Alzheimer's & Cognition

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.

Transcranial photobiomodulation (tPBM), a noninvasive laser light therapy, can improve short-term memory in young adults when applied to the right prefrontal cortex (PFC) of the brain, new research suggests.

Investigators compared the effect of 1,064 nm of tPBM delivered over a 12-minute session to the right PFC vs. three other treatment arms: delivery of the same intervention to the left PFC, delivery of the intervention at a lower frequency, and a sham intervention.

All participants were shown a series of items prior to the intervention and  asked to recall them after the intervention. Those who received tPBM 1,064 nm to the right PFC showed a superior performance of up to 25% in the memory tasks compared with the other groups.

Patients with attention-related conditions, such as attention deficit hyperactivity disorder, “could benefit from this type of treatment, which is safe, simple, and noninvasive, with no side effects,” coinvestigator Dongwei Li, a visiting PhD student at the Centre for Human Brain Health, University of Birmingham, England, said in a news release.

The findings were published online in Science Advances.
 

Differing wavelengths

The researchers note that “in the past decades,” noninvasive brain stimulation technology using transcranial application of direct or alternating electrical or magnetic fields “has been proven to be useful” in the improvement of working memory (WM).

When applied to the right PFC, tPBM has been shown to improve accuracy and speed of reaction time in WM tasks and improvements in “high-order cognitive functions,” such as sustained attention, emotion, and executive functions.

The investigators wanted to assess the impact of tPBM applied to different parts of the brain and at different wavelengths. They conducted four double-blind, sham-controlled experiments encompassing 90 neurotypical college students (mean age, 22 years). Each student participated in only one of the four experiments.

All completed two different tPBM sessions, separated by a week, in which sham and active tPBM were compared. Two different types of change-detection memory tasks were given: one requiring participants to remember the orientation of a series of items before and after the intervention and one other requiring them to remember the color of the items (experiments 1 and 2).

A series of follow-up experiments focused on comparing different wavelengths (1,064 nm vs. 852 nm) and different stimulation sites (right vs. left PFC; experiments 3 and 4).

EEG recordings were obtained during the intervention and the memory tasks.

Each experiment consisted of one active tPBM session and one sham tPBM session, with sessions consisting of 12 minutes of laser light (or sham) intervention. These sessions were conducted on the first and the seventh day; then, on the eighth day, participants were asked to report (or guess) which session was the active tPBM session.
 

Stimulating astrocytes

Results showed that, compared with sham tPBM, there was an improvement in WM capacity and scores by the 1,064 nm intervention in the orientation as well as the color task.

Participants who received the targeted treatment were able to remember between four and five test objects, whereas those with the treatment variations were only able to remember between three and four objects.

“These results support the hypothesis that 1,064 nm tPBM on the right PFC enhances WM capacity,” the investigators wrote.

They also found improvements in WM in participants receiving tPBM vs. sham regardless of whether their performance in the WM task was at a low or high level. This finding held true in both the orientation and the color tasks.

“Therefore, participants with good and poor WM capacity improved after 1,064 nm tPBM,” the researchers noted.

In addition, participants were unable to guess or report whether they had received sham or active tPBM.

EEG monitoring showed changes in brain activity that predicted the improvements in memory performance. In particular, 1,064 tPBM applied to the right PFC increased occipitoparietal contralateral delay activity (CDA), with CDA mediating the WM improvement.

This is “consistent with previous research that CDA is indicative of the number of maintained objects in visual working memory,” the investigators wrote.

Pearson correlation analyses showed that the differences in CDA set-size effects between active and sham session “correlated positively” with the behavioral differences between these sessions. For the orientation task, the r was 0.446 (P < .04); and for the color task, the r was .563 (P < .02).

No similar improvements were found with the 852 nm tPBM.

“We need further research to understand exactly why the tPBM is having this positive effect,” coinvestigator Ole Jensen, PhD, professor in translational neuroscience and codirector of the Centre for Human Brain Health, said in the release.

“It’s possible that the light is stimulating the astrocytes – the powerplants – in the nerve cells within the PFC, and this has a positive effect on the cells’ efficiency,” he noted.

Dr. Jensen added that his team “will also be investigating how long the effects might last. Clearly, if these experiments are to lead to a clinical intervention, we will need to see long-lasting benefits.”
 

Beneficial cognitive, emotional effects

Commenting for this news organization, Francisco Gonzalez-Lima, PhD, professor in the department of psychology, University of Texas at Austin, called the study “well done.”

Dr. Gonzalez-Lima was one of the first researchers to demonstrate that 1,064 nm transcranial infrared laser stimulation “produces beneficial cognitive and emotional effects in humans, including improving visual working memory,” he said.

The current study “reported an additional brain effect linked to the improved visual working memory that consists of an EEG-derived response, which is a new finding,” noted Dr. Gonzales-Lima, who was not involved with the new research.

He added that the same laser method “has been found by the Gonzalez-Lima lab to be effective at improving cognition in older adults and depressed and bipolar patients.”

The study was supported by the National Natural Science Foundation of China, the Ministry of Science and Technology of the People’s Republic of China, and the National Defence Basic Scientific Research Program of China. The investigators and Dr. Gonzalez-Lima report no relevant financial relationships.

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

Transcranial photobiomodulation (tPBM), a noninvasive laser light therapy, can improve short-term memory in young adults when applied to the right prefrontal cortex (PFC) of the brain, new research suggests.

Investigators compared the effect of 1,064 nm of tPBM delivered over a 12-minute session to the right PFC vs. three other treatment arms: delivery of the same intervention to the left PFC, delivery of the intervention at a lower frequency, and a sham intervention.

All participants were shown a series of items prior to the intervention and  asked to recall them after the intervention. Those who received tPBM 1,064 nm to the right PFC showed a superior performance of up to 25% in the memory tasks compared with the other groups.

Patients with attention-related conditions, such as attention deficit hyperactivity disorder, “could benefit from this type of treatment, which is safe, simple, and noninvasive, with no side effects,” coinvestigator Dongwei Li, a visiting PhD student at the Centre for Human Brain Health, University of Birmingham, England, said in a news release.

The findings were published online in Science Advances.
 

Differing wavelengths

The researchers note that “in the past decades,” noninvasive brain stimulation technology using transcranial application of direct or alternating electrical or magnetic fields “has been proven to be useful” in the improvement of working memory (WM).

When applied to the right PFC, tPBM has been shown to improve accuracy and speed of reaction time in WM tasks and improvements in “high-order cognitive functions,” such as sustained attention, emotion, and executive functions.

The investigators wanted to assess the impact of tPBM applied to different parts of the brain and at different wavelengths. They conducted four double-blind, sham-controlled experiments encompassing 90 neurotypical college students (mean age, 22 years). Each student participated in only one of the four experiments.

All completed two different tPBM sessions, separated by a week, in which sham and active tPBM were compared. Two different types of change-detection memory tasks were given: one requiring participants to remember the orientation of a series of items before and after the intervention and one other requiring them to remember the color of the items (experiments 1 and 2).

A series of follow-up experiments focused on comparing different wavelengths (1,064 nm vs. 852 nm) and different stimulation sites (right vs. left PFC; experiments 3 and 4).

EEG recordings were obtained during the intervention and the memory tasks.

Each experiment consisted of one active tPBM session and one sham tPBM session, with sessions consisting of 12 minutes of laser light (or sham) intervention. These sessions were conducted on the first and the seventh day; then, on the eighth day, participants were asked to report (or guess) which session was the active tPBM session.
 

Stimulating astrocytes

Results showed that, compared with sham tPBM, there was an improvement in WM capacity and scores by the 1,064 nm intervention in the orientation as well as the color task.

Participants who received the targeted treatment were able to remember between four and five test objects, whereas those with the treatment variations were only able to remember between three and four objects.

“These results support the hypothesis that 1,064 nm tPBM on the right PFC enhances WM capacity,” the investigators wrote.

They also found improvements in WM in participants receiving tPBM vs. sham regardless of whether their performance in the WM task was at a low or high level. This finding held true in both the orientation and the color tasks.

“Therefore, participants with good and poor WM capacity improved after 1,064 nm tPBM,” the researchers noted.

In addition, participants were unable to guess or report whether they had received sham or active tPBM.

EEG monitoring showed changes in brain activity that predicted the improvements in memory performance. In particular, 1,064 tPBM applied to the right PFC increased occipitoparietal contralateral delay activity (CDA), with CDA mediating the WM improvement.

This is “consistent with previous research that CDA is indicative of the number of maintained objects in visual working memory,” the investigators wrote.

Pearson correlation analyses showed that the differences in CDA set-size effects between active and sham session “correlated positively” with the behavioral differences between these sessions. For the orientation task, the r was 0.446 (P < .04); and for the color task, the r was .563 (P < .02).

No similar improvements were found with the 852 nm tPBM.

“We need further research to understand exactly why the tPBM is having this positive effect,” coinvestigator Ole Jensen, PhD, professor in translational neuroscience and codirector of the Centre for Human Brain Health, said in the release.

“It’s possible that the light is stimulating the astrocytes – the powerplants – in the nerve cells within the PFC, and this has a positive effect on the cells’ efficiency,” he noted.

Dr. Jensen added that his team “will also be investigating how long the effects might last. Clearly, if these experiments are to lead to a clinical intervention, we will need to see long-lasting benefits.”
 

Beneficial cognitive, emotional effects

Commenting for this news organization, Francisco Gonzalez-Lima, PhD, professor in the department of psychology, University of Texas at Austin, called the study “well done.”

Dr. Gonzalez-Lima was one of the first researchers to demonstrate that 1,064 nm transcranial infrared laser stimulation “produces beneficial cognitive and emotional effects in humans, including improving visual working memory,” he said.

The current study “reported an additional brain effect linked to the improved visual working memory that consists of an EEG-derived response, which is a new finding,” noted Dr. Gonzales-Lima, who was not involved with the new research.

He added that the same laser method “has been found by the Gonzalez-Lima lab to be effective at improving cognition in older adults and depressed and bipolar patients.”

The study was supported by the National Natural Science Foundation of China, the Ministry of Science and Technology of the People’s Republic of China, and the National Defence Basic Scientific Research Program of China. The investigators and Dr. Gonzalez-Lima report no relevant financial relationships.

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

Transcranial photobiomodulation (tPBM), a noninvasive laser light therapy, can improve short-term memory in young adults when applied to the right prefrontal cortex (PFC) of the brain, new research suggests.

Investigators compared the effect of 1,064 nm of tPBM delivered over a 12-minute session to the right PFC vs. three other treatment arms: delivery of the same intervention to the left PFC, delivery of the intervention at a lower frequency, and a sham intervention.

All participants were shown a series of items prior to the intervention and  asked to recall them after the intervention. Those who received tPBM 1,064 nm to the right PFC showed a superior performance of up to 25% in the memory tasks compared with the other groups.

Patients with attention-related conditions, such as attention deficit hyperactivity disorder, “could benefit from this type of treatment, which is safe, simple, and noninvasive, with no side effects,” coinvestigator Dongwei Li, a visiting PhD student at the Centre for Human Brain Health, University of Birmingham, England, said in a news release.

The findings were published online in Science Advances.
 

Differing wavelengths

The researchers note that “in the past decades,” noninvasive brain stimulation technology using transcranial application of direct or alternating electrical or magnetic fields “has been proven to be useful” in the improvement of working memory (WM).

When applied to the right PFC, tPBM has been shown to improve accuracy and speed of reaction time in WM tasks and improvements in “high-order cognitive functions,” such as sustained attention, emotion, and executive functions.

The investigators wanted to assess the impact of tPBM applied to different parts of the brain and at different wavelengths. They conducted four double-blind, sham-controlled experiments encompassing 90 neurotypical college students (mean age, 22 years). Each student participated in only one of the four experiments.

All completed two different tPBM sessions, separated by a week, in which sham and active tPBM were compared. Two different types of change-detection memory tasks were given: one requiring participants to remember the orientation of a series of items before and after the intervention and one other requiring them to remember the color of the items (experiments 1 and 2).

A series of follow-up experiments focused on comparing different wavelengths (1,064 nm vs. 852 nm) and different stimulation sites (right vs. left PFC; experiments 3 and 4).

EEG recordings were obtained during the intervention and the memory tasks.

Each experiment consisted of one active tPBM session and one sham tPBM session, with sessions consisting of 12 minutes of laser light (or sham) intervention. These sessions were conducted on the first and the seventh day; then, on the eighth day, participants were asked to report (or guess) which session was the active tPBM session.
 

Stimulating astrocytes

Results showed that, compared with sham tPBM, there was an improvement in WM capacity and scores by the 1,064 nm intervention in the orientation as well as the color task.

Participants who received the targeted treatment were able to remember between four and five test objects, whereas those with the treatment variations were only able to remember between three and four objects.

“These results support the hypothesis that 1,064 nm tPBM on the right PFC enhances WM capacity,” the investigators wrote.

They also found improvements in WM in participants receiving tPBM vs. sham regardless of whether their performance in the WM task was at a low or high level. This finding held true in both the orientation and the color tasks.

“Therefore, participants with good and poor WM capacity improved after 1,064 nm tPBM,” the researchers noted.

In addition, participants were unable to guess or report whether they had received sham or active tPBM.

EEG monitoring showed changes in brain activity that predicted the improvements in memory performance. In particular, 1,064 tPBM applied to the right PFC increased occipitoparietal contralateral delay activity (CDA), with CDA mediating the WM improvement.

This is “consistent with previous research that CDA is indicative of the number of maintained objects in visual working memory,” the investigators wrote.

Pearson correlation analyses showed that the differences in CDA set-size effects between active and sham session “correlated positively” with the behavioral differences between these sessions. For the orientation task, the r was 0.446 (P < .04); and for the color task, the r was .563 (P < .02).

No similar improvements were found with the 852 nm tPBM.

“We need further research to understand exactly why the tPBM is having this positive effect,” coinvestigator Ole Jensen, PhD, professor in translational neuroscience and codirector of the Centre for Human Brain Health, said in the release.

“It’s possible that the light is stimulating the astrocytes – the powerplants – in the nerve cells within the PFC, and this has a positive effect on the cells’ efficiency,” he noted.

Dr. Jensen added that his team “will also be investigating how long the effects might last. Clearly, if these experiments are to lead to a clinical intervention, we will need to see long-lasting benefits.”
 

Beneficial cognitive, emotional effects

Commenting for this news organization, Francisco Gonzalez-Lima, PhD, professor in the department of psychology, University of Texas at Austin, called the study “well done.”

Dr. Gonzalez-Lima was one of the first researchers to demonstrate that 1,064 nm transcranial infrared laser stimulation “produces beneficial cognitive and emotional effects in humans, including improving visual working memory,” he said.

The current study “reported an additional brain effect linked to the improved visual working memory that consists of an EEG-derived response, which is a new finding,” noted Dr. Gonzales-Lima, who was not involved with the new research.

He added that the same laser method “has been found by the Gonzalez-Lima lab to be effective at improving cognition in older adults and depressed and bipolar patients.”

The study was supported by the National Natural Science Foundation of China, the Ministry of Science and Technology of the People’s Republic of China, and the National Defence Basic Scientific Research Program of China. The investigators and Dr. Gonzalez-Lima report no relevant financial relationships.

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

NASHVILLE, TENN. – Patients with dementia and active seizures experience faster cognitive and functional decline and have a greater risk of dying younger than people with dementia who don’t have seizures, according to a multicenter study presented at the 2022 annual meeting of the American Epilepsy Society.

“When we compared patients with seizures with those who did not have seizures, we found that patients with seizures were more likely to have more severe cognitive impairment; they were more likely to have physical dependence and so worse functional outcomes; and they also had higher mortality rates at a younger age,” lead study author Ifrah Zawar, MD, an assistant professor of neurology at the University of Virginia, Charlottesville, said in an interview.

“The average age of mortality for seizure patients was around 72 years and the average age of mortality for nonseizure patients was around 79 years, so there was a 7- to 8-year difference in mortality,” she said.
 

Seizures make matters worse

The study analyzed data on 26,425 patients with dementia, 374 (1.4%) of whom had seizures, collected from 2005 to 2021 at 39 Alzheimer’s disease centers in the United States. Patients who had seizures were significantly younger when cognitive decline began (ages 62.9 vs. 68.4 years, P < .001) and died younger (72.99 vs. 79.72 years, P < .001).

The study also found a number of factors associated with active seizures, including a history of dominant Alzheimer’s disease mutation (odds ratio, 5.55; P < .001), stroke (OR, 3.17; P < .001), transient ischemic attack (OR, 1.72; P = .003), traumatic brain injury (OR, 1.92; P < .001), Parkinson’s disease (OR, 1.79; P = .025), active depression (OR, 1.61; P < .001) and lower education (OR, 0.97; P =.043).

After the study made adjustments for sex and other associated factors, it found that patients with seizures were still at a 76% higher risk of dying younger (hazard ratio, 1.76; P < .001).

The study also determined that patients with seizures had worse functional assessment scores and were more likely to be physically dependent on others (OR, 2.52; P < .001). Seizure patients also performed worse on Mini-Mental Status Examination (18.50 vs. 22.88; P < .001) and Clinical Dementia Rating-Sum of boxes (7.95 vs. 4.28; P < .001) after adjusting for age and duration of cognitive decline.
 

A tip for caregivers

Dr. Zawar acknowledged that differentiating seizures from transient bouts of confusion in people with dementia can be difficult for family members and caregivers, but she offered advice to help them do so. “If they notice any unusual confusion or any altered mentation which is episodic in nature,” she said, “they should bring it to the neurologist’s attention as early as possible, because there are studies that have shown the diagnosis of seizures is delayed, and if they are treated in time they can be well-controlled.” Electroencephalography can also confirm the presence of seizures, she added.

Double whammy

One limitation of this study is the lack of details on the types of seizures the participants had along with the inconsistency of EEGs performed on the study population. “In future studies, I would like to have more EEG data on the types of seizures and the frequency of seizures to assess these factors further,” Dr. Zawar said.

Having more detailed information on the seizures would make the findings more valuable, Andrew J. Cole, MD, director of the epilepsy service at Massachusetts General Hospital in Boston said in an interview. “We know a lot about clinically apparent seizures, as witnessed by this paper, but we still don’t know a whole lot about clinically silent or cryptic or nighttime-only seizures that maybe no one would really recognize as such unless they were specifically looking for them, and this paper doesn’t address that issue,” he said.

While the finding that patients with other neurologic diseases have more seizures even if they also have Alzheimer’s disease isn’t “a huge surprise,” Dr. Cole added. “On the other hand, the paper is important because it shows us that in the course of having Alzheimer’s disease, having seizures also makes your outcome worse, the speed of progression faster, and it complicates the management and living with this disease, and they make that point quite clear.”

Dr. Zawar and Dr. Cole have no relevant disclosures.
 

NASHVILLE, TENN. – Patients with dementia and active seizures experience faster cognitive and functional decline and have a greater risk of dying younger than people with dementia who don’t have seizures, according to a multicenter study presented at the 2022 annual meeting of the American Epilepsy Society.

“When we compared patients with seizures with those who did not have seizures, we found that patients with seizures were more likely to have more severe cognitive impairment; they were more likely to have physical dependence and so worse functional outcomes; and they also had higher mortality rates at a younger age,” lead study author Ifrah Zawar, MD, an assistant professor of neurology at the University of Virginia, Charlottesville, said in an interview.

“The average age of mortality for seizure patients was around 72 years and the average age of mortality for nonseizure patients was around 79 years, so there was a 7- to 8-year difference in mortality,” she said.
 

Seizures make matters worse

The study analyzed data on 26,425 patients with dementia, 374 (1.4%) of whom had seizures, collected from 2005 to 2021 at 39 Alzheimer’s disease centers in the United States. Patients who had seizures were significantly younger when cognitive decline began (ages 62.9 vs. 68.4 years, P < .001) and died younger (72.99 vs. 79.72 years, P < .001).

The study also found a number of factors associated with active seizures, including a history of dominant Alzheimer’s disease mutation (odds ratio, 5.55; P < .001), stroke (OR, 3.17; P < .001), transient ischemic attack (OR, 1.72; P = .003), traumatic brain injury (OR, 1.92; P < .001), Parkinson’s disease (OR, 1.79; P = .025), active depression (OR, 1.61; P < .001) and lower education (OR, 0.97; P =.043).

After the study made adjustments for sex and other associated factors, it found that patients with seizures were still at a 76% higher risk of dying younger (hazard ratio, 1.76; P < .001).

The study also determined that patients with seizures had worse functional assessment scores and were more likely to be physically dependent on others (OR, 2.52; P < .001). Seizure patients also performed worse on Mini-Mental Status Examination (18.50 vs. 22.88; P < .001) and Clinical Dementia Rating-Sum of boxes (7.95 vs. 4.28; P < .001) after adjusting for age and duration of cognitive decline.
 

A tip for caregivers

Dr. Zawar acknowledged that differentiating seizures from transient bouts of confusion in people with dementia can be difficult for family members and caregivers, but she offered advice to help them do so. “If they notice any unusual confusion or any altered mentation which is episodic in nature,” she said, “they should bring it to the neurologist’s attention as early as possible, because there are studies that have shown the diagnosis of seizures is delayed, and if they are treated in time they can be well-controlled.” Electroencephalography can also confirm the presence of seizures, she added.

Double whammy

One limitation of this study is the lack of details on the types of seizures the participants had along with the inconsistency of EEGs performed on the study population. “In future studies, I would like to have more EEG data on the types of seizures and the frequency of seizures to assess these factors further,” Dr. Zawar said.

Having more detailed information on the seizures would make the findings more valuable, Andrew J. Cole, MD, director of the epilepsy service at Massachusetts General Hospital in Boston said in an interview. “We know a lot about clinically apparent seizures, as witnessed by this paper, but we still don’t know a whole lot about clinically silent or cryptic or nighttime-only seizures that maybe no one would really recognize as such unless they were specifically looking for them, and this paper doesn’t address that issue,” he said.

While the finding that patients with other neurologic diseases have more seizures even if they also have Alzheimer’s disease isn’t “a huge surprise,” Dr. Cole added. “On the other hand, the paper is important because it shows us that in the course of having Alzheimer’s disease, having seizures also makes your outcome worse, the speed of progression faster, and it complicates the management and living with this disease, and they make that point quite clear.”

Dr. Zawar and Dr. Cole have no relevant disclosures.
 

NASHVILLE, TENN. – Patients with dementia and active seizures experience faster cognitive and functional decline and have a greater risk of dying younger than people with dementia who don’t have seizures, according to a multicenter study presented at the 2022 annual meeting of the American Epilepsy Society.

“When we compared patients with seizures with those who did not have seizures, we found that patients with seizures were more likely to have more severe cognitive impairment; they were more likely to have physical dependence and so worse functional outcomes; and they also had higher mortality rates at a younger age,” lead study author Ifrah Zawar, MD, an assistant professor of neurology at the University of Virginia, Charlottesville, said in an interview.

“The average age of mortality for seizure patients was around 72 years and the average age of mortality for nonseizure patients was around 79 years, so there was a 7- to 8-year difference in mortality,” she said.
 

Seizures make matters worse

The study analyzed data on 26,425 patients with dementia, 374 (1.4%) of whom had seizures, collected from 2005 to 2021 at 39 Alzheimer’s disease centers in the United States. Patients who had seizures were significantly younger when cognitive decline began (ages 62.9 vs. 68.4 years, P < .001) and died younger (72.99 vs. 79.72 years, P < .001).

The study also found a number of factors associated with active seizures, including a history of dominant Alzheimer’s disease mutation (odds ratio, 5.55; P < .001), stroke (OR, 3.17; P < .001), transient ischemic attack (OR, 1.72; P = .003), traumatic brain injury (OR, 1.92; P < .001), Parkinson’s disease (OR, 1.79; P = .025), active depression (OR, 1.61; P < .001) and lower education (OR, 0.97; P =.043).

After the study made adjustments for sex and other associated factors, it found that patients with seizures were still at a 76% higher risk of dying younger (hazard ratio, 1.76; P < .001).

The study also determined that patients with seizures had worse functional assessment scores and were more likely to be physically dependent on others (OR, 2.52; P < .001). Seizure patients also performed worse on Mini-Mental Status Examination (18.50 vs. 22.88; P < .001) and Clinical Dementia Rating-Sum of boxes (7.95 vs. 4.28; P < .001) after adjusting for age and duration of cognitive decline.
 

A tip for caregivers

Dr. Zawar acknowledged that differentiating seizures from transient bouts of confusion in people with dementia can be difficult for family members and caregivers, but she offered advice to help them do so. “If they notice any unusual confusion or any altered mentation which is episodic in nature,” she said, “they should bring it to the neurologist’s attention as early as possible, because there are studies that have shown the diagnosis of seizures is delayed, and if they are treated in time they can be well-controlled.” Electroencephalography can also confirm the presence of seizures, she added.

Double whammy

One limitation of this study is the lack of details on the types of seizures the participants had along with the inconsistency of EEGs performed on the study population. “In future studies, I would like to have more EEG data on the types of seizures and the frequency of seizures to assess these factors further,” Dr. Zawar said.

Having more detailed information on the seizures would make the findings more valuable, Andrew J. Cole, MD, director of the epilepsy service at Massachusetts General Hospital in Boston said in an interview. “We know a lot about clinically apparent seizures, as witnessed by this paper, but we still don’t know a whole lot about clinically silent or cryptic or nighttime-only seizures that maybe no one would really recognize as such unless they were specifically looking for them, and this paper doesn’t address that issue,” he said.

While the finding that patients with other neurologic diseases have more seizures even if they also have Alzheimer’s disease isn’t “a huge surprise,” Dr. Cole added. “On the other hand, the paper is important because it shows us that in the course of having Alzheimer’s disease, having seizures also makes your outcome worse, the speed of progression faster, and it complicates the management and living with this disease, and they make that point quite clear.”

Dr. Zawar and Dr. Cole have no relevant disclosures.
 

The antidepressant vortioxetine (Trintellix) improved cognition, memory, and depressive symptoms in patients with comorbid major depressive disorder (MDD) and dementia.

The results of the 12-week open-label, single-group study are positive, study investigator Michael Cronquist Christensen, MPA, DrPH, a director with the Lundbeck pharmaceutical company, told this news organization before presenting the results in a poster at the 15th Clinical Trials on Alzheimer’s Disease conference.

“The study confirms earlier findings of improvement in both depressive symptoms and cognitive performance with vortioxetine in patients with depression and dementia and adds to this research that these clinical effects also extend to improvement in health-related quality of life and patients’ daily functioning,” Dr. Christensen said.

“It also demonstrates that patients with depression and comorbid dementia can be safely treated with 20 mg vortioxetine – starting dose of 5 mg for the first week and up-titration to 10 mg at day 8,” he added.

However, he reported that Lundbeck doesn’t plan to seek approval from the U.S. Food and Drug Administration for a new indication. Vortioxetine received FDA approval in 2013 to treat MDD, but 3 years later the agency rejected an expansion of its indication to include cognitive dysfunction.

“Vortioxetine is approved for MDD, but the product can be used in patients with MDD who have other diseases, including other mental illnesses,” Dr. Christensen said.

Potential neurotransmission modulator

Vortioxetine is a selective serotonin reuptake inhibitor and serotonin receptor modulator. According to Dr. Christensen, evidence suggests the drug’s receptor targets “have the potential to modulate neurotransmitter systems that are essential for regulation of cognitive function.”

The researchers recruited 83 individuals aged 55-85 with recurrent MDD that had started before the age of 55. All had MDD episodes within the previous 6 months and comorbid dementia for at least 6 months.

Of the participants, 65.9% were female. In addition, 42.7% had Alzheimer’s disease, 26.8% had mixed-type dementia, and the rest had other types of dementia.

The daily oral dose of vortioxetine started at 5 mg for up to week 1 and then was increased to 10 mg. It was then increased to 20 mg or decreased to 5 mg “based on investigator judgment and patient response.” The average daily dose was 12.3 mg.

In regard to the primary outcome, at week 12 (n = 70), scores on the Montgomery-Åsberg Depression Rating Scale (MADRS) fell by a mean of –12.4 (.78, P < .0001), which researchers deemed to be a significant reduction in severe symptoms.

“A significant and clinically meaningful effect was observed from week 1,” the researchers reported.

“As a basis for comparison, we typically see an improvement around 13-14 points during 8 weeks of antidepressant treatment in adults with MDD who do not have dementia,” Dr. Christensen added.

More than a third of patients (35.7%) saw a reduction in MADRS score by more than 50% at week 12, and 17.2% were considered to have reached MDD depression remission, defined as a MADRS score at or under 10.

For secondary outcomes, the total Digit Symbol Substitution test score grew by 0.65 (standardized effect size) by week 12, showing significant improvement (P < .0001). In addition, participants improved on some other cognitive measures, and Dr. Christensen noted that “significant improvement was also observed in the patients’ health-related quality of life and daily functioning.”

A third of patients had drug-related treatment-emergent adverse events.

Vortioxetine is one of the most expensive antidepressants: It has a list price of $444 a month, and no generic version is currently available.

Small trial, open-label design

In a comment, Claire Sexton, DPhil, senior director of scientific programs and outreach at the Alzheimer’s Association, said the study “reflects a valuable aspect of treatment research because of the close connection between depression and dementia. Depression is a known risk factor for dementia, including Alzheimer’s disease, and those who have dementia may experience depression.”

Alzheimer’s Association

She cautioned, however, that the trial was small and had an open-label design instead of the “gold standard” of a double-blinded trial with a control group.

The study was funded by Lundbeck, where Dr. Christensen is an employee. Another author is a Lundbeck employee, and a third author reported various disclosures. Dr. Sexton reported no disclosures.

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

The antidepressant vortioxetine (Trintellix) improved cognition, memory, and depressive symptoms in patients with comorbid major depressive disorder (MDD) and dementia.

The results of the 12-week open-label, single-group study are positive, study investigator Michael Cronquist Christensen, MPA, DrPH, a director with the Lundbeck pharmaceutical company, told this news organization before presenting the results in a poster at the 15th Clinical Trials on Alzheimer’s Disease conference.

“The study confirms earlier findings of improvement in both depressive symptoms and cognitive performance with vortioxetine in patients with depression and dementia and adds to this research that these clinical effects also extend to improvement in health-related quality of life and patients’ daily functioning,” Dr. Christensen said.

“It also demonstrates that patients with depression and comorbid dementia can be safely treated with 20 mg vortioxetine – starting dose of 5 mg for the first week and up-titration to 10 mg at day 8,” he added.

However, he reported that Lundbeck doesn’t plan to seek approval from the U.S. Food and Drug Administration for a new indication. Vortioxetine received FDA approval in 2013 to treat MDD, but 3 years later the agency rejected an expansion of its indication to include cognitive dysfunction.

“Vortioxetine is approved for MDD, but the product can be used in patients with MDD who have other diseases, including other mental illnesses,” Dr. Christensen said.

Potential neurotransmission modulator

Vortioxetine is a selective serotonin reuptake inhibitor and serotonin receptor modulator. According to Dr. Christensen, evidence suggests the drug’s receptor targets “have the potential to modulate neurotransmitter systems that are essential for regulation of cognitive function.”

The researchers recruited 83 individuals aged 55-85 with recurrent MDD that had started before the age of 55. All had MDD episodes within the previous 6 months and comorbid dementia for at least 6 months.

Of the participants, 65.9% were female. In addition, 42.7% had Alzheimer’s disease, 26.8% had mixed-type dementia, and the rest had other types of dementia.

The daily oral dose of vortioxetine started at 5 mg for up to week 1 and then was increased to 10 mg. It was then increased to 20 mg or decreased to 5 mg “based on investigator judgment and patient response.” The average daily dose was 12.3 mg.

In regard to the primary outcome, at week 12 (n = 70), scores on the Montgomery-Åsberg Depression Rating Scale (MADRS) fell by a mean of –12.4 (.78, P < .0001), which researchers deemed to be a significant reduction in severe symptoms.

“A significant and clinically meaningful effect was observed from week 1,” the researchers reported.

“As a basis for comparison, we typically see an improvement around 13-14 points during 8 weeks of antidepressant treatment in adults with MDD who do not have dementia,” Dr. Christensen added.

More than a third of patients (35.7%) saw a reduction in MADRS score by more than 50% at week 12, and 17.2% were considered to have reached MDD depression remission, defined as a MADRS score at or under 10.

For secondary outcomes, the total Digit Symbol Substitution test score grew by 0.65 (standardized effect size) by week 12, showing significant improvement (P < .0001). In addition, participants improved on some other cognitive measures, and Dr. Christensen noted that “significant improvement was also observed in the patients’ health-related quality of life and daily functioning.”

A third of patients had drug-related treatment-emergent adverse events.

Vortioxetine is one of the most expensive antidepressants: It has a list price of $444 a month, and no generic version is currently available.

Small trial, open-label design

In a comment, Claire Sexton, DPhil, senior director of scientific programs and outreach at the Alzheimer’s Association, said the study “reflects a valuable aspect of treatment research because of the close connection between depression and dementia. Depression is a known risk factor for dementia, including Alzheimer’s disease, and those who have dementia may experience depression.”

Alzheimer’s Association

She cautioned, however, that the trial was small and had an open-label design instead of the “gold standard” of a double-blinded trial with a control group.

The study was funded by Lundbeck, where Dr. Christensen is an employee. Another author is a Lundbeck employee, and a third author reported various disclosures. Dr. Sexton reported no disclosures.

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

The antidepressant vortioxetine (Trintellix) improved cognition, memory, and depressive symptoms in patients with comorbid major depressive disorder (MDD) and dementia.

The results of the 12-week open-label, single-group study are positive, study investigator Michael Cronquist Christensen, MPA, DrPH, a director with the Lundbeck pharmaceutical company, told this news organization before presenting the results in a poster at the 15th Clinical Trials on Alzheimer’s Disease conference.

“The study confirms earlier findings of improvement in both depressive symptoms and cognitive performance with vortioxetine in patients with depression and dementia and adds to this research that these clinical effects also extend to improvement in health-related quality of life and patients’ daily functioning,” Dr. Christensen said.

“It also demonstrates that patients with depression and comorbid dementia can be safely treated with 20 mg vortioxetine – starting dose of 5 mg for the first week and up-titration to 10 mg at day 8,” he added.

However, he reported that Lundbeck doesn’t plan to seek approval from the U.S. Food and Drug Administration for a new indication. Vortioxetine received FDA approval in 2013 to treat MDD, but 3 years later the agency rejected an expansion of its indication to include cognitive dysfunction.

“Vortioxetine is approved for MDD, but the product can be used in patients with MDD who have other diseases, including other mental illnesses,” Dr. Christensen said.

Potential neurotransmission modulator

Vortioxetine is a selective serotonin reuptake inhibitor and serotonin receptor modulator. According to Dr. Christensen, evidence suggests the drug’s receptor targets “have the potential to modulate neurotransmitter systems that are essential for regulation of cognitive function.”

The researchers recruited 83 individuals aged 55-85 with recurrent MDD that had started before the age of 55. All had MDD episodes within the previous 6 months and comorbid dementia for at least 6 months.

Of the participants, 65.9% were female. In addition, 42.7% had Alzheimer’s disease, 26.8% had mixed-type dementia, and the rest had other types of dementia.

The daily oral dose of vortioxetine started at 5 mg for up to week 1 and then was increased to 10 mg. It was then increased to 20 mg or decreased to 5 mg “based on investigator judgment and patient response.” The average daily dose was 12.3 mg.

In regard to the primary outcome, at week 12 (n = 70), scores on the Montgomery-Åsberg Depression Rating Scale (MADRS) fell by a mean of –12.4 (.78, P < .0001), which researchers deemed to be a significant reduction in severe symptoms.

“A significant and clinically meaningful effect was observed from week 1,” the researchers reported.

“As a basis for comparison, we typically see an improvement around 13-14 points during 8 weeks of antidepressant treatment in adults with MDD who do not have dementia,” Dr. Christensen added.

More than a third of patients (35.7%) saw a reduction in MADRS score by more than 50% at week 12, and 17.2% were considered to have reached MDD depression remission, defined as a MADRS score at or under 10.

For secondary outcomes, the total Digit Symbol Substitution test score grew by 0.65 (standardized effect size) by week 12, showing significant improvement (P < .0001). In addition, participants improved on some other cognitive measures, and Dr. Christensen noted that “significant improvement was also observed in the patients’ health-related quality of life and daily functioning.”

A third of patients had drug-related treatment-emergent adverse events.

Vortioxetine is one of the most expensive antidepressants: It has a list price of $444 a month, and no generic version is currently available.

Small trial, open-label design

In a comment, Claire Sexton, DPhil, senior director of scientific programs and outreach at the Alzheimer’s Association, said the study “reflects a valuable aspect of treatment research because of the close connection between depression and dementia. Depression is a known risk factor for dementia, including Alzheimer’s disease, and those who have dementia may experience depression.”

Alzheimer’s Association

She cautioned, however, that the trial was small and had an open-label design instead of the “gold standard” of a double-blinded trial with a control group.

The study was funded by Lundbeck, where Dr. Christensen is an employee. Another author is a Lundbeck employee, and a third author reported various disclosures. Dr. Sexton reported no disclosures.

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