especially in older people, has been demonstrated repeatedly.

“In that context, it is not surprising that less continuous exposure to an established risk factor attenuates the risk for these adverse outcomes,” he said.

Dr. Correll, who was not involved in the study pointed out there is nevertheless a “risk of residual confounding by indication.”

In other words, “people with intermittent benzodiazepine use may have less severe underlying illness and better healthy lifestyle behaviors than those requiring chronic benzodiazepine administration.”

Also commenting on the research, Christian Vinkers, MD, PhD, psychiatrist and professor of stress and resilience, Amsterdam University Medical Centre, said that it confirms “once again that long-term benzodiazepine use should not be encouraged.”

“The risk of falls, as well as cognitive side effects and impaired driving skills, with the risk of road accidents, make chronic overuse of benzodiazepines a public health issue. Of course, there is a small group of patients who should have access to long-term use, but it is reasonable to assume that this group is currently too large,” he added.

The study was funded through a grant from the University of Toronto Department of Psychiatry Excellence Funds. No relevant financial relationships were declared.

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

BARCELONA – Intermittent benzodiazepine use significantly reduces the risk for falls, fractures, and mortality in older adults compared with chronic use of these medications, results of a large-scale study show.

Investigators matched more than 57,000 chronic benzodiazepine users with nearly 114,000 intermittent users and found that, at 1 year, chronic users had an 8% increased risk for emergency department visits and/or hospitalizations for falls.

Chronic users also had a 25% increased risk for hip fracture, a 4% raised risk for ED visits and/or hospitalizations for any reason, and a 23% increased risk for death.

Study investigator Simon J.C. Davies, MD, PhD, MSc, Centre for Addiction & Mental Health, Toronto, said that the research shows that, where possible, patients older than 65 years with anxiety or insomnia who are taking benzodiazepines should not stay on these medications continuously.

However, he acknowledged that, “in practical terms, there will be some who can’t change or do not want to change” their treatment.

The findings were presented at the annual meeting of the European College of Neuropsychopharmacology.
 

Wide range of adverse outcomes

The authors noted that benzodiazepines are used to treat anxiety and insomnia but are associated with a range of adverse outcomes, including falls, fractures, cognitive impairment, and mortality as well as tolerance and dose escalation.

“These risks are especially relevant in older adults,” they added, noting that some guidelines recommend avoiding the drugs in this population, whereas other suggest short-term benzodiazepine use for a maximum of 4 weeks.

Despite this, “benzodiazepines are widely prescribed in older adults.” One study showed that almost 15% of adults aged 65 years or older received at least one benzodiazepine prescription.

Moreover, chronic use is more common in older versus younger patients.

Benzodiazepine use among older adults “used to be higher,” Dr. Davies said in an interview, at around 20%, but the “numbers have come down,” partly because of the introduction of benzodiazepine-like sleep medications but also because of educational efforts.

“There are certainly campaigns in Ontario to educate physicians,” Dr. Davies said, “but I think more broadly people are aware of the activity of these drugs, and the tolerance and other issues.”

To compare the risk associated with chronic versus intermittent use of benzodiazepines in older adults, the team performed a population-based cohort study using linked health care databases in Ontario.

They focused on adults aged 65 years or older with a first benzodiazepine prescription after at least 1 year without taking the drugs.

Chronic benzodiazepine use was defined as 120 days of prescriptions over the first 180 days after the index prescription. Patients who met these criteria were matched with intermittent users in a 2:1 ratio by age and sex.

Patients were then propensity matched using 24 variables, including health system use in the year prior to the index prescription, clinical diagnoses, prior psychiatric health system use, falls, and income level.

The team identified 57,072 chronic benzodiazepine users and 312,468 intermittent users, of whom, 57,041 and 113,839, respectively, were propensity matched.

As expected, chronic users were prescribed benzodiazepines for more days than were the intermittent users over both the initial 180-day exposure period, at 141 days versus 33 days, and again during a further 180-day follow-up period, at 181 days versus 19 days.

Over the follow-up period, the daily lorazepam dose-equivalents of chronic users four times that of intermittent users.

Hospitalizations and/or ED visits for falls were higher among patients in the chronic benzodiazepine group, at 4.6% versus 3.2% in those who took the drugs intermittently.

After adjusting for benzodiazepine dose, the team found that chronic benzodiazepine use was associated with a significant increase in the risk for falls leading to hospital presentation over the 360-day study period, compared with intermittent use (hazard ratio, 1.08; P = .0124).
 

Sex differences

In addition, chronic use was linked to a significantly increased risk for hip fracture (HR, 1.25; P = .0095), and long-term care admission (HR, 1.32; P < .0001).

There was also a significant increase in ED visits and/or hospitalizations for any reason with chronic benzodiazepine use versus intermittent use (HR, 1.04; P = .0007), and an increase in the risk for death (HR, 1.23; P < .0001).

A nonsignificant increased risk for wrist fracture was also associated with chronic use of benzodiazepines (HR, 1.02; P = .8683).

Further analysis revealed some sex differences. For instance, men had a marked increase in the risk for hip fracture with chronic use (HR, 1.50; P = .0154), whereas the risk was not significant in women (HR, 1.16; P = .1332). In addition, mortality risk associated with chronic use was higher in men than in women (HR, 1.39; P < .0001 vs. HR, 1.10; P = .2245).

The decision to discontinue chronic benzodiazepine use can be challenging, said Dr. Davies. “If you’re advising people to stop, what happens to the treatment of their anxiety?”

He said that there are many other treatment options for anxiety that don’t come with tolerance or risk for addiction.

“My position would be that intermittent use is perfectly acceptable while you bide your time to explore other treatments. They may be pharmacological; they may, of course, be lifestyle changes, psychotherapies, and so on,” said Dr. Davies.

If, however, patients feel that chronic benzodiazepine use is their only option, this research informs that decision by quantifying the risks.

“We’ve always known that there was a problem, but there haven’t been high-quality epidemiological studies like this that allowed us to say what the numbers are,” said Dr. Davies.
 

Confirmatory research

In a comment, Christoph U. Correll, MD, professor of psychiatry at Hofstra University, Hempstead, N.Y., noted that the risk associated with benzodiazepine use, especially in older people, has been demonstrated repeatedly.

“In that context, it is not surprising that less continuous exposure to an established risk factor attenuates the risk for these adverse outcomes,” he said.

Dr. Correll, who was not involved in the study pointed out there is nevertheless a “risk of residual confounding by indication.”

In other words, “people with intermittent benzodiazepine use may have less severe underlying illness and better healthy lifestyle behaviors than those requiring chronic benzodiazepine administration.”

Also commenting on the research, Christian Vinkers, MD, PhD, psychiatrist and professor of stress and resilience, Amsterdam University Medical Centre, said that it confirms “once again that long-term benzodiazepine use should not be encouraged.”

“The risk of falls, as well as cognitive side effects and impaired driving skills, with the risk of road accidents, make chronic overuse of benzodiazepines a public health issue. Of course, there is a small group of patients who should have access to long-term use, but it is reasonable to assume that this group is currently too large,” he added.

The study was funded through a grant from the University of Toronto Department of Psychiatry Excellence Funds. No relevant financial relationships were declared.

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