Alzheimer's & Cognition

TOPLINE:

Hormone-modulating therapy for breast cancer may protect older women from Alzheimer’s disease and related dementias, although the protective effect varies by age and race, with the greatest benefit seen in younger Black women.

METHODOLOGY:

• Hormone-modulating therapy is widely used to treat hormone receptor–positive breast cancer, but the cognitive effects of the treatment, including a potential link to dementia, remain unclear.
• To investigate, researchers used the SEER-Medicare linked database to identify women aged 65 years or older with breast cancer who did and did not receive hormone-modulating therapy within 3 years following their diagnosis.
• The researchers excluded women with preexisting Alzheimer’s disease/dementia diagnoses or those who had received hormone-modulating therapy before their breast cancer diagnosis.
• Analyses were adjusted for demographic, sociocultural, and clinical variables, and subgroup analyses evaluated the impact of age, race, and type of hormone-modulating therapy on Alzheimer’s disease/dementia risk.

TAKEAWAY:

• Among the 18,808 women included in the analysis, 66% received hormone-modulating therapy and 34% did not. During the mean follow-up of 12 years, 24% of hormone-modulating therapy users and 28% of nonusers developed Alzheimer’s disease/dementia.
• Overall, hormone-modulating therapy use (vs nonuse) was associated with a significant 7% lower risk for Alzheimer’s disease/dementia (hazard ratio [HR], 0.93; P = .005), with notable age and racial differences.
• Hormone-modulating therapy use was associated with a 24% lower risk for Alzheimer’s disease/dementia in Black women aged 65-74 years (HR, 0.76), but that protective effect decreased to 19% in Black women aged 75 years or older (HR, 0.81). White women aged 65-74 years who received hormone-modulating therapy (vs those who did not) had an 11% lower risk for Alzheimer’s disease/dementia (HR, 0.89), but the association disappeared among those aged 75 years or older (HR, 0.96; 95% CI, 0.90-1.02). Other races demonstrated no significant association between hormone-modulating therapy use and Alzheimer’s disease/dementia.
• Overall, the use of an aromatase inhibitor or a selective estrogen receptor modulator was associated with a significantly lower risk for Alzheimer’s disease/dementia (HR, 0.93 and HR, 0.89, respectively).

IN PRACTICE:

Overall, the retrospective study found that “hormone therapy was associated with protection against [Alzheimer’s/dementia] in women aged 65 years or older with newly diagnosed breast cancer,” with the decrease in risk relatively greater for Black women and women younger than 75 years, the authors concluded.

“The results highlight the critical need for personalized breast cancer treatment plans that are tailored to the individual characteristics of each patient, particularly given the significantly higher likelihood (two to three times more) of Black women developing [Alzheimer’s/dementia], compared with their White counterparts,” the researchers added.
 

SOURCE:

The study, with first author Chao Cai, PhD, Department of Clinical Pharmacy and Outcomes Sciences, University of South Carolina, Columbia, was published online on July 16 in JAMA Network Open.

LIMITATIONS:

The study included only women aged 65 years or older, limiting generalizability to younger women. The dataset lacked genetic information and laboratory data related to dementia. The duration of hormone-modulating therapy use beyond 3 years and specific formulations were not assessed. Potential confounders such as variations in chemotherapy, radiation, and surgery were not fully addressed.

DISCLOSURES:

Support for the study was provided by the National Institutes of Health; Carolina Center on Alzheimer’s Disease and Minority Research pilot project; and the Dean’s Faculty Advancement Fund, University of Pittsburgh, Pennsylvania. The authors reported no relevant disclosures.

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

TOPLINE:

Hormone-modulating therapy for breast cancer may protect older women from Alzheimer’s disease and related dementias, although the protective effect varies by age and race, with the greatest benefit seen in younger Black women.

METHODOLOGY:

• Hormone-modulating therapy is widely used to treat hormone receptor–positive breast cancer, but the cognitive effects of the treatment, including a potential link to dementia, remain unclear.
• To investigate, researchers used the SEER-Medicare linked database to identify women aged 65 years or older with breast cancer who did and did not receive hormone-modulating therapy within 3 years following their diagnosis.
• The researchers excluded women with preexisting Alzheimer’s disease/dementia diagnoses or those who had received hormone-modulating therapy before their breast cancer diagnosis.
• Analyses were adjusted for demographic, sociocultural, and clinical variables, and subgroup analyses evaluated the impact of age, race, and type of hormone-modulating therapy on Alzheimer’s disease/dementia risk.

TAKEAWAY:

• Among the 18,808 women included in the analysis, 66% received hormone-modulating therapy and 34% did not. During the mean follow-up of 12 years, 24% of hormone-modulating therapy users and 28% of nonusers developed Alzheimer’s disease/dementia.
• Overall, hormone-modulating therapy use (vs nonuse) was associated with a significant 7% lower risk for Alzheimer’s disease/dementia (hazard ratio [HR], 0.93; P = .005), with notable age and racial differences.
• Hormone-modulating therapy use was associated with a 24% lower risk for Alzheimer’s disease/dementia in Black women aged 65-74 years (HR, 0.76), but that protective effect decreased to 19% in Black women aged 75 years or older (HR, 0.81). White women aged 65-74 years who received hormone-modulating therapy (vs those who did not) had an 11% lower risk for Alzheimer’s disease/dementia (HR, 0.89), but the association disappeared among those aged 75 years or older (HR, 0.96; 95% CI, 0.90-1.02). Other races demonstrated no significant association between hormone-modulating therapy use and Alzheimer’s disease/dementia.
• Overall, the use of an aromatase inhibitor or a selective estrogen receptor modulator was associated with a significantly lower risk for Alzheimer’s disease/dementia (HR, 0.93 and HR, 0.89, respectively).

IN PRACTICE:

Overall, the retrospective study found that “hormone therapy was associated with protection against [Alzheimer’s/dementia] in women aged 65 years or older with newly diagnosed breast cancer,” with the decrease in risk relatively greater for Black women and women younger than 75 years, the authors concluded.

“The results highlight the critical need for personalized breast cancer treatment plans that are tailored to the individual characteristics of each patient, particularly given the significantly higher likelihood (two to three times more) of Black women developing [Alzheimer’s/dementia], compared with their White counterparts,” the researchers added.
 

SOURCE:

The study, with first author Chao Cai, PhD, Department of Clinical Pharmacy and Outcomes Sciences, University of South Carolina, Columbia, was published online on July 16 in JAMA Network Open.

LIMITATIONS:

The study included only women aged 65 years or older, limiting generalizability to younger women. The dataset lacked genetic information and laboratory data related to dementia. The duration of hormone-modulating therapy use beyond 3 years and specific formulations were not assessed. Potential confounders such as variations in chemotherapy, radiation, and surgery were not fully addressed.

DISCLOSURES:

Support for the study was provided by the National Institutes of Health; Carolina Center on Alzheimer’s Disease and Minority Research pilot project; and the Dean’s Faculty Advancement Fund, University of Pittsburgh, Pennsylvania. The authors reported no relevant disclosures.

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

TOPLINE:

Hormone-modulating therapy for breast cancer may protect older women from Alzheimer’s disease and related dementias, although the protective effect varies by age and race, with the greatest benefit seen in younger Black women.

METHODOLOGY:

• Hormone-modulating therapy is widely used to treat hormone receptor–positive breast cancer, but the cognitive effects of the treatment, including a potential link to dementia, remain unclear.
• To investigate, researchers used the SEER-Medicare linked database to identify women aged 65 years or older with breast cancer who did and did not receive hormone-modulating therapy within 3 years following their diagnosis.
• The researchers excluded women with preexisting Alzheimer’s disease/dementia diagnoses or those who had received hormone-modulating therapy before their breast cancer diagnosis.
• Analyses were adjusted for demographic, sociocultural, and clinical variables, and subgroup analyses evaluated the impact of age, race, and type of hormone-modulating therapy on Alzheimer’s disease/dementia risk.

TAKEAWAY:

• Among the 18,808 women included in the analysis, 66% received hormone-modulating therapy and 34% did not. During the mean follow-up of 12 years, 24% of hormone-modulating therapy users and 28% of nonusers developed Alzheimer’s disease/dementia.
• Overall, hormone-modulating therapy use (vs nonuse) was associated with a significant 7% lower risk for Alzheimer’s disease/dementia (hazard ratio [HR], 0.93; P = .005), with notable age and racial differences.
• Hormone-modulating therapy use was associated with a 24% lower risk for Alzheimer’s disease/dementia in Black women aged 65-74 years (HR, 0.76), but that protective effect decreased to 19% in Black women aged 75 years or older (HR, 0.81). White women aged 65-74 years who received hormone-modulating therapy (vs those who did not) had an 11% lower risk for Alzheimer’s disease/dementia (HR, 0.89), but the association disappeared among those aged 75 years or older (HR, 0.96; 95% CI, 0.90-1.02). Other races demonstrated no significant association between hormone-modulating therapy use and Alzheimer’s disease/dementia.
• Overall, the use of an aromatase inhibitor or a selective estrogen receptor modulator was associated with a significantly lower risk for Alzheimer’s disease/dementia (HR, 0.93 and HR, 0.89, respectively).

IN PRACTICE:

Overall, the retrospective study found that “hormone therapy was associated with protection against [Alzheimer’s/dementia] in women aged 65 years or older with newly diagnosed breast cancer,” with the decrease in risk relatively greater for Black women and women younger than 75 years, the authors concluded.

“The results highlight the critical need for personalized breast cancer treatment plans that are tailored to the individual characteristics of each patient, particularly given the significantly higher likelihood (two to three times more) of Black women developing [Alzheimer’s/dementia], compared with their White counterparts,” the researchers added.
 

SOURCE:

The study, with first author Chao Cai, PhD, Department of Clinical Pharmacy and Outcomes Sciences, University of South Carolina, Columbia, was published online on July 16 in JAMA Network Open.

LIMITATIONS:

The study included only women aged 65 years or older, limiting generalizability to younger women. The dataset lacked genetic information and laboratory data related to dementia. The duration of hormone-modulating therapy use beyond 3 years and specific formulations were not assessed. Potential confounders such as variations in chemotherapy, radiation, and surgery were not fully addressed.

DISCLOSURES:

Support for the study was provided by the National Institutes of Health; Carolina Center on Alzheimer’s Disease and Minority Research pilot project; and the Dean’s Faculty Advancement Fund, University of Pittsburgh, Pennsylvania. The authors reported no relevant disclosures.

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

Advocacy groups for patients with neurologic disorders have become a common feature in the landscape of drug and device development and federal research funding allocation.

On Capitol Hill, advocates have racked up some impressive legislative wins that aim to set a federal agenda for developing new medications.

At the Food and Drug Administration (FDA), advocacy groups played a significant role in several recent high-profile and controversial approvals for drugs for Alzheimer’s disease, Duchenne muscular dystrophy (DMD), and amyotrophic lateral sclerosis (ALS).

Such gains suggest these groups are growing in power. But with these wins come questions about whether large advocacy organizations — some of which receive significant industry funding — wield too much influence.

“You need to think very carefully about how you open these processes up to greater patient involvement,” Matthew S. McCoy, PhD, assistant professor of medical ethics and health policy at the University of Pennsylvania, Philadelphia, told this news organization. It’s important not to “end up with a situation where it’s the best-connected, the most well-resourced, the most-savvy patient organizations that are able to exercise outsize influence.”

Just because a group has deep pockets does not mean that its priorities align with the disease burden. And not every patient population is represented by a professionalized patient advocacy organization, Dr. McCoy noted. “There is the potential for the rich to get richer.”
 

A Seat at the Table

Long ago, the FDA and the National Institutes of Health (NIH) began giving patients a seat at the table, in part because of the path blazed by AIDS activists in the late 1980s and early 1990s, said Dr. McCoy.

Patient advocacy is often visible during FDA advisory committee meetings. The agency usually allows an hour, sometimes more, for members of the public to express support or concerns about the product being reviewed. Patients and caregivers — often aided by advocacy organizations — also submit hundreds, sometimes thousands, of letters before a product review.

The Alzheimer’s Association spent years advocating for approval of the anti-amyloid agent aducanumab (Aduhelm, Biogen/Eisai). In 2020, the organization urged patients and caregivers to submit written and oral testimony to the FDA advisory panel that was reviewing the drug. Despite patients’ pleas, the panel ultimately declined to support the drug’s approval, citing safety concerns and limited evidence of efficacy.

As controversy swirled around the medication — which had the potential for life-threatening brain swelling — advocates continued to apply pressure. Going against the expert panel’s recommendation, in June 2021, the FDA granted accelerated approval prompting three of the panelists to resign in protest.

Aducanumab’s initial price — $56,000 a year — was seen as a major threat to the viability of Medicare. Still, the Alzheimer’s Association stood behind the decision to approve the drug. But by early 2024, Biogen/Eisai said they would stop selling aducanumab, citing other priorities.

Once again patient advocates showed up in March 2022 when the FDA advisers were reviewing Amylyx Pharmaceuticals’ ALS drug Relyvrio (sodium phenylbutyrate and taurursodiol). Trials had showed limited efficacy, but patients testified they would accept greater risk for a chance to be treated with the drug. The committee ultimately voted against approval; 6 months later, the FDA approved Relyvrio anyway.

In April 2024, Amylyx removed Relyvrio from the market following phase 3 trial results that showed no difference between the treatment and placebo.

The drug manufacturer Sarepta Therapeutics, which develops treatments for genetic conditions such as DMD, has a history of working with — and funding — patient advocacy groups. The company encourages nonprofits to apply for grants or sponsorship on its website. At a 2016 advisory committee, when Sarepta was seeking approval of its first DMD therapy eteplirsen (Exondys 51), 52 speakers, most from patient advocacy groups, pleaded for the drug’s approval. When the panel voted no, Sarepta mobilized families to pressure the agency. Exondys was eventually approved.

In June, Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, unilaterally gave final expanded approval to Sarepta Therapeutics’ gene therapy Elevidys for DMD. Dr. Marks overrode his own FDA reviewers, who said the product lacked substantial evidence of efficacy. He acknowledged the drug had not met its primary endpoint but said he found secondary and exploratory endpoints “compelling” and cited an unmet medical need.

In an opinion piece in The Washington Post, Aaron Kesselheim, MD, JD, MPH, the director of the Program on Regulation, Therapeutics, and Law at Brigham and Women’s Hospital, Boston, Massachusetts, and a former member of the FDA’s Peripheral and Central Nervous System Drugs Advisory Committee, questioned the approval stating that it undermined both public trust and manufacturers’ incentives to do the hard work of proving effectiveness.
 

Patient Voices the ‘Secret Sauce’

Drugmakers aren’t alone in seeing the value of having patients speak directly to government entities. When the Michael J. Fox Foundation wanted to gather cosponsors for the National Plan to End Parkinson’s Act, which President Joe Biden signed into law in July, it recruited and trained patients and caregivers for congressional meetings, said Ted Thompson, senior vice president of public policy at the foundation.

Having those individuals “making the personal case for how this disease affects their families ... was really the secret sauce,” in garnering a large number of cosponsors and getting legislation signed into law within 2 years of its introduction, Mr. Thompson told this news organization.

ALS advocacy groups launched a similar campaign to secure passage of the Accelerating Access to Critical Therapies for ALS Act in 2021.

Both pieces of legislation seek to set a federal agenda for developing new therapies in neurodegenerative diseases, in part by directing the FDA and NIH to fund research, engage patients more directly, and form public-private partnerships and councils to spur innovation.

But some said patient advocates are still coming far too late to the party.

“By the time you hear from patient groups at the meetings at the FDA, often the best opportunities for their input are long past,” Leah Zoe Gibson Rand, DPhil, a research scientist with the Program on Regulation, Therapeutics, and Law at Brigham and Women’s Hospital, told this news organization. There should be more focus on the patient perspective earlier in drug development and trial design.

“There are some things that the patient voice could uniquely tell the agency,” said Holly Fernandez Lynch, JD, associate professor of medical ethics and health policy at the University of Pennsylvania. Patients can give insight on what it means to live with a disease, what symptoms are particularly burdensome, and which endpoints matter.

But, she said, “listening to the patient voice cannot mean that FDA just steps aside and lets anything on the market that patients are willing to try.” Individuals “who lack good treatment options have a very good reason to want to try things that haven’t yet been proven.”

If the FDA allows drugs on the market just because patients are willing to try, “5 or 10 years down the road, it’s not at all clear that we would end up with drugs that are better, or drugs that work, or drugs that we know anything more about,” said Dr. Lynch.
 

Does Taking Industry Money Equal Conflicts of Interest?

Many patient advocacy organizations receive funding from drug companies, medical device makers, or other industry sources, but they aren’t always transparent about how much or from which companies, according to studies.

The Alzheimer’s Association continued to push for the approval of aducanumab, even as the group received millions of dollars from the drugmakers. The association was accused of failing to disclose the potential conflict. It still lobbied for approval, even after the FDA advisers in 2020 voted against the drug.

It is not uncommon for individuals who speak in favor of a product’s approval to receive money for transportation and/or lodging from the drug’s manufacturer. In 2018, Dr. McCoy and colleagues reported in JAMA Internal Medicine that, between 2009 and 2017, a quarter of the speakers at the Anesthetic and Analgesic Drug Products Advisory Committee had conflicts of interest (COIs), mostly from industry, and that they were not disclosed in approximately 20% of the instances.

In a 2017 study of 104 large patient advocacy organizations published in The New England Journal of Medicine, Dr. McCoy and colleagues reported that 83% had received funds from industry. At least 39% had a current or former industry executive on the governing board, and 12% had a current or former industry executive in a board leadership position. Of the 104, 38 were focused on cancer and 13 on neurologic conditions. Of these, only 12% had published policies for managing institutional COIs.

Dr. McCoy emphasized the industry’s reliance on partnering with patient groups, particularly during FDA advisory committee meetings. “The sponsors wouldn’t be paying for patients to show up and give these testimonies if they didn’t think it made a difference. The audience isn’t just panel members; it’s also agency officials and maybe elected officials as well.”

“The Fox Foundation, with a $300 million-plus budget, gets about $5-$6 million a year from industry,” said Mr. Thompson. The money is earmarked for the organization’s Parkinson’s Disease Education Consortium; none goes toward advocacy. And, “the foundation has never specifically endorsed a product or device.”

When organizations that receive industry funding back a particular product, “it does appear to be [a conflict], and whether it is an actual one or not, appearances sometimes are all that matter,” said Mr. Thompson.

Dr. Lynch said accepting industry money “is a really significant conflict.” While advocates might need that money to fund advocacy efforts or make grants to advance research priorities, the acceptance might hinder willingness to demand evidence or to complain about a product’s price tag. “You don’t want to bite the hand that feeds you, right?”

Both Dr. McCoy and Dr. Lynch said patient groups — and individual patients — should at a minimum disclose industry funding, especially when speaking at an advisory committee.

Federal agencies and members of Congress actively seek patient input when considering legislation and funding priorities. But the individuals testifying at an advisory committee aren’t likely to represent all patients, and there’s a danger that they are just the loudest voices, said Dr. McCoy.

“We need to think more carefully about how we actually understand the preferences of a big, diverse patient population,” he said.

Dr. Lynch agreed.

Within the ALS community, “a lot of people who take different perspectives than some of those that are the leading voices get shouted down, and their voices get drowned out, and they get attacked on social media,” she said.

The group may be at the table, “but they’re just one voice at the table,” she said.

Dr. McCoy reported that his wife works for the Leukemia & Lymphoma Society, a patient advocacy organization. Dr. Rand reported no relevant financial relationships. Dr. Lynch received funding from Arnold Ventures and the Greenwall Foundation for work related to the FDA and patient advocacy.

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

Advocacy groups for patients with neurologic disorders have become a common feature in the landscape of drug and device development and federal research funding allocation.

On Capitol Hill, advocates have racked up some impressive legislative wins that aim to set a federal agenda for developing new medications.

At the Food and Drug Administration (FDA), advocacy groups played a significant role in several recent high-profile and controversial approvals for drugs for Alzheimer’s disease, Duchenne muscular dystrophy (DMD), and amyotrophic lateral sclerosis (ALS).

Such gains suggest these groups are growing in power. But with these wins come questions about whether large advocacy organizations — some of which receive significant industry funding — wield too much influence.

“You need to think very carefully about how you open these processes up to greater patient involvement,” Matthew S. McCoy, PhD, assistant professor of medical ethics and health policy at the University of Pennsylvania, Philadelphia, told this news organization. It’s important not to “end up with a situation where it’s the best-connected, the most well-resourced, the most-savvy patient organizations that are able to exercise outsize influence.”

Just because a group has deep pockets does not mean that its priorities align with the disease burden. And not every patient population is represented by a professionalized patient advocacy organization, Dr. McCoy noted. “There is the potential for the rich to get richer.”
 

A Seat at the Table

Long ago, the FDA and the National Institutes of Health (NIH) began giving patients a seat at the table, in part because of the path blazed by AIDS activists in the late 1980s and early 1990s, said Dr. McCoy.

Patient advocacy is often visible during FDA advisory committee meetings. The agency usually allows an hour, sometimes more, for members of the public to express support or concerns about the product being reviewed. Patients and caregivers — often aided by advocacy organizations — also submit hundreds, sometimes thousands, of letters before a product review.

The Alzheimer’s Association spent years advocating for approval of the anti-amyloid agent aducanumab (Aduhelm, Biogen/Eisai). In 2020, the organization urged patients and caregivers to submit written and oral testimony to the FDA advisory panel that was reviewing the drug. Despite patients’ pleas, the panel ultimately declined to support the drug’s approval, citing safety concerns and limited evidence of efficacy.

As controversy swirled around the medication — which had the potential for life-threatening brain swelling — advocates continued to apply pressure. Going against the expert panel’s recommendation, in June 2021, the FDA granted accelerated approval prompting three of the panelists to resign in protest.

Aducanumab’s initial price — $56,000 a year — was seen as a major threat to the viability of Medicare. Still, the Alzheimer’s Association stood behind the decision to approve the drug. But by early 2024, Biogen/Eisai said they would stop selling aducanumab, citing other priorities.

Once again patient advocates showed up in March 2022 when the FDA advisers were reviewing Amylyx Pharmaceuticals’ ALS drug Relyvrio (sodium phenylbutyrate and taurursodiol). Trials had showed limited efficacy, but patients testified they would accept greater risk for a chance to be treated with the drug. The committee ultimately voted against approval; 6 months later, the FDA approved Relyvrio anyway.

In April 2024, Amylyx removed Relyvrio from the market following phase 3 trial results that showed no difference between the treatment and placebo.

The drug manufacturer Sarepta Therapeutics, which develops treatments for genetic conditions such as DMD, has a history of working with — and funding — patient advocacy groups. The company encourages nonprofits to apply for grants or sponsorship on its website. At a 2016 advisory committee, when Sarepta was seeking approval of its first DMD therapy eteplirsen (Exondys 51), 52 speakers, most from patient advocacy groups, pleaded for the drug’s approval. When the panel voted no, Sarepta mobilized families to pressure the agency. Exondys was eventually approved.

In June, Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, unilaterally gave final expanded approval to Sarepta Therapeutics’ gene therapy Elevidys for DMD. Dr. Marks overrode his own FDA reviewers, who said the product lacked substantial evidence of efficacy. He acknowledged the drug had not met its primary endpoint but said he found secondary and exploratory endpoints “compelling” and cited an unmet medical need.

In an opinion piece in The Washington Post, Aaron Kesselheim, MD, JD, MPH, the director of the Program on Regulation, Therapeutics, and Law at Brigham and Women’s Hospital, Boston, Massachusetts, and a former member of the FDA’s Peripheral and Central Nervous System Drugs Advisory Committee, questioned the approval stating that it undermined both public trust and manufacturers’ incentives to do the hard work of proving effectiveness.
 

Patient Voices the ‘Secret Sauce’

Drugmakers aren’t alone in seeing the value of having patients speak directly to government entities. When the Michael J. Fox Foundation wanted to gather cosponsors for the National Plan to End Parkinson’s Act, which President Joe Biden signed into law in July, it recruited and trained patients and caregivers for congressional meetings, said Ted Thompson, senior vice president of public policy at the foundation.

Having those individuals “making the personal case for how this disease affects their families ... was really the secret sauce,” in garnering a large number of cosponsors and getting legislation signed into law within 2 years of its introduction, Mr. Thompson told this news organization.

ALS advocacy groups launched a similar campaign to secure passage of the Accelerating Access to Critical Therapies for ALS Act in 2021.

Both pieces of legislation seek to set a federal agenda for developing new therapies in neurodegenerative diseases, in part by directing the FDA and NIH to fund research, engage patients more directly, and form public-private partnerships and councils to spur innovation.

But some said patient advocates are still coming far too late to the party.

“By the time you hear from patient groups at the meetings at the FDA, often the best opportunities for their input are long past,” Leah Zoe Gibson Rand, DPhil, a research scientist with the Program on Regulation, Therapeutics, and Law at Brigham and Women’s Hospital, told this news organization. There should be more focus on the patient perspective earlier in drug development and trial design.

“There are some things that the patient voice could uniquely tell the agency,” said Holly Fernandez Lynch, JD, associate professor of medical ethics and health policy at the University of Pennsylvania. Patients can give insight on what it means to live with a disease, what symptoms are particularly burdensome, and which endpoints matter.

But, she said, “listening to the patient voice cannot mean that FDA just steps aside and lets anything on the market that patients are willing to try.” Individuals “who lack good treatment options have a very good reason to want to try things that haven’t yet been proven.”

If the FDA allows drugs on the market just because patients are willing to try, “5 or 10 years down the road, it’s not at all clear that we would end up with drugs that are better, or drugs that work, or drugs that we know anything more about,” said Dr. Lynch.
 

Does Taking Industry Money Equal Conflicts of Interest?

Many patient advocacy organizations receive funding from drug companies, medical device makers, or other industry sources, but they aren’t always transparent about how much or from which companies, according to studies.

The Alzheimer’s Association continued to push for the approval of aducanumab, even as the group received millions of dollars from the drugmakers. The association was accused of failing to disclose the potential conflict. It still lobbied for approval, even after the FDA advisers in 2020 voted against the drug.

It is not uncommon for individuals who speak in favor of a product’s approval to receive money for transportation and/or lodging from the drug’s manufacturer. In 2018, Dr. McCoy and colleagues reported in JAMA Internal Medicine that, between 2009 and 2017, a quarter of the speakers at the Anesthetic and Analgesic Drug Products Advisory Committee had conflicts of interest (COIs), mostly from industry, and that they were not disclosed in approximately 20% of the instances.

In a 2017 study of 104 large patient advocacy organizations published in The New England Journal of Medicine, Dr. McCoy and colleagues reported that 83% had received funds from industry. At least 39% had a current or former industry executive on the governing board, and 12% had a current or former industry executive in a board leadership position. Of the 104, 38 were focused on cancer and 13 on neurologic conditions. Of these, only 12% had published policies for managing institutional COIs.

Dr. McCoy emphasized the industry’s reliance on partnering with patient groups, particularly during FDA advisory committee meetings. “The sponsors wouldn’t be paying for patients to show up and give these testimonies if they didn’t think it made a difference. The audience isn’t just panel members; it’s also agency officials and maybe elected officials as well.”

“The Fox Foundation, with a $300 million-plus budget, gets about $5-$6 million a year from industry,” said Mr. Thompson. The money is earmarked for the organization’s Parkinson’s Disease Education Consortium; none goes toward advocacy. And, “the foundation has never specifically endorsed a product or device.”

When organizations that receive industry funding back a particular product, “it does appear to be [a conflict], and whether it is an actual one or not, appearances sometimes are all that matter,” said Mr. Thompson.

Dr. Lynch said accepting industry money “is a really significant conflict.” While advocates might need that money to fund advocacy efforts or make grants to advance research priorities, the acceptance might hinder willingness to demand evidence or to complain about a product’s price tag. “You don’t want to bite the hand that feeds you, right?”

Both Dr. McCoy and Dr. Lynch said patient groups — and individual patients — should at a minimum disclose industry funding, especially when speaking at an advisory committee.

Federal agencies and members of Congress actively seek patient input when considering legislation and funding priorities. But the individuals testifying at an advisory committee aren’t likely to represent all patients, and there’s a danger that they are just the loudest voices, said Dr. McCoy.

“We need to think more carefully about how we actually understand the preferences of a big, diverse patient population,” he said.

Dr. Lynch agreed.

Within the ALS community, “a lot of people who take different perspectives than some of those that are the leading voices get shouted down, and their voices get drowned out, and they get attacked on social media,” she said.

The group may be at the table, “but they’re just one voice at the table,” she said.

Dr. McCoy reported that his wife works for the Leukemia & Lymphoma Society, a patient advocacy organization. Dr. Rand reported no relevant financial relationships. Dr. Lynch received funding from Arnold Ventures and the Greenwall Foundation for work related to the FDA and patient advocacy.

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

Advocacy groups for patients with neurologic disorders have become a common feature in the landscape of drug and device development and federal research funding allocation.

On Capitol Hill, advocates have racked up some impressive legislative wins that aim to set a federal agenda for developing new medications.

At the Food and Drug Administration (FDA), advocacy groups played a significant role in several recent high-profile and controversial approvals for drugs for Alzheimer’s disease, Duchenne muscular dystrophy (DMD), and amyotrophic lateral sclerosis (ALS).

Such gains suggest these groups are growing in power. But with these wins come questions about whether large advocacy organizations — some of which receive significant industry funding — wield too much influence.

“You need to think very carefully about how you open these processes up to greater patient involvement,” Matthew S. McCoy, PhD, assistant professor of medical ethics and health policy at the University of Pennsylvania, Philadelphia, told this news organization. It’s important not to “end up with a situation where it’s the best-connected, the most well-resourced, the most-savvy patient organizations that are able to exercise outsize influence.”

Just because a group has deep pockets does not mean that its priorities align with the disease burden. And not every patient population is represented by a professionalized patient advocacy organization, Dr. McCoy noted. “There is the potential for the rich to get richer.”
 

A Seat at the Table

Long ago, the FDA and the National Institutes of Health (NIH) began giving patients a seat at the table, in part because of the path blazed by AIDS activists in the late 1980s and early 1990s, said Dr. McCoy.

Patient advocacy is often visible during FDA advisory committee meetings. The agency usually allows an hour, sometimes more, for members of the public to express support or concerns about the product being reviewed. Patients and caregivers — often aided by advocacy organizations — also submit hundreds, sometimes thousands, of letters before a product review.

The Alzheimer’s Association spent years advocating for approval of the anti-amyloid agent aducanumab (Aduhelm, Biogen/Eisai). In 2020, the organization urged patients and caregivers to submit written and oral testimony to the FDA advisory panel that was reviewing the drug. Despite patients’ pleas, the panel ultimately declined to support the drug’s approval, citing safety concerns and limited evidence of efficacy.

As controversy swirled around the medication — which had the potential for life-threatening brain swelling — advocates continued to apply pressure. Going against the expert panel’s recommendation, in June 2021, the FDA granted accelerated approval prompting three of the panelists to resign in protest.

Aducanumab’s initial price — $56,000 a year — was seen as a major threat to the viability of Medicare. Still, the Alzheimer’s Association stood behind the decision to approve the drug. But by early 2024, Biogen/Eisai said they would stop selling aducanumab, citing other priorities.

Once again patient advocates showed up in March 2022 when the FDA advisers were reviewing Amylyx Pharmaceuticals’ ALS drug Relyvrio (sodium phenylbutyrate and taurursodiol). Trials had showed limited efficacy, but patients testified they would accept greater risk for a chance to be treated with the drug. The committee ultimately voted against approval; 6 months later, the FDA approved Relyvrio anyway.

In April 2024, Amylyx removed Relyvrio from the market following phase 3 trial results that showed no difference between the treatment and placebo.

The drug manufacturer Sarepta Therapeutics, which develops treatments for genetic conditions such as DMD, has a history of working with — and funding — patient advocacy groups. The company encourages nonprofits to apply for grants or sponsorship on its website. At a 2016 advisory committee, when Sarepta was seeking approval of its first DMD therapy eteplirsen (Exondys 51), 52 speakers, most from patient advocacy groups, pleaded for the drug’s approval. When the panel voted no, Sarepta mobilized families to pressure the agency. Exondys was eventually approved.

In June, Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, unilaterally gave final expanded approval to Sarepta Therapeutics’ gene therapy Elevidys for DMD. Dr. Marks overrode his own FDA reviewers, who said the product lacked substantial evidence of efficacy. He acknowledged the drug had not met its primary endpoint but said he found secondary and exploratory endpoints “compelling” and cited an unmet medical need.

In an opinion piece in The Washington Post, Aaron Kesselheim, MD, JD, MPH, the director of the Program on Regulation, Therapeutics, and Law at Brigham and Women’s Hospital, Boston, Massachusetts, and a former member of the FDA’s Peripheral and Central Nervous System Drugs Advisory Committee, questioned the approval stating that it undermined both public trust and manufacturers’ incentives to do the hard work of proving effectiveness.
 

Patient Voices the ‘Secret Sauce’

Drugmakers aren’t alone in seeing the value of having patients speak directly to government entities. When the Michael J. Fox Foundation wanted to gather cosponsors for the National Plan to End Parkinson’s Act, which President Joe Biden signed into law in July, it recruited and trained patients and caregivers for congressional meetings, said Ted Thompson, senior vice president of public policy at the foundation.

Having those individuals “making the personal case for how this disease affects their families ... was really the secret sauce,” in garnering a large number of cosponsors and getting legislation signed into law within 2 years of its introduction, Mr. Thompson told this news organization.

ALS advocacy groups launched a similar campaign to secure passage of the Accelerating Access to Critical Therapies for ALS Act in 2021.

Both pieces of legislation seek to set a federal agenda for developing new therapies in neurodegenerative diseases, in part by directing the FDA and NIH to fund research, engage patients more directly, and form public-private partnerships and councils to spur innovation.

But some said patient advocates are still coming far too late to the party.

“By the time you hear from patient groups at the meetings at the FDA, often the best opportunities for their input are long past,” Leah Zoe Gibson Rand, DPhil, a research scientist with the Program on Regulation, Therapeutics, and Law at Brigham and Women’s Hospital, told this news organization. There should be more focus on the patient perspective earlier in drug development and trial design.

“There are some things that the patient voice could uniquely tell the agency,” said Holly Fernandez Lynch, JD, associate professor of medical ethics and health policy at the University of Pennsylvania. Patients can give insight on what it means to live with a disease, what symptoms are particularly burdensome, and which endpoints matter.

But, she said, “listening to the patient voice cannot mean that FDA just steps aside and lets anything on the market that patients are willing to try.” Individuals “who lack good treatment options have a very good reason to want to try things that haven’t yet been proven.”

If the FDA allows drugs on the market just because patients are willing to try, “5 or 10 years down the road, it’s not at all clear that we would end up with drugs that are better, or drugs that work, or drugs that we know anything more about,” said Dr. Lynch.
 

Does Taking Industry Money Equal Conflicts of Interest?

Many patient advocacy organizations receive funding from drug companies, medical device makers, or other industry sources, but they aren’t always transparent about how much or from which companies, according to studies.

The Alzheimer’s Association continued to push for the approval of aducanumab, even as the group received millions of dollars from the drugmakers. The association was accused of failing to disclose the potential conflict. It still lobbied for approval, even after the FDA advisers in 2020 voted against the drug.

It is not uncommon for individuals who speak in favor of a product’s approval to receive money for transportation and/or lodging from the drug’s manufacturer. In 2018, Dr. McCoy and colleagues reported in JAMA Internal Medicine that, between 2009 and 2017, a quarter of the speakers at the Anesthetic and Analgesic Drug Products Advisory Committee had conflicts of interest (COIs), mostly from industry, and that they were not disclosed in approximately 20% of the instances.

In a 2017 study of 104 large patient advocacy organizations published in The New England Journal of Medicine, Dr. McCoy and colleagues reported that 83% had received funds from industry. At least 39% had a current or former industry executive on the governing board, and 12% had a current or former industry executive in a board leadership position. Of the 104, 38 were focused on cancer and 13 on neurologic conditions. Of these, only 12% had published policies for managing institutional COIs.

Dr. McCoy emphasized the industry’s reliance on partnering with patient groups, particularly during FDA advisory committee meetings. “The sponsors wouldn’t be paying for patients to show up and give these testimonies if they didn’t think it made a difference. The audience isn’t just panel members; it’s also agency officials and maybe elected officials as well.”

“The Fox Foundation, with a $300 million-plus budget, gets about $5-$6 million a year from industry,” said Mr. Thompson. The money is earmarked for the organization’s Parkinson’s Disease Education Consortium; none goes toward advocacy. And, “the foundation has never specifically endorsed a product or device.”

When organizations that receive industry funding back a particular product, “it does appear to be [a conflict], and whether it is an actual one or not, appearances sometimes are all that matter,” said Mr. Thompson.

Dr. Lynch said accepting industry money “is a really significant conflict.” While advocates might need that money to fund advocacy efforts or make grants to advance research priorities, the acceptance might hinder willingness to demand evidence or to complain about a product’s price tag. “You don’t want to bite the hand that feeds you, right?”

Both Dr. McCoy and Dr. Lynch said patient groups — and individual patients — should at a minimum disclose industry funding, especially when speaking at an advisory committee.

Federal agencies and members of Congress actively seek patient input when considering legislation and funding priorities. But the individuals testifying at an advisory committee aren’t likely to represent all patients, and there’s a danger that they are just the loudest voices, said Dr. McCoy.

“We need to think more carefully about how we actually understand the preferences of a big, diverse patient population,” he said.

Dr. Lynch agreed.

Within the ALS community, “a lot of people who take different perspectives than some of those that are the leading voices get shouted down, and their voices get drowned out, and they get attacked on social media,” she said.

The group may be at the table, “but they’re just one voice at the table,” she said.

Dr. McCoy reported that his wife works for the Leukemia & Lymphoma Society, a patient advocacy organization. Dr. Rand reported no relevant financial relationships. Dr. Lynch received funding from Arnold Ventures and the Greenwall Foundation for work related to the FDA and patient advocacy.

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

TOPLINE:

Older adults with untreated hypertension have a 36% increased risk for Alzheimer’s disease (AD) compared with those without hypertension and a 42% increased risk for AD compared with those with treated hypertension.

METHODOLOGY:

• In this meta-analysis, researchers analyzed the data of 31,250 participants aged 60 years or older (mean age, 72.1 years; 41% men) from 14 community-based studies across 14 countries.
• Mean follow-up was 4.2 years, and blood pressure measurements, hypertension diagnosis, and antihypertensive medication use were recorded.
• Overall, 35.9% had no history of hypertension or antihypertensive medication use, 50.7% had a history of hypertension with antihypertensive medication use, and 9.4% had a history of hypertension without antihypertensive medication use.
• The main outcomes were AD and non-AD dementia.

TAKEAWAY:

• In total, 1415 participants developed AD, and 681 developed non-AD dementia.
• Participants with untreated hypertension had a 36% increased risk for AD compared with healthy controls (hazard ratio [HR], 1.36; P = .041) and a 42% increased risk for AD (HR, 1.42; P = .013) compared with those with treated hypertension.
• Compared with healthy controls, patients with treated hypertension did not show an elevated risk for AD (HR, 0.961; P = .6644).
• Patients with both treated (HR, 1.285; P = .027) and untreated (HR, 1.693; P = .003) hypertension had an increased risk for non-AD dementia compared with healthy controls. Patients with treated and untreated hypertension had a similar risk for non-AD dementia.

IN PRACTICE:

“These results suggest that treating high blood pressure as a person ages continues to be a crucial factor in reducing their risk of Alzheimer’s disease,” the lead author Matthew J. Lennon, MD, PhD, said in a press release.

SOURCE:

This study was led by Matthew J. Lennon, MD, PhD, School of Clinical Medicine, UNSW Sydney, Sydney, Australia. It was published online in Neurology.

LIMITATIONS: 

Varied definitions for hypertension across different locations might have led to discrepancies in diagnosis. Additionally, the study did not account for potential confounders such as stroke, transient ischemic attack, and heart disease, which may act as mediators rather than covariates. Furthermore, the study did not report mortality data, which may have affected the interpretation of dementia risk.

DISCLOSURES:

This research was supported by the National Institute on Aging of the National Institutes of Health. Some authors reported ties with several institutions and pharmaceutical companies outside this work. Full disclosures are available in the original article.

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

TOPLINE:

Older adults with untreated hypertension have a 36% increased risk for Alzheimer’s disease (AD) compared with those without hypertension and a 42% increased risk for AD compared with those with treated hypertension.

METHODOLOGY:

• In this meta-analysis, researchers analyzed the data of 31,250 participants aged 60 years or older (mean age, 72.1 years; 41% men) from 14 community-based studies across 14 countries.
• Mean follow-up was 4.2 years, and blood pressure measurements, hypertension diagnosis, and antihypertensive medication use were recorded.
• Overall, 35.9% had no history of hypertension or antihypertensive medication use, 50.7% had a history of hypertension with antihypertensive medication use, and 9.4% had a history of hypertension without antihypertensive medication use.
• The main outcomes were AD and non-AD dementia.

TAKEAWAY:

• In total, 1415 participants developed AD, and 681 developed non-AD dementia.
• Participants with untreated hypertension had a 36% increased risk for AD compared with healthy controls (hazard ratio [HR], 1.36; P = .041) and a 42% increased risk for AD (HR, 1.42; P = .013) compared with those with treated hypertension.
• Compared with healthy controls, patients with treated hypertension did not show an elevated risk for AD (HR, 0.961; P = .6644).
• Patients with both treated (HR, 1.285; P = .027) and untreated (HR, 1.693; P = .003) hypertension had an increased risk for non-AD dementia compared with healthy controls. Patients with treated and untreated hypertension had a similar risk for non-AD dementia.

IN PRACTICE:

“These results suggest that treating high blood pressure as a person ages continues to be a crucial factor in reducing their risk of Alzheimer’s disease,” the lead author Matthew J. Lennon, MD, PhD, said in a press release.

SOURCE:

This study was led by Matthew J. Lennon, MD, PhD, School of Clinical Medicine, UNSW Sydney, Sydney, Australia. It was published online in Neurology.

LIMITATIONS: 

Varied definitions for hypertension across different locations might have led to discrepancies in diagnosis. Additionally, the study did not account for potential confounders such as stroke, transient ischemic attack, and heart disease, which may act as mediators rather than covariates. Furthermore, the study did not report mortality data, which may have affected the interpretation of dementia risk.

DISCLOSURES:

This research was supported by the National Institute on Aging of the National Institutes of Health. Some authors reported ties with several institutions and pharmaceutical companies outside this work. Full disclosures are available in the original article.

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

TOPLINE:

Older adults with untreated hypertension have a 36% increased risk for Alzheimer’s disease (AD) compared with those without hypertension and a 42% increased risk for AD compared with those with treated hypertension.

METHODOLOGY:

• In this meta-analysis, researchers analyzed the data of 31,250 participants aged 60 years or older (mean age, 72.1 years; 41% men) from 14 community-based studies across 14 countries.
• Mean follow-up was 4.2 years, and blood pressure measurements, hypertension diagnosis, and antihypertensive medication use were recorded.
• Overall, 35.9% had no history of hypertension or antihypertensive medication use, 50.7% had a history of hypertension with antihypertensive medication use, and 9.4% had a history of hypertension without antihypertensive medication use.
• The main outcomes were AD and non-AD dementia.

TAKEAWAY:

• In total, 1415 participants developed AD, and 681 developed non-AD dementia.
• Participants with untreated hypertension had a 36% increased risk for AD compared with healthy controls (hazard ratio [HR], 1.36; P = .041) and a 42% increased risk for AD (HR, 1.42; P = .013) compared with those with treated hypertension.
• Compared with healthy controls, patients with treated hypertension did not show an elevated risk for AD (HR, 0.961; P = .6644).
• Patients with both treated (HR, 1.285; P = .027) and untreated (HR, 1.693; P = .003) hypertension had an increased risk for non-AD dementia compared with healthy controls. Patients with treated and untreated hypertension had a similar risk for non-AD dementia.

IN PRACTICE:

“These results suggest that treating high blood pressure as a person ages continues to be a crucial factor in reducing their risk of Alzheimer’s disease,” the lead author Matthew J. Lennon, MD, PhD, said in a press release.

SOURCE:

This study was led by Matthew J. Lennon, MD, PhD, School of Clinical Medicine, UNSW Sydney, Sydney, Australia. It was published online in Neurology.

LIMITATIONS: 

Varied definitions for hypertension across different locations might have led to discrepancies in diagnosis. Additionally, the study did not account for potential confounders such as stroke, transient ischemic attack, and heart disease, which may act as mediators rather than covariates. Furthermore, the study did not report mortality data, which may have affected the interpretation of dementia risk.

DISCLOSURES:

This research was supported by the National Institute on Aging of the National Institutes of Health. Some authors reported ties with several institutions and pharmaceutical companies outside this work. Full disclosures are available in the original article.

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

A growing body of research has increasingly connected hearing loss with a higher risk for dementia. In addition, some studies suggest that wearing hearing aids may help prevent dementia, though one study was recently voluntarily retracted due to methodological errors.

Given the overall evidence, how robust are these associations? And what guidance should clinicians provide to their patients?

Frank Lin, MD, PhD, a clinician and professor of otolaryngology and epidemiology at Johns Hopkins University School of Medicine, Baltimore, emphasized that the evidence from the past 10-15 years strongly links hearing loss to cognitive decline.

While quantifying the exact increase in risk is challenging, Dr. Lin said, “there’s no doubt about it; it’s not trivial.”

With respect to the potential link between hearing aids and dementia prevention, Dr. Lin is involved in the ongoing ACHIEVE randomized trial. Results presented at the 2023 Alzheimer’s Association International Conference and simultaneously published in The Lancet revealed participants who used hearing aids experienced a significant slowing of cognitive decline compared with those who received health education.

“It’s a no-risk intervention that can benefit social function, and for people at risk for cognitive decline, it can actually benefit cognitive health,” Dr. Lin said.
 

Potential Mechanisms

Dr. Lin pointed out that the Lancet Commission on Dementia identifies hearing impairment as one of the most significant risk factors for dementia. Overall, the consensus from most studies is that hearing loss definitely increases the risk for cognitive decline and dementia, he said.

Several hypotheses may explain this connection, and Dr. Lin believes that a combination of three key mechanisms is likely to be central to understanding this link.

The first theory focuses on cognitive load. As people experience age-related hearing changes, “the inner ear is no longer sending signals clearly to the brain,” Dr. Lin explained. This forces the brain to work harder, increasing its cognitive load as it reallocates resources to assist with hearing.

Dr. Lin emphasized that this is a hypothesis and does not prove hearing loss directly causes cognitive decline or dementia. Rather, it suggests that hearing loss accelerates the “unmasking” of cognitive issues. Brain resources that might otherwise buffer against dementia’s pathologic triggers are consumed earlier due to the demands of managing hearing loss.

The second potential mechanism suggests that hearing loss may have detrimental effects on brain structure and function over time — a theory supported by several recent studies.

These studies show that individuals with more severe hearing loss experience faster rates of brain atrophy. The reduced stimulation from poor auditory signals accelerates brain atrophy, Dr. Lin explained.

The third hypothesis focuses on social isolation. Individuals with hearing loss may engage less in social activities, reducing cognitive stimulation and overall social interaction. It’s well-known that social engagement and cognitive stimulation are crucial for maintaining cognitive health over time, Dr. Lin said.

Overall, Dr. Lin believes that the association between hearing loss and an increased risk for cognitive decline likely involves a combination of all three potential mechanisms. It’s not a matter of one theory being right and the others being wrong, he said.
 

The Role of Hearing Aids

However, the jury is out on the role of hearing aids in preventing dementia.

A large observational study published in 2023 in Lancet Public Health was hailed by its investigators as providing “the best evidence to date” that hearing aids could mitigate the impact of hearing loss on dementia (Lancet Public Health. 2023 May;8[5]:e329-e338. doi: 10.1016/S2468-2667[23]00048-8). However, the authors voluntarily retracted the paper in December 2023 due to a coding error.

Despite this, a large meta-analysis published in JAMA Neurology suggested that hearing aids might reduce cognitive decline and dementia risk and even enhance short-term cognitive function.

Additionally, the ACHIEVE study, the first randomized trial to investigate these issues, included nearly 1000 older participants from two populations — those from the ARIC study and healthy volunteers. Participants were randomly assigned to receive either a hearing intervention or education on healthy aging.

Although the primary endpoint of change in standardized neurocognitive scores at year 3 showed no significant difference between the hearing intervention and health education groups, the ARIC cohort experienced a notable 48% reduction in cognitive decline with hearing aids compared with education.

Dr. Lin explained that, due to the study’s design, the control group was healthier than the ARIC cohort, which was at higher risk for cognitive decline due to factors such as age and diabetes. This is where they observed a strong effect of hearing intervention in reducing cognitive decline within just 3 years, Dr. Lin said.

Conversely, the hearing aids had minimal impact on the healthy controls, likely because they had not experienced cognitive decline to begin with. Essentially, the benefits of hearing aids were more apparent once cognitive issues were already present.

“It seems sort of obvious. In a group of people who aren’t at risk for cognitive decline, a hearing intervention isn’t going to benefit their cognition” in the short term, Dr. Lin noted. That said, the investigators are continuing to follow the healthy controls to determine whether hearing aids lower dementia risk over the long term.
 

Which Comes First?

Some experts have questioned the directionality of the link between hearing aids and dementia — do hearing aids reduce dementia risk or are individuals with dementia simply less likely to use them?

Dr. Lin noted that observational studies often have confounders. For instance, people who use hearing aids are often healthier and better educated. This makes it difficult to distinguish the effect of the intervention from the factors that led people to use it, he said.

In contrast, the ACHIEVE trial, a randomized study, was designed to separate these factors from the hearing intervention, Dr. Lin explained.

However, he added that ACHIEVE was not specifically powered to assess dementia development, focusing instead on cognitive decline. The investigators plan long-term follow-up of participants to evaluate the impact on dementia in the future.

So, given the current evidence, what should clinicians tell their patients?

Because all people experience some degree of hearing changes as they age, which can gradually affect communication and social engagement, it’s important for everyone to be aware of their hearing health, Dr. Lin said.

He noted there are apps available that allow individuals to measure their hearing with their phones, including determining their “hearing number.”

With respect to hearing aids, Dr. Lin noted that if individuals have trouble participating in everyday activities, addressing hearing issues and considering a hearing intervention is crucial.

There’s no medical risk associated with hearing aids, he said. Even if they only improve social activities and engagement, that’s a benefit. If they also have potential positive effects on cognitive health, “even better,” he added.

Dr. Lin noted that as of 2022, hearing aids are now available over the counter, a move that has improved accessibility. In addition, new technologies, such as stylish “hearing aid glasses,” are being developed to offer more appealing options and reduce the stigma associated with traditional devices.

People often view hearing loss as a significant life event and are reluctant to admit they need hearing aids. However, focusing on “what’s your hearing?” as a neutral tracking metric could make it easier to adopt new technologies in the future, Lin said.
 

Alzheimer’s Association Weighs in

Heather Snyder, PhD, vice president, Medical & Scientific Relations at the Alzheimer’s Association, echoed Dr. Lin, noting that there has been substantial research showing a link between hearing loss and cognitive decline.

“This association is something that we have seen repeated and replicated in a number of different studies. What we don’t know is the cause and effect,” Dr. Snyder said.

She noted it is unknown whether there is a causal link between hearing loss and cognitive decline and/or whether cognitive decline may contribute to hearing loss. These are some of the “big questions” that remain, said Dr. Snyder.

Still, she noted that hearing health is an important part of quality of life and overall brain health and “should be part of the conversation” between clinicians and their patients.

Discussing the results of the ACHIEVE study, Dr. Snyder highlighted that while the subgroup at higher risk for cognitive decline did experience significant improvement, the overall population did not show a benefit from the intervention.

The brain “is complex,” and it’s unlikely that a single intervention or target will provide all the benefits, Dr. Snyder said.

She emphasized that addressing hearing loss with hearing aids, combined with managing other modifiable risk factors — such as heart and metabolic health, physical activity, and a balanced diet — appears to offer the greatest potential for synergy and preserving cognition.

Drs. Lin and Snyder reported no relevant conflicts of interest.
 

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

A growing body of research has increasingly connected hearing loss with a higher risk for dementia. In addition, some studies suggest that wearing hearing aids may help prevent dementia, though one study was recently voluntarily retracted due to methodological errors.

Given the overall evidence, how robust are these associations? And what guidance should clinicians provide to their patients?

Frank Lin, MD, PhD, a clinician and professor of otolaryngology and epidemiology at Johns Hopkins University School of Medicine, Baltimore, emphasized that the evidence from the past 10-15 years strongly links hearing loss to cognitive decline.

While quantifying the exact increase in risk is challenging, Dr. Lin said, “there’s no doubt about it; it’s not trivial.”

With respect to the potential link between hearing aids and dementia prevention, Dr. Lin is involved in the ongoing ACHIEVE randomized trial. Results presented at the 2023 Alzheimer’s Association International Conference and simultaneously published in The Lancet revealed participants who used hearing aids experienced a significant slowing of cognitive decline compared with those who received health education.

“It’s a no-risk intervention that can benefit social function, and for people at risk for cognitive decline, it can actually benefit cognitive health,” Dr. Lin said.
 

Potential Mechanisms

Dr. Lin pointed out that the Lancet Commission on Dementia identifies hearing impairment as one of the most significant risk factors for dementia. Overall, the consensus from most studies is that hearing loss definitely increases the risk for cognitive decline and dementia, he said.

Several hypotheses may explain this connection, and Dr. Lin believes that a combination of three key mechanisms is likely to be central to understanding this link.

The first theory focuses on cognitive load. As people experience age-related hearing changes, “the inner ear is no longer sending signals clearly to the brain,” Dr. Lin explained. This forces the brain to work harder, increasing its cognitive load as it reallocates resources to assist with hearing.

Dr. Lin emphasized that this is a hypothesis and does not prove hearing loss directly causes cognitive decline or dementia. Rather, it suggests that hearing loss accelerates the “unmasking” of cognitive issues. Brain resources that might otherwise buffer against dementia’s pathologic triggers are consumed earlier due to the demands of managing hearing loss.

The second potential mechanism suggests that hearing loss may have detrimental effects on brain structure and function over time — a theory supported by several recent studies.

These studies show that individuals with more severe hearing loss experience faster rates of brain atrophy. The reduced stimulation from poor auditory signals accelerates brain atrophy, Dr. Lin explained.

The third hypothesis focuses on social isolation. Individuals with hearing loss may engage less in social activities, reducing cognitive stimulation and overall social interaction. It’s well-known that social engagement and cognitive stimulation are crucial for maintaining cognitive health over time, Dr. Lin said.

Overall, Dr. Lin believes that the association between hearing loss and an increased risk for cognitive decline likely involves a combination of all three potential mechanisms. It’s not a matter of one theory being right and the others being wrong, he said.
 

The Role of Hearing Aids

However, the jury is out on the role of hearing aids in preventing dementia.

A large observational study published in 2023 in Lancet Public Health was hailed by its investigators as providing “the best evidence to date” that hearing aids could mitigate the impact of hearing loss on dementia (Lancet Public Health. 2023 May;8[5]:e329-e338. doi: 10.1016/S2468-2667[23]00048-8). However, the authors voluntarily retracted the paper in December 2023 due to a coding error.

Despite this, a large meta-analysis published in JAMA Neurology suggested that hearing aids might reduce cognitive decline and dementia risk and even enhance short-term cognitive function.

Additionally, the ACHIEVE study, the first randomized trial to investigate these issues, included nearly 1000 older participants from two populations — those from the ARIC study and healthy volunteers. Participants were randomly assigned to receive either a hearing intervention or education on healthy aging.

Although the primary endpoint of change in standardized neurocognitive scores at year 3 showed no significant difference between the hearing intervention and health education groups, the ARIC cohort experienced a notable 48% reduction in cognitive decline with hearing aids compared with education.

Dr. Lin explained that, due to the study’s design, the control group was healthier than the ARIC cohort, which was at higher risk for cognitive decline due to factors such as age and diabetes. This is where they observed a strong effect of hearing intervention in reducing cognitive decline within just 3 years, Dr. Lin said.

Conversely, the hearing aids had minimal impact on the healthy controls, likely because they had not experienced cognitive decline to begin with. Essentially, the benefits of hearing aids were more apparent once cognitive issues were already present.

“It seems sort of obvious. In a group of people who aren’t at risk for cognitive decline, a hearing intervention isn’t going to benefit their cognition” in the short term, Dr. Lin noted. That said, the investigators are continuing to follow the healthy controls to determine whether hearing aids lower dementia risk over the long term.
 

Which Comes First?

Some experts have questioned the directionality of the link between hearing aids and dementia — do hearing aids reduce dementia risk or are individuals with dementia simply less likely to use them?

Dr. Lin noted that observational studies often have confounders. For instance, people who use hearing aids are often healthier and better educated. This makes it difficult to distinguish the effect of the intervention from the factors that led people to use it, he said.

In contrast, the ACHIEVE trial, a randomized study, was designed to separate these factors from the hearing intervention, Dr. Lin explained.

However, he added that ACHIEVE was not specifically powered to assess dementia development, focusing instead on cognitive decline. The investigators plan long-term follow-up of participants to evaluate the impact on dementia in the future.

So, given the current evidence, what should clinicians tell their patients?

Because all people experience some degree of hearing changes as they age, which can gradually affect communication and social engagement, it’s important for everyone to be aware of their hearing health, Dr. Lin said.

He noted there are apps available that allow individuals to measure their hearing with their phones, including determining their “hearing number.”

With respect to hearing aids, Dr. Lin noted that if individuals have trouble participating in everyday activities, addressing hearing issues and considering a hearing intervention is crucial.

There’s no medical risk associated with hearing aids, he said. Even if they only improve social activities and engagement, that’s a benefit. If they also have potential positive effects on cognitive health, “even better,” he added.

Dr. Lin noted that as of 2022, hearing aids are now available over the counter, a move that has improved accessibility. In addition, new technologies, such as stylish “hearing aid glasses,” are being developed to offer more appealing options and reduce the stigma associated with traditional devices.

People often view hearing loss as a significant life event and are reluctant to admit they need hearing aids. However, focusing on “what’s your hearing?” as a neutral tracking metric could make it easier to adopt new technologies in the future, Lin said.
 

Alzheimer’s Association Weighs in

Heather Snyder, PhD, vice president, Medical & Scientific Relations at the Alzheimer’s Association, echoed Dr. Lin, noting that there has been substantial research showing a link between hearing loss and cognitive decline.

“This association is something that we have seen repeated and replicated in a number of different studies. What we don’t know is the cause and effect,” Dr. Snyder said.

She noted it is unknown whether there is a causal link between hearing loss and cognitive decline and/or whether cognitive decline may contribute to hearing loss. These are some of the “big questions” that remain, said Dr. Snyder.

Still, she noted that hearing health is an important part of quality of life and overall brain health and “should be part of the conversation” between clinicians and their patients.

Discussing the results of the ACHIEVE study, Dr. Snyder highlighted that while the subgroup at higher risk for cognitive decline did experience significant improvement, the overall population did not show a benefit from the intervention.

The brain “is complex,” and it’s unlikely that a single intervention or target will provide all the benefits, Dr. Snyder said.

She emphasized that addressing hearing loss with hearing aids, combined with managing other modifiable risk factors — such as heart and metabolic health, physical activity, and a balanced diet — appears to offer the greatest potential for synergy and preserving cognition.

Drs. Lin and Snyder reported no relevant conflicts of interest.
 

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

A growing body of research has increasingly connected hearing loss with a higher risk for dementia. In addition, some studies suggest that wearing hearing aids may help prevent dementia, though one study was recently voluntarily retracted due to methodological errors.

Given the overall evidence, how robust are these associations? And what guidance should clinicians provide to their patients?

Frank Lin, MD, PhD, a clinician and professor of otolaryngology and epidemiology at Johns Hopkins University School of Medicine, Baltimore, emphasized that the evidence from the past 10-15 years strongly links hearing loss to cognitive decline.

While quantifying the exact increase in risk is challenging, Dr. Lin said, “there’s no doubt about it; it’s not trivial.”

With respect to the potential link between hearing aids and dementia prevention, Dr. Lin is involved in the ongoing ACHIEVE randomized trial. Results presented at the 2023 Alzheimer’s Association International Conference and simultaneously published in The Lancet revealed participants who used hearing aids experienced a significant slowing of cognitive decline compared with those who received health education.

“It’s a no-risk intervention that can benefit social function, and for people at risk for cognitive decline, it can actually benefit cognitive health,” Dr. Lin said.
 

Potential Mechanisms

Dr. Lin pointed out that the Lancet Commission on Dementia identifies hearing impairment as one of the most significant risk factors for dementia. Overall, the consensus from most studies is that hearing loss definitely increases the risk for cognitive decline and dementia, he said.

Several hypotheses may explain this connection, and Dr. Lin believes that a combination of three key mechanisms is likely to be central to understanding this link.

The first theory focuses on cognitive load. As people experience age-related hearing changes, “the inner ear is no longer sending signals clearly to the brain,” Dr. Lin explained. This forces the brain to work harder, increasing its cognitive load as it reallocates resources to assist with hearing.

Dr. Lin emphasized that this is a hypothesis and does not prove hearing loss directly causes cognitive decline or dementia. Rather, it suggests that hearing loss accelerates the “unmasking” of cognitive issues. Brain resources that might otherwise buffer against dementia’s pathologic triggers are consumed earlier due to the demands of managing hearing loss.

The second potential mechanism suggests that hearing loss may have detrimental effects on brain structure and function over time — a theory supported by several recent studies.

These studies show that individuals with more severe hearing loss experience faster rates of brain atrophy. The reduced stimulation from poor auditory signals accelerates brain atrophy, Dr. Lin explained.

The third hypothesis focuses on social isolation. Individuals with hearing loss may engage less in social activities, reducing cognitive stimulation and overall social interaction. It’s well-known that social engagement and cognitive stimulation are crucial for maintaining cognitive health over time, Dr. Lin said.

Overall, Dr. Lin believes that the association between hearing loss and an increased risk for cognitive decline likely involves a combination of all three potential mechanisms. It’s not a matter of one theory being right and the others being wrong, he said.
 

The Role of Hearing Aids

However, the jury is out on the role of hearing aids in preventing dementia.

A large observational study published in 2023 in Lancet Public Health was hailed by its investigators as providing “the best evidence to date” that hearing aids could mitigate the impact of hearing loss on dementia (Lancet Public Health. 2023 May;8[5]:e329-e338. doi: 10.1016/S2468-2667[23]00048-8). However, the authors voluntarily retracted the paper in December 2023 due to a coding error.

Despite this, a large meta-analysis published in JAMA Neurology suggested that hearing aids might reduce cognitive decline and dementia risk and even enhance short-term cognitive function.

Additionally, the ACHIEVE study, the first randomized trial to investigate these issues, included nearly 1000 older participants from two populations — those from the ARIC study and healthy volunteers. Participants were randomly assigned to receive either a hearing intervention or education on healthy aging.

Although the primary endpoint of change in standardized neurocognitive scores at year 3 showed no significant difference between the hearing intervention and health education groups, the ARIC cohort experienced a notable 48% reduction in cognitive decline with hearing aids compared with education.

Dr. Lin explained that, due to the study’s design, the control group was healthier than the ARIC cohort, which was at higher risk for cognitive decline due to factors such as age and diabetes. This is where they observed a strong effect of hearing intervention in reducing cognitive decline within just 3 years, Dr. Lin said.

Conversely, the hearing aids had minimal impact on the healthy controls, likely because they had not experienced cognitive decline to begin with. Essentially, the benefits of hearing aids were more apparent once cognitive issues were already present.

“It seems sort of obvious. In a group of people who aren’t at risk for cognitive decline, a hearing intervention isn’t going to benefit their cognition” in the short term, Dr. Lin noted. That said, the investigators are continuing to follow the healthy controls to determine whether hearing aids lower dementia risk over the long term.
 

Which Comes First?

Some experts have questioned the directionality of the link between hearing aids and dementia — do hearing aids reduce dementia risk or are individuals with dementia simply less likely to use them?

Dr. Lin noted that observational studies often have confounders. For instance, people who use hearing aids are often healthier and better educated. This makes it difficult to distinguish the effect of the intervention from the factors that led people to use it, he said.

In contrast, the ACHIEVE trial, a randomized study, was designed to separate these factors from the hearing intervention, Dr. Lin explained.

However, he added that ACHIEVE was not specifically powered to assess dementia development, focusing instead on cognitive decline. The investigators plan long-term follow-up of participants to evaluate the impact on dementia in the future.

So, given the current evidence, what should clinicians tell their patients?

Because all people experience some degree of hearing changes as they age, which can gradually affect communication and social engagement, it’s important for everyone to be aware of their hearing health, Dr. Lin said.

He noted there are apps available that allow individuals to measure their hearing with their phones, including determining their “hearing number.”

With respect to hearing aids, Dr. Lin noted that if individuals have trouble participating in everyday activities, addressing hearing issues and considering a hearing intervention is crucial.

There’s no medical risk associated with hearing aids, he said. Even if they only improve social activities and engagement, that’s a benefit. If they also have potential positive effects on cognitive health, “even better,” he added.

Dr. Lin noted that as of 2022, hearing aids are now available over the counter, a move that has improved accessibility. In addition, new technologies, such as stylish “hearing aid glasses,” are being developed to offer more appealing options and reduce the stigma associated with traditional devices.

People often view hearing loss as a significant life event and are reluctant to admit they need hearing aids. However, focusing on “what’s your hearing?” as a neutral tracking metric could make it easier to adopt new technologies in the future, Lin said.
 

Alzheimer’s Association Weighs in

Heather Snyder, PhD, vice president, Medical & Scientific Relations at the Alzheimer’s Association, echoed Dr. Lin, noting that there has been substantial research showing a link between hearing loss and cognitive decline.

“This association is something that we have seen repeated and replicated in a number of different studies. What we don’t know is the cause and effect,” Dr. Snyder said.

She noted it is unknown whether there is a causal link between hearing loss and cognitive decline and/or whether cognitive decline may contribute to hearing loss. These are some of the “big questions” that remain, said Dr. Snyder.

Still, she noted that hearing health is an important part of quality of life and overall brain health and “should be part of the conversation” between clinicians and their patients.

Discussing the results of the ACHIEVE study, Dr. Snyder highlighted that while the subgroup at higher risk for cognitive decline did experience significant improvement, the overall population did not show a benefit from the intervention.

The brain “is complex,” and it’s unlikely that a single intervention or target will provide all the benefits, Dr. Snyder said.

She emphasized that addressing hearing loss with hearing aids, combined with managing other modifiable risk factors — such as heart and metabolic health, physical activity, and a balanced diet — appears to offer the greatest potential for synergy and preserving cognition.

Drs. Lin and Snyder reported no relevant conflicts of interest.
 

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

In the case of a hip fracture, operating on a patient with dementia can be a difficult decision to make. Indeed, surgery exposes patients with dementia to a higher mortality rate, more delirium and postoperative complications, and a greater loss of mobility than patients of the same age without cognitive impairments. For patients with dementia in institutional settings, survival is better for those who undergo surgery than for those who do not. But what about the prognosis of surgery vs no surgery for patients with dementia who live at home?

To answer this question, researchers in the United States conducted a cohort study using Medicare data. This retrospective study included patients aged 66 years and older with dementia who were living at home and not placed in institutions and who had a hip fracture between January 2017 and June 2018. Patients with incomplete observations, particularly regarding the location and type of residence (home/institution), were excluded from the analysis. Fractures were categorized as (i) fractures of the head and neck, (ii) pertrochanteric, (iii) subtrochanteric, and (iv) multiple/complex. The type and severity (mild, moderate, or severe) of dementia were identified using the diagnostic code list in the International Statistical Classification of Diseases, Tenth Revision.
 

Examining Mortality

The primary outcome was mortality at 30, 90, and 180 days. Secondary outcomes included hospital delirium; the need for subsequent hospitalization (within 6 months) or home health services (within 10 days); and intensive care interventions such as dialysis, intubation, resuscitation maneuvers, mechanical ventilation, or the insertion of a feeding tube.

Postoperative medical facility admissions were distinguished according to whether there was a plan to return home. To compare the surgery and nonsurgery groups, an inverse propensity score analysis was conducted within subgroups determined by fracture type, comorbidities (using the Elixhauser score), the person or entity responsible for admission (ie, physician, clinic, hospital, etc.), dual eligibility (Medicare and Medicaid), place of residence (ie, urban or rural), race, and sex. Dementia severity was estimated using a frailty index on the basis of evaluation tests that were systematically collected in the Medicare database.
 

Results Favored Surgery

Among 56,209 patients with dementia who were admitted for a hip fracture (73.0% women; mean age, 86.4 ± 7.0 years), 33,142 (59.0%) underwent surgery and 23,067 (41.0%) did not. Among surgically treated patients, 73.3% had fractures of the head or neck of the femur, and 40.2% had moderate to severe dementia. The nonsurgically treated fractures were 78.5% pertrochanteric. Comorbidities were evenly distributed between the two groups.

At 180 days, mortality was 31.8% in the surgery group compared with 45.7% in the nonsurgery group, resulting in a significant reduction in the unadjusted relative risk (RR) for death in favor of surgery (RR, 0.67; 95% CI, 0.60-0.76; P < .001). Among patients with mild dementia and a fracture of the head or neck of the femur, mortality at 180 days was 26.5% among surgical patients and 34.9% among nonsurgical patients (RR, 0.67; 95% CI, 0.60-0.76; P < .001). After the investigators adjusted for risk according to propensity score, the benefit of surgery remained significant at 30, 90, and 180 days, regardless of dementia severity. There was no significant difference in mortality for other types of hip fractures between the surgery and nonsurgery groups, however.

The adjusted RR for in-hospital delirium was 1.23 (P = .008), which was significant for the surgery group, but only for those with moderate to severe dementia. There were also fewer permanent placements (P < .001) among the surgically treated patients, and fewer patients with mild dementia required nurse care at home. There was no difference in resuscitation maneuvers between surgery and nonsurgery patients, whether the dementia was mild or not. For patients with a fracture of the head or neck of the femur, there was no difference in the likelihood of rehabilitation admission within 180 days, whether they were operated on or not.
 

Ethical Considerations

This study can inform discussions among healthcare professionals, patients, and patients’ families about which goals to set and which strategy to choose. The main interest of this study lies in its comparison of outcomes between patients with dementia who were operated on and those who were not, rather than comparing patients with and without dementia. Among patients with dementia living at home with a fracture of the head or neck of the femur, those who underwent surgery had a lower risk for death than those who did not, regardless of the severity of dementia.

It is noteworthy that less than two thirds of patients with dementia underwent surgery, which contradicts recommendations for almost routine surgery for patients with dementia. This observation raises questions about respecting patient wishes and advance directives when known, possible detrimental delays in referrals, and legal-medical issues.

Furthermore, the treatment choices of American surgeons are clearly influenced by the type of hip fracture. Fractures of the head and neck of the femur are typically treated with prosthetic arthroplasty, which simplifies postoperative care, compared with osteosynthesis. The latter procedure is more often used for extra-articular hip fractures but entails higher risks. While survival is an apparently more easily achievable goal through surgery, ethical considerations about other treatment objectives such as pain control, functional recovery, and treatment adequacy cannot be overlooked. It is worth noting that the French National Authority for Health issued recommendations in 2018 regarding the care pathway for patients hospitalized for a hip fracture within an orthogeriatric organization.

This story was translated from JIM, which is part of the Medscape Medical News professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

In the case of a hip fracture, operating on a patient with dementia can be a difficult decision to make. Indeed, surgery exposes patients with dementia to a higher mortality rate, more delirium and postoperative complications, and a greater loss of mobility than patients of the same age without cognitive impairments. For patients with dementia in institutional settings, survival is better for those who undergo surgery than for those who do not. But what about the prognosis of surgery vs no surgery for patients with dementia who live at home?

To answer this question, researchers in the United States conducted a cohort study using Medicare data. This retrospective study included patients aged 66 years and older with dementia who were living at home and not placed in institutions and who had a hip fracture between January 2017 and June 2018. Patients with incomplete observations, particularly regarding the location and type of residence (home/institution), were excluded from the analysis. Fractures were categorized as (i) fractures of the head and neck, (ii) pertrochanteric, (iii) subtrochanteric, and (iv) multiple/complex. The type and severity (mild, moderate, or severe) of dementia were identified using the diagnostic code list in the International Statistical Classification of Diseases, Tenth Revision.
 

Examining Mortality

The primary outcome was mortality at 30, 90, and 180 days. Secondary outcomes included hospital delirium; the need for subsequent hospitalization (within 6 months) or home health services (within 10 days); and intensive care interventions such as dialysis, intubation, resuscitation maneuvers, mechanical ventilation, or the insertion of a feeding tube.

Postoperative medical facility admissions were distinguished according to whether there was a plan to return home. To compare the surgery and nonsurgery groups, an inverse propensity score analysis was conducted within subgroups determined by fracture type, comorbidities (using the Elixhauser score), the person or entity responsible for admission (ie, physician, clinic, hospital, etc.), dual eligibility (Medicare and Medicaid), place of residence (ie, urban or rural), race, and sex. Dementia severity was estimated using a frailty index on the basis of evaluation tests that were systematically collected in the Medicare database.
 

Results Favored Surgery

Among 56,209 patients with dementia who were admitted for a hip fracture (73.0% women; mean age, 86.4 ± 7.0 years), 33,142 (59.0%) underwent surgery and 23,067 (41.0%) did not. Among surgically treated patients, 73.3% had fractures of the head or neck of the femur, and 40.2% had moderate to severe dementia. The nonsurgically treated fractures were 78.5% pertrochanteric. Comorbidities were evenly distributed between the two groups.

At 180 days, mortality was 31.8% in the surgery group compared with 45.7% in the nonsurgery group, resulting in a significant reduction in the unadjusted relative risk (RR) for death in favor of surgery (RR, 0.67; 95% CI, 0.60-0.76; P < .001). Among patients with mild dementia and a fracture of the head or neck of the femur, mortality at 180 days was 26.5% among surgical patients and 34.9% among nonsurgical patients (RR, 0.67; 95% CI, 0.60-0.76; P < .001). After the investigators adjusted for risk according to propensity score, the benefit of surgery remained significant at 30, 90, and 180 days, regardless of dementia severity. There was no significant difference in mortality for other types of hip fractures between the surgery and nonsurgery groups, however.

The adjusted RR for in-hospital delirium was 1.23 (P = .008), which was significant for the surgery group, but only for those with moderate to severe dementia. There were also fewer permanent placements (P < .001) among the surgically treated patients, and fewer patients with mild dementia required nurse care at home. There was no difference in resuscitation maneuvers between surgery and nonsurgery patients, whether the dementia was mild or not. For patients with a fracture of the head or neck of the femur, there was no difference in the likelihood of rehabilitation admission within 180 days, whether they were operated on or not.
 

Ethical Considerations

This study can inform discussions among healthcare professionals, patients, and patients’ families about which goals to set and which strategy to choose. The main interest of this study lies in its comparison of outcomes between patients with dementia who were operated on and those who were not, rather than comparing patients with and without dementia. Among patients with dementia living at home with a fracture of the head or neck of the femur, those who underwent surgery had a lower risk for death than those who did not, regardless of the severity of dementia.

It is noteworthy that less than two thirds of patients with dementia underwent surgery, which contradicts recommendations for almost routine surgery for patients with dementia. This observation raises questions about respecting patient wishes and advance directives when known, possible detrimental delays in referrals, and legal-medical issues.

Furthermore, the treatment choices of American surgeons are clearly influenced by the type of hip fracture. Fractures of the head and neck of the femur are typically treated with prosthetic arthroplasty, which simplifies postoperative care, compared with osteosynthesis. The latter procedure is more often used for extra-articular hip fractures but entails higher risks. While survival is an apparently more easily achievable goal through surgery, ethical considerations about other treatment objectives such as pain control, functional recovery, and treatment adequacy cannot be overlooked. It is worth noting that the French National Authority for Health issued recommendations in 2018 regarding the care pathway for patients hospitalized for a hip fracture within an orthogeriatric organization.

This story was translated from JIM, which is part of the Medscape Medical News professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

In the case of a hip fracture, operating on a patient with dementia can be a difficult decision to make. Indeed, surgery exposes patients with dementia to a higher mortality rate, more delirium and postoperative complications, and a greater loss of mobility than patients of the same age without cognitive impairments. For patients with dementia in institutional settings, survival is better for those who undergo surgery than for those who do not. But what about the prognosis of surgery vs no surgery for patients with dementia who live at home?

To answer this question, researchers in the United States conducted a cohort study using Medicare data. This retrospective study included patients aged 66 years and older with dementia who were living at home and not placed in institutions and who had a hip fracture between January 2017 and June 2018. Patients with incomplete observations, particularly regarding the location and type of residence (home/institution), were excluded from the analysis. Fractures were categorized as (i) fractures of the head and neck, (ii) pertrochanteric, (iii) subtrochanteric, and (iv) multiple/complex. The type and severity (mild, moderate, or severe) of dementia were identified using the diagnostic code list in the International Statistical Classification of Diseases, Tenth Revision.
 

Examining Mortality

The primary outcome was mortality at 30, 90, and 180 days. Secondary outcomes included hospital delirium; the need for subsequent hospitalization (within 6 months) or home health services (within 10 days); and intensive care interventions such as dialysis, intubation, resuscitation maneuvers, mechanical ventilation, or the insertion of a feeding tube.

Postoperative medical facility admissions were distinguished according to whether there was a plan to return home. To compare the surgery and nonsurgery groups, an inverse propensity score analysis was conducted within subgroups determined by fracture type, comorbidities (using the Elixhauser score), the person or entity responsible for admission (ie, physician, clinic, hospital, etc.), dual eligibility (Medicare and Medicaid), place of residence (ie, urban or rural), race, and sex. Dementia severity was estimated using a frailty index on the basis of evaluation tests that were systematically collected in the Medicare database.
 

Results Favored Surgery

Among 56,209 patients with dementia who were admitted for a hip fracture (73.0% women; mean age, 86.4 ± 7.0 years), 33,142 (59.0%) underwent surgery and 23,067 (41.0%) did not. Among surgically treated patients, 73.3% had fractures of the head or neck of the femur, and 40.2% had moderate to severe dementia. The nonsurgically treated fractures were 78.5% pertrochanteric. Comorbidities were evenly distributed between the two groups.

At 180 days, mortality was 31.8% in the surgery group compared with 45.7% in the nonsurgery group, resulting in a significant reduction in the unadjusted relative risk (RR) for death in favor of surgery (RR, 0.67; 95% CI, 0.60-0.76; P < .001). Among patients with mild dementia and a fracture of the head or neck of the femur, mortality at 180 days was 26.5% among surgical patients and 34.9% among nonsurgical patients (RR, 0.67; 95% CI, 0.60-0.76; P < .001). After the investigators adjusted for risk according to propensity score, the benefit of surgery remained significant at 30, 90, and 180 days, regardless of dementia severity. There was no significant difference in mortality for other types of hip fractures between the surgery and nonsurgery groups, however.

The adjusted RR for in-hospital delirium was 1.23 (P = .008), which was significant for the surgery group, but only for those with moderate to severe dementia. There were also fewer permanent placements (P < .001) among the surgically treated patients, and fewer patients with mild dementia required nurse care at home. There was no difference in resuscitation maneuvers between surgery and nonsurgery patients, whether the dementia was mild or not. For patients with a fracture of the head or neck of the femur, there was no difference in the likelihood of rehabilitation admission within 180 days, whether they were operated on or not.
 

Ethical Considerations

This study can inform discussions among healthcare professionals, patients, and patients’ families about which goals to set and which strategy to choose. The main interest of this study lies in its comparison of outcomes between patients with dementia who were operated on and those who were not, rather than comparing patients with and without dementia. Among patients with dementia living at home with a fracture of the head or neck of the femur, those who underwent surgery had a lower risk for death than those who did not, regardless of the severity of dementia.

It is noteworthy that less than two thirds of patients with dementia underwent surgery, which contradicts recommendations for almost routine surgery for patients with dementia. This observation raises questions about respecting patient wishes and advance directives when known, possible detrimental delays in referrals, and legal-medical issues.

Furthermore, the treatment choices of American surgeons are clearly influenced by the type of hip fracture. Fractures of the head and neck of the femur are typically treated with prosthetic arthroplasty, which simplifies postoperative care, compared with osteosynthesis. The latter procedure is more often used for extra-articular hip fractures but entails higher risks. While survival is an apparently more easily achievable goal through surgery, ethical considerations about other treatment objectives such as pain control, functional recovery, and treatment adequacy cannot be overlooked. It is worth noting that the French National Authority for Health issued recommendations in 2018 regarding the care pathway for patients hospitalized for a hip fracture within an orthogeriatric organization.

This story was translated from JIM, which is part of the Medscape Medical News professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

In 2019, 57 million people worldwide were living with dementia, a figure expected to soar to 153 million by 2050. A recent Lancet Commission report suggests that nearly half of dementia cases could be prevented or delayed by addressing 14 modifiable risk factors, including impaired vision. 

The report’s authors recommend that vision-loss screening and treatment be universally available. But are these recommendations warranted? What is the evidence? What is the potential mechanism? And what are the potential implications for clinical practice? 

Worldwide, the prevalence of avoidable vision loss and blindness in adults aged 50 years or older is estimated to hover around 13%.

“There is now overwhelming evidence that vision impairment in later life is associated with more rapid cognitive decline and an increased risk of dementia,” said Joshua Ehrlich, MD, MPH, associate professor in ophthalmology and visual sciences, the Institute for Social Research at the University of Michigan, Ann Arbor. 

The evidence includes a meta-analysis of 14 prospective cohort studies with roughly 6.2 million older adults who were cognitively intact at baseline. Over the course of up to 14 years, 171,888 developed dementia. Vision loss was associated with a pooled relative risk (RR) for dementia of 1.47. 

A separate meta-analysis also identified an increased risk for dementia (RR, 1.38) with visual loss. When broken down into different eye conditions, an increased dementia risk was associated with cataracts and diabetic retinopathy but not with glaucoma or age-related macular degeneration.

A US study that followed roughly 3000 older adults with cataracts and normal cognition at baseline for more than 20 years found that those who had cataract extraction had significantly reduced risk for dementia compared with those who did not have cataract extraction (hazard ratio, 0.71), after controlling for age, race, APOE genotype, education, smoking, and an extensive list of comorbidities. 
 

Causation or Coincidence?

The mechanisms behind these associations might be related to underlying illness, such as diabetes, which is a risk factor for dementia; vision loss itself, as might be suggested by a possible effect of cataract surgery; or shared neuropathologic processes in the retina and the brain. 

A longitudinal study from Korea that included roughly 6 million adults showed that dementia risk increased with severity of visual loss, which supports the hypothesis that vision loss in itself might be causal or that there is a dose-response effect to a shared causal factor. 

“Work is still needed to sort out” exactly how visual deficits may raise dementia risk, although several hypotheses exist, Dr. Ehrlich said. 

For example, “decreased input to the brain via the visual pathways may directly induce brain changes. Also, consequences of vision loss, like social isolation, physical inactivity, and depression, are themselves risk factors for dementia and may explain the pathways through which vision impairment increases risk,” he said. 

Is the link causal? “We’ll never know definitively because we can’t randomize people to not get cataract surgery versus getting cataract surgery, because we know that improving vision improves quality of life, so we’d never want to do that. But the new evidence that’s come in over the last 5 years or so is pretty promising,” said Esme Fuller-Thomson, PhD, director of the Institute for Life Course and Aging and professor, Department of Family and Community Medicine and Faculty of Nursing, at the University of Toronto, Ontario, Canada.

She noted that results of two studies that have looked at this “seem to indicate that those who have cataract surgery are not nearly at as high risk of dementia as those who have cataracts but don’t have the surgery. That’s leaning towards causality.”

A study published in July suggests that cataracts increase dementia risk through vascular and non–Alzheimer’s disease mechanisms. 
 

Clear Clinical Implications 

Dr. Ehrlich said that evidence for an association between untreated vision loss and dementia risk and potential modification by treatment has clear implications for care. 

“Loss of vision impacts so many aspects of people’s lives beyond just how they see the world and losing vision in later life is not a normal part of aging. Thus, when older adults experience vision loss, this should be a cause for concern and prompt an immediate referral to an eye care professional,” he noted. 

Dr. Fuller-Thomson agrees. “Addressing vision loss will certainly help people see better and function at a higher level and improve quality of life, and it seems probable that it might decrease dementia risk so it’s a win-win,” she said.

In her own research, Dr. Fuller-Thomson has found that the combination of hearing loss and vision loss is linked to an eightfold increased risk for cognitive impairment.

“The idea is that vision and/or hearing loss makes it harder for you to be physically active, to be socially engaged, to be mentally stimulated. They are equally important in terms of social isolation, which could lead to loneliness, and we know that loneliness is not good for dementia,” she said.

“With dual sensory impairment, you don’t have as much information coming in — your brain is not engaged as much — and having an engaged brain, doing hobbies, having intellectually stimulating conversation, all of those are factors are associated with lowering risk of dementia,” Dr. Fuller-Thomson said.

The latest Lancet Commission report noted that treatment for visual loss is “effective and cost-effective” for an estimated 90% of people. However, across the world, particularly in low- and middle-income countries, visual loss often goes untreated. 

“A clear opportunity for dementia prevention exists with treatment of visual loss,” the report concluded.

Dr. Ehrlich and Dr. Fuller-Thomson have no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

In 2019, 57 million people worldwide were living with dementia, a figure expected to soar to 153 million by 2050. A recent Lancet Commission report suggests that nearly half of dementia cases could be prevented or delayed by addressing 14 modifiable risk factors, including impaired vision. 

The report’s authors recommend that vision-loss screening and treatment be universally available. But are these recommendations warranted? What is the evidence? What is the potential mechanism? And what are the potential implications for clinical practice? 

Worldwide, the prevalence of avoidable vision loss and blindness in adults aged 50 years or older is estimated to hover around 13%.

“There is now overwhelming evidence that vision impairment in later life is associated with more rapid cognitive decline and an increased risk of dementia,” said Joshua Ehrlich, MD, MPH, associate professor in ophthalmology and visual sciences, the Institute for Social Research at the University of Michigan, Ann Arbor. 

The evidence includes a meta-analysis of 14 prospective cohort studies with roughly 6.2 million older adults who were cognitively intact at baseline. Over the course of up to 14 years, 171,888 developed dementia. Vision loss was associated with a pooled relative risk (RR) for dementia of 1.47. 

A separate meta-analysis also identified an increased risk for dementia (RR, 1.38) with visual loss. When broken down into different eye conditions, an increased dementia risk was associated with cataracts and diabetic retinopathy but not with glaucoma or age-related macular degeneration.

A US study that followed roughly 3000 older adults with cataracts and normal cognition at baseline for more than 20 years found that those who had cataract extraction had significantly reduced risk for dementia compared with those who did not have cataract extraction (hazard ratio, 0.71), after controlling for age, race, APOE genotype, education, smoking, and an extensive list of comorbidities. 
 

Causation or Coincidence?

The mechanisms behind these associations might be related to underlying illness, such as diabetes, which is a risk factor for dementia; vision loss itself, as might be suggested by a possible effect of cataract surgery; or shared neuropathologic processes in the retina and the brain. 

A longitudinal study from Korea that included roughly 6 million adults showed that dementia risk increased with severity of visual loss, which supports the hypothesis that vision loss in itself might be causal or that there is a dose-response effect to a shared causal factor. 

“Work is still needed to sort out” exactly how visual deficits may raise dementia risk, although several hypotheses exist, Dr. Ehrlich said. 

For example, “decreased input to the brain via the visual pathways may directly induce brain changes. Also, consequences of vision loss, like social isolation, physical inactivity, and depression, are themselves risk factors for dementia and may explain the pathways through which vision impairment increases risk,” he said. 

Is the link causal? “We’ll never know definitively because we can’t randomize people to not get cataract surgery versus getting cataract surgery, because we know that improving vision improves quality of life, so we’d never want to do that. But the new evidence that’s come in over the last 5 years or so is pretty promising,” said Esme Fuller-Thomson, PhD, director of the Institute for Life Course and Aging and professor, Department of Family and Community Medicine and Faculty of Nursing, at the University of Toronto, Ontario, Canada.

She noted that results of two studies that have looked at this “seem to indicate that those who have cataract surgery are not nearly at as high risk of dementia as those who have cataracts but don’t have the surgery. That’s leaning towards causality.”

A study published in July suggests that cataracts increase dementia risk through vascular and non–Alzheimer’s disease mechanisms. 
 

Clear Clinical Implications 

Dr. Ehrlich said that evidence for an association between untreated vision loss and dementia risk and potential modification by treatment has clear implications for care. 

“Loss of vision impacts so many aspects of people’s lives beyond just how they see the world and losing vision in later life is not a normal part of aging. Thus, when older adults experience vision loss, this should be a cause for concern and prompt an immediate referral to an eye care professional,” he noted. 

Dr. Fuller-Thomson agrees. “Addressing vision loss will certainly help people see better and function at a higher level and improve quality of life, and it seems probable that it might decrease dementia risk so it’s a win-win,” she said.

In her own research, Dr. Fuller-Thomson has found that the combination of hearing loss and vision loss is linked to an eightfold increased risk for cognitive impairment.

“The idea is that vision and/or hearing loss makes it harder for you to be physically active, to be socially engaged, to be mentally stimulated. They are equally important in terms of social isolation, which could lead to loneliness, and we know that loneliness is not good for dementia,” she said.

“With dual sensory impairment, you don’t have as much information coming in — your brain is not engaged as much — and having an engaged brain, doing hobbies, having intellectually stimulating conversation, all of those are factors are associated with lowering risk of dementia,” Dr. Fuller-Thomson said.

The latest Lancet Commission report noted that treatment for visual loss is “effective and cost-effective” for an estimated 90% of people. However, across the world, particularly in low- and middle-income countries, visual loss often goes untreated. 

“A clear opportunity for dementia prevention exists with treatment of visual loss,” the report concluded.

Dr. Ehrlich and Dr. Fuller-Thomson have no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

In 2019, 57 million people worldwide were living with dementia, a figure expected to soar to 153 million by 2050. A recent Lancet Commission report suggests that nearly half of dementia cases could be prevented or delayed by addressing 14 modifiable risk factors, including impaired vision. 

The report’s authors recommend that vision-loss screening and treatment be universally available. But are these recommendations warranted? What is the evidence? What is the potential mechanism? And what are the potential implications for clinical practice? 

Worldwide, the prevalence of avoidable vision loss and blindness in adults aged 50 years or older is estimated to hover around 13%.

“There is now overwhelming evidence that vision impairment in later life is associated with more rapid cognitive decline and an increased risk of dementia,” said Joshua Ehrlich, MD, MPH, associate professor in ophthalmology and visual sciences, the Institute for Social Research at the University of Michigan, Ann Arbor. 

The evidence includes a meta-analysis of 14 prospective cohort studies with roughly 6.2 million older adults who were cognitively intact at baseline. Over the course of up to 14 years, 171,888 developed dementia. Vision loss was associated with a pooled relative risk (RR) for dementia of 1.47. 

A separate meta-analysis also identified an increased risk for dementia (RR, 1.38) with visual loss. When broken down into different eye conditions, an increased dementia risk was associated with cataracts and diabetic retinopathy but not with glaucoma or age-related macular degeneration.

A US study that followed roughly 3000 older adults with cataracts and normal cognition at baseline for more than 20 years found that those who had cataract extraction had significantly reduced risk for dementia compared with those who did not have cataract extraction (hazard ratio, 0.71), after controlling for age, race, APOE genotype, education, smoking, and an extensive list of comorbidities. 
 

Causation or Coincidence?

The mechanisms behind these associations might be related to underlying illness, such as diabetes, which is a risk factor for dementia; vision loss itself, as might be suggested by a possible effect of cataract surgery; or shared neuropathologic processes in the retina and the brain. 

A longitudinal study from Korea that included roughly 6 million adults showed that dementia risk increased with severity of visual loss, which supports the hypothesis that vision loss in itself might be causal or that there is a dose-response effect to a shared causal factor. 

“Work is still needed to sort out” exactly how visual deficits may raise dementia risk, although several hypotheses exist, Dr. Ehrlich said. 

For example, “decreased input to the brain via the visual pathways may directly induce brain changes. Also, consequences of vision loss, like social isolation, physical inactivity, and depression, are themselves risk factors for dementia and may explain the pathways through which vision impairment increases risk,” he said. 

Is the link causal? “We’ll never know definitively because we can’t randomize people to not get cataract surgery versus getting cataract surgery, because we know that improving vision improves quality of life, so we’d never want to do that. But the new evidence that’s come in over the last 5 years or so is pretty promising,” said Esme Fuller-Thomson, PhD, director of the Institute for Life Course and Aging and professor, Department of Family and Community Medicine and Faculty of Nursing, at the University of Toronto, Ontario, Canada.

She noted that results of two studies that have looked at this “seem to indicate that those who have cataract surgery are not nearly at as high risk of dementia as those who have cataracts but don’t have the surgery. That’s leaning towards causality.”

A study published in July suggests that cataracts increase dementia risk through vascular and non–Alzheimer’s disease mechanisms. 
 

Clear Clinical Implications 

Dr. Ehrlich said that evidence for an association between untreated vision loss and dementia risk and potential modification by treatment has clear implications for care. 

“Loss of vision impacts so many aspects of people’s lives beyond just how they see the world and losing vision in later life is not a normal part of aging. Thus, when older adults experience vision loss, this should be a cause for concern and prompt an immediate referral to an eye care professional,” he noted. 

Dr. Fuller-Thomson agrees. “Addressing vision loss will certainly help people see better and function at a higher level and improve quality of life, and it seems probable that it might decrease dementia risk so it’s a win-win,” she said.

In her own research, Dr. Fuller-Thomson has found that the combination of hearing loss and vision loss is linked to an eightfold increased risk for cognitive impairment.

“The idea is that vision and/or hearing loss makes it harder for you to be physically active, to be socially engaged, to be mentally stimulated. They are equally important in terms of social isolation, which could lead to loneliness, and we know that loneliness is not good for dementia,” she said.

“With dual sensory impairment, you don’t have as much information coming in — your brain is not engaged as much — and having an engaged brain, doing hobbies, having intellectually stimulating conversation, all of those are factors are associated with lowering risk of dementia,” Dr. Fuller-Thomson said.

The latest Lancet Commission report noted that treatment for visual loss is “effective and cost-effective” for an estimated 90% of people. However, across the world, particularly in low- and middle-income countries, visual loss often goes untreated. 

“A clear opportunity for dementia prevention exists with treatment of visual loss,” the report concluded.

Dr. Ehrlich and Dr. Fuller-Thomson have no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

At least 25% of unresponsive patients with a disorder of consciousness show signs of brain activity, an estimate that is higher than previous studies suggest.

“We found that at least 1 in 4 patients who are unresponsive to commands might actually be quite present and highly cognitive,” said study investigator Nicholas D. Schiff, MD, Feil Family Brain & Mind Research Institute and Department of Neurology, Weill Cornell Medicine, Rockefeller University Hospital, New York.

“In other words, if you go to the bedside and carefully examine someone with a severe brain injury and find no evidence of responsiveness, no one has been able to give you an a priori number to say how likely you are to be wrong in thinking this person is actually unaware, not processing language, and not capable of high-level cognitive work. And the answer to that now is at least 1 in 4 times.”

The findings were published online in The New England Journal of Medicine.
 

Clinical Implications? 

Cognitive motor dissociation (CMD) is a condition whereby patients with a severe brain injury who are unresponsive to commands at the bedside show brain activity on functional MRI (fMRI) or electroencephalography (EEG) when presented with selective motor imagery commands, such as “imagine playing tennis,” or “ imagine opening and closing your hand.”

Previous research shows that CMD is present in 10%-20% of people with a disorder of consciousness, a rate similar to that in patients with acute or chronic brain injury.

Understanding that a patient who appears unconscious has signs of cognitive processing could change the way clinicians and family interact with such individuals. Unresponsive patients who are aware may eventually be able to harness emerging communication technologies such as brain-computer interfaces.

In addition, knowing an individual’s CMD status could aid in prognosis. “We know from one study that there’s a four times increased likelihood that patients will be independent in a year in their function if they have cognitive motor dissociation,” said Dr. Schiff.

Unlike most previous studies of CMD, which were conducted at single sites and had relatively small cohorts, this new study included 353 adults with a disorder of consciousness (mean age, 37.9 years; 64% male) at six multinational sites.

Participants were recruited using a variety of methods, including consecutive enrollment of critically ill patients in the intensive care unit and enrollment of those with chronic illness or injury who were in the postacute phase of brain injury.
 

Response to Commands

Study participants were at different stages of recovery from an acute brain injury that had occurred an average of 8 months before the study started.

To determine the presence or absence of an observable response to commands among participants, trained staff used the Coma Recovery Scale–Revised (CRS-R); scores on this instrument range from 0 to 23, and higher scores indicate better neurobehavioral function.

About 40% of individuals were diagnosed with coma or vegetative state, 29% with minimally conscious state–minus, and 22% with minimally conscious state–plus. In all, 10% had emerged from a minimally conscious state.

Researchers assessed response to timed and repeated commands using fMRI or EEG in participants without an observable response to verbal commands, including those with a behavioral diagnosis of coma, vegetative state, or minimally conscious state–minus, and in participants with an observable response to verbal commands.

Of the 353 study participants, 61% underwent at least one fMRI assessment and 74% at least one EEG assessment. Both fMRI and EEG were performed in 35% of participants.

Dr. Schiff explained the two assessment types provide slightly different information, in that they measuring different types of brain signals. He also noted that although “every medical center in the world” has EEG, many do not have fMRI.

The brain imaging assessments captured brain activity within the motor area of the frontal cortex when tasked with motor imagery.

Of the 241 participants deemed to be in a coma or vegetative state or minimally conscious state–minus on the basis of CRS-R score, 60 (25%) had a response to commands on task-based fMRI, task-based EEG, or both.

The percentage of participants with CMD varied across study sites, from 2% to 45%, but Dr. Schiff said the reason for this is unclear. 

The proportion of participants with CMD may have been even higher if all individuals had been assessed with both imaging techniques, he said.
 

Higher Rate of Awareness Than in Previous Research

The investigators noted that the percentage of participants with CMD in their study was up to 10 percentage points higher than in previous studies. This may be due to the multimodal approach that classified participants undergoing assessment with both fMRI and EEG on the basis of responses on either technique, they said. 

The median age was lower among participants with CMD than those without CMD (30.5 years vs 45.3 years).

Compared with participants without CMD, a higher percentage of those with such dissociation had brain trauma as an etiologic factor (65% vs 38%) and a diagnosis of minimally conscious state–minus on the CRS-R (53% vs 38%).

Among people with CMD, 18% were assessed with fMRI only, 22% with EEG only, and 60% with both fMRI and EEG.

Dr. Schiff noted that the use of both fMRI and EEG appears to be more sensitive in detecting brain activity during tasks compared with use of one of these techniques alone.

Of the 112 participants with a diagnosis of minimally conscious state–plus or who had emerged from the minimally conscious state, 38% had a response to commands on task-based fMRI, task-based EEG, or both. Among these participants, 23% were assessed with fMRI only, 19% with EEG only, and 58% with both fMRI and EEG.

Research shows “it’s very clear that people with severe brain injury continue to get better over time,” noted Dr. Schiff. “Every month and week matters, and so it probably is the case that a lot of these patients are picking up the level of recovery, and the later we go out to measure them, the more likely we are to find people who are CMD than not.”

These new results should prompt further study to explore whether detection of CMD can lead to improved outcomes, the investigators noted. “In addition, the standardization, validation, and simplification of task-based fMRI and EEG methods that are used to detect cognitive motor dissociation are needed to prompt widespread clinical integration of these techniques and investigation of the bioethical implications of the findings.”

All study participants with chronic brain injury had survived their initial illness or injury and had access to a research facility with advanced fMRI and EEG capabilities. “This survival bias may reflect greater cognitive reserve and resilience over time among the participants. As such, the results of our study may not be generalizable to the overall population of patients with cognitive motor dissociation,” the investigators wrote.

Another study limitation was that participating sites used heterogeneous strategies to acquire, analyze, and interpret data, which led to differences in the number, type, and ordering of the cognitive tasks assessed on fMRI and EEG.

“These differences, along with variations in recruitment strategies and participant characteristics, may have contributed to the unequal percentage of participants with cognitive motor dissociation observed at each site. Our findings may therefore not be generalizable across all centers,” the researchers wrote. 

Only a few academic medical centers have the specially trained personnel and techniques needed to assess patients for CMD — which, the researchers noted, limits the feasibility of performing these assessments in general practice.
 

Challenging Research

Commenting on the research, Aarti Sarwal, MD, professor of neurology and section chief, Neurocritical Care, Virginia Commonwealth University, Richmond, Virginia, noted that this was a “very challenging” study to perform, given that only a few academic centers are equipped to perform both fMRI and quantitative EEG analysis.

“In general, finding patients this far out, who have access to clinical, radiological, and electrophysiological testing and were provided good care enough to receive these, is a mammoth task in itself.” 

Dr. Sarwal said the study builds on efforts of the Curing Coma campaign , a clinical, scientific, and public health effort of the Neurocritical Care Society to tackle the concept of coma as a treatable medical entity.

“It continues to highlight the challenges of prognostication in acute brain injured patients by showing a higher presence of cognitive function than previously perceived,” she said.

Dr. Sarwal believes that the study’s largest impact is underscoring the need for more research into understanding the degree and quality of cognitive processing in patients with a disorder of consciousness. But it also underlines the need for a “healthy debate” on the cost/benefit analysis of pursuing such research, given the limited number of patients with access to resources. 

“This debate needs to include the caregivers and families outside the traditional realms of stakeholders overseeing the science.” 

Although communication with comatose patients is still “a ways away,” this research is “a step in the right direction,” said Dr. Sarwal. 

The study was funded by the James S. McDonnell Foundation and others. Dr. Schiff and Dr. Sarwal report no relevant financial disclosures.
 

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

At least 25% of unresponsive patients with a disorder of consciousness show signs of brain activity, an estimate that is higher than previous studies suggest.

“We found that at least 1 in 4 patients who are unresponsive to commands might actually be quite present and highly cognitive,” said study investigator Nicholas D. Schiff, MD, Feil Family Brain & Mind Research Institute and Department of Neurology, Weill Cornell Medicine, Rockefeller University Hospital, New York.

“In other words, if you go to the bedside and carefully examine someone with a severe brain injury and find no evidence of responsiveness, no one has been able to give you an a priori number to say how likely you are to be wrong in thinking this person is actually unaware, not processing language, and not capable of high-level cognitive work. And the answer to that now is at least 1 in 4 times.”

The findings were published online in The New England Journal of Medicine.
 

Clinical Implications? 

Cognitive motor dissociation (CMD) is a condition whereby patients with a severe brain injury who are unresponsive to commands at the bedside show brain activity on functional MRI (fMRI) or electroencephalography (EEG) when presented with selective motor imagery commands, such as “imagine playing tennis,” or “ imagine opening and closing your hand.”

Previous research shows that CMD is present in 10%-20% of people with a disorder of consciousness, a rate similar to that in patients with acute or chronic brain injury.

Understanding that a patient who appears unconscious has signs of cognitive processing could change the way clinicians and family interact with such individuals. Unresponsive patients who are aware may eventually be able to harness emerging communication technologies such as brain-computer interfaces.

In addition, knowing an individual’s CMD status could aid in prognosis. “We know from one study that there’s a four times increased likelihood that patients will be independent in a year in their function if they have cognitive motor dissociation,” said Dr. Schiff.

Unlike most previous studies of CMD, which were conducted at single sites and had relatively small cohorts, this new study included 353 adults with a disorder of consciousness (mean age, 37.9 years; 64% male) at six multinational sites.

Participants were recruited using a variety of methods, including consecutive enrollment of critically ill patients in the intensive care unit and enrollment of those with chronic illness or injury who were in the postacute phase of brain injury.
 

Response to Commands

Study participants were at different stages of recovery from an acute brain injury that had occurred an average of 8 months before the study started.

To determine the presence or absence of an observable response to commands among participants, trained staff used the Coma Recovery Scale–Revised (CRS-R); scores on this instrument range from 0 to 23, and higher scores indicate better neurobehavioral function.

About 40% of individuals were diagnosed with coma or vegetative state, 29% with minimally conscious state–minus, and 22% with minimally conscious state–plus. In all, 10% had emerged from a minimally conscious state.

Researchers assessed response to timed and repeated commands using fMRI or EEG in participants without an observable response to verbal commands, including those with a behavioral diagnosis of coma, vegetative state, or minimally conscious state–minus, and in participants with an observable response to verbal commands.

Of the 353 study participants, 61% underwent at least one fMRI assessment and 74% at least one EEG assessment. Both fMRI and EEG were performed in 35% of participants.

Dr. Schiff explained the two assessment types provide slightly different information, in that they measuring different types of brain signals. He also noted that although “every medical center in the world” has EEG, many do not have fMRI.

The brain imaging assessments captured brain activity within the motor area of the frontal cortex when tasked with motor imagery.

Of the 241 participants deemed to be in a coma or vegetative state or minimally conscious state–minus on the basis of CRS-R score, 60 (25%) had a response to commands on task-based fMRI, task-based EEG, or both.

The percentage of participants with CMD varied across study sites, from 2% to 45%, but Dr. Schiff said the reason for this is unclear. 

The proportion of participants with CMD may have been even higher if all individuals had been assessed with both imaging techniques, he said.
 

Higher Rate of Awareness Than in Previous Research

The investigators noted that the percentage of participants with CMD in their study was up to 10 percentage points higher than in previous studies. This may be due to the multimodal approach that classified participants undergoing assessment with both fMRI and EEG on the basis of responses on either technique, they said. 

The median age was lower among participants with CMD than those without CMD (30.5 years vs 45.3 years).

Compared with participants without CMD, a higher percentage of those with such dissociation had brain trauma as an etiologic factor (65% vs 38%) and a diagnosis of minimally conscious state–minus on the CRS-R (53% vs 38%).

Among people with CMD, 18% were assessed with fMRI only, 22% with EEG only, and 60% with both fMRI and EEG.

Dr. Schiff noted that the use of both fMRI and EEG appears to be more sensitive in detecting brain activity during tasks compared with use of one of these techniques alone.

Of the 112 participants with a diagnosis of minimally conscious state–plus or who had emerged from the minimally conscious state, 38% had a response to commands on task-based fMRI, task-based EEG, or both. Among these participants, 23% were assessed with fMRI only, 19% with EEG only, and 58% with both fMRI and EEG.

Research shows “it’s very clear that people with severe brain injury continue to get better over time,” noted Dr. Schiff. “Every month and week matters, and so it probably is the case that a lot of these patients are picking up the level of recovery, and the later we go out to measure them, the more likely we are to find people who are CMD than not.”

These new results should prompt further study to explore whether detection of CMD can lead to improved outcomes, the investigators noted. “In addition, the standardization, validation, and simplification of task-based fMRI and EEG methods that are used to detect cognitive motor dissociation are needed to prompt widespread clinical integration of these techniques and investigation of the bioethical implications of the findings.”

All study participants with chronic brain injury had survived their initial illness or injury and had access to a research facility with advanced fMRI and EEG capabilities. “This survival bias may reflect greater cognitive reserve and resilience over time among the participants. As such, the results of our study may not be generalizable to the overall population of patients with cognitive motor dissociation,” the investigators wrote.

Another study limitation was that participating sites used heterogeneous strategies to acquire, analyze, and interpret data, which led to differences in the number, type, and ordering of the cognitive tasks assessed on fMRI and EEG.

“These differences, along with variations in recruitment strategies and participant characteristics, may have contributed to the unequal percentage of participants with cognitive motor dissociation observed at each site. Our findings may therefore not be generalizable across all centers,” the researchers wrote. 

Only a few academic medical centers have the specially trained personnel and techniques needed to assess patients for CMD — which, the researchers noted, limits the feasibility of performing these assessments in general practice.
 

Challenging Research

Commenting on the research, Aarti Sarwal, MD, professor of neurology and section chief, Neurocritical Care, Virginia Commonwealth University, Richmond, Virginia, noted that this was a “very challenging” study to perform, given that only a few academic centers are equipped to perform both fMRI and quantitative EEG analysis.

“In general, finding patients this far out, who have access to clinical, radiological, and electrophysiological testing and were provided good care enough to receive these, is a mammoth task in itself.” 

Dr. Sarwal said the study builds on efforts of the Curing Coma campaign , a clinical, scientific, and public health effort of the Neurocritical Care Society to tackle the concept of coma as a treatable medical entity.

“It continues to highlight the challenges of prognostication in acute brain injured patients by showing a higher presence of cognitive function than previously perceived,” she said.

Dr. Sarwal believes that the study’s largest impact is underscoring the need for more research into understanding the degree and quality of cognitive processing in patients with a disorder of consciousness. But it also underlines the need for a “healthy debate” on the cost/benefit analysis of pursuing such research, given the limited number of patients with access to resources. 

“This debate needs to include the caregivers and families outside the traditional realms of stakeholders overseeing the science.” 

Although communication with comatose patients is still “a ways away,” this research is “a step in the right direction,” said Dr. Sarwal. 

The study was funded by the James S. McDonnell Foundation and others. Dr. Schiff and Dr. Sarwal report no relevant financial disclosures.
 

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

At least 25% of unresponsive patients with a disorder of consciousness show signs of brain activity, an estimate that is higher than previous studies suggest.

“We found that at least 1 in 4 patients who are unresponsive to commands might actually be quite present and highly cognitive,” said study investigator Nicholas D. Schiff, MD, Feil Family Brain & Mind Research Institute and Department of Neurology, Weill Cornell Medicine, Rockefeller University Hospital, New York.

“In other words, if you go to the bedside and carefully examine someone with a severe brain injury and find no evidence of responsiveness, no one has been able to give you an a priori number to say how likely you are to be wrong in thinking this person is actually unaware, not processing language, and not capable of high-level cognitive work. And the answer to that now is at least 1 in 4 times.”

The findings were published online in The New England Journal of Medicine.
 

Clinical Implications? 

Cognitive motor dissociation (CMD) is a condition whereby patients with a severe brain injury who are unresponsive to commands at the bedside show brain activity on functional MRI (fMRI) or electroencephalography (EEG) when presented with selective motor imagery commands, such as “imagine playing tennis,” or “ imagine opening and closing your hand.”

Previous research shows that CMD is present in 10%-20% of people with a disorder of consciousness, a rate similar to that in patients with acute or chronic brain injury.

Understanding that a patient who appears unconscious has signs of cognitive processing could change the way clinicians and family interact with such individuals. Unresponsive patients who are aware may eventually be able to harness emerging communication technologies such as brain-computer interfaces.

In addition, knowing an individual’s CMD status could aid in prognosis. “We know from one study that there’s a four times increased likelihood that patients will be independent in a year in their function if they have cognitive motor dissociation,” said Dr. Schiff.

Unlike most previous studies of CMD, which were conducted at single sites and had relatively small cohorts, this new study included 353 adults with a disorder of consciousness (mean age, 37.9 years; 64% male) at six multinational sites.

Participants were recruited using a variety of methods, including consecutive enrollment of critically ill patients in the intensive care unit and enrollment of those with chronic illness or injury who were in the postacute phase of brain injury.
 

Response to Commands

Study participants were at different stages of recovery from an acute brain injury that had occurred an average of 8 months before the study started.

To determine the presence or absence of an observable response to commands among participants, trained staff used the Coma Recovery Scale–Revised (CRS-R); scores on this instrument range from 0 to 23, and higher scores indicate better neurobehavioral function.

About 40% of individuals were diagnosed with coma or vegetative state, 29% with minimally conscious state–minus, and 22% with minimally conscious state–plus. In all, 10% had emerged from a minimally conscious state.

Researchers assessed response to timed and repeated commands using fMRI or EEG in participants without an observable response to verbal commands, including those with a behavioral diagnosis of coma, vegetative state, or minimally conscious state–minus, and in participants with an observable response to verbal commands.

Of the 353 study participants, 61% underwent at least one fMRI assessment and 74% at least one EEG assessment. Both fMRI and EEG were performed in 35% of participants.

Dr. Schiff explained the two assessment types provide slightly different information, in that they measuring different types of brain signals. He also noted that although “every medical center in the world” has EEG, many do not have fMRI.

The brain imaging assessments captured brain activity within the motor area of the frontal cortex when tasked with motor imagery.

Of the 241 participants deemed to be in a coma or vegetative state or minimally conscious state–minus on the basis of CRS-R score, 60 (25%) had a response to commands on task-based fMRI, task-based EEG, or both.

The percentage of participants with CMD varied across study sites, from 2% to 45%, but Dr. Schiff said the reason for this is unclear. 

The proportion of participants with CMD may have been even higher if all individuals had been assessed with both imaging techniques, he said.
 

Higher Rate of Awareness Than in Previous Research

The investigators noted that the percentage of participants with CMD in their study was up to 10 percentage points higher than in previous studies. This may be due to the multimodal approach that classified participants undergoing assessment with both fMRI and EEG on the basis of responses on either technique, they said. 

The median age was lower among participants with CMD than those without CMD (30.5 years vs 45.3 years).

Compared with participants without CMD, a higher percentage of those with such dissociation had brain trauma as an etiologic factor (65% vs 38%) and a diagnosis of minimally conscious state–minus on the CRS-R (53% vs 38%).

Among people with CMD, 18% were assessed with fMRI only, 22% with EEG only, and 60% with both fMRI and EEG.

Dr. Schiff noted that the use of both fMRI and EEG appears to be more sensitive in detecting brain activity during tasks compared with use of one of these techniques alone.

Of the 112 participants with a diagnosis of minimally conscious state–plus or who had emerged from the minimally conscious state, 38% had a response to commands on task-based fMRI, task-based EEG, or both. Among these participants, 23% were assessed with fMRI only, 19% with EEG only, and 58% with both fMRI and EEG.

Research shows “it’s very clear that people with severe brain injury continue to get better over time,” noted Dr. Schiff. “Every month and week matters, and so it probably is the case that a lot of these patients are picking up the level of recovery, and the later we go out to measure them, the more likely we are to find people who are CMD than not.”

These new results should prompt further study to explore whether detection of CMD can lead to improved outcomes, the investigators noted. “In addition, the standardization, validation, and simplification of task-based fMRI and EEG methods that are used to detect cognitive motor dissociation are needed to prompt widespread clinical integration of these techniques and investigation of the bioethical implications of the findings.”

All study participants with chronic brain injury had survived their initial illness or injury and had access to a research facility with advanced fMRI and EEG capabilities. “This survival bias may reflect greater cognitive reserve and resilience over time among the participants. As such, the results of our study may not be generalizable to the overall population of patients with cognitive motor dissociation,” the investigators wrote.

Another study limitation was that participating sites used heterogeneous strategies to acquire, analyze, and interpret data, which led to differences in the number, type, and ordering of the cognitive tasks assessed on fMRI and EEG.

“These differences, along with variations in recruitment strategies and participant characteristics, may have contributed to the unequal percentage of participants with cognitive motor dissociation observed at each site. Our findings may therefore not be generalizable across all centers,” the researchers wrote. 

Only a few academic medical centers have the specially trained personnel and techniques needed to assess patients for CMD — which, the researchers noted, limits the feasibility of performing these assessments in general practice.
 

Challenging Research

Commenting on the research, Aarti Sarwal, MD, professor of neurology and section chief, Neurocritical Care, Virginia Commonwealth University, Richmond, Virginia, noted that this was a “very challenging” study to perform, given that only a few academic centers are equipped to perform both fMRI and quantitative EEG analysis.

“In general, finding patients this far out, who have access to clinical, radiological, and electrophysiological testing and were provided good care enough to receive these, is a mammoth task in itself.” 

Dr. Sarwal said the study builds on efforts of the Curing Coma campaign , a clinical, scientific, and public health effort of the Neurocritical Care Society to tackle the concept of coma as a treatable medical entity.

“It continues to highlight the challenges of prognostication in acute brain injured patients by showing a higher presence of cognitive function than previously perceived,” she said.

Dr. Sarwal believes that the study’s largest impact is underscoring the need for more research into understanding the degree and quality of cognitive processing in patients with a disorder of consciousness. But it also underlines the need for a “healthy debate” on the cost/benefit analysis of pursuing such research, given the limited number of patients with access to resources. 

“This debate needs to include the caregivers and families outside the traditional realms of stakeholders overseeing the science.” 

Although communication with comatose patients is still “a ways away,” this research is “a step in the right direction,” said Dr. Sarwal. 

The study was funded by the James S. McDonnell Foundation and others. Dr. Schiff and Dr. Sarwal report no relevant financial disclosures.
 

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

A new report on the preventability of dementia is both exciting and paradigm-shifting. The new study, published in The Lancet by the Lancet Commission on Dementia, estimates that close to 50% of cases of dementia worldwide can be prevented or delayed by improving 14 modifiable risk factors. 

This is paradigm-shifting because dementia is often perceived as an inevitable consequence of the aging process, with a major genetic component. But this study suggests that modifying these risk factors can benefit everyone, irrespective of genetic risk, and that it’s important to have a life-course approach. It’s never too early or too late to start to modify these factors. 

We’ve known for a long time that many chronic diseases are highly preventable and modifiable. Some that come to mind are type 2 diabetes, coronary heart disease, and even certain forms of cancer. Modifiable risk factors include cigarette smoking, diet, physical activity, and maintaining a healthy weight. This study suggests that many of the same risk factors and more are relevant to reducing risk for dementia. 

Let’s go through the risk factors, many of which are behavioral. These risk factors include lifestyle factors such as lack of physical activity, cigarette smoking, excessive alcohol consumption, and obesity. The cardiovascular or vascular-specific risk factors include not only those behavioral factors but also hypertension, high LDL cholesterol, and diabetes. Cognitive engagement–specific risk factors include social isolation, which is a major risk factor for dementia, as well as untreated hearing or vision loss, which can exacerbate social isolation and depression, and low educational attainment, which can be related to less cognitive engagement.

They also mention traumatic brain injury from an accident or contact sports without head protection as a risk factor, and the environmental risk factor of air pollution or poor air quality. 

Two of these risk factors are new since the previous report in 2020: elevated LDL cholesterol and untreated vision loss, both of which are quite treatable. Overall, these findings suggest that a lot can be done to lower dementia risk, but it requires individual behavior modifications as well as a comprehensive approach with involvement of the healthcare system for improved screening, access, and public policy to reduce air pollution.

Some of these risk factors are more relevant to women, especially the social isolation that is so common later in life in women. In the United States, close to two out of three patients with dementia are women.

So, informing our patients about these risk factors and what can be done in terms of behavior modification, increased screening, and treatment for these conditions can go a long way in helping our patients reduce their risk for dementia.
 

Dr. Manson is professor of medicine and the Michael and Lee Bell Professor of Women’s Health, Harvard Medical School, chief, Division of Preventive Medicine, Brigham and Women’s Hospital, Boston, and past president, North American Menopause Society, 2011-2012. She disclosed receiving study pill donation and infrastructure support from Mars Symbioscience (for the COSMOS trial).

A version of this article appeared on Medscape.com.

A new report on the preventability of dementia is both exciting and paradigm-shifting. The new study, published in The Lancet by the Lancet Commission on Dementia, estimates that close to 50% of cases of dementia worldwide can be prevented or delayed by improving 14 modifiable risk factors. 

This is paradigm-shifting because dementia is often perceived as an inevitable consequence of the aging process, with a major genetic component. But this study suggests that modifying these risk factors can benefit everyone, irrespective of genetic risk, and that it’s important to have a life-course approach. It’s never too early or too late to start to modify these factors. 

We’ve known for a long time that many chronic diseases are highly preventable and modifiable. Some that come to mind are type 2 diabetes, coronary heart disease, and even certain forms of cancer. Modifiable risk factors include cigarette smoking, diet, physical activity, and maintaining a healthy weight. This study suggests that many of the same risk factors and more are relevant to reducing risk for dementia. 

Let’s go through the risk factors, many of which are behavioral. These risk factors include lifestyle factors such as lack of physical activity, cigarette smoking, excessive alcohol consumption, and obesity. The cardiovascular or vascular-specific risk factors include not only those behavioral factors but also hypertension, high LDL cholesterol, and diabetes. Cognitive engagement–specific risk factors include social isolation, which is a major risk factor for dementia, as well as untreated hearing or vision loss, which can exacerbate social isolation and depression, and low educational attainment, which can be related to less cognitive engagement.

They also mention traumatic brain injury from an accident or contact sports without head protection as a risk factor, and the environmental risk factor of air pollution or poor air quality. 

Two of these risk factors are new since the previous report in 2020: elevated LDL cholesterol and untreated vision loss, both of which are quite treatable. Overall, these findings suggest that a lot can be done to lower dementia risk, but it requires individual behavior modifications as well as a comprehensive approach with involvement of the healthcare system for improved screening, access, and public policy to reduce air pollution.

Some of these risk factors are more relevant to women, especially the social isolation that is so common later in life in women. In the United States, close to two out of three patients with dementia are women.

So, informing our patients about these risk factors and what can be done in terms of behavior modification, increased screening, and treatment for these conditions can go a long way in helping our patients reduce their risk for dementia.
 

Dr. Manson is professor of medicine and the Michael and Lee Bell Professor of Women’s Health, Harvard Medical School, chief, Division of Preventive Medicine, Brigham and Women’s Hospital, Boston, and past president, North American Menopause Society, 2011-2012. She disclosed receiving study pill donation and infrastructure support from Mars Symbioscience (for the COSMOS trial).

A version of this article appeared on Medscape.com.

A new report on the preventability of dementia is both exciting and paradigm-shifting. The new study, published in The Lancet by the Lancet Commission on Dementia, estimates that close to 50% of cases of dementia worldwide can be prevented or delayed by improving 14 modifiable risk factors. 

This is paradigm-shifting because dementia is often perceived as an inevitable consequence of the aging process, with a major genetic component. But this study suggests that modifying these risk factors can benefit everyone, irrespective of genetic risk, and that it’s important to have a life-course approach. It’s never too early or too late to start to modify these factors. 

We’ve known for a long time that many chronic diseases are highly preventable and modifiable. Some that come to mind are type 2 diabetes, coronary heart disease, and even certain forms of cancer. Modifiable risk factors include cigarette smoking, diet, physical activity, and maintaining a healthy weight. This study suggests that many of the same risk factors and more are relevant to reducing risk for dementia. 

Let’s go through the risk factors, many of which are behavioral. These risk factors include lifestyle factors such as lack of physical activity, cigarette smoking, excessive alcohol consumption, and obesity. The cardiovascular or vascular-specific risk factors include not only those behavioral factors but also hypertension, high LDL cholesterol, and diabetes. Cognitive engagement–specific risk factors include social isolation, which is a major risk factor for dementia, as well as untreated hearing or vision loss, which can exacerbate social isolation and depression, and low educational attainment, which can be related to less cognitive engagement.

They also mention traumatic brain injury from an accident or contact sports without head protection as a risk factor, and the environmental risk factor of air pollution or poor air quality. 

Two of these risk factors are new since the previous report in 2020: elevated LDL cholesterol and untreated vision loss, both of which are quite treatable. Overall, these findings suggest that a lot can be done to lower dementia risk, but it requires individual behavior modifications as well as a comprehensive approach with involvement of the healthcare system for improved screening, access, and public policy to reduce air pollution.

Some of these risk factors are more relevant to women, especially the social isolation that is so common later in life in women. In the United States, close to two out of three patients with dementia are women.

So, informing our patients about these risk factors and what can be done in terms of behavior modification, increased screening, and treatment for these conditions can go a long way in helping our patients reduce their risk for dementia.
 

Dr. Manson is professor of medicine and the Michael and Lee Bell Professor of Women’s Health, Harvard Medical School, chief, Division of Preventive Medicine, Brigham and Women’s Hospital, Boston, and past president, North American Menopause Society, 2011-2012. She disclosed receiving study pill donation and infrastructure support from Mars Symbioscience (for the COSMOS trial).

A version of this article appeared on Medscape.com.

Once again, America is deeply divided before a national election, with people on each side convinced of the horrors that will be visited upon us if the other side wins. 

’Tis the season — and regrettably, not to be jolly but to be worried.

As a neuroscientist, I am especially aware of the deleterious mental and physical impact of chronic worry on our citizenry. That’s because worry is not “all in your head.” Chronic mild stress drives a panoply of negative changes in your body and brain that add to your risk for physical and neurologic troubles. We modern humans live in a world of worry which appears to be progressively growing.
 

Flight or Fight

Worry stems from the brain’s rather remarkable ability to foresee and reflexively respond to threat. Our “fight or flight” brain machinery probably arose in our vertebrate ancestors more than 300 million years ago. The fact that we have machinery akin to that possessed by lizards or tigers or shrews is testimony to its crucial contribution to our species’ survival.

As the phrase “fight or flight” suggests, a brain that senses trouble immediately biases certain body and brain functions. As it shifts into a higher-alert mode, it increases the energy supplies in our blood and supports other changes that facilitate faster and stronger reactions, while it shuts down less essential processes which do not contribute to hiding, fighting, or running like hell.

This hyperreactive response is initiated in the amygdala in the anterior brain, which identifies “what’s happening” as immediately or potentially threatening. The now-activated amygdala generates a response in the hypothalamus that provokes an immediate increase of adrenaline and cortisol in the body, and cortisol and noradrenaline in the brain. Both sharply speed up our physical and neurologic reactivity. In the brain, that is achieved by increasing the level of excitability of neurons across the forebrain. Depending on the perceived level of threat, an excitable brain will be just a little or a lot more “on alert,” just a little or a lot faster to respond, and just a little or a lot better at remembering the specific “warning” events that trigger this lizard-brain response. 

Alas, this machinery was designed to be engaged every so often when a potentially dangerous surprise arises in life. When the worry and stress are persistent, the brain experiences a kind of neurologic “burn-out” of its fight versus flight machinery.
 

Dangers of Nonstop Anxiety and Stress

A consistently stressed-out brain turns down its production and release of noradrenaline, and the brain becomes less attentive, less engaged. This sets the brain on the path to an anxiety (and then a depressive) disorder, and, in the longer term, to cognitive losses in memory and executive control systems, and to emotional distortions that can lead to substance abuse or other addictions.

Our political distress is but one source of persistent worry and stress. Worry is a modern plague. The head counts of individuals seeking psychiatric or psychological health are at an all-time high in the United States. Near-universal low-level stressors, such as 2 years of COVID, insecurities about the changing demands of our professional and private lives, and a deeply divided body politic are unequivocally affecting American brain health.

The brain also collaborates in our body’s response to stress. Its regulation of hormonal responses and its autonomic nervous system’s mediated responses contribute to elevated blood sugar levels, to craving high-sugar foods, to elevated blood pressure, and to weaker immune responses. This all contributes to higher risks for cardiovascular and other dietary- and immune system–related disease. And ultimately, to shorter lifespans.
 

Strategies to Address Neurologic Changes Arising From Chronic Stress

There are many things you can try to bring your worry back to a manageable (and even productive) level.

• Engage in a “reset” strategy several times a day to bring your amygdala and locus coeruleus back under control. It takes a minute (or five) of calm, positive meditation to take your brain to a happy, optimistic place. Or use a mindfulness exercise to quiet down that overactive amygdala.
• Talk to people. Keeping your worries to yourself can compound them. Hashing through your concerns with a family member, friend, professional coach, or therapist can help put them in perspective and may allow you to come up with strategies to identify and neurologically respond to your sources of stress.
• Exercise, both physically and mentally. Do what works for you, whether it’s a run, a long walk, pumping iron, playing racquetball — anything that promotes physical release. Exercise your brain too. Engage in a project or activity that is mentally demanding. Personally, I like to garden and do online brain exercises. There’s nothing quite like yanking out weeds or hitting a new personal best at a cognitive exercise for me to notch a sense of accomplishment to counterbalance the unresolved issues driving my worry.
• Accept the uncertainty. Life is full of uncertainty. To paraphrase from Yale theologian Reinhold Niebuhr’s “Serenity Prayer”: Have the serenity to accept what you cannot help, the courage to change what you can, and the wisdom to recognize one from the other.

And, please, be assured that you’ll make it through this election season.

Dr. Merzenich, professor emeritus, Department of Neuroscience, University of California San Francisco, disclosed ties with Posit Science. He is often credited with discovering lifelong plasticity, with being the first to harness plasticity for human benefit (in his co-invention of the cochlear implant), and for pioneering the field of plasticity-based computerized brain exercise. He is a Kavli Laureate in Neuroscience, and he has been honored by each of the US National Academies of Sciences, Engineering, and Medicine. He may be most widely known for a series of specials on the brain on public television. His current focus is  BrainHQ, a brain exercise app.

A version of this article appeared on Medscape.com.

Once again, America is deeply divided before a national election, with people on each side convinced of the horrors that will be visited upon us if the other side wins. 

’Tis the season — and regrettably, not to be jolly but to be worried.

As a neuroscientist, I am especially aware of the deleterious mental and physical impact of chronic worry on our citizenry. That’s because worry is not “all in your head.” Chronic mild stress drives a panoply of negative changes in your body and brain that add to your risk for physical and neurologic troubles. We modern humans live in a world of worry which appears to be progressively growing.
 

Flight or Fight

Worry stems from the brain’s rather remarkable ability to foresee and reflexively respond to threat. Our “fight or flight” brain machinery probably arose in our vertebrate ancestors more than 300 million years ago. The fact that we have machinery akin to that possessed by lizards or tigers or shrews is testimony to its crucial contribution to our species’ survival.

As the phrase “fight or flight” suggests, a brain that senses trouble immediately biases certain body and brain functions. As it shifts into a higher-alert mode, it increases the energy supplies in our blood and supports other changes that facilitate faster and stronger reactions, while it shuts down less essential processes which do not contribute to hiding, fighting, or running like hell.

This hyperreactive response is initiated in the amygdala in the anterior brain, which identifies “what’s happening” as immediately or potentially threatening. The now-activated amygdala generates a response in the hypothalamus that provokes an immediate increase of adrenaline and cortisol in the body, and cortisol and noradrenaline in the brain. Both sharply speed up our physical and neurologic reactivity. In the brain, that is achieved by increasing the level of excitability of neurons across the forebrain. Depending on the perceived level of threat, an excitable brain will be just a little or a lot more “on alert,” just a little or a lot faster to respond, and just a little or a lot better at remembering the specific “warning” events that trigger this lizard-brain response. 

Alas, this machinery was designed to be engaged every so often when a potentially dangerous surprise arises in life. When the worry and stress are persistent, the brain experiences a kind of neurologic “burn-out” of its fight versus flight machinery.
 

Dangers of Nonstop Anxiety and Stress

A consistently stressed-out brain turns down its production and release of noradrenaline, and the brain becomes less attentive, less engaged. This sets the brain on the path to an anxiety (and then a depressive) disorder, and, in the longer term, to cognitive losses in memory and executive control systems, and to emotional distortions that can lead to substance abuse or other addictions.

Our political distress is but one source of persistent worry and stress. Worry is a modern plague. The head counts of individuals seeking psychiatric or psychological health are at an all-time high in the United States. Near-universal low-level stressors, such as 2 years of COVID, insecurities about the changing demands of our professional and private lives, and a deeply divided body politic are unequivocally affecting American brain health.

The brain also collaborates in our body’s response to stress. Its regulation of hormonal responses and its autonomic nervous system’s mediated responses contribute to elevated blood sugar levels, to craving high-sugar foods, to elevated blood pressure, and to weaker immune responses. This all contributes to higher risks for cardiovascular and other dietary- and immune system–related disease. And ultimately, to shorter lifespans.
 

Strategies to Address Neurologic Changes Arising From Chronic Stress

There are many things you can try to bring your worry back to a manageable (and even productive) level.

• Engage in a “reset” strategy several times a day to bring your amygdala and locus coeruleus back under control. It takes a minute (or five) of calm, positive meditation to take your brain to a happy, optimistic place. Or use a mindfulness exercise to quiet down that overactive amygdala.
• Talk to people. Keeping your worries to yourself can compound them. Hashing through your concerns with a family member, friend, professional coach, or therapist can help put them in perspective and may allow you to come up with strategies to identify and neurologically respond to your sources of stress.
• Exercise, both physically and mentally. Do what works for you, whether it’s a run, a long walk, pumping iron, playing racquetball — anything that promotes physical release. Exercise your brain too. Engage in a project or activity that is mentally demanding. Personally, I like to garden and do online brain exercises. There’s nothing quite like yanking out weeds or hitting a new personal best at a cognitive exercise for me to notch a sense of accomplishment to counterbalance the unresolved issues driving my worry.
• Accept the uncertainty. Life is full of uncertainty. To paraphrase from Yale theologian Reinhold Niebuhr’s “Serenity Prayer”: Have the serenity to accept what you cannot help, the courage to change what you can, and the wisdom to recognize one from the other.

And, please, be assured that you’ll make it through this election season.

Dr. Merzenich, professor emeritus, Department of Neuroscience, University of California San Francisco, disclosed ties with Posit Science. He is often credited with discovering lifelong plasticity, with being the first to harness plasticity for human benefit (in his co-invention of the cochlear implant), and for pioneering the field of plasticity-based computerized brain exercise. He is a Kavli Laureate in Neuroscience, and he has been honored by each of the US National Academies of Sciences, Engineering, and Medicine. He may be most widely known for a series of specials on the brain on public television. His current focus is  BrainHQ, a brain exercise app.

A version of this article appeared on Medscape.com.

Once again, America is deeply divided before a national election, with people on each side convinced of the horrors that will be visited upon us if the other side wins. 

’Tis the season — and regrettably, not to be jolly but to be worried.

As a neuroscientist, I am especially aware of the deleterious mental and physical impact of chronic worry on our citizenry. That’s because worry is not “all in your head.” Chronic mild stress drives a panoply of negative changes in your body and brain that add to your risk for physical and neurologic troubles. We modern humans live in a world of worry which appears to be progressively growing.
 

Flight or Fight

Worry stems from the brain’s rather remarkable ability to foresee and reflexively respond to threat. Our “fight or flight” brain machinery probably arose in our vertebrate ancestors more than 300 million years ago. The fact that we have machinery akin to that possessed by lizards or tigers or shrews is testimony to its crucial contribution to our species’ survival.

As the phrase “fight or flight” suggests, a brain that senses trouble immediately biases certain body and brain functions. As it shifts into a higher-alert mode, it increases the energy supplies in our blood and supports other changes that facilitate faster and stronger reactions, while it shuts down less essential processes which do not contribute to hiding, fighting, or running like hell.

This hyperreactive response is initiated in the amygdala in the anterior brain, which identifies “what’s happening” as immediately or potentially threatening. The now-activated amygdala generates a response in the hypothalamus that provokes an immediate increase of adrenaline and cortisol in the body, and cortisol and noradrenaline in the brain. Both sharply speed up our physical and neurologic reactivity. In the brain, that is achieved by increasing the level of excitability of neurons across the forebrain. Depending on the perceived level of threat, an excitable brain will be just a little or a lot more “on alert,” just a little or a lot faster to respond, and just a little or a lot better at remembering the specific “warning” events that trigger this lizard-brain response. 

Alas, this machinery was designed to be engaged every so often when a potentially dangerous surprise arises in life. When the worry and stress are persistent, the brain experiences a kind of neurologic “burn-out” of its fight versus flight machinery.
 

Dangers of Nonstop Anxiety and Stress

A consistently stressed-out brain turns down its production and release of noradrenaline, and the brain becomes less attentive, less engaged. This sets the brain on the path to an anxiety (and then a depressive) disorder, and, in the longer term, to cognitive losses in memory and executive control systems, and to emotional distortions that can lead to substance abuse or other addictions.

Our political distress is but one source of persistent worry and stress. Worry is a modern plague. The head counts of individuals seeking psychiatric or psychological health are at an all-time high in the United States. Near-universal low-level stressors, such as 2 years of COVID, insecurities about the changing demands of our professional and private lives, and a deeply divided body politic are unequivocally affecting American brain health.

The brain also collaborates in our body’s response to stress. Its regulation of hormonal responses and its autonomic nervous system’s mediated responses contribute to elevated blood sugar levels, to craving high-sugar foods, to elevated blood pressure, and to weaker immune responses. This all contributes to higher risks for cardiovascular and other dietary- and immune system–related disease. And ultimately, to shorter lifespans.
 

Strategies to Address Neurologic Changes Arising From Chronic Stress

There are many things you can try to bring your worry back to a manageable (and even productive) level.

• Engage in a “reset” strategy several times a day to bring your amygdala and locus coeruleus back under control. It takes a minute (or five) of calm, positive meditation to take your brain to a happy, optimistic place. Or use a mindfulness exercise to quiet down that overactive amygdala.
• Talk to people. Keeping your worries to yourself can compound them. Hashing through your concerns with a family member, friend, professional coach, or therapist can help put them in perspective and may allow you to come up with strategies to identify and neurologically respond to your sources of stress.
• Exercise, both physically and mentally. Do what works for you, whether it’s a run, a long walk, pumping iron, playing racquetball — anything that promotes physical release. Exercise your brain too. Engage in a project or activity that is mentally demanding. Personally, I like to garden and do online brain exercises. There’s nothing quite like yanking out weeds or hitting a new personal best at a cognitive exercise for me to notch a sense of accomplishment to counterbalance the unresolved issues driving my worry.
• Accept the uncertainty. Life is full of uncertainty. To paraphrase from Yale theologian Reinhold Niebuhr’s “Serenity Prayer”: Have the serenity to accept what you cannot help, the courage to change what you can, and the wisdom to recognize one from the other.

And, please, be assured that you’ll make it through this election season.

Dr. Merzenich, professor emeritus, Department of Neuroscience, University of California San Francisco, disclosed ties with Posit Science. He is often credited with discovering lifelong plasticity, with being the first to harness plasticity for human benefit (in his co-invention of the cochlear implant), and for pioneering the field of plasticity-based computerized brain exercise. He is a Kavli Laureate in Neuroscience, and he has been honored by each of the US National Academies of Sciences, Engineering, and Medicine. He may be most widely known for a series of specials on the brain on public television. His current focus is  BrainHQ, a brain exercise app.

A version of this article appeared on Medscape.com.

TOPLINE:

Both chronic and new-onset anxiety are linked to a threefold increased risk for dementia onset in later life, new research shows.

METHODOLOGY:

• A total of 2132 participants aged 55-85 years (mean age, 76 years) were recruited from the Hunter Community Study. Of these, 53% were women.
• Participants were assessed over three different waves, 5 years apart. Demographic and health-related data were captured at wave 1.
• Researchers used the Kessler Psychological Distress Scale (K10) to measure anxiety at two points: Baseline (wave 1) and first follow-up (wave 2), with a 5-year interval between them. Anxiety was classified as chronic if present during both waves, resolved if only present at wave 1, and new if only appearing at wave 2.
• The primary outcome, incident all-cause dementia, during the follow-up period (maximum 13 years after baseline) was identified using the International Classification of Disease-10 codes.

TAKEAWAY:

• Out of 2132 cognitively healthy participants, 64 developed dementia, with an average time to diagnosis of 10 years. Chronic anxiety was linked to a 2.8-fold increased risk for dementia, while new-onset anxiety was associated with a 3.2-fold increased risk (P = .01).
• Participants younger than 70 years with chronic anxiety had a 4.6-fold increased risk for dementia (P = .03), and those with new-onset anxiety had a 7.2 times higher risk for dementia (P = .004).
• There was no significant risk for dementia in participants with anxiety that had resolved.
• Investigators speculated that individuals with anxiety were more likely to engage in unhealthy lifestyle behaviors, such as poor diet and smoking, which can lead to cardiovascular disease — a condition strongly associated with dementia.

IN PRACTICE: 

“This prospective cohort study used causal inference methods to explore the role of anxiety in promoting the development of dementia,” lead author Kay Khaing, MMed, The University of Newcastle, Australia, wrote in a press release. “The findings suggest that anxiety may be a new risk factor to target in the prevention of dementia and also indicate that treating anxiety may reduce this risk.”

SOURCE: 

Kay Khaing, MMed, of The University of Newcastle, Australia, led the study, which was published online in the Journal of the American Geriatrics Society.

LIMITATIONS: 

Anxiety was measured using K10, which assessed symptoms experienced in the most recent 4 weeks, raising concerns about its accuracy over the entire observation period. The authors acknowledged that despite using a combination of the total K10 score and the anxiety subscale, the overlap of anxiety and depression might not be fully disentangled, leading to residual confounding by depression. Additionally, 33% of participants were lost to follow-up, and those lost had higher anxiety rates at baseline, potentially leading to missing cases of dementia and affecting the effect estimate.

DISCLOSURES: 

This study did not report any funding or conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article appeared on Medscape.com.

TOPLINE:

Both chronic and new-onset anxiety are linked to a threefold increased risk for dementia onset in later life, new research shows.

METHODOLOGY:

• A total of 2132 participants aged 55-85 years (mean age, 76 years) were recruited from the Hunter Community Study. Of these, 53% were women.
• Participants were assessed over three different waves, 5 years apart. Demographic and health-related data were captured at wave 1.
• Researchers used the Kessler Psychological Distress Scale (K10) to measure anxiety at two points: Baseline (wave 1) and first follow-up (wave 2), with a 5-year interval between them. Anxiety was classified as chronic if present during both waves, resolved if only present at wave 1, and new if only appearing at wave 2.
• The primary outcome, incident all-cause dementia, during the follow-up period (maximum 13 years after baseline) was identified using the International Classification of Disease-10 codes.

TAKEAWAY:

• Out of 2132 cognitively healthy participants, 64 developed dementia, with an average time to diagnosis of 10 years. Chronic anxiety was linked to a 2.8-fold increased risk for dementia, while new-onset anxiety was associated with a 3.2-fold increased risk (P = .01).
• Participants younger than 70 years with chronic anxiety had a 4.6-fold increased risk for dementia (P = .03), and those with new-onset anxiety had a 7.2 times higher risk for dementia (P = .004).
• There was no significant risk for dementia in participants with anxiety that had resolved.
• Investigators speculated that individuals with anxiety were more likely to engage in unhealthy lifestyle behaviors, such as poor diet and smoking, which can lead to cardiovascular disease — a condition strongly associated with dementia.

IN PRACTICE: 

“This prospective cohort study used causal inference methods to explore the role of anxiety in promoting the development of dementia,” lead author Kay Khaing, MMed, The University of Newcastle, Australia, wrote in a press release. “The findings suggest that anxiety may be a new risk factor to target in the prevention of dementia and also indicate that treating anxiety may reduce this risk.”

SOURCE: 

Kay Khaing, MMed, of The University of Newcastle, Australia, led the study, which was published online in the Journal of the American Geriatrics Society.

LIMITATIONS: 

Anxiety was measured using K10, which assessed symptoms experienced in the most recent 4 weeks, raising concerns about its accuracy over the entire observation period. The authors acknowledged that despite using a combination of the total K10 score and the anxiety subscale, the overlap of anxiety and depression might not be fully disentangled, leading to residual confounding by depression. Additionally, 33% of participants were lost to follow-up, and those lost had higher anxiety rates at baseline, potentially leading to missing cases of dementia and affecting the effect estimate.

DISCLOSURES: 

This study did not report any funding or conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article appeared on Medscape.com.

TOPLINE:

Both chronic and new-onset anxiety are linked to a threefold increased risk for dementia onset in later life, new research shows.

METHODOLOGY:

• A total of 2132 participants aged 55-85 years (mean age, 76 years) were recruited from the Hunter Community Study. Of these, 53% were women.
• Participants were assessed over three different waves, 5 years apart. Demographic and health-related data were captured at wave 1.
• Researchers used the Kessler Psychological Distress Scale (K10) to measure anxiety at two points: Baseline (wave 1) and first follow-up (wave 2), with a 5-year interval between them. Anxiety was classified as chronic if present during both waves, resolved if only present at wave 1, and new if only appearing at wave 2.
• The primary outcome, incident all-cause dementia, during the follow-up period (maximum 13 years after baseline) was identified using the International Classification of Disease-10 codes.

TAKEAWAY:

• Out of 2132 cognitively healthy participants, 64 developed dementia, with an average time to diagnosis of 10 years. Chronic anxiety was linked to a 2.8-fold increased risk for dementia, while new-onset anxiety was associated with a 3.2-fold increased risk (P = .01).
• Participants younger than 70 years with chronic anxiety had a 4.6-fold increased risk for dementia (P = .03), and those with new-onset anxiety had a 7.2 times higher risk for dementia (P = .004).
• There was no significant risk for dementia in participants with anxiety that had resolved.
• Investigators speculated that individuals with anxiety were more likely to engage in unhealthy lifestyle behaviors, such as poor diet and smoking, which can lead to cardiovascular disease — a condition strongly associated with dementia.

IN PRACTICE: 

“This prospective cohort study used causal inference methods to explore the role of anxiety in promoting the development of dementia,” lead author Kay Khaing, MMed, The University of Newcastle, Australia, wrote in a press release. “The findings suggest that anxiety may be a new risk factor to target in the prevention of dementia and also indicate that treating anxiety may reduce this risk.”

SOURCE: 

Kay Khaing, MMed, of The University of Newcastle, Australia, led the study, which was published online in the Journal of the American Geriatrics Society.

LIMITATIONS: 

Anxiety was measured using K10, which assessed symptoms experienced in the most recent 4 weeks, raising concerns about its accuracy over the entire observation period. The authors acknowledged that despite using a combination of the total K10 score and the anxiety subscale, the overlap of anxiety and depression might not be fully disentangled, leading to residual confounding by depression. Additionally, 33% of participants were lost to follow-up, and those lost had higher anxiety rates at baseline, potentially leading to missing cases of dementia and affecting the effect estimate.

DISCLOSURES: 

This study did not report any funding or conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article appeared on Medscape.com.