Alzheimer's & Cognition

Antihypertensive medications that stimulate rather than inhibit type 2 and 4 angiotensin II receptors can lower the rate of dementia among new users of these medications, new research suggests.

Results from a cohort study of more than 57,000 older Medicare beneficiaries showed that the initiation of antihypertensives that stimulate the receptors was linked to a 16% lower risk for incident Alzheimer’s disease and related dementia (ADRD) and an 18% lower risk for vascular dementia compared with those that inhibit the receptors.

“Achieving appropriate blood pressure control is essential for maximizing brain health, and this promising research suggests certain antihypertensives could yield brain benefit compared to others,” lead study author Zachary A. Marcum, PharmD, PhD, associate professor, University of Washington School of Pharmacy, Seattle, told this news organization.

The findings were published online in JAMA Network Open.
 

Medicare beneficiaries

Previous observational studies showed that antihypertensive medications that stimulate type 2 and 4 angiotensin II receptors, in comparison with those that don’t, were associated with lower rates of dementia. However, those studies included individuals with prevalent hypertension and were relatively small.

The new retrospective cohort study included a random sample of 57,773 Medicare beneficiaries aged at least 65 years with new-onset hypertension. The mean age of participants was 73.8 years, 62.9% were women, and 86.9% were White.

Over the course of the study, some participants filled at least one prescription for a stimulating angiotensin II receptor type 2 and 4, such as angiotensin II receptor type 1 blockers, dihydropyridine calcium channel blockers, and thiazide diuretics.

Others participants filled a prescription for an inhibiting type 2 and 4 angiotensin II receptors, including angiotensin-converting enzyme (ACE) inhibitors, beta-blockers, and nondihydropyridine calcium channel blockers.

“All these medications lower blood pressure, but they do it in different ways,” said Dr. Marcum.

The researchers were interested in the varying activity of these drugs at the type 2 and 4 angiotensin II receptors.

For each 30-day interval, they categorized beneficiaries into four groups: a stimulating medication group (n = 4,879) consisting of individuals mostly taking stimulating antihypertensives; an inhibiting medication group (n = 10,303) that mostly included individuals prescribed this type of antihypertensive; a mixed group (n = 2,179) that included a combination of the first two classifications; and a nonuser group (n = 40,413) of individuals who were not using either type of drug.

The primary outcome was time to first occurrence of ADRD. The secondary outcome was time to first occurrence of vascular dementia.

Researchers controlled for cardiovascular risk factors and sociodemographic characteristics, such as age, sex, race/ethnicity, and receipt of low-income subsidy.
 

Unanswered questions

After adjustments, results showed that initiation of an antihypertensive medication regimen that exclusively stimulates, rather than inhibits, type 2 and 4 angiotensin II receptors was associated with a 16% lower risk for incident ADRD over a follow-up of just under 7 years (hazard ratio, 0.84; 95% confidence interval, 0.79-0.90; P < .001).

The mixed regimen was also associated with statistically significant (P = .001) reduced odds of ADRD compared with the inhibiting medications.

As for vascular dementia, use of stimulating vs. inhibiting medications was associated with an 18% lower risk (HR, 0.82; 95% CI, 0.69-0.96; P = .02).

Again, use of the mixed regimen was associated with reduced risk of vascular dementia compared with the inhibiting medications (P = .03).

A variety of potential mechanisms might explain the superiority of stimulating agents when it comes to dementia risk, said Dr. Marcum. These could include, for example, increased blood flow to the brain and reduced amyloid.

“But more mechanistic work is needed as well as evaluation of dose responses, because that’s not something we looked at in this study,” Dr. Marcum said. “There are still a lot of unanswered questions.”
 

Stimulators instead of inhibitors?

The results of the current analysis come on the heels of some previous work showing the benefits of lowering blood pressure. For example, the Systolic Blood Pressure Intervention Trial (SPRINT) showed that targeting a systolic blood pressure below 120 mm Hg significantly reduces risk for heart disease, stroke, and death from these diseases.

But in contrast to previous research, the current study included only beneficiaries with incident hypertension and new use of antihypertensive medications, and it adjusted for time-varying confounding.

Prescribing stimulating instead of inhibiting treatments could make a difference at the population level, Dr. Marcum noted.

“If we could shift the prescribing a little bit from inhibiting to stimulating, that could possibly reduce dementia risk,” he said.

However, “we’re not suggesting [that all patients] have their regimen switched,” he added.

That’s because inhibiting medications still have an important place in the antihypertensive treatment armamentarium, Dr. Marcum noted. As an example, beta-blockers are used post heart attack.

As well, factors such as cost and side effects should be taken into consideration when prescribing an antihypertensive drug.

The new results could be used to set up a comparison in a future randomized controlled trial that would provide the strongest evidence for estimating causal effects of treatments, said Dr. Marcum.
 

‘More convincing’

Carlos G. Santos-Gallego, MD, Icahn School of Medicine at Mount Sinai, New York, said the study is “more convincing” than previous related research, as it has a larger sample size and a longer follow-up.

“And the exquisite statistical analysis gives more robustness, more solidity, to the hypothesis that drugs that stimulate type 2 and 4 angiotensin II receptors might be protective for dementia,” said Dr. Santos-Gallego, who was not involved with the research.

However, he noted that the retrospective study had some limitations, including the underdiagnosis of dementia. “The diagnosis of dementia is, honestly, very poorly done in the clinical setting,” he said.

As well, the study could be subject to “confounding by indication,” Dr. Santos-Gallego said. “There could be a third variable, another confounding factor, that’s responsible both for the dementia and for the prescription of these drugs,” he added.

For example, he noted that comorbidities such as atrial fibrillation, myocardial infarction, and heart failure might increase the risk of dementia.

He agreed with the investigators that a randomized clinical trial would address these limitations. “All comorbidities would be equally shared” in the randomized groups, and all participants would be given “a specific test for dementia at the same time,” Dr. Santos-Gallego said.

Still, he noted that the new results are in keeping with hypertension guidelines that recommend stimulating drugs.

“This trial definitely shows that the current hypertension guidelines are good treatment for our patients, not only to control blood pressure and not only to prevent infarction to prevent stroke but also to prevent dementia,” said Dr. Santos-Gallego.

Also commenting for this news organization, Heather Snyder, PhD, vice president of medical and scientific relations at the Alzheimer’s Association, said the new data provide “clarity” on why previous research had differing results on the effect of antihypertensives on cognition.

Among the caveats of this new analysis is that “it’s unclear if the demographics in this study are fully representative of Medicare beneficiaries,” said Dr. Snyder.

She, too, said a clinical trial is important “to understand if there is a preventative and/or treatment potential in the medications that stimulate type 2 and 4 angiotensin II receptors.”

The study received funding from the National Institute on Aging. Dr. Marcum and Dr. Santos-Gallego have reported no relevant financial relationships.

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

Antihypertensive medications that stimulate rather than inhibit type 2 and 4 angiotensin II receptors can lower the rate of dementia among new users of these medications, new research suggests.

Results from a cohort study of more than 57,000 older Medicare beneficiaries showed that the initiation of antihypertensives that stimulate the receptors was linked to a 16% lower risk for incident Alzheimer’s disease and related dementia (ADRD) and an 18% lower risk for vascular dementia compared with those that inhibit the receptors.

“Achieving appropriate blood pressure control is essential for maximizing brain health, and this promising research suggests certain antihypertensives could yield brain benefit compared to others,” lead study author Zachary A. Marcum, PharmD, PhD, associate professor, University of Washington School of Pharmacy, Seattle, told this news organization.

The findings were published online in JAMA Network Open.
 

Medicare beneficiaries

Previous observational studies showed that antihypertensive medications that stimulate type 2 and 4 angiotensin II receptors, in comparison with those that don’t, were associated with lower rates of dementia. However, those studies included individuals with prevalent hypertension and were relatively small.

The new retrospective cohort study included a random sample of 57,773 Medicare beneficiaries aged at least 65 years with new-onset hypertension. The mean age of participants was 73.8 years, 62.9% were women, and 86.9% were White.

Over the course of the study, some participants filled at least one prescription for a stimulating angiotensin II receptor type 2 and 4, such as angiotensin II receptor type 1 blockers, dihydropyridine calcium channel blockers, and thiazide diuretics.

Others participants filled a prescription for an inhibiting type 2 and 4 angiotensin II receptors, including angiotensin-converting enzyme (ACE) inhibitors, beta-blockers, and nondihydropyridine calcium channel blockers.

“All these medications lower blood pressure, but they do it in different ways,” said Dr. Marcum.

The researchers were interested in the varying activity of these drugs at the type 2 and 4 angiotensin II receptors.

For each 30-day interval, they categorized beneficiaries into four groups: a stimulating medication group (n = 4,879) consisting of individuals mostly taking stimulating antihypertensives; an inhibiting medication group (n = 10,303) that mostly included individuals prescribed this type of antihypertensive; a mixed group (n = 2,179) that included a combination of the first two classifications; and a nonuser group (n = 40,413) of individuals who were not using either type of drug.

The primary outcome was time to first occurrence of ADRD. The secondary outcome was time to first occurrence of vascular dementia.

Researchers controlled for cardiovascular risk factors and sociodemographic characteristics, such as age, sex, race/ethnicity, and receipt of low-income subsidy.
 

Unanswered questions

After adjustments, results showed that initiation of an antihypertensive medication regimen that exclusively stimulates, rather than inhibits, type 2 and 4 angiotensin II receptors was associated with a 16% lower risk for incident ADRD over a follow-up of just under 7 years (hazard ratio, 0.84; 95% confidence interval, 0.79-0.90; P < .001).

The mixed regimen was also associated with statistically significant (P = .001) reduced odds of ADRD compared with the inhibiting medications.

As for vascular dementia, use of stimulating vs. inhibiting medications was associated with an 18% lower risk (HR, 0.82; 95% CI, 0.69-0.96; P = .02).

Again, use of the mixed regimen was associated with reduced risk of vascular dementia compared with the inhibiting medications (P = .03).

A variety of potential mechanisms might explain the superiority of stimulating agents when it comes to dementia risk, said Dr. Marcum. These could include, for example, increased blood flow to the brain and reduced amyloid.

“But more mechanistic work is needed as well as evaluation of dose responses, because that’s not something we looked at in this study,” Dr. Marcum said. “There are still a lot of unanswered questions.”
 

Stimulators instead of inhibitors?

The results of the current analysis come on the heels of some previous work showing the benefits of lowering blood pressure. For example, the Systolic Blood Pressure Intervention Trial (SPRINT) showed that targeting a systolic blood pressure below 120 mm Hg significantly reduces risk for heart disease, stroke, and death from these diseases.

But in contrast to previous research, the current study included only beneficiaries with incident hypertension and new use of antihypertensive medications, and it adjusted for time-varying confounding.

Prescribing stimulating instead of inhibiting treatments could make a difference at the population level, Dr. Marcum noted.

“If we could shift the prescribing a little bit from inhibiting to stimulating, that could possibly reduce dementia risk,” he said.

However, “we’re not suggesting [that all patients] have their regimen switched,” he added.

That’s because inhibiting medications still have an important place in the antihypertensive treatment armamentarium, Dr. Marcum noted. As an example, beta-blockers are used post heart attack.

As well, factors such as cost and side effects should be taken into consideration when prescribing an antihypertensive drug.

The new results could be used to set up a comparison in a future randomized controlled trial that would provide the strongest evidence for estimating causal effects of treatments, said Dr. Marcum.
 

‘More convincing’

Carlos G. Santos-Gallego, MD, Icahn School of Medicine at Mount Sinai, New York, said the study is “more convincing” than previous related research, as it has a larger sample size and a longer follow-up.

“And the exquisite statistical analysis gives more robustness, more solidity, to the hypothesis that drugs that stimulate type 2 and 4 angiotensin II receptors might be protective for dementia,” said Dr. Santos-Gallego, who was not involved with the research.

However, he noted that the retrospective study had some limitations, including the underdiagnosis of dementia. “The diagnosis of dementia is, honestly, very poorly done in the clinical setting,” he said.

As well, the study could be subject to “confounding by indication,” Dr. Santos-Gallego said. “There could be a third variable, another confounding factor, that’s responsible both for the dementia and for the prescription of these drugs,” he added.

For example, he noted that comorbidities such as atrial fibrillation, myocardial infarction, and heart failure might increase the risk of dementia.

He agreed with the investigators that a randomized clinical trial would address these limitations. “All comorbidities would be equally shared” in the randomized groups, and all participants would be given “a specific test for dementia at the same time,” Dr. Santos-Gallego said.

Still, he noted that the new results are in keeping with hypertension guidelines that recommend stimulating drugs.

“This trial definitely shows that the current hypertension guidelines are good treatment for our patients, not only to control blood pressure and not only to prevent infarction to prevent stroke but also to prevent dementia,” said Dr. Santos-Gallego.

Also commenting for this news organization, Heather Snyder, PhD, vice president of medical and scientific relations at the Alzheimer’s Association, said the new data provide “clarity” on why previous research had differing results on the effect of antihypertensives on cognition.

Among the caveats of this new analysis is that “it’s unclear if the demographics in this study are fully representative of Medicare beneficiaries,” said Dr. Snyder.

She, too, said a clinical trial is important “to understand if there is a preventative and/or treatment potential in the medications that stimulate type 2 and 4 angiotensin II receptors.”

The study received funding from the National Institute on Aging. Dr. Marcum and Dr. Santos-Gallego have reported no relevant financial relationships.

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

Antihypertensive medications that stimulate rather than inhibit type 2 and 4 angiotensin II receptors can lower the rate of dementia among new users of these medications, new research suggests.

Results from a cohort study of more than 57,000 older Medicare beneficiaries showed that the initiation of antihypertensives that stimulate the receptors was linked to a 16% lower risk for incident Alzheimer’s disease and related dementia (ADRD) and an 18% lower risk for vascular dementia compared with those that inhibit the receptors.

“Achieving appropriate blood pressure control is essential for maximizing brain health, and this promising research suggests certain antihypertensives could yield brain benefit compared to others,” lead study author Zachary A. Marcum, PharmD, PhD, associate professor, University of Washington School of Pharmacy, Seattle, told this news organization.

The findings were published online in JAMA Network Open.
 

Medicare beneficiaries

Previous observational studies showed that antihypertensive medications that stimulate type 2 and 4 angiotensin II receptors, in comparison with those that don’t, were associated with lower rates of dementia. However, those studies included individuals with prevalent hypertension and were relatively small.

The new retrospective cohort study included a random sample of 57,773 Medicare beneficiaries aged at least 65 years with new-onset hypertension. The mean age of participants was 73.8 years, 62.9% were women, and 86.9% were White.

Over the course of the study, some participants filled at least one prescription for a stimulating angiotensin II receptor type 2 and 4, such as angiotensin II receptor type 1 blockers, dihydropyridine calcium channel blockers, and thiazide diuretics.

Others participants filled a prescription for an inhibiting type 2 and 4 angiotensin II receptors, including angiotensin-converting enzyme (ACE) inhibitors, beta-blockers, and nondihydropyridine calcium channel blockers.

“All these medications lower blood pressure, but they do it in different ways,” said Dr. Marcum.

The researchers were interested in the varying activity of these drugs at the type 2 and 4 angiotensin II receptors.

For each 30-day interval, they categorized beneficiaries into four groups: a stimulating medication group (n = 4,879) consisting of individuals mostly taking stimulating antihypertensives; an inhibiting medication group (n = 10,303) that mostly included individuals prescribed this type of antihypertensive; a mixed group (n = 2,179) that included a combination of the first two classifications; and a nonuser group (n = 40,413) of individuals who were not using either type of drug.

The primary outcome was time to first occurrence of ADRD. The secondary outcome was time to first occurrence of vascular dementia.

Researchers controlled for cardiovascular risk factors and sociodemographic characteristics, such as age, sex, race/ethnicity, and receipt of low-income subsidy.
 

Unanswered questions

After adjustments, results showed that initiation of an antihypertensive medication regimen that exclusively stimulates, rather than inhibits, type 2 and 4 angiotensin II receptors was associated with a 16% lower risk for incident ADRD over a follow-up of just under 7 years (hazard ratio, 0.84; 95% confidence interval, 0.79-0.90; P < .001).

The mixed regimen was also associated with statistically significant (P = .001) reduced odds of ADRD compared with the inhibiting medications.

As for vascular dementia, use of stimulating vs. inhibiting medications was associated with an 18% lower risk (HR, 0.82; 95% CI, 0.69-0.96; P = .02).

Again, use of the mixed regimen was associated with reduced risk of vascular dementia compared with the inhibiting medications (P = .03).

A variety of potential mechanisms might explain the superiority of stimulating agents when it comes to dementia risk, said Dr. Marcum. These could include, for example, increased blood flow to the brain and reduced amyloid.

“But more mechanistic work is needed as well as evaluation of dose responses, because that’s not something we looked at in this study,” Dr. Marcum said. “There are still a lot of unanswered questions.”
 

Stimulators instead of inhibitors?

The results of the current analysis come on the heels of some previous work showing the benefits of lowering blood pressure. For example, the Systolic Blood Pressure Intervention Trial (SPRINT) showed that targeting a systolic blood pressure below 120 mm Hg significantly reduces risk for heart disease, stroke, and death from these diseases.

But in contrast to previous research, the current study included only beneficiaries with incident hypertension and new use of antihypertensive medications, and it adjusted for time-varying confounding.

Prescribing stimulating instead of inhibiting treatments could make a difference at the population level, Dr. Marcum noted.

“If we could shift the prescribing a little bit from inhibiting to stimulating, that could possibly reduce dementia risk,” he said.

However, “we’re not suggesting [that all patients] have their regimen switched,” he added.

That’s because inhibiting medications still have an important place in the antihypertensive treatment armamentarium, Dr. Marcum noted. As an example, beta-blockers are used post heart attack.

As well, factors such as cost and side effects should be taken into consideration when prescribing an antihypertensive drug.

The new results could be used to set up a comparison in a future randomized controlled trial that would provide the strongest evidence for estimating causal effects of treatments, said Dr. Marcum.
 

‘More convincing’

Carlos G. Santos-Gallego, MD, Icahn School of Medicine at Mount Sinai, New York, said the study is “more convincing” than previous related research, as it has a larger sample size and a longer follow-up.

“And the exquisite statistical analysis gives more robustness, more solidity, to the hypothesis that drugs that stimulate type 2 and 4 angiotensin II receptors might be protective for dementia,” said Dr. Santos-Gallego, who was not involved with the research.

However, he noted that the retrospective study had some limitations, including the underdiagnosis of dementia. “The diagnosis of dementia is, honestly, very poorly done in the clinical setting,” he said.

As well, the study could be subject to “confounding by indication,” Dr. Santos-Gallego said. “There could be a third variable, another confounding factor, that’s responsible both for the dementia and for the prescription of these drugs,” he added.

For example, he noted that comorbidities such as atrial fibrillation, myocardial infarction, and heart failure might increase the risk of dementia.

He agreed with the investigators that a randomized clinical trial would address these limitations. “All comorbidities would be equally shared” in the randomized groups, and all participants would be given “a specific test for dementia at the same time,” Dr. Santos-Gallego said.

Still, he noted that the new results are in keeping with hypertension guidelines that recommend stimulating drugs.

“This trial definitely shows that the current hypertension guidelines are good treatment for our patients, not only to control blood pressure and not only to prevent infarction to prevent stroke but also to prevent dementia,” said Dr. Santos-Gallego.

Also commenting for this news organization, Heather Snyder, PhD, vice president of medical and scientific relations at the Alzheimer’s Association, said the new data provide “clarity” on why previous research had differing results on the effect of antihypertensives on cognition.

Among the caveats of this new analysis is that “it’s unclear if the demographics in this study are fully representative of Medicare beneficiaries,” said Dr. Snyder.

She, too, said a clinical trial is important “to understand if there is a preventative and/or treatment potential in the medications that stimulate type 2 and 4 angiotensin II receptors.”

The study received funding from the National Institute on Aging. Dr. Marcum and Dr. Santos-Gallego have reported no relevant financial relationships.

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

Dementia prevalence is 61% higher among older people with moderate to severe hearing loss compared with those with normal hearing, new national data show.

Investigators also found that even mild hearing loss was associated with increased dementia risk, although it was not statistically significant, and that hearing aid use was tied to a 32% decrease in dementia prevalence.

“Every 10-decibel increase in hearing loss was associated with 16% greater prevalence of dementia, such that prevalence of dementia in older adults with moderate or greater hearing loss was 61% higher than prevalence in those with normal hearing,” lead investigator Alison Huang, PhD, senior research associate in epidemiology at Johns Hopkins Bloomberg School of Public Health and core faculty in the Cochlear Center for Hearing and Public Health, Baltimore, Md., told this news organization.

The findings were published online in JAMA.
 

Dose-dependent effect

For the study, researchers analyzed data on 2,413 community-dwelling participants in the National Health and Aging Trends Study, a nationally representative, continuous panel study of U.S. Medicare beneficiaries aged 65 and older.

Data from the study were collected during in-home interviews, setting it apart from previous work that relied on data collected in a clinical setting, Dr. Huang said.

“This study was able to capture more vulnerable populations, such as the oldest old and older adults with disabilities, typically excluded from prior epidemiologic studies of the hearing loss–dementia association that use clinic-based data collection, which only captures people who have the ability and means to get to clinics,” Dr. Huang said.

Weighted hearing loss prevalence was 36.7% for mild and 29.8% for moderate to severe hearing loss, and weighted prevalence of dementia was 10.3%.

Those with moderate to severe hearing loss were 61% more likely to have dementia than those with normal hearing (prevalence ratio, 1.61; 95% confidence interval, 1.09-2.38).

Dementia prevalence increased with increasing severity of hearing loss: normal hearing: 6.19% (95% CI, 4.31-8.80); mild hearing loss: 8.93% (95% CI, 6.99-11.34); moderate/severe hearing loss: 16.52% (95% CI, 13.81-19.64). But only moderate to severe hearing loss showed a statistically significant association with dementia (P = .02).

Dementia prevalence increased 16% per 10-decibel increase in hearing loss (prevalence ratio 1.16; P < .001).

Among the 853 individuals in the study with moderate to severe hearing loss, those who used hearing aids (n = 414) had a 32% lower risk of dementia compared with those who didn’t use assistive devices (prevalence ratio, 0.68; 95% CI, 0.47-1.00). This news organization last month reported on similar data published in JAMA Neurology suggesting that hearing aids reduce dementia risk.

“With this study, we were able to refine our understanding of the strength of the hearing loss–dementia association in a study more representative of older adults in the United States,” said Dr. Huang.
 

Robust association

Commenting on the findings, Justin S. Golub, MD, associate professor in the department of otolaryngology–head and neck surgery at Columbia University, New York, said the study supports earlier research and suggests a “robust” association between hearing loss and dementia.

“The particular advantage of this study was that it was high quality and nationally representative,” Dr. Golub said. “It is also among a smaller set of studies that have shown hearing aid use to be associated with lower risk of dementia.”

Although not statistically significant, researchers did find increasing prevalence of dementia among people with only mild hearing loss, and clinicians should take note, said Dr. Golub, who was not involved with this study.

“We would expect the relationship between mild hearing loss and dementia to be weaker than severe hearing loss and dementia and, as a result, it might take more participants to show an association among the mild group,” Dr. Golub said.

“Even though this particular study did not specifically find a relationship between mild hearing loss and dementia, I would still recommend people to start treating their hearing loss when it is early,” Dr. Golub added.

The study was funded by the National Institute on Aging. Dr. Golub reports no relevant financial relationships.

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

Dementia prevalence is 61% higher among older people with moderate to severe hearing loss compared with those with normal hearing, new national data show.

Investigators also found that even mild hearing loss was associated with increased dementia risk, although it was not statistically significant, and that hearing aid use was tied to a 32% decrease in dementia prevalence.

“Every 10-decibel increase in hearing loss was associated with 16% greater prevalence of dementia, such that prevalence of dementia in older adults with moderate or greater hearing loss was 61% higher than prevalence in those with normal hearing,” lead investigator Alison Huang, PhD, senior research associate in epidemiology at Johns Hopkins Bloomberg School of Public Health and core faculty in the Cochlear Center for Hearing and Public Health, Baltimore, Md., told this news organization.

The findings were published online in JAMA.
 

Dose-dependent effect

For the study, researchers analyzed data on 2,413 community-dwelling participants in the National Health and Aging Trends Study, a nationally representative, continuous panel study of U.S. Medicare beneficiaries aged 65 and older.

Data from the study were collected during in-home interviews, setting it apart from previous work that relied on data collected in a clinical setting, Dr. Huang said.

“This study was able to capture more vulnerable populations, such as the oldest old and older adults with disabilities, typically excluded from prior epidemiologic studies of the hearing loss–dementia association that use clinic-based data collection, which only captures people who have the ability and means to get to clinics,” Dr. Huang said.

Weighted hearing loss prevalence was 36.7% for mild and 29.8% for moderate to severe hearing loss, and weighted prevalence of dementia was 10.3%.

Those with moderate to severe hearing loss were 61% more likely to have dementia than those with normal hearing (prevalence ratio, 1.61; 95% confidence interval, 1.09-2.38).

Dementia prevalence increased with increasing severity of hearing loss: normal hearing: 6.19% (95% CI, 4.31-8.80); mild hearing loss: 8.93% (95% CI, 6.99-11.34); moderate/severe hearing loss: 16.52% (95% CI, 13.81-19.64). But only moderate to severe hearing loss showed a statistically significant association with dementia (P = .02).

Dementia prevalence increased 16% per 10-decibel increase in hearing loss (prevalence ratio 1.16; P < .001).

Among the 853 individuals in the study with moderate to severe hearing loss, those who used hearing aids (n = 414) had a 32% lower risk of dementia compared with those who didn’t use assistive devices (prevalence ratio, 0.68; 95% CI, 0.47-1.00). This news organization last month reported on similar data published in JAMA Neurology suggesting that hearing aids reduce dementia risk.

“With this study, we were able to refine our understanding of the strength of the hearing loss–dementia association in a study more representative of older adults in the United States,” said Dr. Huang.
 

Robust association

Commenting on the findings, Justin S. Golub, MD, associate professor in the department of otolaryngology–head and neck surgery at Columbia University, New York, said the study supports earlier research and suggests a “robust” association between hearing loss and dementia.

“The particular advantage of this study was that it was high quality and nationally representative,” Dr. Golub said. “It is also among a smaller set of studies that have shown hearing aid use to be associated with lower risk of dementia.”

Although not statistically significant, researchers did find increasing prevalence of dementia among people with only mild hearing loss, and clinicians should take note, said Dr. Golub, who was not involved with this study.

“We would expect the relationship between mild hearing loss and dementia to be weaker than severe hearing loss and dementia and, as a result, it might take more participants to show an association among the mild group,” Dr. Golub said.

“Even though this particular study did not specifically find a relationship between mild hearing loss and dementia, I would still recommend people to start treating their hearing loss when it is early,” Dr. Golub added.

The study was funded by the National Institute on Aging. Dr. Golub reports no relevant financial relationships.

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

Dementia prevalence is 61% higher among older people with moderate to severe hearing loss compared with those with normal hearing, new national data show.

Investigators also found that even mild hearing loss was associated with increased dementia risk, although it was not statistically significant, and that hearing aid use was tied to a 32% decrease in dementia prevalence.

“Every 10-decibel increase in hearing loss was associated with 16% greater prevalence of dementia, such that prevalence of dementia in older adults with moderate or greater hearing loss was 61% higher than prevalence in those with normal hearing,” lead investigator Alison Huang, PhD, senior research associate in epidemiology at Johns Hopkins Bloomberg School of Public Health and core faculty in the Cochlear Center for Hearing and Public Health, Baltimore, Md., told this news organization.

The findings were published online in JAMA.
 

Dose-dependent effect

For the study, researchers analyzed data on 2,413 community-dwelling participants in the National Health and Aging Trends Study, a nationally representative, continuous panel study of U.S. Medicare beneficiaries aged 65 and older.

Data from the study were collected during in-home interviews, setting it apart from previous work that relied on data collected in a clinical setting, Dr. Huang said.

“This study was able to capture more vulnerable populations, such as the oldest old and older adults with disabilities, typically excluded from prior epidemiologic studies of the hearing loss–dementia association that use clinic-based data collection, which only captures people who have the ability and means to get to clinics,” Dr. Huang said.

Weighted hearing loss prevalence was 36.7% for mild and 29.8% for moderate to severe hearing loss, and weighted prevalence of dementia was 10.3%.

Those with moderate to severe hearing loss were 61% more likely to have dementia than those with normal hearing (prevalence ratio, 1.61; 95% confidence interval, 1.09-2.38).

Dementia prevalence increased with increasing severity of hearing loss: normal hearing: 6.19% (95% CI, 4.31-8.80); mild hearing loss: 8.93% (95% CI, 6.99-11.34); moderate/severe hearing loss: 16.52% (95% CI, 13.81-19.64). But only moderate to severe hearing loss showed a statistically significant association with dementia (P = .02).

Dementia prevalence increased 16% per 10-decibel increase in hearing loss (prevalence ratio 1.16; P < .001).

Among the 853 individuals in the study with moderate to severe hearing loss, those who used hearing aids (n = 414) had a 32% lower risk of dementia compared with those who didn’t use assistive devices (prevalence ratio, 0.68; 95% CI, 0.47-1.00). This news organization last month reported on similar data published in JAMA Neurology suggesting that hearing aids reduce dementia risk.

“With this study, we were able to refine our understanding of the strength of the hearing loss–dementia association in a study more representative of older adults in the United States,” said Dr. Huang.
 

Robust association

Commenting on the findings, Justin S. Golub, MD, associate professor in the department of otolaryngology–head and neck surgery at Columbia University, New York, said the study supports earlier research and suggests a “robust” association between hearing loss and dementia.

“The particular advantage of this study was that it was high quality and nationally representative,” Dr. Golub said. “It is also among a smaller set of studies that have shown hearing aid use to be associated with lower risk of dementia.”

Although not statistically significant, researchers did find increasing prevalence of dementia among people with only mild hearing loss, and clinicians should take note, said Dr. Golub, who was not involved with this study.

“We would expect the relationship between mild hearing loss and dementia to be weaker than severe hearing loss and dementia and, as a result, it might take more participants to show an association among the mild group,” Dr. Golub said.

“Even though this particular study did not specifically find a relationship between mild hearing loss and dementia, I would still recommend people to start treating their hearing loss when it is early,” Dr. Golub added.

The study was funded by the National Institute on Aging. Dr. Golub reports no relevant financial relationships.

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

This transcript has been edited for clarity.

Robert D. Glatter, MD: Welcome. I’m Dr. Robert Glatter, medical advisor for Medscape Emergency Medicine. Joining me today is Sandeep Jauhar, a practicing cardiologist and professor of medicine at Northwell Health, a frequent New York Times op-ed contributor, and highly regarded author of the upcoming book “My Father’s Brain: Life in the Shadow of Alzheimer’s.”

We are here today to discuss the rationale for age competency exams for practicing physicians.

Sandeep Jauhar, MD: Thanks for having me.

Dr. Glatter: Your recent op-ed piece in the New York Times caught my eye. In your piece, you refer to a 2020 survey in which almost one-third of licensed doctors in the United States were 60 years of age or older, up from a quarter in 2010. You also state that, due to a 20% prevalence of mild cognitive impairment in persons older than 65, practicing physicians above this age should probably be screened by a battery of tests to ensure that their reasoning and cognitive abilities are intact. The title of the article is “How Would You Feel About a 100-Year-Old Doctor?”

How would you envision such a process? What aspects of day-to-day functioning would the exams truly be evaluating?

Dr. Jauhar: A significant number of people over 65 have measurable cognitive impairment. By cognitive impairment, we’re not talking about dementia. The best estimates are that 1 in 10 people over age 65 have dementia, and roughly 1 in 5 have what’s called MCI, or mild cognitive impairment, which is cognitive impairment out of proportion to what you’d expect from normal aging. It’s a significant issue.

The argument that I made in the op-ed is that neurocognitive assessment is important. That’s not to say that everyone over age 65 has significant cognitive impairment or that older doctors can’t practice medicine safely and effectively. They absolutely can. The question is, do we leave neurocognitive assessment to physicians who may possibly be suffering from impairment?

In dementia, people very often have impaired self-awareness, a condition called anosognosia, which is a neurological term for not being aware of your own impairment because of your impairment.

I would argue that, instead of having voluntary neurocognitive screening, it should be mandated. The question is how to do that effectively, fairly, and transparently.

One could argue a gerontocracy in medicine today, where there are so many older physicians. What do we do about that? That really is something that I think needs to be debated.

Dr. Glatter: The question I have is, if we (that is, physicians and the health care profession) don’t take care of this, someone’s going to do it for us. We need to jump on this now while we have the opportunity. The AMA has been opposed to this, except when you have reason to suspect cognitive decline or are concerned about patient safety. A mandatory age of retirement is certainly something they’re not for, and we know this.

Your argument in your op-ed piece is very well thought out, and you lay the groundwork for testing (looking at someone’s memory, coordination, processing speed, and other executive functions). Certainly, for a psychiatrist, hearing is important, and for a dermatologist, vision is important. For a surgeon, there are other issues. Based on the specialty, we must be careful to see the important aspects of functioning. I am sure you would agree with this.

Dr. Jauhar: Obviously, the hand skills that are important for ophthalmological surgery certainly aren’t required for office-based psychological counseling, for example. We have to be smart about how we assess impairment.

You describe the spectrum of actions. On the one hand, there’s mandatory retirement at the age of 65 or 70 years. We know that commercial pilots are mandated to essentially retire at 65, and air-traffic controllers must retire in their late 50s.

We know that there’s a large amount of variability in competence. There are internists in their 80s with whom I’ve worked, and I’m absolutely wowed by their experience and judgment. There are new medical resident graduates who don’t really seem to have the requisite level of competence that would make me feel comfortable to have them as my doctor or a doctor for a member of my family.

To mandate retirement, I think the AMA is absolutely right. To not call for any kind of competency testing, to me, seems equally unwise. Because at the end of the day, you have to balance individual physician needs or wants to continue practicing with patient safety. I haven’t really come across too many physicians who say, “There’s absolutely no need for a competency testing.”

We have to meet somewhere in the middle. The middle is either voluntary cognitive competency testing or mandatory. I would argue that, because we know that as the brain changes we have cognitive impairment, but we’re not always aware that we need help, mandatory testing is the way.

One other thing that you mentioned was about having the solution imposed on us. You and I are doctors. We deal with bureaucracy. We deal with poorly thought-out solutions to issues in health care that make our lives that much more difficult. I don’t want that solution imposed on us by some outside agency. I think we need to figure this out within medicine and figure out the right way of doing it.

The AMA is on board with this. They haven’t called for mandatory testing, but they have said that if testing were to occur, these are the guidelines. The guidelines are fair and equitable, not too time-consuming, transparent, and not punitive. If someone comes out and doesn’t test well, we shouldn’t force them out of the profession. We can find ways to use their experience to help train younger doctors, for example.

Dr. Glatter: I wanted to segue to an area where there has been some challenge to the legality of these mandatory types of age restrictions and imposing the exams as well. There’s been a lawsuit as well by the EEOC [Equal Employment Opportunity Commission], on behalf of Yale. Basically, there’s been a concern that ageism is part of what’s going on. Yale now screens their providers beginning at age 70, and they have a program. UCSD [University of California, San Diego] has a program in place. Obviously, these institutions are looking at it. This is a very small part of the overall picture.

Health care systems overall, we’re talking about a fraction of them in the country are really addressing the issue of competency exams. The question is, where do we go from here? How do we get engagement or adoption and get physicians as a whole to embrace this concept?

Dr. Jauhar: The EEOC filed a lawsuit on behalf of the Yale medical staff that argued that Yale’s plan to do vision testing and neurocognitive screening – there may be a physical exam also – constitutes age discrimination because it’s reserved for doctors over the age of 70. Those are the physicians who are most likely to have cognitive impairment.

We have rules already for impaired physicians who are, for example, addicted to illicit drugs or have alcohol abuse. We already have some of those measures in place. This is focused on cognitive impairment in aging physicians because cognitive impairment is an issue that arises with aging. We have to be clear about that.

Most younger physicians will not have measurable cognitive impairment that would impair their ability to practice. To force young physicians (for example, physicians in their forties) to undergo such screening, all in the name of preventing age discrimination, doesn’t strike me as being a good use of resources. They’re more likely to be false positives, as you know from Bayesian statistics. When you have low pretest probability, you’re more likely to get false positives.

How are we going to screen hundreds of thousands of physicians? We have to make a choice about the group that really is more likely to benefit from such screening. Very few hospitals are addressing this issue and it’s going to become more important.

Dr. Glatter: Surgeons have been particularly active in pushing for age-based screening. In 2016, the American College of Surgeons started making surgeons at age 65-70 undergo voluntary health and neurocognitive assessments, and encouraged physicians to disclose any concerning findings as part of their professional obligation, which is pretty impressive in my mind.

Surgeons’ skill set is quite demanding physically and technically. That the Society of Surgical Chairs took it upon themselves to institute this is pretty telling.

Dr. Jauhar: The overall society called for screening, but then in a separate survey of surgical chairs, the idea was advanced that we should have mandatory retirement. Now, I don’t particularly agree with that.

I’ve seen it, where you have the aging surgeon who was a star in their day, and no one wants to say anything when their skills have visibly degraded, and no one wants to carry that torch and tell them that they need to retire. What happens is people whisper, and unfortunately, bad outcomes have to occur before people tend to get involved, and that’s what I’m trying to prevent.

Dr. Glatter: The question is whether older physicians have worse patient outcomes. The evidence is inconclusive, but studies have shown higher mortality rates for cardiovascular surgeons in terms of the procedures that they do. On the flip side, there are also higher mortality rates for GI surgery performed by younger surgeons. It’s a mixed bag.

Dr. Jauhar: For specialized surgery, you need the accrual of a certain amount of experience. The optimal age is about 60, because they’ve seen many things and they’ve seen complications. They don’t have a hand tremor yet so they’re still functioning well, and they’ve accrued a lot of experience. We have to be smart about who we screen.

There’s a learning curve in surgery. By no means am I arguing that younger surgeons are better surgeons. I would say that there’s probably a tipping point where once you get past a certain age and physical deterioration starts to take effect, that can overshadow the accrual of cognitive and surgical experience. We have to balance those things.

I would say neurocognitive screening and vision testing are important, but exactly what do you measure? How much of a hand tremor would constitute a risk? These things have to be figured out. I just want doctors to be leading the charge here and not have this imposed by bureaucrats.

Dr. Glatter: I was reading that some doctors have had these exams administered and they can really pass cognitive aspects of the exam, but there have been nuances in the actual practicing of medicine, day-to-day functioning, which they’re not good at.

Someone made a comment that the only way to know if a doctor can do well in practice is to observe their practice and observe them taking care of patients. In other words, you can game the system and pass the cognitive exam in some form but then have a problem practicing medicine.

Dr. Jauhar: Ultimately, outcomes have to be measured. We can’t adopt such a granular approach for every aging physician. There has to be some sort of screening that maybe raises a red flag and then hospitals and department chairs need to investigate further. What are the outcomes? What are people saying in the operating room? I think the screening is just that; it’s a way of opening the door to further investigation, but it’s not a witch hunt.

I have the highest respect for older physicians, and I learn from them every day, honestly, especially in my field (cardiology), because some of the older physicians can hear and see things on physical exam that I didn’t even know existed. There’s much to be learned from them.

This is not intended to be a witch hunt or to try to get rid of older physicians – by any means. We want to avoid some of the outcomes that I read about in the New York Times comments section. It’s not fair to our patients not to do at least some sort of screening to prevent those kinds of mistakes.

Dr. Glatter: I wanted to go back to data from Yale between October 2016 and January 2019, where 141 Yale clinicians who ranged in age from 69 to 92 years completed cognitive assessments. Of those, 18 clinicians, or about 13% of those tested, demonstrated cognitive deficits that were “deemed likely to impair their ability to practice medicine independently.” That’s telling. These are subtleties, but they’re important to identify. I would love to get your comment on that.

Dr. Jauhar: It’s in keeping with what we know about the proportion of our older citizens who have cognitive impairment. About 10% have dementia and about 20% have at least mild cognitive impairment. That’s in keeping with what we know, and this was a general screening.

There are certain programs, like in San Diego, for example, where physicians are referred, and so there’s a selection bias. But this was just general screening. It’s worrisome. I’m an aging physician myself. I want fairness in this process because I’m going to be assessed as well.

I just don’t really understand yet why there’s so much circling of the wagons and so much resistance. It seems like it would be good for physicians also to be removed from situations where they might get into potential litigation because of mistakes and physical or visual impairment. It seems like it’d be good for patients and physicians alike.

Dr. Glatter: It’s difficult to give up your profession, change fields, or become administrative at some point, and [decide] when to make that transition. As we all get older, we’re not going to have the ability to do what we did in our 20s, 30s, and so forth.

Dr. Jauhar: Much of the resistance is coming from doctors who are used to high levels of autonomy. I’m certainly sympathetic to that because I don’t want anyone telling me how to practice. The reason this is coming up and hasn’t come up in the past is not because of loss of autonomy but because of an actual demographic change. Many physicians were trained in the 1960s, ’70s, or ’80s. They’re getting to retirement age but they’re not retiring, and we can speculate as to why that is.

In America’s educational system, doctors incur a huge amount of debt. I know physicians who are still paying off their debt and they’re in their 50s and 60s, so I’m very sympathetic to that. I’m not trying to force doctors out of practicing. I just want whoever is practicing to be competent and to practice safely. We have to figure out how to do that.

Dr. Glatter: The fact that there is a shortage of physicians forecast in the next 10-15 years makes many physicians reluctant to retire. They feel like they want to be part of that support network and we don’t want to have a dire situation, especially in the rural areas. We’re not immune from aging. We’re human beings. We all have to realize that.

Dr. Jauhar: I know that the ACC is starting to debate this issue, in part because of my op-ed. My hope is that it will start a conversation and we will institute a plan that comes from physicians and serves our patients, and doesn’t serve some cottage industry of testing or serve the needs of insurers or bureaucrats. It has to serve the doctor-patient relationship.

Dr. Glatter: In some random surveys that I’ve read, up to 30%-40% of physicians do support some type of age-based screening or competency assessment. The needle’s moving. It’s just not there yet. I think that wider adoption is coming.

Dr. Jauhar: Data are coming as more hospitals start to adopt these late practitioner programs. Some of the data that came out of Yale, for example, are very important. We’re going to see more published data in this area, and it will clarify what we need to do and how big the problem is.

Dr. Glatter: I want to thank you again for your time and for writing the op-ed because it certainly was well read and opened the eyes of not only physicians, but also the public at large. It’s a conversation that has to be had. Thank you for doing this.

Dr. Jauhar: Thanks for inviting me, Robert. It was a pleasure to talk to you.

Dr. Glatter is assistant professor of emergency medicine, department of emergency medicine, at Hofstra University, Hempstead, N.Y. Dr. Jauhar is director of the heart failure program, Long Island Jewish Medical Center, New Hyde Park, N.Y. Neither Dr. Glatter nor Dr. Jauhar reported any relevant conflicts of interest.

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

This transcript has been edited for clarity.

Robert D. Glatter, MD: Welcome. I’m Dr. Robert Glatter, medical advisor for Medscape Emergency Medicine. Joining me today is Sandeep Jauhar, a practicing cardiologist and professor of medicine at Northwell Health, a frequent New York Times op-ed contributor, and highly regarded author of the upcoming book “My Father’s Brain: Life in the Shadow of Alzheimer’s.”

We are here today to discuss the rationale for age competency exams for practicing physicians.

Sandeep Jauhar, MD: Thanks for having me.

Dr. Glatter: Your recent op-ed piece in the New York Times caught my eye. In your piece, you refer to a 2020 survey in which almost one-third of licensed doctors in the United States were 60 years of age or older, up from a quarter in 2010. You also state that, due to a 20% prevalence of mild cognitive impairment in persons older than 65, practicing physicians above this age should probably be screened by a battery of tests to ensure that their reasoning and cognitive abilities are intact. The title of the article is “How Would You Feel About a 100-Year-Old Doctor?”

How would you envision such a process? What aspects of day-to-day functioning would the exams truly be evaluating?

Dr. Jauhar: A significant number of people over 65 have measurable cognitive impairment. By cognitive impairment, we’re not talking about dementia. The best estimates are that 1 in 10 people over age 65 have dementia, and roughly 1 in 5 have what’s called MCI, or mild cognitive impairment, which is cognitive impairment out of proportion to what you’d expect from normal aging. It’s a significant issue.

The argument that I made in the op-ed is that neurocognitive assessment is important. That’s not to say that everyone over age 65 has significant cognitive impairment or that older doctors can’t practice medicine safely and effectively. They absolutely can. The question is, do we leave neurocognitive assessment to physicians who may possibly be suffering from impairment?

In dementia, people very often have impaired self-awareness, a condition called anosognosia, which is a neurological term for not being aware of your own impairment because of your impairment.

I would argue that, instead of having voluntary neurocognitive screening, it should be mandated. The question is how to do that effectively, fairly, and transparently.

One could argue a gerontocracy in medicine today, where there are so many older physicians. What do we do about that? That really is something that I think needs to be debated.

Dr. Glatter: The question I have is, if we (that is, physicians and the health care profession) don’t take care of this, someone’s going to do it for us. We need to jump on this now while we have the opportunity. The AMA has been opposed to this, except when you have reason to suspect cognitive decline or are concerned about patient safety. A mandatory age of retirement is certainly something they’re not for, and we know this.

Your argument in your op-ed piece is very well thought out, and you lay the groundwork for testing (looking at someone’s memory, coordination, processing speed, and other executive functions). Certainly, for a psychiatrist, hearing is important, and for a dermatologist, vision is important. For a surgeon, there are other issues. Based on the specialty, we must be careful to see the important aspects of functioning. I am sure you would agree with this.

Dr. Jauhar: Obviously, the hand skills that are important for ophthalmological surgery certainly aren’t required for office-based psychological counseling, for example. We have to be smart about how we assess impairment.

You describe the spectrum of actions. On the one hand, there’s mandatory retirement at the age of 65 or 70 years. We know that commercial pilots are mandated to essentially retire at 65, and air-traffic controllers must retire in their late 50s.

We know that there’s a large amount of variability in competence. There are internists in their 80s with whom I’ve worked, and I’m absolutely wowed by their experience and judgment. There are new medical resident graduates who don’t really seem to have the requisite level of competence that would make me feel comfortable to have them as my doctor or a doctor for a member of my family.

To mandate retirement, I think the AMA is absolutely right. To not call for any kind of competency testing, to me, seems equally unwise. Because at the end of the day, you have to balance individual physician needs or wants to continue practicing with patient safety. I haven’t really come across too many physicians who say, “There’s absolutely no need for a competency testing.”

We have to meet somewhere in the middle. The middle is either voluntary cognitive competency testing or mandatory. I would argue that, because we know that as the brain changes we have cognitive impairment, but we’re not always aware that we need help, mandatory testing is the way.

One other thing that you mentioned was about having the solution imposed on us. You and I are doctors. We deal with bureaucracy. We deal with poorly thought-out solutions to issues in health care that make our lives that much more difficult. I don’t want that solution imposed on us by some outside agency. I think we need to figure this out within medicine and figure out the right way of doing it.

The AMA is on board with this. They haven’t called for mandatory testing, but they have said that if testing were to occur, these are the guidelines. The guidelines are fair and equitable, not too time-consuming, transparent, and not punitive. If someone comes out and doesn’t test well, we shouldn’t force them out of the profession. We can find ways to use their experience to help train younger doctors, for example.

Dr. Glatter: I wanted to segue to an area where there has been some challenge to the legality of these mandatory types of age restrictions and imposing the exams as well. There’s been a lawsuit as well by the EEOC [Equal Employment Opportunity Commission], on behalf of Yale. Basically, there’s been a concern that ageism is part of what’s going on. Yale now screens their providers beginning at age 70, and they have a program. UCSD [University of California, San Diego] has a program in place. Obviously, these institutions are looking at it. This is a very small part of the overall picture.

Health care systems overall, we’re talking about a fraction of them in the country are really addressing the issue of competency exams. The question is, where do we go from here? How do we get engagement or adoption and get physicians as a whole to embrace this concept?

Dr. Jauhar: The EEOC filed a lawsuit on behalf of the Yale medical staff that argued that Yale’s plan to do vision testing and neurocognitive screening – there may be a physical exam also – constitutes age discrimination because it’s reserved for doctors over the age of 70. Those are the physicians who are most likely to have cognitive impairment.

We have rules already for impaired physicians who are, for example, addicted to illicit drugs or have alcohol abuse. We already have some of those measures in place. This is focused on cognitive impairment in aging physicians because cognitive impairment is an issue that arises with aging. We have to be clear about that.

Most younger physicians will not have measurable cognitive impairment that would impair their ability to practice. To force young physicians (for example, physicians in their forties) to undergo such screening, all in the name of preventing age discrimination, doesn’t strike me as being a good use of resources. They’re more likely to be false positives, as you know from Bayesian statistics. When you have low pretest probability, you’re more likely to get false positives.

How are we going to screen hundreds of thousands of physicians? We have to make a choice about the group that really is more likely to benefit from such screening. Very few hospitals are addressing this issue and it’s going to become more important.

Dr. Glatter: Surgeons have been particularly active in pushing for age-based screening. In 2016, the American College of Surgeons started making surgeons at age 65-70 undergo voluntary health and neurocognitive assessments, and encouraged physicians to disclose any concerning findings as part of their professional obligation, which is pretty impressive in my mind.

Surgeons’ skill set is quite demanding physically and technically. That the Society of Surgical Chairs took it upon themselves to institute this is pretty telling.

Dr. Jauhar: The overall society called for screening, but then in a separate survey of surgical chairs, the idea was advanced that we should have mandatory retirement. Now, I don’t particularly agree with that.

I’ve seen it, where you have the aging surgeon who was a star in their day, and no one wants to say anything when their skills have visibly degraded, and no one wants to carry that torch and tell them that they need to retire. What happens is people whisper, and unfortunately, bad outcomes have to occur before people tend to get involved, and that’s what I’m trying to prevent.

Dr. Glatter: The question is whether older physicians have worse patient outcomes. The evidence is inconclusive, but studies have shown higher mortality rates for cardiovascular surgeons in terms of the procedures that they do. On the flip side, there are also higher mortality rates for GI surgery performed by younger surgeons. It’s a mixed bag.

Dr. Jauhar: For specialized surgery, you need the accrual of a certain amount of experience. The optimal age is about 60, because they’ve seen many things and they’ve seen complications. They don’t have a hand tremor yet so they’re still functioning well, and they’ve accrued a lot of experience. We have to be smart about who we screen.

There’s a learning curve in surgery. By no means am I arguing that younger surgeons are better surgeons. I would say that there’s probably a tipping point where once you get past a certain age and physical deterioration starts to take effect, that can overshadow the accrual of cognitive and surgical experience. We have to balance those things.

I would say neurocognitive screening and vision testing are important, but exactly what do you measure? How much of a hand tremor would constitute a risk? These things have to be figured out. I just want doctors to be leading the charge here and not have this imposed by bureaucrats.

Dr. Glatter: I was reading that some doctors have had these exams administered and they can really pass cognitive aspects of the exam, but there have been nuances in the actual practicing of medicine, day-to-day functioning, which they’re not good at.

Someone made a comment that the only way to know if a doctor can do well in practice is to observe their practice and observe them taking care of patients. In other words, you can game the system and pass the cognitive exam in some form but then have a problem practicing medicine.

Dr. Jauhar: Ultimately, outcomes have to be measured. We can’t adopt such a granular approach for every aging physician. There has to be some sort of screening that maybe raises a red flag and then hospitals and department chairs need to investigate further. What are the outcomes? What are people saying in the operating room? I think the screening is just that; it’s a way of opening the door to further investigation, but it’s not a witch hunt.

I have the highest respect for older physicians, and I learn from them every day, honestly, especially in my field (cardiology), because some of the older physicians can hear and see things on physical exam that I didn’t even know existed. There’s much to be learned from them.

This is not intended to be a witch hunt or to try to get rid of older physicians – by any means. We want to avoid some of the outcomes that I read about in the New York Times comments section. It’s not fair to our patients not to do at least some sort of screening to prevent those kinds of mistakes.

Dr. Glatter: I wanted to go back to data from Yale between October 2016 and January 2019, where 141 Yale clinicians who ranged in age from 69 to 92 years completed cognitive assessments. Of those, 18 clinicians, or about 13% of those tested, demonstrated cognitive deficits that were “deemed likely to impair their ability to practice medicine independently.” That’s telling. These are subtleties, but they’re important to identify. I would love to get your comment on that.

Dr. Jauhar: It’s in keeping with what we know about the proportion of our older citizens who have cognitive impairment. About 10% have dementia and about 20% have at least mild cognitive impairment. That’s in keeping with what we know, and this was a general screening.

There are certain programs, like in San Diego, for example, where physicians are referred, and so there’s a selection bias. But this was just general screening. It’s worrisome. I’m an aging physician myself. I want fairness in this process because I’m going to be assessed as well.

I just don’t really understand yet why there’s so much circling of the wagons and so much resistance. It seems like it would be good for physicians also to be removed from situations where they might get into potential litigation because of mistakes and physical or visual impairment. It seems like it’d be good for patients and physicians alike.

Dr. Glatter: It’s difficult to give up your profession, change fields, or become administrative at some point, and [decide] when to make that transition. As we all get older, we’re not going to have the ability to do what we did in our 20s, 30s, and so forth.

Dr. Jauhar: Much of the resistance is coming from doctors who are used to high levels of autonomy. I’m certainly sympathetic to that because I don’t want anyone telling me how to practice. The reason this is coming up and hasn’t come up in the past is not because of loss of autonomy but because of an actual demographic change. Many physicians were trained in the 1960s, ’70s, or ’80s. They’re getting to retirement age but they’re not retiring, and we can speculate as to why that is.

In America’s educational system, doctors incur a huge amount of debt. I know physicians who are still paying off their debt and they’re in their 50s and 60s, so I’m very sympathetic to that. I’m not trying to force doctors out of practicing. I just want whoever is practicing to be competent and to practice safely. We have to figure out how to do that.

Dr. Glatter: The fact that there is a shortage of physicians forecast in the next 10-15 years makes many physicians reluctant to retire. They feel like they want to be part of that support network and we don’t want to have a dire situation, especially in the rural areas. We’re not immune from aging. We’re human beings. We all have to realize that.

Dr. Jauhar: I know that the ACC is starting to debate this issue, in part because of my op-ed. My hope is that it will start a conversation and we will institute a plan that comes from physicians and serves our patients, and doesn’t serve some cottage industry of testing or serve the needs of insurers or bureaucrats. It has to serve the doctor-patient relationship.

Dr. Glatter: In some random surveys that I’ve read, up to 30%-40% of physicians do support some type of age-based screening or competency assessment. The needle’s moving. It’s just not there yet. I think that wider adoption is coming.

Dr. Jauhar: Data are coming as more hospitals start to adopt these late practitioner programs. Some of the data that came out of Yale, for example, are very important. We’re going to see more published data in this area, and it will clarify what we need to do and how big the problem is.

Dr. Glatter: I want to thank you again for your time and for writing the op-ed because it certainly was well read and opened the eyes of not only physicians, but also the public at large. It’s a conversation that has to be had. Thank you for doing this.

Dr. Jauhar: Thanks for inviting me, Robert. It was a pleasure to talk to you.

Dr. Glatter is assistant professor of emergency medicine, department of emergency medicine, at Hofstra University, Hempstead, N.Y. Dr. Jauhar is director of the heart failure program, Long Island Jewish Medical Center, New Hyde Park, N.Y. Neither Dr. Glatter nor Dr. Jauhar reported any relevant conflicts of interest.

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

This transcript has been edited for clarity.

Robert D. Glatter, MD: Welcome. I’m Dr. Robert Glatter, medical advisor for Medscape Emergency Medicine. Joining me today is Sandeep Jauhar, a practicing cardiologist and professor of medicine at Northwell Health, a frequent New York Times op-ed contributor, and highly regarded author of the upcoming book “My Father’s Brain: Life in the Shadow of Alzheimer’s.”

We are here today to discuss the rationale for age competency exams for practicing physicians.

Sandeep Jauhar, MD: Thanks for having me.

Dr. Glatter: Your recent op-ed piece in the New York Times caught my eye. In your piece, you refer to a 2020 survey in which almost one-third of licensed doctors in the United States were 60 years of age or older, up from a quarter in 2010. You also state that, due to a 20% prevalence of mild cognitive impairment in persons older than 65, practicing physicians above this age should probably be screened by a battery of tests to ensure that their reasoning and cognitive abilities are intact. The title of the article is “How Would You Feel About a 100-Year-Old Doctor?”

How would you envision such a process? What aspects of day-to-day functioning would the exams truly be evaluating?

Dr. Jauhar: A significant number of people over 65 have measurable cognitive impairment. By cognitive impairment, we’re not talking about dementia. The best estimates are that 1 in 10 people over age 65 have dementia, and roughly 1 in 5 have what’s called MCI, or mild cognitive impairment, which is cognitive impairment out of proportion to what you’d expect from normal aging. It’s a significant issue.

The argument that I made in the op-ed is that neurocognitive assessment is important. That’s not to say that everyone over age 65 has significant cognitive impairment or that older doctors can’t practice medicine safely and effectively. They absolutely can. The question is, do we leave neurocognitive assessment to physicians who may possibly be suffering from impairment?

In dementia, people very often have impaired self-awareness, a condition called anosognosia, which is a neurological term for not being aware of your own impairment because of your impairment.

I would argue that, instead of having voluntary neurocognitive screening, it should be mandated. The question is how to do that effectively, fairly, and transparently.

One could argue a gerontocracy in medicine today, where there are so many older physicians. What do we do about that? That really is something that I think needs to be debated.

Dr. Glatter: The question I have is, if we (that is, physicians and the health care profession) don’t take care of this, someone’s going to do it for us. We need to jump on this now while we have the opportunity. The AMA has been opposed to this, except when you have reason to suspect cognitive decline or are concerned about patient safety. A mandatory age of retirement is certainly something they’re not for, and we know this.

Your argument in your op-ed piece is very well thought out, and you lay the groundwork for testing (looking at someone’s memory, coordination, processing speed, and other executive functions). Certainly, for a psychiatrist, hearing is important, and for a dermatologist, vision is important. For a surgeon, there are other issues. Based on the specialty, we must be careful to see the important aspects of functioning. I am sure you would agree with this.

Dr. Jauhar: Obviously, the hand skills that are important for ophthalmological surgery certainly aren’t required for office-based psychological counseling, for example. We have to be smart about how we assess impairment.

You describe the spectrum of actions. On the one hand, there’s mandatory retirement at the age of 65 or 70 years. We know that commercial pilots are mandated to essentially retire at 65, and air-traffic controllers must retire in their late 50s.

We know that there’s a large amount of variability in competence. There are internists in their 80s with whom I’ve worked, and I’m absolutely wowed by their experience and judgment. There are new medical resident graduates who don’t really seem to have the requisite level of competence that would make me feel comfortable to have them as my doctor or a doctor for a member of my family.

To mandate retirement, I think the AMA is absolutely right. To not call for any kind of competency testing, to me, seems equally unwise. Because at the end of the day, you have to balance individual physician needs or wants to continue practicing with patient safety. I haven’t really come across too many physicians who say, “There’s absolutely no need for a competency testing.”

We have to meet somewhere in the middle. The middle is either voluntary cognitive competency testing or mandatory. I would argue that, because we know that as the brain changes we have cognitive impairment, but we’re not always aware that we need help, mandatory testing is the way.

One other thing that you mentioned was about having the solution imposed on us. You and I are doctors. We deal with bureaucracy. We deal with poorly thought-out solutions to issues in health care that make our lives that much more difficult. I don’t want that solution imposed on us by some outside agency. I think we need to figure this out within medicine and figure out the right way of doing it.

The AMA is on board with this. They haven’t called for mandatory testing, but they have said that if testing were to occur, these are the guidelines. The guidelines are fair and equitable, not too time-consuming, transparent, and not punitive. If someone comes out and doesn’t test well, we shouldn’t force them out of the profession. We can find ways to use their experience to help train younger doctors, for example.

Dr. Glatter: I wanted to segue to an area where there has been some challenge to the legality of these mandatory types of age restrictions and imposing the exams as well. There’s been a lawsuit as well by the EEOC [Equal Employment Opportunity Commission], on behalf of Yale. Basically, there’s been a concern that ageism is part of what’s going on. Yale now screens their providers beginning at age 70, and they have a program. UCSD [University of California, San Diego] has a program in place. Obviously, these institutions are looking at it. This is a very small part of the overall picture.

Health care systems overall, we’re talking about a fraction of them in the country are really addressing the issue of competency exams. The question is, where do we go from here? How do we get engagement or adoption and get physicians as a whole to embrace this concept?

Dr. Jauhar: The EEOC filed a lawsuit on behalf of the Yale medical staff that argued that Yale’s plan to do vision testing and neurocognitive screening – there may be a physical exam also – constitutes age discrimination because it’s reserved for doctors over the age of 70. Those are the physicians who are most likely to have cognitive impairment.

We have rules already for impaired physicians who are, for example, addicted to illicit drugs or have alcohol abuse. We already have some of those measures in place. This is focused on cognitive impairment in aging physicians because cognitive impairment is an issue that arises with aging. We have to be clear about that.

Most younger physicians will not have measurable cognitive impairment that would impair their ability to practice. To force young physicians (for example, physicians in their forties) to undergo such screening, all in the name of preventing age discrimination, doesn’t strike me as being a good use of resources. They’re more likely to be false positives, as you know from Bayesian statistics. When you have low pretest probability, you’re more likely to get false positives.

How are we going to screen hundreds of thousands of physicians? We have to make a choice about the group that really is more likely to benefit from such screening. Very few hospitals are addressing this issue and it’s going to become more important.

Dr. Glatter: Surgeons have been particularly active in pushing for age-based screening. In 2016, the American College of Surgeons started making surgeons at age 65-70 undergo voluntary health and neurocognitive assessments, and encouraged physicians to disclose any concerning findings as part of their professional obligation, which is pretty impressive in my mind.

Surgeons’ skill set is quite demanding physically and technically. That the Society of Surgical Chairs took it upon themselves to institute this is pretty telling.

Dr. Jauhar: The overall society called for screening, but then in a separate survey of surgical chairs, the idea was advanced that we should have mandatory retirement. Now, I don’t particularly agree with that.

I’ve seen it, where you have the aging surgeon who was a star in their day, and no one wants to say anything when their skills have visibly degraded, and no one wants to carry that torch and tell them that they need to retire. What happens is people whisper, and unfortunately, bad outcomes have to occur before people tend to get involved, and that’s what I’m trying to prevent.

Dr. Glatter: The question is whether older physicians have worse patient outcomes. The evidence is inconclusive, but studies have shown higher mortality rates for cardiovascular surgeons in terms of the procedures that they do. On the flip side, there are also higher mortality rates for GI surgery performed by younger surgeons. It’s a mixed bag.

Dr. Jauhar: For specialized surgery, you need the accrual of a certain amount of experience. The optimal age is about 60, because they’ve seen many things and they’ve seen complications. They don’t have a hand tremor yet so they’re still functioning well, and they’ve accrued a lot of experience. We have to be smart about who we screen.

There’s a learning curve in surgery. By no means am I arguing that younger surgeons are better surgeons. I would say that there’s probably a tipping point where once you get past a certain age and physical deterioration starts to take effect, that can overshadow the accrual of cognitive and surgical experience. We have to balance those things.

I would say neurocognitive screening and vision testing are important, but exactly what do you measure? How much of a hand tremor would constitute a risk? These things have to be figured out. I just want doctors to be leading the charge here and not have this imposed by bureaucrats.

Dr. Glatter: I was reading that some doctors have had these exams administered and they can really pass cognitive aspects of the exam, but there have been nuances in the actual practicing of medicine, day-to-day functioning, which they’re not good at.

Someone made a comment that the only way to know if a doctor can do well in practice is to observe their practice and observe them taking care of patients. In other words, you can game the system and pass the cognitive exam in some form but then have a problem practicing medicine.

Dr. Jauhar: Ultimately, outcomes have to be measured. We can’t adopt such a granular approach for every aging physician. There has to be some sort of screening that maybe raises a red flag and then hospitals and department chairs need to investigate further. What are the outcomes? What are people saying in the operating room? I think the screening is just that; it’s a way of opening the door to further investigation, but it’s not a witch hunt.

I have the highest respect for older physicians, and I learn from them every day, honestly, especially in my field (cardiology), because some of the older physicians can hear and see things on physical exam that I didn’t even know existed. There’s much to be learned from them.

This is not intended to be a witch hunt or to try to get rid of older physicians – by any means. We want to avoid some of the outcomes that I read about in the New York Times comments section. It’s not fair to our patients not to do at least some sort of screening to prevent those kinds of mistakes.

Dr. Glatter: I wanted to go back to data from Yale between October 2016 and January 2019, where 141 Yale clinicians who ranged in age from 69 to 92 years completed cognitive assessments. Of those, 18 clinicians, or about 13% of those tested, demonstrated cognitive deficits that were “deemed likely to impair their ability to practice medicine independently.” That’s telling. These are subtleties, but they’re important to identify. I would love to get your comment on that.

Dr. Jauhar: It’s in keeping with what we know about the proportion of our older citizens who have cognitive impairment. About 10% have dementia and about 20% have at least mild cognitive impairment. That’s in keeping with what we know, and this was a general screening.

There are certain programs, like in San Diego, for example, where physicians are referred, and so there’s a selection bias. But this was just general screening. It’s worrisome. I’m an aging physician myself. I want fairness in this process because I’m going to be assessed as well.

I just don’t really understand yet why there’s so much circling of the wagons and so much resistance. It seems like it would be good for physicians also to be removed from situations where they might get into potential litigation because of mistakes and physical or visual impairment. It seems like it’d be good for patients and physicians alike.

Dr. Glatter: It’s difficult to give up your profession, change fields, or become administrative at some point, and [decide] when to make that transition. As we all get older, we’re not going to have the ability to do what we did in our 20s, 30s, and so forth.

Dr. Jauhar: Much of the resistance is coming from doctors who are used to high levels of autonomy. I’m certainly sympathetic to that because I don’t want anyone telling me how to practice. The reason this is coming up and hasn’t come up in the past is not because of loss of autonomy but because of an actual demographic change. Many physicians were trained in the 1960s, ’70s, or ’80s. They’re getting to retirement age but they’re not retiring, and we can speculate as to why that is.

In America’s educational system, doctors incur a huge amount of debt. I know physicians who are still paying off their debt and they’re in their 50s and 60s, so I’m very sympathetic to that. I’m not trying to force doctors out of practicing. I just want whoever is practicing to be competent and to practice safely. We have to figure out how to do that.

Dr. Glatter: The fact that there is a shortage of physicians forecast in the next 10-15 years makes many physicians reluctant to retire. They feel like they want to be part of that support network and we don’t want to have a dire situation, especially in the rural areas. We’re not immune from aging. We’re human beings. We all have to realize that.

Dr. Jauhar: I know that the ACC is starting to debate this issue, in part because of my op-ed. My hope is that it will start a conversation and we will institute a plan that comes from physicians and serves our patients, and doesn’t serve some cottage industry of testing or serve the needs of insurers or bureaucrats. It has to serve the doctor-patient relationship.

Dr. Glatter: In some random surveys that I’ve read, up to 30%-40% of physicians do support some type of age-based screening or competency assessment. The needle’s moving. It’s just not there yet. I think that wider adoption is coming.

Dr. Jauhar: Data are coming as more hospitals start to adopt these late practitioner programs. Some of the data that came out of Yale, for example, are very important. We’re going to see more published data in this area, and it will clarify what we need to do and how big the problem is.

Dr. Glatter: I want to thank you again for your time and for writing the op-ed because it certainly was well read and opened the eyes of not only physicians, but also the public at large. It’s a conversation that has to be had. Thank you for doing this.

Dr. Jauhar: Thanks for inviting me, Robert. It was a pleasure to talk to you.

Dr. Glatter is assistant professor of emergency medicine, department of emergency medicine, at Hofstra University, Hempstead, N.Y. Dr. Jauhar is director of the heart failure program, Long Island Jewish Medical Center, New Hyde Park, N.Y. Neither Dr. Glatter nor Dr. Jauhar reported any relevant conflicts of interest.

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

The highly anticipated Alzheimer’s drug lecanemab was granted accelerated approval status on Jan. 6 by the FDA, offering hope where there has been little for patients and their families affected by the devastating disease.

More than 6 million people in the United States live with Alzheimer’s.

It’s not a cure, but the drug, given intravenously every 2 weeks, has shown moderate positive effects in clinical trials in slowing early-stage disease.

But many are wary. As explained in an editorial in the journal The Lancet, “The Alzheimer’s disease community has become accustomed to false hope, disappointment, and controversy.”

Some worry about lecanemab’s safety as some people in clinical trials experienced serious side effects of bleeding and swelling in the brain. Scientists recently attributed a third death to lecanemab, brand name Leqembi, though the drugmaker disputed the medication was the cause.

So what should patients and their families make of this news? Here we answer some of the top questions surrounding the drug.
 

What does the FDA action mean?

The FDA granted accelerated approval to Leqembi after it showed positive trial results in slowing the progression of early-stage disease.

The FDA can grant accelerated approval for drugs that treat serious conditions and fill an unmet medical need while drugs continue to be studied in larger trials.

With the FDA approval in hand, doctors can now prescribe the medication.

Rebecca Edelmayer, PhD, the Alzheimer’s Association senior director of scientific engagement, says that with the FDA’s move, ramping up manufacturing – and eventually nationwide distribution and implementation – will take some time.

“Ask your doctor about availability,” she says. “The main issue is that, without insurance and Medicare coverage of this class of treatments, access for those who could benefit from the newly approved treatment will only be available to those who can pay out-of-pocket. Without coverage, people simply won’t be able to get the treatment.”

The Washington Post reports that with accelerated approval, drugmaker Eisai is expected to immediately apply for full FDA approval, which wouldn’t be likely to come before later this year. Full approval could help clear the path for Medicare coverage of the drug.
 

Potential benefit?

Those who got Leqembi in a clinical trial for 18 months experienced 27% less decline in memory and thinking relative to the group who got a placebo. It also reduced amyloid in the brain, the sticky protein that builds up in the brains of people with Alzheimer’s and is considered a hallmark of the disease.

Howard Fillit, MD, cofounder and chief science officer of the Alzheimer’s Drug Discovery Foundation, says, “It’s the first phase 3 study in our field of a disease-modifying drug where the clinical efficacy was very clear.”
 

Concerns about side effects

The drug has raised safety concerns as it has been linked with certain serious adverse events, including brain swelling and bleeding. In the trial, 14% of patients who received the drug experienced side effects that included brain swelling and bleeding, compared with about 11% in the placebo group.

Scientists have reportedly linked three deaths during the clinical trial to lecanemab, though it is unclear whether it caused the deaths.

Dr. Fillit notes that the first two people who died were on blood thinners when they received lecanemab.

“There are things about the use of the drug in the real world that we need to work out, especially in the context of people with comorbidities,” he says.

The third death is a little different, Dr. Fillit says. The patient, who had a stroke, showed signs of vasculitis, or inflammation of the blood vessels.

“We don’t know exactly what happened, but we do know it was very, very rare” among the people involved in the trials, he says.

Dr. Edelmayer says that the most common reported side effects during the trials were infusion-related reactions, headache, and amyloid-related imaging abnormalities (ARIA). According to the FDA, these abnormalities “are known to occur with antibodies of this class. ARIA usually does not have symptoms, although serious and life-threatening events rarely may occur.”

The FDA has added these as warnings to the drug’s label, describing the possible infusion-related reactions as flu-like symptoms, nausea, vomiting, and changes in blood pressure.
 

How much will it cost?

Eisai says that lecanemab will cost $26,500 a year.

In a draft report released in December, the Institute for Clinical and Economic Review said a price ranging from $8,500 to $20,600 a year would make the drug cost-effective. While the group has no authority to set prices, many large health insurers consider its reports when they negotiate prices and some drugmakers take into account ICER’s recommendations when setting prices.

An editorial in The Lancet last month warns that the cost will likely be “prohibitive” for low- and middle-income countries and many health systems don’t have the infrastructure for a widespread rollout.
 

Will Medicare cover it?

The Centers for Medicare & Medicaid Services, which runs Medicare, which covers most people with Alzheimer’s, has indicated it won’t broadly cover amyloid-lowering drugs until the drug gets full U.S. approval based on clinical benefits, as opposed to accelerated approval.

That means people would have to pay thousands out of pocket at first to get it.

The CMS decision effectively denies Medicare coverage of fast-tracked FDA-approved medications for Alzheimer’s disease unless the person is enrolled in an approved clinical trial.

On Dec. 19, the Alzheimer’s Association filed a formal request asking CMS to remove the trial-only requirement and provide full and unrestricted coverage for FDA-approved Alzheimer’s treatments.

CMS says in a statement issued after the announcement: “Because Eisai’s product, lecanemab, was granted accelerated approval by the FDA, it falls under CMS’s existing national coverage determination. CMS is examining available information and may reconsider its current coverage based on this review.”

“If lecanemab subsequently receives traditional FDA approval, CMS would provide broader coverage,” the statement says.
 

Who benefits most from this drug?

Lecanemab is a treatment for people with early-stage Alzheimer’s disease who have amyloid in their brain. This means people with other types of dementia, or those in the later stages of Alzheimer’s disease, are not likely to improve with this drug.

Who makes lecanemab?  

Japan-based Eisai is developing the drug, a monoclonal antibody, in collaboration with the U.S. company Biogen.

What’s the Alzheimer’s Association’s view?

The association urged accelerated FDA approval. In a statement, it says it “welcomes and is further encouraged” by the clinical trial results.

It says data published in the New England Journal of Medicine confirms lecanemab “can meaningfully change the course of the disease for people in the earliest stages of Alzheimer’s disease.”

“We are energized at the progress we are seeing in the research pipeline. The science is telling us that although antiamyloid treatments are not a cure – they are not going to be the end of treating Alzheimer’s – they are certainly the beginning,” Dr. Edelmayer says.
 

Are there alternatives?

The FDA gave accelerated approval to Biogen to produce another drug for Alzheimer’s, Aduhelm (aducanemab), in 2021, but the move was controversial as the drug’s effectiveness was widely questioned. It has since largely been pulled from the market.

Aduhelm had been the first approved early-stage Alzheimer’s treatment since 2003.

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

The highly anticipated Alzheimer’s drug lecanemab was granted accelerated approval status on Jan. 6 by the FDA, offering hope where there has been little for patients and their families affected by the devastating disease.

More than 6 million people in the United States live with Alzheimer’s.

It’s not a cure, but the drug, given intravenously every 2 weeks, has shown moderate positive effects in clinical trials in slowing early-stage disease.

But many are wary. As explained in an editorial in the journal The Lancet, “The Alzheimer’s disease community has become accustomed to false hope, disappointment, and controversy.”

Some worry about lecanemab’s safety as some people in clinical trials experienced serious side effects of bleeding and swelling in the brain. Scientists recently attributed a third death to lecanemab, brand name Leqembi, though the drugmaker disputed the medication was the cause.

So what should patients and their families make of this news? Here we answer some of the top questions surrounding the drug.
 

What does the FDA action mean?

The FDA granted accelerated approval to Leqembi after it showed positive trial results in slowing the progression of early-stage disease.

The FDA can grant accelerated approval for drugs that treat serious conditions and fill an unmet medical need while drugs continue to be studied in larger trials.

With the FDA approval in hand, doctors can now prescribe the medication.

Rebecca Edelmayer, PhD, the Alzheimer’s Association senior director of scientific engagement, says that with the FDA’s move, ramping up manufacturing – and eventually nationwide distribution and implementation – will take some time.

“Ask your doctor about availability,” she says. “The main issue is that, without insurance and Medicare coverage of this class of treatments, access for those who could benefit from the newly approved treatment will only be available to those who can pay out-of-pocket. Without coverage, people simply won’t be able to get the treatment.”

The Washington Post reports that with accelerated approval, drugmaker Eisai is expected to immediately apply for full FDA approval, which wouldn’t be likely to come before later this year. Full approval could help clear the path for Medicare coverage of the drug.
 

Potential benefit?

Those who got Leqembi in a clinical trial for 18 months experienced 27% less decline in memory and thinking relative to the group who got a placebo. It also reduced amyloid in the brain, the sticky protein that builds up in the brains of people with Alzheimer’s and is considered a hallmark of the disease.

Howard Fillit, MD, cofounder and chief science officer of the Alzheimer’s Drug Discovery Foundation, says, “It’s the first phase 3 study in our field of a disease-modifying drug where the clinical efficacy was very clear.”
 

Concerns about side effects

The drug has raised safety concerns as it has been linked with certain serious adverse events, including brain swelling and bleeding. In the trial, 14% of patients who received the drug experienced side effects that included brain swelling and bleeding, compared with about 11% in the placebo group.

Scientists have reportedly linked three deaths during the clinical trial to lecanemab, though it is unclear whether it caused the deaths.

Dr. Fillit notes that the first two people who died were on blood thinners when they received lecanemab.

“There are things about the use of the drug in the real world that we need to work out, especially in the context of people with comorbidities,” he says.

The third death is a little different, Dr. Fillit says. The patient, who had a stroke, showed signs of vasculitis, or inflammation of the blood vessels.

“We don’t know exactly what happened, but we do know it was very, very rare” among the people involved in the trials, he says.

Dr. Edelmayer says that the most common reported side effects during the trials were infusion-related reactions, headache, and amyloid-related imaging abnormalities (ARIA). According to the FDA, these abnormalities “are known to occur with antibodies of this class. ARIA usually does not have symptoms, although serious and life-threatening events rarely may occur.”

The FDA has added these as warnings to the drug’s label, describing the possible infusion-related reactions as flu-like symptoms, nausea, vomiting, and changes in blood pressure.
 

How much will it cost?

Eisai says that lecanemab will cost $26,500 a year.

In a draft report released in December, the Institute for Clinical and Economic Review said a price ranging from $8,500 to $20,600 a year would make the drug cost-effective. While the group has no authority to set prices, many large health insurers consider its reports when they negotiate prices and some drugmakers take into account ICER’s recommendations when setting prices.

An editorial in The Lancet last month warns that the cost will likely be “prohibitive” for low- and middle-income countries and many health systems don’t have the infrastructure for a widespread rollout.
 

Will Medicare cover it?

The Centers for Medicare & Medicaid Services, which runs Medicare, which covers most people with Alzheimer’s, has indicated it won’t broadly cover amyloid-lowering drugs until the drug gets full U.S. approval based on clinical benefits, as opposed to accelerated approval.

That means people would have to pay thousands out of pocket at first to get it.

The CMS decision effectively denies Medicare coverage of fast-tracked FDA-approved medications for Alzheimer’s disease unless the person is enrolled in an approved clinical trial.

On Dec. 19, the Alzheimer’s Association filed a formal request asking CMS to remove the trial-only requirement and provide full and unrestricted coverage for FDA-approved Alzheimer’s treatments.

CMS says in a statement issued after the announcement: “Because Eisai’s product, lecanemab, was granted accelerated approval by the FDA, it falls under CMS’s existing national coverage determination. CMS is examining available information and may reconsider its current coverage based on this review.”

“If lecanemab subsequently receives traditional FDA approval, CMS would provide broader coverage,” the statement says.
 

Who benefits most from this drug?

Lecanemab is a treatment for people with early-stage Alzheimer’s disease who have amyloid in their brain. This means people with other types of dementia, or those in the later stages of Alzheimer’s disease, are not likely to improve with this drug.

Who makes lecanemab?  

Japan-based Eisai is developing the drug, a monoclonal antibody, in collaboration with the U.S. company Biogen.

What’s the Alzheimer’s Association’s view?

The association urged accelerated FDA approval. In a statement, it says it “welcomes and is further encouraged” by the clinical trial results.

It says data published in the New England Journal of Medicine confirms lecanemab “can meaningfully change the course of the disease for people in the earliest stages of Alzheimer’s disease.”

“We are energized at the progress we are seeing in the research pipeline. The science is telling us that although antiamyloid treatments are not a cure – they are not going to be the end of treating Alzheimer’s – they are certainly the beginning,” Dr. Edelmayer says.
 

Are there alternatives?

The FDA gave accelerated approval to Biogen to produce another drug for Alzheimer’s, Aduhelm (aducanemab), in 2021, but the move was controversial as the drug’s effectiveness was widely questioned. It has since largely been pulled from the market.

Aduhelm had been the first approved early-stage Alzheimer’s treatment since 2003.

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

The highly anticipated Alzheimer’s drug lecanemab was granted accelerated approval status on Jan. 6 by the FDA, offering hope where there has been little for patients and their families affected by the devastating disease.

More than 6 million people in the United States live with Alzheimer’s.

It’s not a cure, but the drug, given intravenously every 2 weeks, has shown moderate positive effects in clinical trials in slowing early-stage disease.

But many are wary. As explained in an editorial in the journal The Lancet, “The Alzheimer’s disease community has become accustomed to false hope, disappointment, and controversy.”

Some worry about lecanemab’s safety as some people in clinical trials experienced serious side effects of bleeding and swelling in the brain. Scientists recently attributed a third death to lecanemab, brand name Leqembi, though the drugmaker disputed the medication was the cause.

So what should patients and their families make of this news? Here we answer some of the top questions surrounding the drug.
 

What does the FDA action mean?

The FDA granted accelerated approval to Leqembi after it showed positive trial results in slowing the progression of early-stage disease.

The FDA can grant accelerated approval for drugs that treat serious conditions and fill an unmet medical need while drugs continue to be studied in larger trials.

With the FDA approval in hand, doctors can now prescribe the medication.

Rebecca Edelmayer, PhD, the Alzheimer’s Association senior director of scientific engagement, says that with the FDA’s move, ramping up manufacturing – and eventually nationwide distribution and implementation – will take some time.

“Ask your doctor about availability,” she says. “The main issue is that, without insurance and Medicare coverage of this class of treatments, access for those who could benefit from the newly approved treatment will only be available to those who can pay out-of-pocket. Without coverage, people simply won’t be able to get the treatment.”

The Washington Post reports that with accelerated approval, drugmaker Eisai is expected to immediately apply for full FDA approval, which wouldn’t be likely to come before later this year. Full approval could help clear the path for Medicare coverage of the drug.
 

Potential benefit?

Those who got Leqembi in a clinical trial for 18 months experienced 27% less decline in memory and thinking relative to the group who got a placebo. It also reduced amyloid in the brain, the sticky protein that builds up in the brains of people with Alzheimer’s and is considered a hallmark of the disease.

Howard Fillit, MD, cofounder and chief science officer of the Alzheimer’s Drug Discovery Foundation, says, “It’s the first phase 3 study in our field of a disease-modifying drug where the clinical efficacy was very clear.”
 

Concerns about side effects

The drug has raised safety concerns as it has been linked with certain serious adverse events, including brain swelling and bleeding. In the trial, 14% of patients who received the drug experienced side effects that included brain swelling and bleeding, compared with about 11% in the placebo group.

Scientists have reportedly linked three deaths during the clinical trial to lecanemab, though it is unclear whether it caused the deaths.

Dr. Fillit notes that the first two people who died were on blood thinners when they received lecanemab.

“There are things about the use of the drug in the real world that we need to work out, especially in the context of people with comorbidities,” he says.

The third death is a little different, Dr. Fillit says. The patient, who had a stroke, showed signs of vasculitis, or inflammation of the blood vessels.

“We don’t know exactly what happened, but we do know it was very, very rare” among the people involved in the trials, he says.

Dr. Edelmayer says that the most common reported side effects during the trials were infusion-related reactions, headache, and amyloid-related imaging abnormalities (ARIA). According to the FDA, these abnormalities “are known to occur with antibodies of this class. ARIA usually does not have symptoms, although serious and life-threatening events rarely may occur.”

The FDA has added these as warnings to the drug’s label, describing the possible infusion-related reactions as flu-like symptoms, nausea, vomiting, and changes in blood pressure.
 

How much will it cost?

Eisai says that lecanemab will cost $26,500 a year.

In a draft report released in December, the Institute for Clinical and Economic Review said a price ranging from $8,500 to $20,600 a year would make the drug cost-effective. While the group has no authority to set prices, many large health insurers consider its reports when they negotiate prices and some drugmakers take into account ICER’s recommendations when setting prices.

An editorial in The Lancet last month warns that the cost will likely be “prohibitive” for low- and middle-income countries and many health systems don’t have the infrastructure for a widespread rollout.
 

Will Medicare cover it?

The Centers for Medicare & Medicaid Services, which runs Medicare, which covers most people with Alzheimer’s, has indicated it won’t broadly cover amyloid-lowering drugs until the drug gets full U.S. approval based on clinical benefits, as opposed to accelerated approval.

That means people would have to pay thousands out of pocket at first to get it.

The CMS decision effectively denies Medicare coverage of fast-tracked FDA-approved medications for Alzheimer’s disease unless the person is enrolled in an approved clinical trial.

On Dec. 19, the Alzheimer’s Association filed a formal request asking CMS to remove the trial-only requirement and provide full and unrestricted coverage for FDA-approved Alzheimer’s treatments.

CMS says in a statement issued after the announcement: “Because Eisai’s product, lecanemab, was granted accelerated approval by the FDA, it falls under CMS’s existing national coverage determination. CMS is examining available information and may reconsider its current coverage based on this review.”

“If lecanemab subsequently receives traditional FDA approval, CMS would provide broader coverage,” the statement says.
 

Who benefits most from this drug?

Lecanemab is a treatment for people with early-stage Alzheimer’s disease who have amyloid in their brain. This means people with other types of dementia, or those in the later stages of Alzheimer’s disease, are not likely to improve with this drug.

Who makes lecanemab?  

Japan-based Eisai is developing the drug, a monoclonal antibody, in collaboration with the U.S. company Biogen.

What’s the Alzheimer’s Association’s view?

The association urged accelerated FDA approval. In a statement, it says it “welcomes and is further encouraged” by the clinical trial results.

It says data published in the New England Journal of Medicine confirms lecanemab “can meaningfully change the course of the disease for people in the earliest stages of Alzheimer’s disease.”

“We are energized at the progress we are seeing in the research pipeline. The science is telling us that although antiamyloid treatments are not a cure – they are not going to be the end of treating Alzheimer’s – they are certainly the beginning,” Dr. Edelmayer says.
 

Are there alternatives?

The FDA gave accelerated approval to Biogen to produce another drug for Alzheimer’s, Aduhelm (aducanemab), in 2021, but the move was controversial as the drug’s effectiveness was widely questioned. It has since largely been pulled from the market.

Aduhelm had been the first approved early-stage Alzheimer’s treatment since 2003.

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

The U.S. Food and Drug Administration has approved the anti–amyloid-beta protofibril antibody lecanemab (Leqembi, Eisai) for the treatment of early Alzheimer’s disease.

Like its controversial cousin aducanumab (Aduhelm, Biogen/Eisai), lecanemab was approved under the FDA’s accelerated approval pathway, which can be used to fast-track a drug that provides a meaningful therapeutic advantage over existing treatments for a serious or life-threatening illness.

Unlike aducanumab, however, there was no formal FDA advisory committee meeting on lecanemab prior to approval.

“Alzheimer’s disease immeasurably incapacitates the lives of those who suffer from it and has devastating effects on their loved ones,” Billy Dunn, MD, director of the Office of Neuroscience in the FDA’s Center for Drug Evaluation and Research, said in a press release.

“This treatment option is the latest therapy to target and affect the underlying disease process of Alzheimer’s, instead of only treating the symptoms of the disease,” Dr. Dunn added.

Eisai has reported that lecanemab will cost $26,500 a year.

Modest benefit, adverse events

The FDA noted, “The labeling states that treatment with Leqembi should be initiated in patients with mild cognitive impairment or mild dementia stage of disease, the population in which treatment was studied in clinical trials.”

The agency approved the treatment on the basis of findings from the CLARITY AD trial, which showed modest cognitive benefit for patients with early AD – but at a cost of increased risk for amyloid-related edema and effusions.

The trial enrolled 1,795 adults with mild cognitive impairment or early Alzheimer’s disease in whom amyloid pathology in the brain had been confirmed. Treatment consisted of lecanemab 10 mg/kg biweekly or matching placebo.

After 18 months of treatment, lecanemab slowed cognitive decline by 27%, compared with placebo, as measured by the Clinical Dementia Rating–Sum of Boxes (CDR-SB). This was an absolute difference of 0.45 points (change from baseline, 1.21 for lecanemab vs. 1.66 with placebo; P < .001).

While the results are “welcome news,” a 0.45-point difference on the CDR-SB might not be clinically meaningful, authors of a recent editorial in The Lancet cautioned.

Amyloid-related imaging abnormalities that manifest as edema or microhemorrhages also occurred in one in five patients taking lecanemab.

In addition, a newly published case report in The New England Journal of Medicine describes a patient with Alzheimer’s disease who was taking lecanemab and who died after experiencing numerous intracerebral hemorrhages during treatment with tissue plasminogen activator (tPA) for acute ischemic stroke.

“The findings raise the possibility of cerebral hemorrhages and necrotizing vasculopathy associated with tPA infusion in a patient with cerebrovascular amyloid who had received lecanemab,” the authors wrote.
 

Alzheimer’s Association reaction

Still, in anticipation of accelerated approval of lecanemab and the antiamyloid drug donanemab (Eli Lilly), which the FDA has also fast-tracked, the Alzheimer’s Association filed a formal request last month with the Centers for Medicare & Medicaid Services asking that it provide full and unrestricted coverage for FDA-approved Alzheimer’s disease treatments.

In a letter addressed to CMS administrator Chiquita Brooks-LaSure, the association asked the agency to remove the requirements for “coverage with evidence development” in its national coverage determination for FDA-approved antiamyloid monoclonal antibodies.

“Each day matters when it comes to slowing the progression of this disease,” Joanne Pike, DrPH, president and CEO for the Alzheimer’s Association, noted in a news release at the time.

“The current CMS policy to severely limit access to these treatments eliminates people’s options, is resulting in continued irreversible disease progression, and contributes to greater health inequities. That’s not acceptable,” Dr. Pike added.

After news of today’s approval was released, Dr. Pike noted in a new release, “The Alzheimer’s Association welcomes and celebrates this action by the FDA. We now have a second approved treatment that changes the course of Alzheimer’s disease in a meaningful way for people in the early stages of the disease.”

Maria C. Carrillo, PhD, chief science officer at the Alzheimer’s Association, called today’s approval “a milestone achievement.”

“The progress we’ve seen in not only this class of treatments but also in the diversification of treatment types and targets over the past few years is exciting and provides real hope to those impacted by this devastating disease,” Dr. Carrillo said.
 

Critical issues

Commenting on the approval, Alvaro Pascual-Leone, MD, PhD, professor of neurology at Harvard Medical School, Boston, and chief medical officer at Linus Health, said FDA approval of lecanemab and its adoption in the clinic represent a “very exciting development and prospect; but arguably some critical issues need to be considered.”

He noted that the health care system “is not currently prepared to cope with the challenges and demands of lecanemab,” as well as future pharmacologic agents.

“First, we need better workflows to identify suitable patients who can most benefit from this treatment,” said Dr. Pascual-Leone. He added that beyond identification of cognitive difficulties, amyloid status will need to be determined.

“Presently, this requires expensive and invasive tests,” such as positron-emission tomography scans or lumbar punctures for cerebrospinal fluid analysis. However, these are not fully covered by insurance companies and would be challenging to fully scale, he noted.

“In addition to screening, health systems will need to resolve the logistics challenges around the administration of lecanemab with twice-monthly infusions and the need for careful longitudinal evaluations for potential side effects,” said Dr. Pascual-Leone.

“While lecanemab may represent the first disease-modifying therapy widely available for early Alzheimer’s disease, the likely more promising approach is the addition of other therapies to lecanemab as part of a multi-intervention strategy combining pharmacologic and nonpharmacologic interventions,” he added.

Dr. Pascual-Leone has served as a paid member on scientific advisory boards for Neuroelectrics, Magstim, TetraNeuron, Skin2Neuron, MedRhythms, and Hearts Radiant and is a cofounder of TI Solutions and Linus Health.

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

This article was updated 1/9/23.

The U.S. Food and Drug Administration has approved the anti–amyloid-beta protofibril antibody lecanemab (Leqembi, Eisai) for the treatment of early Alzheimer’s disease.

Like its controversial cousin aducanumab (Aduhelm, Biogen/Eisai), lecanemab was approved under the FDA’s accelerated approval pathway, which can be used to fast-track a drug that provides a meaningful therapeutic advantage over existing treatments for a serious or life-threatening illness.

Unlike aducanumab, however, there was no formal FDA advisory committee meeting on lecanemab prior to approval.

“Alzheimer’s disease immeasurably incapacitates the lives of those who suffer from it and has devastating effects on their loved ones,” Billy Dunn, MD, director of the Office of Neuroscience in the FDA’s Center for Drug Evaluation and Research, said in a press release.

“This treatment option is the latest therapy to target and affect the underlying disease process of Alzheimer’s, instead of only treating the symptoms of the disease,” Dr. Dunn added.

Eisai has reported that lecanemab will cost $26,500 a year.

Modest benefit, adverse events

The FDA noted, “The labeling states that treatment with Leqembi should be initiated in patients with mild cognitive impairment or mild dementia stage of disease, the population in which treatment was studied in clinical trials.”

The agency approved the treatment on the basis of findings from the CLARITY AD trial, which showed modest cognitive benefit for patients with early AD – but at a cost of increased risk for amyloid-related edema and effusions.

The trial enrolled 1,795 adults with mild cognitive impairment or early Alzheimer’s disease in whom amyloid pathology in the brain had been confirmed. Treatment consisted of lecanemab 10 mg/kg biweekly or matching placebo.

After 18 months of treatment, lecanemab slowed cognitive decline by 27%, compared with placebo, as measured by the Clinical Dementia Rating–Sum of Boxes (CDR-SB). This was an absolute difference of 0.45 points (change from baseline, 1.21 for lecanemab vs. 1.66 with placebo; P < .001).

While the results are “welcome news,” a 0.45-point difference on the CDR-SB might not be clinically meaningful, authors of a recent editorial in The Lancet cautioned.

Amyloid-related imaging abnormalities that manifest as edema or microhemorrhages also occurred in one in five patients taking lecanemab.

In addition, a newly published case report in The New England Journal of Medicine describes a patient with Alzheimer’s disease who was taking lecanemab and who died after experiencing numerous intracerebral hemorrhages during treatment with tissue plasminogen activator (tPA) for acute ischemic stroke.

“The findings raise the possibility of cerebral hemorrhages and necrotizing vasculopathy associated with tPA infusion in a patient with cerebrovascular amyloid who had received lecanemab,” the authors wrote.
 

Alzheimer’s Association reaction

Still, in anticipation of accelerated approval of lecanemab and the antiamyloid drug donanemab (Eli Lilly), which the FDA has also fast-tracked, the Alzheimer’s Association filed a formal request last month with the Centers for Medicare & Medicaid Services asking that it provide full and unrestricted coverage for FDA-approved Alzheimer’s disease treatments.

In a letter addressed to CMS administrator Chiquita Brooks-LaSure, the association asked the agency to remove the requirements for “coverage with evidence development” in its national coverage determination for FDA-approved antiamyloid monoclonal antibodies.

“Each day matters when it comes to slowing the progression of this disease,” Joanne Pike, DrPH, president and CEO for the Alzheimer’s Association, noted in a news release at the time.

“The current CMS policy to severely limit access to these treatments eliminates people’s options, is resulting in continued irreversible disease progression, and contributes to greater health inequities. That’s not acceptable,” Dr. Pike added.

After news of today’s approval was released, Dr. Pike noted in a new release, “The Alzheimer’s Association welcomes and celebrates this action by the FDA. We now have a second approved treatment that changes the course of Alzheimer’s disease in a meaningful way for people in the early stages of the disease.”

Maria C. Carrillo, PhD, chief science officer at the Alzheimer’s Association, called today’s approval “a milestone achievement.”

“The progress we’ve seen in not only this class of treatments but also in the diversification of treatment types and targets over the past few years is exciting and provides real hope to those impacted by this devastating disease,” Dr. Carrillo said.
 

Critical issues

Commenting on the approval, Alvaro Pascual-Leone, MD, PhD, professor of neurology at Harvard Medical School, Boston, and chief medical officer at Linus Health, said FDA approval of lecanemab and its adoption in the clinic represent a “very exciting development and prospect; but arguably some critical issues need to be considered.”

He noted that the health care system “is not currently prepared to cope with the challenges and demands of lecanemab,” as well as future pharmacologic agents.

“First, we need better workflows to identify suitable patients who can most benefit from this treatment,” said Dr. Pascual-Leone. He added that beyond identification of cognitive difficulties, amyloid status will need to be determined.

“Presently, this requires expensive and invasive tests,” such as positron-emission tomography scans or lumbar punctures for cerebrospinal fluid analysis. However, these are not fully covered by insurance companies and would be challenging to fully scale, he noted.

“In addition to screening, health systems will need to resolve the logistics challenges around the administration of lecanemab with twice-monthly infusions and the need for careful longitudinal evaluations for potential side effects,” said Dr. Pascual-Leone.

“While lecanemab may represent the first disease-modifying therapy widely available for early Alzheimer’s disease, the likely more promising approach is the addition of other therapies to lecanemab as part of a multi-intervention strategy combining pharmacologic and nonpharmacologic interventions,” he added.

Dr. Pascual-Leone has served as a paid member on scientific advisory boards for Neuroelectrics, Magstim, TetraNeuron, Skin2Neuron, MedRhythms, and Hearts Radiant and is a cofounder of TI Solutions and Linus Health.

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

This article was updated 1/9/23.

The U.S. Food and Drug Administration has approved the anti–amyloid-beta protofibril antibody lecanemab (Leqembi, Eisai) for the treatment of early Alzheimer’s disease.

Like its controversial cousin aducanumab (Aduhelm, Biogen/Eisai), lecanemab was approved under the FDA’s accelerated approval pathway, which can be used to fast-track a drug that provides a meaningful therapeutic advantage over existing treatments for a serious or life-threatening illness.

Unlike aducanumab, however, there was no formal FDA advisory committee meeting on lecanemab prior to approval.

“Alzheimer’s disease immeasurably incapacitates the lives of those who suffer from it and has devastating effects on their loved ones,” Billy Dunn, MD, director of the Office of Neuroscience in the FDA’s Center for Drug Evaluation and Research, said in a press release.

“This treatment option is the latest therapy to target and affect the underlying disease process of Alzheimer’s, instead of only treating the symptoms of the disease,” Dr. Dunn added.

Eisai has reported that lecanemab will cost $26,500 a year.

Modest benefit, adverse events

The FDA noted, “The labeling states that treatment with Leqembi should be initiated in patients with mild cognitive impairment or mild dementia stage of disease, the population in which treatment was studied in clinical trials.”

The agency approved the treatment on the basis of findings from the CLARITY AD trial, which showed modest cognitive benefit for patients with early AD – but at a cost of increased risk for amyloid-related edema and effusions.

The trial enrolled 1,795 adults with mild cognitive impairment or early Alzheimer’s disease in whom amyloid pathology in the brain had been confirmed. Treatment consisted of lecanemab 10 mg/kg biweekly or matching placebo.

After 18 months of treatment, lecanemab slowed cognitive decline by 27%, compared with placebo, as measured by the Clinical Dementia Rating–Sum of Boxes (CDR-SB). This was an absolute difference of 0.45 points (change from baseline, 1.21 for lecanemab vs. 1.66 with placebo; P < .001).

While the results are “welcome news,” a 0.45-point difference on the CDR-SB might not be clinically meaningful, authors of a recent editorial in The Lancet cautioned.

Amyloid-related imaging abnormalities that manifest as edema or microhemorrhages also occurred in one in five patients taking lecanemab.

In addition, a newly published case report in The New England Journal of Medicine describes a patient with Alzheimer’s disease who was taking lecanemab and who died after experiencing numerous intracerebral hemorrhages during treatment with tissue plasminogen activator (tPA) for acute ischemic stroke.

“The findings raise the possibility of cerebral hemorrhages and necrotizing vasculopathy associated with tPA infusion in a patient with cerebrovascular amyloid who had received lecanemab,” the authors wrote.
 

Alzheimer’s Association reaction

Still, in anticipation of accelerated approval of lecanemab and the antiamyloid drug donanemab (Eli Lilly), which the FDA has also fast-tracked, the Alzheimer’s Association filed a formal request last month with the Centers for Medicare & Medicaid Services asking that it provide full and unrestricted coverage for FDA-approved Alzheimer’s disease treatments.

In a letter addressed to CMS administrator Chiquita Brooks-LaSure, the association asked the agency to remove the requirements for “coverage with evidence development” in its national coverage determination for FDA-approved antiamyloid monoclonal antibodies.

“Each day matters when it comes to slowing the progression of this disease,” Joanne Pike, DrPH, president and CEO for the Alzheimer’s Association, noted in a news release at the time.

“The current CMS policy to severely limit access to these treatments eliminates people’s options, is resulting in continued irreversible disease progression, and contributes to greater health inequities. That’s not acceptable,” Dr. Pike added.

After news of today’s approval was released, Dr. Pike noted in a new release, “The Alzheimer’s Association welcomes and celebrates this action by the FDA. We now have a second approved treatment that changes the course of Alzheimer’s disease in a meaningful way for people in the early stages of the disease.”

Maria C. Carrillo, PhD, chief science officer at the Alzheimer’s Association, called today’s approval “a milestone achievement.”

“The progress we’ve seen in not only this class of treatments but also in the diversification of treatment types and targets over the past few years is exciting and provides real hope to those impacted by this devastating disease,” Dr. Carrillo said.
 

Critical issues

Commenting on the approval, Alvaro Pascual-Leone, MD, PhD, professor of neurology at Harvard Medical School, Boston, and chief medical officer at Linus Health, said FDA approval of lecanemab and its adoption in the clinic represent a “very exciting development and prospect; but arguably some critical issues need to be considered.”

He noted that the health care system “is not currently prepared to cope with the challenges and demands of lecanemab,” as well as future pharmacologic agents.

“First, we need better workflows to identify suitable patients who can most benefit from this treatment,” said Dr. Pascual-Leone. He added that beyond identification of cognitive difficulties, amyloid status will need to be determined.

“Presently, this requires expensive and invasive tests,” such as positron-emission tomography scans or lumbar punctures for cerebrospinal fluid analysis. However, these are not fully covered by insurance companies and would be challenging to fully scale, he noted.

“In addition to screening, health systems will need to resolve the logistics challenges around the administration of lecanemab with twice-monthly infusions and the need for careful longitudinal evaluations for potential side effects,” said Dr. Pascual-Leone.

“While lecanemab may represent the first disease-modifying therapy widely available for early Alzheimer’s disease, the likely more promising approach is the addition of other therapies to lecanemab as part of a multi-intervention strategy combining pharmacologic and nonpharmacologic interventions,” he added.

Dr. Pascual-Leone has served as a paid member on scientific advisory boards for Neuroelectrics, Magstim, TetraNeuron, Skin2Neuron, MedRhythms, and Hearts Radiant and is a cofounder of TI Solutions and Linus Health.

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

This article was updated 1/9/23.

Food and Drug Administration officials are concerned about the safety of legal cannabis-infused foods and supplements and may recommend regulating the products later in 2023, according to a new report.

The products can have drug-like effects on the body and contain CBD (cannabidiol) and THC (tetrahydrocannabinol). Both CBD and THC can be derived from hemp, which was legalized by Congress in 2018. 

“Given what we know about the safety of CBD so far, it raises concerns for FDA about whether these existing regulatory pathways for food and dietary supplements are appropriate for this substance,” FDA Principal Deputy Commissioner Janet Woodcock, MD, told The Wall Street Journal. 

A 2021 FDA report valued the CBD market at $4.6 billion and projected it to quadruple by 2026. The only FDA-approved CBD product is an oil called Epidiolex, which can be prescribed for the seizure-associated disease epilepsy. Research on CBD to treat other diseases is ongoing.

Food, beverage, and beauty products containing CBD are sold in stores and online in many forms, including oils, vaporized liquids, and oil-based capsules, but “research supporting the drug’s benefits is still limited,” the Mayo Clinic said.

Recently, investigations have found that many CBD products also contain THC, which can be derived from legal hemp in a form that is referred to as Delta 8 and produces a psychoactive high. The CDC warned in 2022 that people “mistook” THC products for CBD products, which are often sold at the same stores, and experienced “adverse events.”

The Centers for Disease Control and Prevention and FDA warn that much is unknown about CBD and delta-8 products. The CDC says known CBD risks include liver damage; interference with other drugs you are taking, which may lead to injury or serious side effects; drowsiness or sleepiness; diarrhea or changes in appetite; changes in mood, such as crankiness; potential negative effects on fetuses during pregnancy or on babies during breastfeeding; or unintentional poisoning of children when mistaking THC products for CBD products or due to containing other ingredients such as THC or pesticides.

“I don’t think that we can have the perfect be the enemy of the good when we’re looking at such a vast market that is so available and utilized,” Norman Birenbaum, a senior FDA adviser who is working on the regulatory issue, told the Journal. “You’ve got a widely unregulated market.”

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

Food and Drug Administration officials are concerned about the safety of legal cannabis-infused foods and supplements and may recommend regulating the products later in 2023, according to a new report.

The products can have drug-like effects on the body and contain CBD (cannabidiol) and THC (tetrahydrocannabinol). Both CBD and THC can be derived from hemp, which was legalized by Congress in 2018. 

“Given what we know about the safety of CBD so far, it raises concerns for FDA about whether these existing regulatory pathways for food and dietary supplements are appropriate for this substance,” FDA Principal Deputy Commissioner Janet Woodcock, MD, told The Wall Street Journal. 

A 2021 FDA report valued the CBD market at $4.6 billion and projected it to quadruple by 2026. The only FDA-approved CBD product is an oil called Epidiolex, which can be prescribed for the seizure-associated disease epilepsy. Research on CBD to treat other diseases is ongoing.

Food, beverage, and beauty products containing CBD are sold in stores and online in many forms, including oils, vaporized liquids, and oil-based capsules, but “research supporting the drug’s benefits is still limited,” the Mayo Clinic said.

Recently, investigations have found that many CBD products also contain THC, which can be derived from legal hemp in a form that is referred to as Delta 8 and produces a psychoactive high. The CDC warned in 2022 that people “mistook” THC products for CBD products, which are often sold at the same stores, and experienced “adverse events.”

The Centers for Disease Control and Prevention and FDA warn that much is unknown about CBD and delta-8 products. The CDC says known CBD risks include liver damage; interference with other drugs you are taking, which may lead to injury or serious side effects; drowsiness or sleepiness; diarrhea or changes in appetite; changes in mood, such as crankiness; potential negative effects on fetuses during pregnancy or on babies during breastfeeding; or unintentional poisoning of children when mistaking THC products for CBD products or due to containing other ingredients such as THC or pesticides.

“I don’t think that we can have the perfect be the enemy of the good when we’re looking at such a vast market that is so available and utilized,” Norman Birenbaum, a senior FDA adviser who is working on the regulatory issue, told the Journal. “You’ve got a widely unregulated market.”

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

Food and Drug Administration officials are concerned about the safety of legal cannabis-infused foods and supplements and may recommend regulating the products later in 2023, according to a new report.

The products can have drug-like effects on the body and contain CBD (cannabidiol) and THC (tetrahydrocannabinol). Both CBD and THC can be derived from hemp, which was legalized by Congress in 2018. 

“Given what we know about the safety of CBD so far, it raises concerns for FDA about whether these existing regulatory pathways for food and dietary supplements are appropriate for this substance,” FDA Principal Deputy Commissioner Janet Woodcock, MD, told The Wall Street Journal. 

A 2021 FDA report valued the CBD market at $4.6 billion and projected it to quadruple by 2026. The only FDA-approved CBD product is an oil called Epidiolex, which can be prescribed for the seizure-associated disease epilepsy. Research on CBD to treat other diseases is ongoing.

Food, beverage, and beauty products containing CBD are sold in stores and online in many forms, including oils, vaporized liquids, and oil-based capsules, but “research supporting the drug’s benefits is still limited,” the Mayo Clinic said.

Recently, investigations have found that many CBD products also contain THC, which can be derived from legal hemp in a form that is referred to as Delta 8 and produces a psychoactive high. The CDC warned in 2022 that people “mistook” THC products for CBD products, which are often sold at the same stores, and experienced “adverse events.”

The Centers for Disease Control and Prevention and FDA warn that much is unknown about CBD and delta-8 products. The CDC says known CBD risks include liver damage; interference with other drugs you are taking, which may lead to injury or serious side effects; drowsiness or sleepiness; diarrhea or changes in appetite; changes in mood, such as crankiness; potential negative effects on fetuses during pregnancy or on babies during breastfeeding; or unintentional poisoning of children when mistaking THC products for CBD products or due to containing other ingredients such as THC or pesticides.

“I don’t think that we can have the perfect be the enemy of the good when we’re looking at such a vast market that is so available and utilized,” Norman Birenbaum, a senior FDA adviser who is working on the regulatory issue, told the Journal. “You’ve got a widely unregulated market.”

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

A new study shows a strong correlation between muscle strength, mobility, and brain volume, including in the hippocampus that underlies memory function, in adults with Alzheimer’s disease (AD). 

Investigators found statistically significant relationships between better handgrip strength and mobility and hippocampal and lobar brain volumes in 38 cognitively impaired adults with biomarker evidence of AD.

“The implication is that muscular strength and mobility influence brain health and can potentially be modified to improve outcomes in persons with Alzheimer’s,” study investigator Cyrus Raji, MD, PhD, Mallinckrodt Institute of Radiology, Washington University, St. Louis, told this news organization.

The study was published online in the Journal of Alzheimer’s Disease.
 

Brain-body connection

The researchers measured handgrip strength in patients’ dominant and nondominant hands using a hand dynamometer and calculated handgrip asymmetry. Mobility was measured via the 2-minute walk test. Together, the test results were used to categorize patients as “frail” or “not frail.”

They measured regional brain volumes using Neuroreader (Brainreader), a U.S. Food and Drug Administration–approved software application that measures brain volumes on MRI scans.

The investigators found higher nondominant handgrip strength was significantly associated with larger volumes in the hippocampal volume (P = .02). In addition, higher dominant handgrip strength correlated with higher frontal lobe volume (P = .02).

Results also showed higher scores on the 2-minute walk test were associated with larger hippocampal (P = .04), frontal (P = .01), temporal (P = .03), parietal (P = .009), and occipital lobe (P = .005) volumes. Frailty was associated with reduced frontal, temporal, and parietal lobe volumes.

“In this study we combined objective evaluations of frailty with measurable determinants of brain structure on MRI to demonstrate a link between frailty and brain health in patients with both biomarker evidence of AD and cognitive impairment,” study investigator Somayeh Meysami, MD, with Pacific Brain Health Center, Pacific Neuroscience Institute Foundation (PNI), Santa Monica, Calif., told this news organization.

The researchers noted that it’s possible that interventions specifically focused on improving ambulatory mobility and handgrip strength could be beneficial in improving dementia trajectories.
 

‘Use it or lose it’

The chief limitation of the study is the cross-sectional design that precludes drawing firm conclusions about the causal relationships between handgrip strength and changes in brain structure. 

In addition, the study used a relatively small convenience sample of outpatients from a specialty memory clinic.

The researchers say future longitudinal analyses with a larger sample size will be important to better understand the possible directions of causality between handgrip strength and progression of atrophy in AD.

However, despite these limitations, the findings emphasize the importance of “body-brain connections,” added David A. Merrill, MD, PhD, director of the Pacific Brain Health Center at PNI.

“Training our muscles helps sustain our brains and vice versa. It’s ‘use it or lose it’ for both body and mind. Exercise remains among the best strategies for maintaining a healthy body and mind with aging,” Dr. Merrill said in an interview.

“While it’s long been appreciated that aerobic training helps the brain, these findings add to the importance of strength training in supporting successful aging,” he added.

This work was supported by Providence St. Joseph Health, Seattle; Saint John’s Health Center Foundation; Pacific Neuroscience Institute Foundation; and the National Institutes of Health. Dr. Raji is a consultant for Brainreader, Apollo Health, Pacific Neuroscience Foundation, and Neurevolution. Dr. Merrill and Dr. Meysami reported no relevant disclosures.

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

A new study shows a strong correlation between muscle strength, mobility, and brain volume, including in the hippocampus that underlies memory function, in adults with Alzheimer’s disease (AD). 

Investigators found statistically significant relationships between better handgrip strength and mobility and hippocampal and lobar brain volumes in 38 cognitively impaired adults with biomarker evidence of AD.

“The implication is that muscular strength and mobility influence brain health and can potentially be modified to improve outcomes in persons with Alzheimer’s,” study investigator Cyrus Raji, MD, PhD, Mallinckrodt Institute of Radiology, Washington University, St. Louis, told this news organization.

The study was published online in the Journal of Alzheimer’s Disease.
 

Brain-body connection

The researchers measured handgrip strength in patients’ dominant and nondominant hands using a hand dynamometer and calculated handgrip asymmetry. Mobility was measured via the 2-minute walk test. Together, the test results were used to categorize patients as “frail” or “not frail.”

They measured regional brain volumes using Neuroreader (Brainreader), a U.S. Food and Drug Administration–approved software application that measures brain volumes on MRI scans.

The investigators found higher nondominant handgrip strength was significantly associated with larger volumes in the hippocampal volume (P = .02). In addition, higher dominant handgrip strength correlated with higher frontal lobe volume (P = .02).

Results also showed higher scores on the 2-minute walk test were associated with larger hippocampal (P = .04), frontal (P = .01), temporal (P = .03), parietal (P = .009), and occipital lobe (P = .005) volumes. Frailty was associated with reduced frontal, temporal, and parietal lobe volumes.

“In this study we combined objective evaluations of frailty with measurable determinants of brain structure on MRI to demonstrate a link between frailty and brain health in patients with both biomarker evidence of AD and cognitive impairment,” study investigator Somayeh Meysami, MD, with Pacific Brain Health Center, Pacific Neuroscience Institute Foundation (PNI), Santa Monica, Calif., told this news organization.

The researchers noted that it’s possible that interventions specifically focused on improving ambulatory mobility and handgrip strength could be beneficial in improving dementia trajectories.
 

‘Use it or lose it’

The chief limitation of the study is the cross-sectional design that precludes drawing firm conclusions about the causal relationships between handgrip strength and changes in brain structure. 

In addition, the study used a relatively small convenience sample of outpatients from a specialty memory clinic.

The researchers say future longitudinal analyses with a larger sample size will be important to better understand the possible directions of causality between handgrip strength and progression of atrophy in AD.

However, despite these limitations, the findings emphasize the importance of “body-brain connections,” added David A. Merrill, MD, PhD, director of the Pacific Brain Health Center at PNI.

“Training our muscles helps sustain our brains and vice versa. It’s ‘use it or lose it’ for both body and mind. Exercise remains among the best strategies for maintaining a healthy body and mind with aging,” Dr. Merrill said in an interview.

“While it’s long been appreciated that aerobic training helps the brain, these findings add to the importance of strength training in supporting successful aging,” he added.

This work was supported by Providence St. Joseph Health, Seattle; Saint John’s Health Center Foundation; Pacific Neuroscience Institute Foundation; and the National Institutes of Health. Dr. Raji is a consultant for Brainreader, Apollo Health, Pacific Neuroscience Foundation, and Neurevolution. Dr. Merrill and Dr. Meysami reported no relevant disclosures.

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

A new study shows a strong correlation between muscle strength, mobility, and brain volume, including in the hippocampus that underlies memory function, in adults with Alzheimer’s disease (AD). 

Investigators found statistically significant relationships between better handgrip strength and mobility and hippocampal and lobar brain volumes in 38 cognitively impaired adults with biomarker evidence of AD.

“The implication is that muscular strength and mobility influence brain health and can potentially be modified to improve outcomes in persons with Alzheimer’s,” study investigator Cyrus Raji, MD, PhD, Mallinckrodt Institute of Radiology, Washington University, St. Louis, told this news organization.

The study was published online in the Journal of Alzheimer’s Disease.
 

Brain-body connection

The researchers measured handgrip strength in patients’ dominant and nondominant hands using a hand dynamometer and calculated handgrip asymmetry. Mobility was measured via the 2-minute walk test. Together, the test results were used to categorize patients as “frail” or “not frail.”

They measured regional brain volumes using Neuroreader (Brainreader), a U.S. Food and Drug Administration–approved software application that measures brain volumes on MRI scans.

The investigators found higher nondominant handgrip strength was significantly associated with larger volumes in the hippocampal volume (P = .02). In addition, higher dominant handgrip strength correlated with higher frontal lobe volume (P = .02).

Results also showed higher scores on the 2-minute walk test were associated with larger hippocampal (P = .04), frontal (P = .01), temporal (P = .03), parietal (P = .009), and occipital lobe (P = .005) volumes. Frailty was associated with reduced frontal, temporal, and parietal lobe volumes.

“In this study we combined objective evaluations of frailty with measurable determinants of brain structure on MRI to demonstrate a link between frailty and brain health in patients with both biomarker evidence of AD and cognitive impairment,” study investigator Somayeh Meysami, MD, with Pacific Brain Health Center, Pacific Neuroscience Institute Foundation (PNI), Santa Monica, Calif., told this news organization.

The researchers noted that it’s possible that interventions specifically focused on improving ambulatory mobility and handgrip strength could be beneficial in improving dementia trajectories.
 

‘Use it or lose it’

The chief limitation of the study is the cross-sectional design that precludes drawing firm conclusions about the causal relationships between handgrip strength and changes in brain structure. 

In addition, the study used a relatively small convenience sample of outpatients from a specialty memory clinic.

The researchers say future longitudinal analyses with a larger sample size will be important to better understand the possible directions of causality between handgrip strength and progression of atrophy in AD.

However, despite these limitations, the findings emphasize the importance of “body-brain connections,” added David A. Merrill, MD, PhD, director of the Pacific Brain Health Center at PNI.

“Training our muscles helps sustain our brains and vice versa. It’s ‘use it or lose it’ for both body and mind. Exercise remains among the best strategies for maintaining a healthy body and mind with aging,” Dr. Merrill said in an interview.

“While it’s long been appreciated that aerobic training helps the brain, these findings add to the importance of strength training in supporting successful aging,” he added.

This work was supported by Providence St. Joseph Health, Seattle; Saint John’s Health Center Foundation; Pacific Neuroscience Institute Foundation; and the National Institutes of Health. Dr. Raji is a consultant for Brainreader, Apollo Health, Pacific Neuroscience Foundation, and Neurevolution. Dr. Merrill and Dr. Meysami reported no relevant disclosures.

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

The Alzheimer’s Association has filed a formal request with the Centers for Medicare & Medicaid Services that it provide full and unrestricted coverage for Alzheimer’s disease (AD) treatments approved by the U.S. Food and Drug Administration.

In a letter addressed to CMS administrator Chiquita Brooks-LaSure, MPP, the association has asked the agency to remove the requirements for “coverage with evidence development” in its national coverage determination for FDA-approved anti-amyloid monoclonal antibodies.

The CMS coverage restrictions for anti-amyloid drugs were finalized in April on the basis of data available at the time.

Since then, new data from the CLARITY AD trial “clearly demonstrate a meaningful clinical benefit” from the investigational anti-amyloid agent lecanemab (Eisai/Biogen), Robert Egge, chief public policy officer for the Alzheimer’s Association, told this news organization.

The CLARITY AD results were published in the New England Journal of Medicine. Lecanemab is currently under accelerated review at the FDA.

The Alzheimer’s Association’s letter to the CMS includes a joint statement signed by more than 200 AD researchers and experts. All agree that the lecanemab results represent “significant new evidence” that necessitates reconsidering the restrictions on anti-amyloid agents.

“CMS has said it would look at new evidence, and now that evidence is here. We believe CMS recognizes this evidence for lecanemab is stronger than that for many treatments Medicare routinely covers,” Mr. Egge said.
 

‘No time to waste’

“With the timing of accelerated approvals for both lecanemab and donanemab in the next few months, the Alzheimer’s Association wants to ensure, if approved, that patients can access these treatments,” Mr. Egge noted.

“Because revisions to National Coverage Determinations can be a lengthy process, CMS needs to act quickly to minimize delays. People living with Alzheimer’s disease don’t have time to waste,” he added.

The Alzheimer’s Association estimates that every day, more than 2,000 individuals aged 65 or older may transition from mild dementia due to AD to a more advanced stage of the disease in which they may no longer be eligible for lecanemab and the other anti-amyloid agents currently being tested.

“Each day matters when it comes to slowing the progression of this disease,” Joanne Pike, DrPH, president and incoming chief executive officer for the Alzheimer’s Association, noted in a news release.

“The current CMS policy to severely limit access to these treatments eliminates people’s options, is resulting in continued irreversible disease progression, and contributes to greater health inequities. That’s not acceptable,” Dr. Pike said.

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

The Alzheimer’s Association has filed a formal request with the Centers for Medicare & Medicaid Services that it provide full and unrestricted coverage for Alzheimer’s disease (AD) treatments approved by the U.S. Food and Drug Administration.

In a letter addressed to CMS administrator Chiquita Brooks-LaSure, MPP, the association has asked the agency to remove the requirements for “coverage with evidence development” in its national coverage determination for FDA-approved anti-amyloid monoclonal antibodies.

The CMS coverage restrictions for anti-amyloid drugs were finalized in April on the basis of data available at the time.

Since then, new data from the CLARITY AD trial “clearly demonstrate a meaningful clinical benefit” from the investigational anti-amyloid agent lecanemab (Eisai/Biogen), Robert Egge, chief public policy officer for the Alzheimer’s Association, told this news organization.

The CLARITY AD results were published in the New England Journal of Medicine. Lecanemab is currently under accelerated review at the FDA.

The Alzheimer’s Association’s letter to the CMS includes a joint statement signed by more than 200 AD researchers and experts. All agree that the lecanemab results represent “significant new evidence” that necessitates reconsidering the restrictions on anti-amyloid agents.

“CMS has said it would look at new evidence, and now that evidence is here. We believe CMS recognizes this evidence for lecanemab is stronger than that for many treatments Medicare routinely covers,” Mr. Egge said.
 

‘No time to waste’

“With the timing of accelerated approvals for both lecanemab and donanemab in the next few months, the Alzheimer’s Association wants to ensure, if approved, that patients can access these treatments,” Mr. Egge noted.

“Because revisions to National Coverage Determinations can be a lengthy process, CMS needs to act quickly to minimize delays. People living with Alzheimer’s disease don’t have time to waste,” he added.

The Alzheimer’s Association estimates that every day, more than 2,000 individuals aged 65 or older may transition from mild dementia due to AD to a more advanced stage of the disease in which they may no longer be eligible for lecanemab and the other anti-amyloid agents currently being tested.

“Each day matters when it comes to slowing the progression of this disease,” Joanne Pike, DrPH, president and incoming chief executive officer for the Alzheimer’s Association, noted in a news release.

“The current CMS policy to severely limit access to these treatments eliminates people’s options, is resulting in continued irreversible disease progression, and contributes to greater health inequities. That’s not acceptable,” Dr. Pike said.

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

The Alzheimer’s Association has filed a formal request with the Centers for Medicare & Medicaid Services that it provide full and unrestricted coverage for Alzheimer’s disease (AD) treatments approved by the U.S. Food and Drug Administration.

In a letter addressed to CMS administrator Chiquita Brooks-LaSure, MPP, the association has asked the agency to remove the requirements for “coverage with evidence development” in its national coverage determination for FDA-approved anti-amyloid monoclonal antibodies.

The CMS coverage restrictions for anti-amyloid drugs were finalized in April on the basis of data available at the time.

Since then, new data from the CLARITY AD trial “clearly demonstrate a meaningful clinical benefit” from the investigational anti-amyloid agent lecanemab (Eisai/Biogen), Robert Egge, chief public policy officer for the Alzheimer’s Association, told this news organization.

The CLARITY AD results were published in the New England Journal of Medicine. Lecanemab is currently under accelerated review at the FDA.

The Alzheimer’s Association’s letter to the CMS includes a joint statement signed by more than 200 AD researchers and experts. All agree that the lecanemab results represent “significant new evidence” that necessitates reconsidering the restrictions on anti-amyloid agents.

“CMS has said it would look at new evidence, and now that evidence is here. We believe CMS recognizes this evidence for lecanemab is stronger than that for many treatments Medicare routinely covers,” Mr. Egge said.
 

‘No time to waste’

“With the timing of accelerated approvals for both lecanemab and donanemab in the next few months, the Alzheimer’s Association wants to ensure, if approved, that patients can access these treatments,” Mr. Egge noted.

“Because revisions to National Coverage Determinations can be a lengthy process, CMS needs to act quickly to minimize delays. People living with Alzheimer’s disease don’t have time to waste,” he added.

The Alzheimer’s Association estimates that every day, more than 2,000 individuals aged 65 or older may transition from mild dementia due to AD to a more advanced stage of the disease in which they may no longer be eligible for lecanemab and the other anti-amyloid agents currently being tested.

“Each day matters when it comes to slowing the progression of this disease,” Joanne Pike, DrPH, president and incoming chief executive officer for the Alzheimer’s Association, noted in a news release.

“The current CMS policy to severely limit access to these treatments eliminates people’s options, is resulting in continued irreversible disease progression, and contributes to greater health inequities. That’s not acceptable,” Dr. Pike said.

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

SAN FRANCISCO – In a widely anticipated report, researchers reported that a phase 3 study showed statistically significant improvements in patients with agitation related to Alzheimer’s disease (AD) who took the atypical antipsychotic brexpiprazole (Rexulti).

Members of a panel of dementia specialists here at the 15th Clinical Trials on Alzheimer’s Disease (CTAD) conference said that the results were encouraging. But they also noted that the available data make it difficult to understand the impact of the drug on the day-to-day life on patients.

“I’d like to be able to translate that into something else to understand the risk benefit calculus,” said neurologist and neuroscientist Alireza Atri, MD, PhD, of Banner Sun Health Research Institute in Phoenix. “How does it affect the patients themselves, their quality of life, and the family members and their burden?”

Currently, there’s no Food and Drug Administration–approved treatment for agitation in AD.

In 2015, the FDA approved brexpiprazole, an oral medication, as a treatment for schizophrenia and an adjunctive treatment for major depressive disorder (MDD). It is an expensive drug with an average retail price per GoodRx of $1,582 per month, and no generic is available.

Researchers released the results of a trio of phase 3 clinical trials at CTAD that examined various doses of brexpiprazole. The results of the first two trials had been released earlier in 2018.
 

Three trials

All trials were multicenter, 12-week, randomized, double-blind and placebo-controlled.

Study participants were aged 55-90 years, had probable AD diagnoses, and had agitation per various scales. The average age in the groups was 74 years, 56.0%-61.7% were women, and 94.3%-98.1% were White.

The first trial examined two fixed doses (1 mg/d, n = 137; and 2 mg/d, n = 140) or placebo (n = 136). “The study initially included a 0.5 mg/day arm,” the researchers reported, “which was removed in a protocol amendment, and patients randomized to that arm were not included in efficacy analyses.”

The second trial looked at a flexible dose (0.5-2 mg/d, n = 133) or placebo (n = 137).

In a CTAD presentation, Nanco Hefting of Lundbeck, a codeveloper of the drug, said that the researchers learned from the first two trials that 2 mg/d might be an appropriate dose, and the FDA recommended they also examine 3 mg/day. As a result, the third trial examined two fixed doses (2 mg/d, n = 75; 3 mg/d, n = 153; or placebo, n = 117).

In the third trial, both the placebo and drug groups improved per a measurement of agitation; those in the drug group improved somewhat more.

The mean change in baseline on the Cohen-Mansfield Agitation Inventory scale – the primary endpoint – was –5.32 for the 2-mg/d and 3-mg/d groups vs. placebo (P = .0026); the score in the placebo group fell by about 18 and by about 22 in the drug group.

The key secondary endpoint was an improvement from baseline to week 12 in the Clinical Global Impression–Severity (CGI-S) score related to agitation. Compared with the placebo group, this score was –0.27 in the drug group (P = .0078). Both scores hovered around –1.0.

Safety data show the percentage of treatment-emergent events ranged from 45.9% in the placebo group to 49.0%-56.8% for brexpiprazole in the three trials. The percentage of these events leading to discontinuation was 6.3% among those receiving the drug and 3.4% in the placebo group.

University of Exeter dementia researcher Clive Ballard, MD, MB ChB, one of the panelists who discussed the research after the CTAD presentation, praised the trials as “well-conducted” and said that he was pleased that subjects in institutions were included. “It’s not an easy environment to do trials in. They should be really commended for doing for doing that.”

But he echoed fellow panelist Dr. Atri by noting that more data are needed to understand how well the drug works. “I would like to see the effect sizes and a little bit more detail to understand the clinical meaningfulness of that level of benefit.”

What’s next? A spokeswoman for Otsuka, a codeveloper of brexpiprazole, said that it hopes to hear in 2023 about a supplemental new drug application that was filed in November 2022.

Otsuka and Lundbeck funded the research. Mr. Hefting is an employee of Lundbeck, and several other authors work for Lundbeck or Otsuka. The single non-employee author reports various disclosures. Disclosures for Dr. Atri and Dr. Ballard were not provided.
 

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

SAN FRANCISCO – In a widely anticipated report, researchers reported that a phase 3 study showed statistically significant improvements in patients with agitation related to Alzheimer’s disease (AD) who took the atypical antipsychotic brexpiprazole (Rexulti).

Members of a panel of dementia specialists here at the 15th Clinical Trials on Alzheimer’s Disease (CTAD) conference said that the results were encouraging. But they also noted that the available data make it difficult to understand the impact of the drug on the day-to-day life on patients.

“I’d like to be able to translate that into something else to understand the risk benefit calculus,” said neurologist and neuroscientist Alireza Atri, MD, PhD, of Banner Sun Health Research Institute in Phoenix. “How does it affect the patients themselves, their quality of life, and the family members and their burden?”

Currently, there’s no Food and Drug Administration–approved treatment for agitation in AD.

In 2015, the FDA approved brexpiprazole, an oral medication, as a treatment for schizophrenia and an adjunctive treatment for major depressive disorder (MDD). It is an expensive drug with an average retail price per GoodRx of $1,582 per month, and no generic is available.

Researchers released the results of a trio of phase 3 clinical trials at CTAD that examined various doses of brexpiprazole. The results of the first two trials had been released earlier in 2018.
 

Three trials

All trials were multicenter, 12-week, randomized, double-blind and placebo-controlled.

Study participants were aged 55-90 years, had probable AD diagnoses, and had agitation per various scales. The average age in the groups was 74 years, 56.0%-61.7% were women, and 94.3%-98.1% were White.

The first trial examined two fixed doses (1 mg/d, n = 137; and 2 mg/d, n = 140) or placebo (n = 136). “The study initially included a 0.5 mg/day arm,” the researchers reported, “which was removed in a protocol amendment, and patients randomized to that arm were not included in efficacy analyses.”

The second trial looked at a flexible dose (0.5-2 mg/d, n = 133) or placebo (n = 137).

In a CTAD presentation, Nanco Hefting of Lundbeck, a codeveloper of the drug, said that the researchers learned from the first two trials that 2 mg/d might be an appropriate dose, and the FDA recommended they also examine 3 mg/day. As a result, the third trial examined two fixed doses (2 mg/d, n = 75; 3 mg/d, n = 153; or placebo, n = 117).

In the third trial, both the placebo and drug groups improved per a measurement of agitation; those in the drug group improved somewhat more.

The mean change in baseline on the Cohen-Mansfield Agitation Inventory scale – the primary endpoint – was –5.32 for the 2-mg/d and 3-mg/d groups vs. placebo (P = .0026); the score in the placebo group fell by about 18 and by about 22 in the drug group.

The key secondary endpoint was an improvement from baseline to week 12 in the Clinical Global Impression–Severity (CGI-S) score related to agitation. Compared with the placebo group, this score was –0.27 in the drug group (P = .0078). Both scores hovered around –1.0.

Safety data show the percentage of treatment-emergent events ranged from 45.9% in the placebo group to 49.0%-56.8% for brexpiprazole in the three trials. The percentage of these events leading to discontinuation was 6.3% among those receiving the drug and 3.4% in the placebo group.

University of Exeter dementia researcher Clive Ballard, MD, MB ChB, one of the panelists who discussed the research after the CTAD presentation, praised the trials as “well-conducted” and said that he was pleased that subjects in institutions were included. “It’s not an easy environment to do trials in. They should be really commended for doing for doing that.”

But he echoed fellow panelist Dr. Atri by noting that more data are needed to understand how well the drug works. “I would like to see the effect sizes and a little bit more detail to understand the clinical meaningfulness of that level of benefit.”

What’s next? A spokeswoman for Otsuka, a codeveloper of brexpiprazole, said that it hopes to hear in 2023 about a supplemental new drug application that was filed in November 2022.

Otsuka and Lundbeck funded the research. Mr. Hefting is an employee of Lundbeck, and several other authors work for Lundbeck or Otsuka. The single non-employee author reports various disclosures. Disclosures for Dr. Atri and Dr. Ballard were not provided.
 

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

SAN FRANCISCO – In a widely anticipated report, researchers reported that a phase 3 study showed statistically significant improvements in patients with agitation related to Alzheimer’s disease (AD) who took the atypical antipsychotic brexpiprazole (Rexulti).

Members of a panel of dementia specialists here at the 15th Clinical Trials on Alzheimer’s Disease (CTAD) conference said that the results were encouraging. But they also noted that the available data make it difficult to understand the impact of the drug on the day-to-day life on patients.

“I’d like to be able to translate that into something else to understand the risk benefit calculus,” said neurologist and neuroscientist Alireza Atri, MD, PhD, of Banner Sun Health Research Institute in Phoenix. “How does it affect the patients themselves, their quality of life, and the family members and their burden?”

Currently, there’s no Food and Drug Administration–approved treatment for agitation in AD.

In 2015, the FDA approved brexpiprazole, an oral medication, as a treatment for schizophrenia and an adjunctive treatment for major depressive disorder (MDD). It is an expensive drug with an average retail price per GoodRx of $1,582 per month, and no generic is available.

Researchers released the results of a trio of phase 3 clinical trials at CTAD that examined various doses of brexpiprazole. The results of the first two trials had been released earlier in 2018.
 

Three trials

All trials were multicenter, 12-week, randomized, double-blind and placebo-controlled.

Study participants were aged 55-90 years, had probable AD diagnoses, and had agitation per various scales. The average age in the groups was 74 years, 56.0%-61.7% were women, and 94.3%-98.1% were White.

The first trial examined two fixed doses (1 mg/d, n = 137; and 2 mg/d, n = 140) or placebo (n = 136). “The study initially included a 0.5 mg/day arm,” the researchers reported, “which was removed in a protocol amendment, and patients randomized to that arm were not included in efficacy analyses.”

The second trial looked at a flexible dose (0.5-2 mg/d, n = 133) or placebo (n = 137).

In a CTAD presentation, Nanco Hefting of Lundbeck, a codeveloper of the drug, said that the researchers learned from the first two trials that 2 mg/d might be an appropriate dose, and the FDA recommended they also examine 3 mg/day. As a result, the third trial examined two fixed doses (2 mg/d, n = 75; 3 mg/d, n = 153; or placebo, n = 117).

In the third trial, both the placebo and drug groups improved per a measurement of agitation; those in the drug group improved somewhat more.

The mean change in baseline on the Cohen-Mansfield Agitation Inventory scale – the primary endpoint – was –5.32 for the 2-mg/d and 3-mg/d groups vs. placebo (P = .0026); the score in the placebo group fell by about 18 and by about 22 in the drug group.

The key secondary endpoint was an improvement from baseline to week 12 in the Clinical Global Impression–Severity (CGI-S) score related to agitation. Compared with the placebo group, this score was –0.27 in the drug group (P = .0078). Both scores hovered around –1.0.

Safety data show the percentage of treatment-emergent events ranged from 45.9% in the placebo group to 49.0%-56.8% for brexpiprazole in the three trials. The percentage of these events leading to discontinuation was 6.3% among those receiving the drug and 3.4% in the placebo group.

University of Exeter dementia researcher Clive Ballard, MD, MB ChB, one of the panelists who discussed the research after the CTAD presentation, praised the trials as “well-conducted” and said that he was pleased that subjects in institutions were included. “It’s not an easy environment to do trials in. They should be really commended for doing for doing that.”

But he echoed fellow panelist Dr. Atri by noting that more data are needed to understand how well the drug works. “I would like to see the effect sizes and a little bit more detail to understand the clinical meaningfulness of that level of benefit.”

What’s next? A spokeswoman for Otsuka, a codeveloper of brexpiprazole, said that it hopes to hear in 2023 about a supplemental new drug application that was filed in November 2022.

Otsuka and Lundbeck funded the research. Mr. Hefting is an employee of Lundbeck, and several other authors work for Lundbeck or Otsuka. The single non-employee author reports various disclosures. Disclosures for Dr. Atri and Dr. Ballard were not provided.
 

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

Welcome to Impact Factor, your weekly dose of commentary on a new medical study. I’m Dr. F. Perry Wilson of the Yale School of Medicine.

We are coming to the end of the year, which always makes me think about getting older. Despite the fact that aging is, definitionally, inexorable, we continue to search for ways to avoid the losses that come with age, whether that is strength, beauty, or our cognitive powers. Much like the search for the fountain of youth, many promising leads have ultimately led to dead ends. And yet, I had high hopes for a trial that focused on two cornerstones of wellness – exercise and mindfulness – to address the subjective loss of memory that comes with aging. Alas, meditation and exercise do not appear to be the fountain of youth.

I’m talking about this study, appearing in JAMA, known as the MEDEX trial.

It’s a clever design: a 2 x 2 factorial randomized trial where participants could be randomized to a mindfulness intervention, an exercise intervention, both, or neither.

Courtesy Dr. F. Perry Wilson

In this manner, you can test multiple hypotheses exploiting a shared control group. Or as a mentor of mine used to say, you get two trials for the price of one and a half.

The participants were older adults, aged 65-84, living in the community. They had to be relatively sedentary at baseline and not engaging in mindfulness practices. They had to subjectively report some memory or concentration issues but had to be cognitively intact, based on a standard dementia screening test. In other words, these are your average older people who are worried that they aren’t as sharp as they used to be.

The interventions themselves were fairly intense. The exercise group had instructor-led sessions for 90 minutes twice a week for the first 6 months of the study, once a week thereafter. And participants were encouraged to exercise at home such that they had a total of 300 minutes of weekly exercise.

The mindfulness program was characterized by eight weekly classes of 2.5 hours each as well as a half-day retreat to teach the tenets of mindfulness and meditation, with monthly refreshers thereafter. Participants were instructed to meditate for 60 minutes a day in addition to the classes.

For the 144 people who were randomized to both meditation and exercise, this trial amounted to something of a part-time job. So you might think that adherence to the interventions was low, but apparently that’s not the case. Attendance to the mindfulness classes was over 90%, and over 80% for the exercise classes. And diary-based reporting of home efforts was also pretty good.

The control group wasn’t left to their own devices. Recognizing that the community aspect of exercise or mindfulness classes might convey a benefit independent of the actual exercise or mindfulness, the control group met on a similar schedule to discuss health education, but no mention of exercise or mindfulness occurred in that setting.

The primary outcome was change in memory and executive function scores across a battery of neuropsychologic testing, but the story is told in just a few pictures.

Memory scores improved in all three groups – mindfulness, exercise, and health education – over time. Cognitive composite score improved in all three groups similarly. There was no synergistic effect of mindfulness and exercise either. Basically, everyone got a bit better.

But the study did way more than look at scores on tests. Researchers used MRI to measure brain anatomic outcomes as well. And the surprising thing is that virtually none of these outcomes were different between the groups either.

Hippocampal volume decreased a bit in all the groups. Dorsolateral prefrontal cortex volume was flat. There was no change in scores measuring tasks of daily living.

When you see negative results like this, right away you worry that the intervention wasn’t properly delivered. Were these people really exercising and meditating? Well, the authors showed that individuals randomized to exercise, at least, had less sleep latency, greater aerobic fitness, and greater strength. So we know something was happening.

They then asked, would the people in the exercise group with the greatest changes in those physiologic parameters show some improvement in cognitive parameters? In other words, we know you were exercising because you got stronger and are sleeping better; is your memory better? The answer? Surprisingly, still no. Even in that honestly somewhat cherry-picked group, the interventions had no effect.

Could it be that the control was inappropriate, that the “health education” intervention was actually so helpful that it obscured the benefits of exercise and meditation? After all, cognitive scores did improve in all groups. The authors doubt it. They say they think the improvement in cognitive scores reflects the fact that patients had learned a bit about how to take the tests. This is pretty common in the neuropsychiatric literature.

So here we are and I just want to say, well, shoot. This is not the result I wanted. And I think the reason I’m so disappointed is because aging and the loss of cognitive faculties that comes with aging are just sort of scary. We are all looking for some control over that fear, and how nice it would be to be able to tell ourselves not to worry – that we won’t have those problems as we get older because we exercise, or meditate, or drink red wine, or don’t drink wine, or whatever. And while I have no doubt that staying healthier physically will keep you healthier mentally, it may take more than one simple thing to move the needle.

Dr. Wilson is associate professor, department of medicine, and director of the Clinical and Translational Research Accelerator at Yale University, New Haven, Conn. He reported no conflicts of interest.

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

Welcome to Impact Factor, your weekly dose of commentary on a new medical study. I’m Dr. F. Perry Wilson of the Yale School of Medicine.

We are coming to the end of the year, which always makes me think about getting older. Despite the fact that aging is, definitionally, inexorable, we continue to search for ways to avoid the losses that come with age, whether that is strength, beauty, or our cognitive powers. Much like the search for the fountain of youth, many promising leads have ultimately led to dead ends. And yet, I had high hopes for a trial that focused on two cornerstones of wellness – exercise and mindfulness – to address the subjective loss of memory that comes with aging. Alas, meditation and exercise do not appear to be the fountain of youth.

I’m talking about this study, appearing in JAMA, known as the MEDEX trial.

It’s a clever design: a 2 x 2 factorial randomized trial where participants could be randomized to a mindfulness intervention, an exercise intervention, both, or neither.

Courtesy Dr. F. Perry Wilson

In this manner, you can test multiple hypotheses exploiting a shared control group. Or as a mentor of mine used to say, you get two trials for the price of one and a half.

The participants were older adults, aged 65-84, living in the community. They had to be relatively sedentary at baseline and not engaging in mindfulness practices. They had to subjectively report some memory or concentration issues but had to be cognitively intact, based on a standard dementia screening test. In other words, these are your average older people who are worried that they aren’t as sharp as they used to be.

The interventions themselves were fairly intense. The exercise group had instructor-led sessions for 90 minutes twice a week for the first 6 months of the study, once a week thereafter. And participants were encouraged to exercise at home such that they had a total of 300 minutes of weekly exercise.

The mindfulness program was characterized by eight weekly classes of 2.5 hours each as well as a half-day retreat to teach the tenets of mindfulness and meditation, with monthly refreshers thereafter. Participants were instructed to meditate for 60 minutes a day in addition to the classes.

For the 144 people who were randomized to both meditation and exercise, this trial amounted to something of a part-time job. So you might think that adherence to the interventions was low, but apparently that’s not the case. Attendance to the mindfulness classes was over 90%, and over 80% for the exercise classes. And diary-based reporting of home efforts was also pretty good.

The control group wasn’t left to their own devices. Recognizing that the community aspect of exercise or mindfulness classes might convey a benefit independent of the actual exercise or mindfulness, the control group met on a similar schedule to discuss health education, but no mention of exercise or mindfulness occurred in that setting.

The primary outcome was change in memory and executive function scores across a battery of neuropsychologic testing, but the story is told in just a few pictures.

Memory scores improved in all three groups – mindfulness, exercise, and health education – over time. Cognitive composite score improved in all three groups similarly. There was no synergistic effect of mindfulness and exercise either. Basically, everyone got a bit better.

But the study did way more than look at scores on tests. Researchers used MRI to measure brain anatomic outcomes as well. And the surprising thing is that virtually none of these outcomes were different between the groups either.

Hippocampal volume decreased a bit in all the groups. Dorsolateral prefrontal cortex volume was flat. There was no change in scores measuring tasks of daily living.

When you see negative results like this, right away you worry that the intervention wasn’t properly delivered. Were these people really exercising and meditating? Well, the authors showed that individuals randomized to exercise, at least, had less sleep latency, greater aerobic fitness, and greater strength. So we know something was happening.

They then asked, would the people in the exercise group with the greatest changes in those physiologic parameters show some improvement in cognitive parameters? In other words, we know you were exercising because you got stronger and are sleeping better; is your memory better? The answer? Surprisingly, still no. Even in that honestly somewhat cherry-picked group, the interventions had no effect.

Could it be that the control was inappropriate, that the “health education” intervention was actually so helpful that it obscured the benefits of exercise and meditation? After all, cognitive scores did improve in all groups. The authors doubt it. They say they think the improvement in cognitive scores reflects the fact that patients had learned a bit about how to take the tests. This is pretty common in the neuropsychiatric literature.

So here we are and I just want to say, well, shoot. This is not the result I wanted. And I think the reason I’m so disappointed is because aging and the loss of cognitive faculties that comes with aging are just sort of scary. We are all looking for some control over that fear, and how nice it would be to be able to tell ourselves not to worry – that we won’t have those problems as we get older because we exercise, or meditate, or drink red wine, or don’t drink wine, or whatever. And while I have no doubt that staying healthier physically will keep you healthier mentally, it may take more than one simple thing to move the needle.

Dr. Wilson is associate professor, department of medicine, and director of the Clinical and Translational Research Accelerator at Yale University, New Haven, Conn. He reported no conflicts of interest.

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

Welcome to Impact Factor, your weekly dose of commentary on a new medical study. I’m Dr. F. Perry Wilson of the Yale School of Medicine.

We are coming to the end of the year, which always makes me think about getting older. Despite the fact that aging is, definitionally, inexorable, we continue to search for ways to avoid the losses that come with age, whether that is strength, beauty, or our cognitive powers. Much like the search for the fountain of youth, many promising leads have ultimately led to dead ends. And yet, I had high hopes for a trial that focused on two cornerstones of wellness – exercise and mindfulness – to address the subjective loss of memory that comes with aging. Alas, meditation and exercise do not appear to be the fountain of youth.

I’m talking about this study, appearing in JAMA, known as the MEDEX trial.

It’s a clever design: a 2 x 2 factorial randomized trial where participants could be randomized to a mindfulness intervention, an exercise intervention, both, or neither.

Courtesy Dr. F. Perry Wilson

In this manner, you can test multiple hypotheses exploiting a shared control group. Or as a mentor of mine used to say, you get two trials for the price of one and a half.

The participants were older adults, aged 65-84, living in the community. They had to be relatively sedentary at baseline and not engaging in mindfulness practices. They had to subjectively report some memory or concentration issues but had to be cognitively intact, based on a standard dementia screening test. In other words, these are your average older people who are worried that they aren’t as sharp as they used to be.

The interventions themselves were fairly intense. The exercise group had instructor-led sessions for 90 minutes twice a week for the first 6 months of the study, once a week thereafter. And participants were encouraged to exercise at home such that they had a total of 300 minutes of weekly exercise.

The mindfulness program was characterized by eight weekly classes of 2.5 hours each as well as a half-day retreat to teach the tenets of mindfulness and meditation, with monthly refreshers thereafter. Participants were instructed to meditate for 60 minutes a day in addition to the classes.

For the 144 people who were randomized to both meditation and exercise, this trial amounted to something of a part-time job. So you might think that adherence to the interventions was low, but apparently that’s not the case. Attendance to the mindfulness classes was over 90%, and over 80% for the exercise classes. And diary-based reporting of home efforts was also pretty good.

The control group wasn’t left to their own devices. Recognizing that the community aspect of exercise or mindfulness classes might convey a benefit independent of the actual exercise or mindfulness, the control group met on a similar schedule to discuss health education, but no mention of exercise or mindfulness occurred in that setting.

The primary outcome was change in memory and executive function scores across a battery of neuropsychologic testing, but the story is told in just a few pictures.

Memory scores improved in all three groups – mindfulness, exercise, and health education – over time. Cognitive composite score improved in all three groups similarly. There was no synergistic effect of mindfulness and exercise either. Basically, everyone got a bit better.

But the study did way more than look at scores on tests. Researchers used MRI to measure brain anatomic outcomes as well. And the surprising thing is that virtually none of these outcomes were different between the groups either.

Hippocampal volume decreased a bit in all the groups. Dorsolateral prefrontal cortex volume was flat. There was no change in scores measuring tasks of daily living.

When you see negative results like this, right away you worry that the intervention wasn’t properly delivered. Were these people really exercising and meditating? Well, the authors showed that individuals randomized to exercise, at least, had less sleep latency, greater aerobic fitness, and greater strength. So we know something was happening.

They then asked, would the people in the exercise group with the greatest changes in those physiologic parameters show some improvement in cognitive parameters? In other words, we know you were exercising because you got stronger and are sleeping better; is your memory better? The answer? Surprisingly, still no. Even in that honestly somewhat cherry-picked group, the interventions had no effect.

Could it be that the control was inappropriate, that the “health education” intervention was actually so helpful that it obscured the benefits of exercise and meditation? After all, cognitive scores did improve in all groups. The authors doubt it. They say they think the improvement in cognitive scores reflects the fact that patients had learned a bit about how to take the tests. This is pretty common in the neuropsychiatric literature.

So here we are and I just want to say, well, shoot. This is not the result I wanted. And I think the reason I’m so disappointed is because aging and the loss of cognitive faculties that comes with aging are just sort of scary. We are all looking for some control over that fear, and how nice it would be to be able to tell ourselves not to worry – that we won’t have those problems as we get older because we exercise, or meditate, or drink red wine, or don’t drink wine, or whatever. And while I have no doubt that staying healthier physically will keep you healthier mentally, it may take more than one simple thing to move the needle.

Dr. Wilson is associate professor, department of medicine, and director of the Clinical and Translational Research Accelerator at Yale University, New Haven, Conn. He reported no conflicts of interest.

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