Alzheimer's & Cognition

Medicare has received a key endorsement of its plan to restrict payment for the controversial Alzheimer’s disease (AD) drug aducanumab (Aduhelm) – but also drew pleas from other groups for more generous reimbursement of the drug, as well as expected similar medications currently in development.

The Centers for Medicare & Medicaid Services received more than 9,900 comments on its plan, according to the current tally posted on its website. However, it is unclear when the final count will be available.

CMS intends to limit federal payment for monoclonal antibodies that target amyloid to clinical trials. Among supporters of this approach is the influential Medicare Payment Advisory Commission, an expert panel that helps Congress and CMS manage the federal health program.

Opponents of the CMS plan include several pharmaceutical companies. Patient and consumer groups, individuals, and lawmakers had mixed views.

CMS officials will weigh the feedback provided in the comments when setting a final coverage policy for aducanumab. It is expected the agency’s final decision will be announced on April 11.
 

Ongoing debate

The comments submitted to CMS reflect ongoing debate about whether the evidence proves aducanumab provides significant clinical benefit.

The Food and Drug Administration’s unusual approach to clearing the drug for U.S. sales triggered a review of its management of the accelerated approval process by the Office of Inspector General for the Department of Health & Human Services.

The FDA granted an accelerated approval for aducanumab in June based on evidence that the drug clears amyloid in the brain. However, it is unclear whether clearing the protein from the brain results in clinical benefit.

Usually, accelerated approvals precede the completion of phase 3 drug trials, with the FDA allowing early access to a medicine while awaiting confirmatory trials.

In the case of aducanumab, results of the phase 3 confirmatory trials ENGAGE and EMERGE were available at the time of FDA approval. However, interpretation of the findings is controversial.

Biogen contends that the amyloid-clearing effect of the higher dose of aducanumab shown in EMERGE indicates the drug has clinical potential. However, others argue that amyloid clearance does not indicate clinical benefit.

Limiting Medicare coverage of aducanumab for treatment of AD means “the progression of disease, for nearly all beneficiaries, would continue unabated,” Biogen wrote in its comment to CMS.
 

Conflicting data

Supporters of the CMS plan have a different view of the trial data. They note the failure of aducanumab in the companion ENGAGE trial, while also questioning the magnitude of benefit suggested by even the most positive data cited for the drug in the EMERGE trial.

Both studies used the Clinical Dementia Rating-Sum of Boxes (CDR-SB) score, an 18-point scale measuring cognition and function.

In his comment to CMS, MedPAC chairman Michael E. Chernew, PhD, noted the change in CDR-SB score of 0.39 in EMERGE’s high-dose aducanumab group. CMS has described this as being “less than the 1-2 point change that has been suggested as a minimal clinically important difference,” Dr. Chernew wrote.

MedPAC does not normally comment on Medicare coverage decisions, but did so in this case because of its significance and because of the potential fiscal implications, he noted.

“Though there is only limited, conflicting data on Aduhelm’s clinical effectiveness, Medicare would pay a high price for the product,” Dr. Chernew wrote, pointing out the $28,200 annual U.S. price of the drug.

MedPAC thus endorsed the coverage-with-evidence-development (CED) pathway. Under this approach, Medicare would pay for these drugs when used in clinical trials that meet certain criteria.
 

Legal challenge?

In its comment to CMS, Biogen questioned the agency’s legal grounds for limiting coverage of aducanumab. A mandate on clinical trials as part of the CED proposal “runs afoul of the Administrative Procedure Act’s prohibition against arbitrary and capricious agency action,” Biogen said.

The drug company argued that its own planned follow-on studies would provide the kind of data Medicare officials want to see. It also argued for greater use of observational data, including real-world evidence, and of information from Medicare claims.

Roche’s Genentech, which is also developing antiamyloid drugs for AD, echoed some of Biogen’s concerns about the aducanumab plan.

CMS’ CED plan would be “unnecessarily restrictive and discouraging for patients living with this destructive disease,” David Burt, executive director for federal government affairs at Genentech, wrote in a comment to CMS.

CMS should clarify that the CED requirement would not apply to cases of FDA-approved antiamyloid therapies that have demonstrated “clinically meaningful improvement,” Mr. Burt added. He noted there are phase 3 trials of drugs in this class that could soon produce data.

CMS should “fully consider the broad ramifications and significant unintended consequences of prematurely placing unduly severe restrictions on the entire class of antiamyloid monoclonal antibodies,” Mr. Burt wrote.
 

Health care inequity

In its comment to CMS, Biogen also noted the Medicare proposal would “compound the already pervasive inequities in access to treatment and will ultimately prove highly detrimental to health equity.”

There are already concerns about the access of Black and Latinx patients to clinical trials. The planned CED approach would tightly restrict access to aducanumab, as well as expected follow-ons in the amyloid-directed monoclonal antibody (mAb) drug class, the company said.

“Many of the trial sites for Aduhelm, as well as for other amyloid-directed [monoclonal antibodies] are not hospital-based outpatient settings, but include infusion centers, private practices, and medical research centers,” Biogen wrote.

Patient groups such as UsAgainstAlzheimer’s told CMS the CED approach would worsen disparities, despite the aim of Medicare officials to increase participation of Black and Latinx patients in future testing.

“CMS will be hard-pressed to achieve diversity if such hospitals are the only locations where Medicare beneficiaries are able to access mAbs,” USAgainstAlzheimer’s wrote in a Feb. 10 comment.

In contrast, the nonprofit National Center for Health Research praised CMS for what it described as an effort to address a lack of representation of Black and Latinx patients in earlier aducanumab research.

However, the NCHR also suggested CMS revise its plan to mandate that clinical trials include patients who are representative of the national population diagnosed with AD.

“Rather than being concerned about the percentage of patients in specific racial and ethnic groups, we propose that CMS include sufficient numbers of patients in different racial, ethnic, and age groups to ensure that there is enough statistical power for subgroup analyses to determine safety and efficacy for each of the major demographic groups,” the NCHR wrote.
 

Patient health, Medicare at risk

On Feb. 8, a group of House Republican lawmakers asked CMS to reverse its stance. In a publicly released letter, Rep. Cathy McMorris Rodgers of Washington state, the ranking Republican on the House Energy and Commerce Committee, and colleagues urged broader coverage of aducanumab.

In the letter, the group emphasized the idea of aducanumab as a potential treatment for patients with Down syndrome who are at risk for AD.

“The link between Down Syndrome and AD is still being researched by scientists,” Rep. Rodgers and colleagues wrote.

“However, there appears to be a correlation between the additional 21st chromosome present in people with Down Syndrome and the chromosome’s gene that makes amyloid precursor proteins and can cause a build-up of the beta-amyloid plaques common amongst those with AD,” they add.

On the other hand, CMS garnered earlier support from influential Democrats. On Jan. 13, House Energy and Commerce Chairman Frank Pallone Jr (D-N.J.) and House Oversight and Reform Chairwoman Carolyn B. Maloney (D-N.Y.) released a letter praising CMS for its plan for covering aducanumab.

In addition to the HHS-OIG review of the FDA’s approval of the drug, the two House committees are in the midst of their own investigation of the agency’s decision to clear the drug.

“Any broader coverage determination before there is clarity on Aduhelm’s approval process and findings from the myriad ongoing investigations may put the health of millions of Alzheimer’s patients on the line and the financial stability of the nation’s health insurance program for American seniors at risk,” Rep. Pallone and Rep. Maloney wrote.

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

Medicare has received a key endorsement of its plan to restrict payment for the controversial Alzheimer’s disease (AD) drug aducanumab (Aduhelm) – but also drew pleas from other groups for more generous reimbursement of the drug, as well as expected similar medications currently in development.

The Centers for Medicare & Medicaid Services received more than 9,900 comments on its plan, according to the current tally posted on its website. However, it is unclear when the final count will be available.

CMS intends to limit federal payment for monoclonal antibodies that target amyloid to clinical trials. Among supporters of this approach is the influential Medicare Payment Advisory Commission, an expert panel that helps Congress and CMS manage the federal health program.

Opponents of the CMS plan include several pharmaceutical companies. Patient and consumer groups, individuals, and lawmakers had mixed views.

CMS officials will weigh the feedback provided in the comments when setting a final coverage policy for aducanumab. It is expected the agency’s final decision will be announced on April 11.
 

Ongoing debate

The comments submitted to CMS reflect ongoing debate about whether the evidence proves aducanumab provides significant clinical benefit.

The Food and Drug Administration’s unusual approach to clearing the drug for U.S. sales triggered a review of its management of the accelerated approval process by the Office of Inspector General for the Department of Health & Human Services.

The FDA granted an accelerated approval for aducanumab in June based on evidence that the drug clears amyloid in the brain. However, it is unclear whether clearing the protein from the brain results in clinical benefit.

Usually, accelerated approvals precede the completion of phase 3 drug trials, with the FDA allowing early access to a medicine while awaiting confirmatory trials.

In the case of aducanumab, results of the phase 3 confirmatory trials ENGAGE and EMERGE were available at the time of FDA approval. However, interpretation of the findings is controversial.

Biogen contends that the amyloid-clearing effect of the higher dose of aducanumab shown in EMERGE indicates the drug has clinical potential. However, others argue that amyloid clearance does not indicate clinical benefit.

Limiting Medicare coverage of aducanumab for treatment of AD means “the progression of disease, for nearly all beneficiaries, would continue unabated,” Biogen wrote in its comment to CMS.
 

Conflicting data

Supporters of the CMS plan have a different view of the trial data. They note the failure of aducanumab in the companion ENGAGE trial, while also questioning the magnitude of benefit suggested by even the most positive data cited for the drug in the EMERGE trial.

Both studies used the Clinical Dementia Rating-Sum of Boxes (CDR-SB) score, an 18-point scale measuring cognition and function.

In his comment to CMS, MedPAC chairman Michael E. Chernew, PhD, noted the change in CDR-SB score of 0.39 in EMERGE’s high-dose aducanumab group. CMS has described this as being “less than the 1-2 point change that has been suggested as a minimal clinically important difference,” Dr. Chernew wrote.

MedPAC does not normally comment on Medicare coverage decisions, but did so in this case because of its significance and because of the potential fiscal implications, he noted.

“Though there is only limited, conflicting data on Aduhelm’s clinical effectiveness, Medicare would pay a high price for the product,” Dr. Chernew wrote, pointing out the $28,200 annual U.S. price of the drug.

MedPAC thus endorsed the coverage-with-evidence-development (CED) pathway. Under this approach, Medicare would pay for these drugs when used in clinical trials that meet certain criteria.
 

Legal challenge?

In its comment to CMS, Biogen questioned the agency’s legal grounds for limiting coverage of aducanumab. A mandate on clinical trials as part of the CED proposal “runs afoul of the Administrative Procedure Act’s prohibition against arbitrary and capricious agency action,” Biogen said.

The drug company argued that its own planned follow-on studies would provide the kind of data Medicare officials want to see. It also argued for greater use of observational data, including real-world evidence, and of information from Medicare claims.

Roche’s Genentech, which is also developing antiamyloid drugs for AD, echoed some of Biogen’s concerns about the aducanumab plan.

CMS’ CED plan would be “unnecessarily restrictive and discouraging for patients living with this destructive disease,” David Burt, executive director for federal government affairs at Genentech, wrote in a comment to CMS.

CMS should clarify that the CED requirement would not apply to cases of FDA-approved antiamyloid therapies that have demonstrated “clinically meaningful improvement,” Mr. Burt added. He noted there are phase 3 trials of drugs in this class that could soon produce data.

CMS should “fully consider the broad ramifications and significant unintended consequences of prematurely placing unduly severe restrictions on the entire class of antiamyloid monoclonal antibodies,” Mr. Burt wrote.
 

Health care inequity

In its comment to CMS, Biogen also noted the Medicare proposal would “compound the already pervasive inequities in access to treatment and will ultimately prove highly detrimental to health equity.”

There are already concerns about the access of Black and Latinx patients to clinical trials. The planned CED approach would tightly restrict access to aducanumab, as well as expected follow-ons in the amyloid-directed monoclonal antibody (mAb) drug class, the company said.

“Many of the trial sites for Aduhelm, as well as for other amyloid-directed [monoclonal antibodies] are not hospital-based outpatient settings, but include infusion centers, private practices, and medical research centers,” Biogen wrote.

Patient groups such as UsAgainstAlzheimer’s told CMS the CED approach would worsen disparities, despite the aim of Medicare officials to increase participation of Black and Latinx patients in future testing.

“CMS will be hard-pressed to achieve diversity if such hospitals are the only locations where Medicare beneficiaries are able to access mAbs,” USAgainstAlzheimer’s wrote in a Feb. 10 comment.

In contrast, the nonprofit National Center for Health Research praised CMS for what it described as an effort to address a lack of representation of Black and Latinx patients in earlier aducanumab research.

However, the NCHR also suggested CMS revise its plan to mandate that clinical trials include patients who are representative of the national population diagnosed with AD.

“Rather than being concerned about the percentage of patients in specific racial and ethnic groups, we propose that CMS include sufficient numbers of patients in different racial, ethnic, and age groups to ensure that there is enough statistical power for subgroup analyses to determine safety and efficacy for each of the major demographic groups,” the NCHR wrote.
 

Patient health, Medicare at risk

On Feb. 8, a group of House Republican lawmakers asked CMS to reverse its stance. In a publicly released letter, Rep. Cathy McMorris Rodgers of Washington state, the ranking Republican on the House Energy and Commerce Committee, and colleagues urged broader coverage of aducanumab.

In the letter, the group emphasized the idea of aducanumab as a potential treatment for patients with Down syndrome who are at risk for AD.

“The link between Down Syndrome and AD is still being researched by scientists,” Rep. Rodgers and colleagues wrote.

“However, there appears to be a correlation between the additional 21st chromosome present in people with Down Syndrome and the chromosome’s gene that makes amyloid precursor proteins and can cause a build-up of the beta-amyloid plaques common amongst those with AD,” they add.

On the other hand, CMS garnered earlier support from influential Democrats. On Jan. 13, House Energy and Commerce Chairman Frank Pallone Jr (D-N.J.) and House Oversight and Reform Chairwoman Carolyn B. Maloney (D-N.Y.) released a letter praising CMS for its plan for covering aducanumab.

In addition to the HHS-OIG review of the FDA’s approval of the drug, the two House committees are in the midst of their own investigation of the agency’s decision to clear the drug.

“Any broader coverage determination before there is clarity on Aduhelm’s approval process and findings from the myriad ongoing investigations may put the health of millions of Alzheimer’s patients on the line and the financial stability of the nation’s health insurance program for American seniors at risk,” Rep. Pallone and Rep. Maloney wrote.

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

Medicare has received a key endorsement of its plan to restrict payment for the controversial Alzheimer’s disease (AD) drug aducanumab (Aduhelm) – but also drew pleas from other groups for more generous reimbursement of the drug, as well as expected similar medications currently in development.

The Centers for Medicare & Medicaid Services received more than 9,900 comments on its plan, according to the current tally posted on its website. However, it is unclear when the final count will be available.

CMS intends to limit federal payment for monoclonal antibodies that target amyloid to clinical trials. Among supporters of this approach is the influential Medicare Payment Advisory Commission, an expert panel that helps Congress and CMS manage the federal health program.

Opponents of the CMS plan include several pharmaceutical companies. Patient and consumer groups, individuals, and lawmakers had mixed views.

CMS officials will weigh the feedback provided in the comments when setting a final coverage policy for aducanumab. It is expected the agency’s final decision will be announced on April 11.
 

Ongoing debate

The comments submitted to CMS reflect ongoing debate about whether the evidence proves aducanumab provides significant clinical benefit.

The Food and Drug Administration’s unusual approach to clearing the drug for U.S. sales triggered a review of its management of the accelerated approval process by the Office of Inspector General for the Department of Health & Human Services.

The FDA granted an accelerated approval for aducanumab in June based on evidence that the drug clears amyloid in the brain. However, it is unclear whether clearing the protein from the brain results in clinical benefit.

Usually, accelerated approvals precede the completion of phase 3 drug trials, with the FDA allowing early access to a medicine while awaiting confirmatory trials.

In the case of aducanumab, results of the phase 3 confirmatory trials ENGAGE and EMERGE were available at the time of FDA approval. However, interpretation of the findings is controversial.

Biogen contends that the amyloid-clearing effect of the higher dose of aducanumab shown in EMERGE indicates the drug has clinical potential. However, others argue that amyloid clearance does not indicate clinical benefit.

Limiting Medicare coverage of aducanumab for treatment of AD means “the progression of disease, for nearly all beneficiaries, would continue unabated,” Biogen wrote in its comment to CMS.
 

Conflicting data

Supporters of the CMS plan have a different view of the trial data. They note the failure of aducanumab in the companion ENGAGE trial, while also questioning the magnitude of benefit suggested by even the most positive data cited for the drug in the EMERGE trial.

Both studies used the Clinical Dementia Rating-Sum of Boxes (CDR-SB) score, an 18-point scale measuring cognition and function.

In his comment to CMS, MedPAC chairman Michael E. Chernew, PhD, noted the change in CDR-SB score of 0.39 in EMERGE’s high-dose aducanumab group. CMS has described this as being “less than the 1-2 point change that has been suggested as a minimal clinically important difference,” Dr. Chernew wrote.

MedPAC does not normally comment on Medicare coverage decisions, but did so in this case because of its significance and because of the potential fiscal implications, he noted.

“Though there is only limited, conflicting data on Aduhelm’s clinical effectiveness, Medicare would pay a high price for the product,” Dr. Chernew wrote, pointing out the $28,200 annual U.S. price of the drug.

MedPAC thus endorsed the coverage-with-evidence-development (CED) pathway. Under this approach, Medicare would pay for these drugs when used in clinical trials that meet certain criteria.
 

Legal challenge?

In its comment to CMS, Biogen questioned the agency’s legal grounds for limiting coverage of aducanumab. A mandate on clinical trials as part of the CED proposal “runs afoul of the Administrative Procedure Act’s prohibition against arbitrary and capricious agency action,” Biogen said.

The drug company argued that its own planned follow-on studies would provide the kind of data Medicare officials want to see. It also argued for greater use of observational data, including real-world evidence, and of information from Medicare claims.

Roche’s Genentech, which is also developing antiamyloid drugs for AD, echoed some of Biogen’s concerns about the aducanumab plan.

CMS’ CED plan would be “unnecessarily restrictive and discouraging for patients living with this destructive disease,” David Burt, executive director for federal government affairs at Genentech, wrote in a comment to CMS.

CMS should clarify that the CED requirement would not apply to cases of FDA-approved antiamyloid therapies that have demonstrated “clinically meaningful improvement,” Mr. Burt added. He noted there are phase 3 trials of drugs in this class that could soon produce data.

CMS should “fully consider the broad ramifications and significant unintended consequences of prematurely placing unduly severe restrictions on the entire class of antiamyloid monoclonal antibodies,” Mr. Burt wrote.
 

Health care inequity

In its comment to CMS, Biogen also noted the Medicare proposal would “compound the already pervasive inequities in access to treatment and will ultimately prove highly detrimental to health equity.”

There are already concerns about the access of Black and Latinx patients to clinical trials. The planned CED approach would tightly restrict access to aducanumab, as well as expected follow-ons in the amyloid-directed monoclonal antibody (mAb) drug class, the company said.

“Many of the trial sites for Aduhelm, as well as for other amyloid-directed [monoclonal antibodies] are not hospital-based outpatient settings, but include infusion centers, private practices, and medical research centers,” Biogen wrote.

Patient groups such as UsAgainstAlzheimer’s told CMS the CED approach would worsen disparities, despite the aim of Medicare officials to increase participation of Black and Latinx patients in future testing.

“CMS will be hard-pressed to achieve diversity if such hospitals are the only locations where Medicare beneficiaries are able to access mAbs,” USAgainstAlzheimer’s wrote in a Feb. 10 comment.

In contrast, the nonprofit National Center for Health Research praised CMS for what it described as an effort to address a lack of representation of Black and Latinx patients in earlier aducanumab research.

However, the NCHR also suggested CMS revise its plan to mandate that clinical trials include patients who are representative of the national population diagnosed with AD.

“Rather than being concerned about the percentage of patients in specific racial and ethnic groups, we propose that CMS include sufficient numbers of patients in different racial, ethnic, and age groups to ensure that there is enough statistical power for subgroup analyses to determine safety and efficacy for each of the major demographic groups,” the NCHR wrote.
 

Patient health, Medicare at risk

On Feb. 8, a group of House Republican lawmakers asked CMS to reverse its stance. In a publicly released letter, Rep. Cathy McMorris Rodgers of Washington state, the ranking Republican on the House Energy and Commerce Committee, and colleagues urged broader coverage of aducanumab.

In the letter, the group emphasized the idea of aducanumab as a potential treatment for patients with Down syndrome who are at risk for AD.

“The link between Down Syndrome and AD is still being researched by scientists,” Rep. Rodgers and colleagues wrote.

“However, there appears to be a correlation between the additional 21st chromosome present in people with Down Syndrome and the chromosome’s gene that makes amyloid precursor proteins and can cause a build-up of the beta-amyloid plaques common amongst those with AD,” they add.

On the other hand, CMS garnered earlier support from influential Democrats. On Jan. 13, House Energy and Commerce Chairman Frank Pallone Jr (D-N.J.) and House Oversight and Reform Chairwoman Carolyn B. Maloney (D-N.Y.) released a letter praising CMS for its plan for covering aducanumab.

In addition to the HHS-OIG review of the FDA’s approval of the drug, the two House committees are in the midst of their own investigation of the agency’s decision to clear the drug.

“Any broader coverage determination before there is clarity on Aduhelm’s approval process and findings from the myriad ongoing investigations may put the health of millions of Alzheimer’s patients on the line and the financial stability of the nation’s health insurance program for American seniors at risk,” Rep. Pallone and Rep. Maloney wrote.

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

A high level of education, superior academic performance, and excellent written language skills may predict the reversal of mild cognitive impairment (MCI) to normal cognitive function, new research shows.

The investigators found individuals with these factors, which are all markers of cognitive reserve, had a significantly greater chance of reversion from MCI to normal cognition (NC) than progression from MCI to dementia.

In a cohort study of more than 600 women aged 75 years or older, about a third of those with MCI reverted to NC at some point during follow-up, which sends “an encouraging message,” study author Suzanne Tyas, PhD, associate professor, University of Waterloo (Ont.), said in an interview.

“That’s a positive thing for people to keep in mind when they’re thinking about prognosis. Some of these novel characteristics we’ve identified might be useful in thinking about how likely a particular patient might be to improve versus decline cognitively,” Dr. Tyas added.

The findings were published online Feb. 4, 2022, in the journal Neurology.
 

Highly educated cohort

As the population ages, the number of individuals experiencing age-related conditions, including dementia, increases. There is no cure for most dementia types so prevention is key – and preventing dementia requires understanding its risk factors, Dr. Tyas noted.

The analysis included participants from the Nun Study, a longitudinal study of aging and cognition among members of the School Sisters of Notre Dame in the United States. All were 75 and older at baseline, which was from 1991 to 1993; about 14.5% were older than 90 years.

Participants were generally highly educated, with 84.5% attaining an undergraduate or graduate degree. They also had a similar socioeconomic status, level of social supports, marital and reproductive history, and alcohol and tobacco use.

Researchers examined cognitive function at baseline and then about annually until death or end of the 12th round of assessments. They used five measures from the Consortium to Establish a Registry for Alzheimer’s Disease neuropsychological battery to categorize subjects into NC, MCI, or dementia: Delayed Word Recall, Verbal Fluency, Boston Naming, Constructional Praxis, and the Mini-Mental State Exam.

The current analysis focused on the 619 participants with data on apolipoprotein E (apo E) epsilon-4 genotyping and education. From convent archives, investigators also had access to the nuns’ early high school academic performance in English, Latin, algebra, and geometry.

“Typically we only have data for [overall] education. But I know from teaching that there’s a difference between people who just pass my courses and graduate with a university degree versus those who really excel,” Dr. Tyas said.

The researchers also assessed handwriting samples from before the participants entered the religious order. From these, they scored “idea density,” which is the number of ideas contained in the writing and “grammatical complexity,” which includes structure, use of clauses, subclauses, and so on.
 

Dementia not inevitable

Results showed 472 of the 619 participants had MCI during the study period. About 30.3% of these showed at least one reverse transition from MCI to NC during a mean follow-up of 8.6 years; 83.9% went on to develop dementia.

This shows converting from MCI to NC occurs relatively frequently, Dr. Tyas noted.

“This is encouraging because some people think that if they have a diagnosis of MCI they are inevitably going to decline to dementia,” she added.

The researchers also used complicated modeling of transition rates over time between NC, MCI, and dementia and adjusted for participants who died. They estimated relative risk of reversion versus progression for age, apo E, and potential cognitive reserve indicators.

Not surprisingly, younger age (90 years or less) and absence of apo E epsilon-4 allele contributed to a significantly higher rate for reversion from MCI to NC versus progression from MCI to dementia.

However, although age and apo E are known risk factors for dementia, these have not been examined in the context of whether individuals with MCI are more likely to improve or decline, said Dr. Tyas.

Higher educational attainment, the traditional indicator of cognitive reserve, was associated with a significantly higher relative risk for reversion from MCI to NC versus progression from MCI to dementia (RR, 2.6) for a bachelor’s degree versus less education.

There was a greater RR for even higher education after adjusting for age and apo E epsilon-4 status.
 

Language skills key

Interestingly, the investigators also found a significant association with good grades in high school English but not other subjects (RR for higher vs. lower English grades, 1.83; 95% confidence interval, 1.07-3.14).

In addition, they found both characteristics of written language skills (idea density and grammatical complexity) were significant predictors of conversion to NC.

“Those with high levels of idea density were four times more likely to improve to normal cognition than progress to dementia, and the effect was even stronger for grammatical structure. Those individuals with higher levels were almost six times more likely to improve than decline,” Dr. Tyas reported.

The RR for higher versus lower idea density was 3.93 (95% CI, 1.3-11.9) and the RR for higher versus lower grammatical complexity was 5.78 (95% CI, 1.56-21.42).

These new results could be useful when planning future clinical trials, Dr. Tyas noted. “MCI in some people is going to improve even without any treatment, and this should be taken into consideration when recruiting participants to a study and when interpreting the results.

“You don’t want something to look like it’s a benefit of the treatment when in fact these individuals would have just reverted on their own,” she added.
 

Research implications

Commenting on the findings, Claire Sexton, DPhil, director of scientific programs and outreach at the Alzheimer’s Association, noted that, in “this study of highly educated, older women,” transitions from MCI to NC “were about equally common” as transitions from MCI to dementia.

“As advances are made in early detection of dementia, and treatments are developed and marketed for people living with MCI, this article’s findings are important to inform discussions of prognosis with patients and [to the] design of clinical trials,” Dr. Sexton said.

The study was funded by the Canadian Institutes of Health Research and the Natural Sciences and Engineering Research Council of Canada. Funding for the Nun Study at the University of Kentucky was provided by the U.S. National Institute of Aging and the Kleberg Foundation. Dr. Tyas has disclosed no relevant financial relationships.

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

A high level of education, superior academic performance, and excellent written language skills may predict the reversal of mild cognitive impairment (MCI) to normal cognitive function, new research shows.

The investigators found individuals with these factors, which are all markers of cognitive reserve, had a significantly greater chance of reversion from MCI to normal cognition (NC) than progression from MCI to dementia.

In a cohort study of more than 600 women aged 75 years or older, about a third of those with MCI reverted to NC at some point during follow-up, which sends “an encouraging message,” study author Suzanne Tyas, PhD, associate professor, University of Waterloo (Ont.), said in an interview.

“That’s a positive thing for people to keep in mind when they’re thinking about prognosis. Some of these novel characteristics we’ve identified might be useful in thinking about how likely a particular patient might be to improve versus decline cognitively,” Dr. Tyas added.

The findings were published online Feb. 4, 2022, in the journal Neurology.
 

Highly educated cohort

As the population ages, the number of individuals experiencing age-related conditions, including dementia, increases. There is no cure for most dementia types so prevention is key – and preventing dementia requires understanding its risk factors, Dr. Tyas noted.

The analysis included participants from the Nun Study, a longitudinal study of aging and cognition among members of the School Sisters of Notre Dame in the United States. All were 75 and older at baseline, which was from 1991 to 1993; about 14.5% were older than 90 years.

Participants were generally highly educated, with 84.5% attaining an undergraduate or graduate degree. They also had a similar socioeconomic status, level of social supports, marital and reproductive history, and alcohol and tobacco use.

Researchers examined cognitive function at baseline and then about annually until death or end of the 12th round of assessments. They used five measures from the Consortium to Establish a Registry for Alzheimer’s Disease neuropsychological battery to categorize subjects into NC, MCI, or dementia: Delayed Word Recall, Verbal Fluency, Boston Naming, Constructional Praxis, and the Mini-Mental State Exam.

The current analysis focused on the 619 participants with data on apolipoprotein E (apo E) epsilon-4 genotyping and education. From convent archives, investigators also had access to the nuns’ early high school academic performance in English, Latin, algebra, and geometry.

“Typically we only have data for [overall] education. But I know from teaching that there’s a difference between people who just pass my courses and graduate with a university degree versus those who really excel,” Dr. Tyas said.

The researchers also assessed handwriting samples from before the participants entered the religious order. From these, they scored “idea density,” which is the number of ideas contained in the writing and “grammatical complexity,” which includes structure, use of clauses, subclauses, and so on.
 

Dementia not inevitable

Results showed 472 of the 619 participants had MCI during the study period. About 30.3% of these showed at least one reverse transition from MCI to NC during a mean follow-up of 8.6 years; 83.9% went on to develop dementia.

This shows converting from MCI to NC occurs relatively frequently, Dr. Tyas noted.

“This is encouraging because some people think that if they have a diagnosis of MCI they are inevitably going to decline to dementia,” she added.

The researchers also used complicated modeling of transition rates over time between NC, MCI, and dementia and adjusted for participants who died. They estimated relative risk of reversion versus progression for age, apo E, and potential cognitive reserve indicators.

Not surprisingly, younger age (90 years or less) and absence of apo E epsilon-4 allele contributed to a significantly higher rate for reversion from MCI to NC versus progression from MCI to dementia.

However, although age and apo E are known risk factors for dementia, these have not been examined in the context of whether individuals with MCI are more likely to improve or decline, said Dr. Tyas.

Higher educational attainment, the traditional indicator of cognitive reserve, was associated with a significantly higher relative risk for reversion from MCI to NC versus progression from MCI to dementia (RR, 2.6) for a bachelor’s degree versus less education.

There was a greater RR for even higher education after adjusting for age and apo E epsilon-4 status.
 

Language skills key

Interestingly, the investigators also found a significant association with good grades in high school English but not other subjects (RR for higher vs. lower English grades, 1.83; 95% confidence interval, 1.07-3.14).

In addition, they found both characteristics of written language skills (idea density and grammatical complexity) were significant predictors of conversion to NC.

“Those with high levels of idea density were four times more likely to improve to normal cognition than progress to dementia, and the effect was even stronger for grammatical structure. Those individuals with higher levels were almost six times more likely to improve than decline,” Dr. Tyas reported.

The RR for higher versus lower idea density was 3.93 (95% CI, 1.3-11.9) and the RR for higher versus lower grammatical complexity was 5.78 (95% CI, 1.56-21.42).

These new results could be useful when planning future clinical trials, Dr. Tyas noted. “MCI in some people is going to improve even without any treatment, and this should be taken into consideration when recruiting participants to a study and when interpreting the results.

“You don’t want something to look like it’s a benefit of the treatment when in fact these individuals would have just reverted on their own,” she added.
 

Research implications

Commenting on the findings, Claire Sexton, DPhil, director of scientific programs and outreach at the Alzheimer’s Association, noted that, in “this study of highly educated, older women,” transitions from MCI to NC “were about equally common” as transitions from MCI to dementia.

“As advances are made in early detection of dementia, and treatments are developed and marketed for people living with MCI, this article’s findings are important to inform discussions of prognosis with patients and [to the] design of clinical trials,” Dr. Sexton said.

The study was funded by the Canadian Institutes of Health Research and the Natural Sciences and Engineering Research Council of Canada. Funding for the Nun Study at the University of Kentucky was provided by the U.S. National Institute of Aging and the Kleberg Foundation. Dr. Tyas has disclosed no relevant financial relationships.

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

A high level of education, superior academic performance, and excellent written language skills may predict the reversal of mild cognitive impairment (MCI) to normal cognitive function, new research shows.

The investigators found individuals with these factors, which are all markers of cognitive reserve, had a significantly greater chance of reversion from MCI to normal cognition (NC) than progression from MCI to dementia.

In a cohort study of more than 600 women aged 75 years or older, about a third of those with MCI reverted to NC at some point during follow-up, which sends “an encouraging message,” study author Suzanne Tyas, PhD, associate professor, University of Waterloo (Ont.), said in an interview.

“That’s a positive thing for people to keep in mind when they’re thinking about prognosis. Some of these novel characteristics we’ve identified might be useful in thinking about how likely a particular patient might be to improve versus decline cognitively,” Dr. Tyas added.

The findings were published online Feb. 4, 2022, in the journal Neurology.
 

Highly educated cohort

As the population ages, the number of individuals experiencing age-related conditions, including dementia, increases. There is no cure for most dementia types so prevention is key – and preventing dementia requires understanding its risk factors, Dr. Tyas noted.

The analysis included participants from the Nun Study, a longitudinal study of aging and cognition among members of the School Sisters of Notre Dame in the United States. All were 75 and older at baseline, which was from 1991 to 1993; about 14.5% were older than 90 years.

Participants were generally highly educated, with 84.5% attaining an undergraduate or graduate degree. They also had a similar socioeconomic status, level of social supports, marital and reproductive history, and alcohol and tobacco use.

Researchers examined cognitive function at baseline and then about annually until death or end of the 12th round of assessments. They used five measures from the Consortium to Establish a Registry for Alzheimer’s Disease neuropsychological battery to categorize subjects into NC, MCI, or dementia: Delayed Word Recall, Verbal Fluency, Boston Naming, Constructional Praxis, and the Mini-Mental State Exam.

The current analysis focused on the 619 participants with data on apolipoprotein E (apo E) epsilon-4 genotyping and education. From convent archives, investigators also had access to the nuns’ early high school academic performance in English, Latin, algebra, and geometry.

“Typically we only have data for [overall] education. But I know from teaching that there’s a difference between people who just pass my courses and graduate with a university degree versus those who really excel,” Dr. Tyas said.

The researchers also assessed handwriting samples from before the participants entered the religious order. From these, they scored “idea density,” which is the number of ideas contained in the writing and “grammatical complexity,” which includes structure, use of clauses, subclauses, and so on.
 

Dementia not inevitable

Results showed 472 of the 619 participants had MCI during the study period. About 30.3% of these showed at least one reverse transition from MCI to NC during a mean follow-up of 8.6 years; 83.9% went on to develop dementia.

This shows converting from MCI to NC occurs relatively frequently, Dr. Tyas noted.

“This is encouraging because some people think that if they have a diagnosis of MCI they are inevitably going to decline to dementia,” she added.

The researchers also used complicated modeling of transition rates over time between NC, MCI, and dementia and adjusted for participants who died. They estimated relative risk of reversion versus progression for age, apo E, and potential cognitive reserve indicators.

Not surprisingly, younger age (90 years or less) and absence of apo E epsilon-4 allele contributed to a significantly higher rate for reversion from MCI to NC versus progression from MCI to dementia.

However, although age and apo E are known risk factors for dementia, these have not been examined in the context of whether individuals with MCI are more likely to improve or decline, said Dr. Tyas.

Higher educational attainment, the traditional indicator of cognitive reserve, was associated with a significantly higher relative risk for reversion from MCI to NC versus progression from MCI to dementia (RR, 2.6) for a bachelor’s degree versus less education.

There was a greater RR for even higher education after adjusting for age and apo E epsilon-4 status.
 

Language skills key

Interestingly, the investigators also found a significant association with good grades in high school English but not other subjects (RR for higher vs. lower English grades, 1.83; 95% confidence interval, 1.07-3.14).

In addition, they found both characteristics of written language skills (idea density and grammatical complexity) were significant predictors of conversion to NC.

“Those with high levels of idea density were four times more likely to improve to normal cognition than progress to dementia, and the effect was even stronger for grammatical structure. Those individuals with higher levels were almost six times more likely to improve than decline,” Dr. Tyas reported.

The RR for higher versus lower idea density was 3.93 (95% CI, 1.3-11.9) and the RR for higher versus lower grammatical complexity was 5.78 (95% CI, 1.56-21.42).

These new results could be useful when planning future clinical trials, Dr. Tyas noted. “MCI in some people is going to improve even without any treatment, and this should be taken into consideration when recruiting participants to a study and when interpreting the results.

“You don’t want something to look like it’s a benefit of the treatment when in fact these individuals would have just reverted on their own,” she added.
 

Research implications

Commenting on the findings, Claire Sexton, DPhil, director of scientific programs and outreach at the Alzheimer’s Association, noted that, in “this study of highly educated, older women,” transitions from MCI to NC “were about equally common” as transitions from MCI to dementia.

“As advances are made in early detection of dementia, and treatments are developed and marketed for people living with MCI, this article’s findings are important to inform discussions of prognosis with patients and [to the] design of clinical trials,” Dr. Sexton said.

The study was funded by the Canadian Institutes of Health Research and the Natural Sciences and Engineering Research Council of Canada. Funding for the Nun Study at the University of Kentucky was provided by the U.S. National Institute of Aging and the Kleberg Foundation. Dr. Tyas has disclosed no relevant financial relationships.

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

Nearly one-third of adults over age 65 developed one or more new medical conditions in the weeks following a COVID-19 infection, according to new research.

The findings of the observational study, which were published in the BMJ, show the risk of a new condition being triggered by COVID is more than twice as high in seniors, compared with younger patients. Plus, the researchers observed an even higher risk among those who were hospitalized, with nearly half (46%) of patients having developed new conditions after the acute COVID-19 infection period.

Respiratory failure with shortness of breath was the most common postacute sequela, but a wide range of heart, kidney, lung, liver, cognitive, mental health, and other conditions were diagnosed at least 3 weeks after initial infection and persisted beyond 30 days.

This is one of the first studies to specifically describe the incidence and severity of new conditions triggered by COVID-19 infection in a general sample of older adults, said study author Ken Cohen MD, FACP, executive director of translational research at Optum Labs and national senior medical director at Optum Care.

“Much of what has been published on the postacute sequelae of COVID-19 has been predominantly from a younger population, and many of the patients had been hospitalized,” Dr. Cohen noted. “This was the first study to focus on a large population of seniors, most of whom did not require hospitalization.”

Dr. Cohen and colleagues reviewed the health insurance records of more than 133,000 Medicare beneficiaries aged 65 or older who were diagnosed with COVID-19 before April 2020. They also matched individuals by age, race, sex, hospitalization status, and other factors to comparison groups without COVID-19 (one from 2020 and one from 2019), and to a group diagnosed with other lower respiratory tract viral infections before the pandemic.
 

Risk of developing new conditions was higher in hospitalized

After acute COVID-19 infection, 32% of seniors sought medical care for at least one new medical condition in 2020, compared with 21% of uninfected people in the same year.

The most commonly observed conditions included:

• Respiratory failure (7.55% higher risk).
• Fatigue (5.66% higher risk).
• High blood pressure (4.43% higher risk).
• Memory problems (2.63% higher risk).
• Kidney injury (2.59% higher risk).
• Mental health diagnoses (2.5% higher risk).
• Blood-clotting disorders (1.47 % higher risk).
• Heart rhythm disorders (2.9% higher risk).

The risk of developing new conditions was even higher among those 23,486 who were hospitalized in 2020. Those individuals showed a 23.6% higher risk for developing at least one new condition, compared with uninfected seniors in the same year. Also, patients older than 75 had a higher risk for neurological disorders, including dementia, encephalopathy, and memory problems. The researchers also found that respiratory failure and kidney injury were significantly more likely to affect men and Black patients.

When those who had COVID were compared with the group with other lower respiratory viral infections before the pandemic, only the risks of respiratory failure (2.39% higher), dementia (0.71% higher), and fatigue (0.18% higher) were higher.

Primary care providers can learn from these data to better evaluate and manage their geriatric patients with COVID-19 infection, said Amit Shah, MD, a geriatrician with the Mayo Clinic in Phoenix, in an interview.

“We must assess older patients who have had COVID-19 for more than just improvement from the respiratory symptoms of COVID-19 in post-COVID follow-up visits,” he said. “Older individuals with frailty have vulnerability to subsequent complications from severe illnesses and it is common to see post-illness diagnoses, such as new diagnosis of delirium; dementia; or renal, respiratory, or cardiac issues that is precipitated by the original illness. This study confirms that this is likely the case with COVID-19 as well.

“Primary care physicians should be vigilant for these complications, including attention to the rehabilitation needs of older patients with longer-term postviral fatigue from COVID-19,” Dr. Shah added.
 

Data predates ‘Omicron wave’

It remains uncertain whether sequelae will differ with the Omicron variant, but the findings remain applicable, Dr. Cohen said.

“We know that illness from the Omicron variant is on average less severe in those that have been vaccinated. However, throughout the Omicron wave, individuals who have not been vaccinated continue to have significant rates of serious illness and hospitalization,” he said.

“Our findings showed that serious illness with hospitalization was associated with a higher rate of sequelae. It can therefore be inferred that the rates of sequelae seen in our study would continue to occur in unvaccinated individuals who contract Omicron, but might occur less frequently in vaccinated individuals who contract Omicron and have less severe illness.”

Dr. Cohen serves as a consultant for Pfizer. Dr. Shah has disclosed no relevant financial relationships.

Nearly one-third of adults over age 65 developed one or more new medical conditions in the weeks following a COVID-19 infection, according to new research.

The findings of the observational study, which were published in the BMJ, show the risk of a new condition being triggered by COVID is more than twice as high in seniors, compared with younger patients. Plus, the researchers observed an even higher risk among those who were hospitalized, with nearly half (46%) of patients having developed new conditions after the acute COVID-19 infection period.

Respiratory failure with shortness of breath was the most common postacute sequela, but a wide range of heart, kidney, lung, liver, cognitive, mental health, and other conditions were diagnosed at least 3 weeks after initial infection and persisted beyond 30 days.

This is one of the first studies to specifically describe the incidence and severity of new conditions triggered by COVID-19 infection in a general sample of older adults, said study author Ken Cohen MD, FACP, executive director of translational research at Optum Labs and national senior medical director at Optum Care.

“Much of what has been published on the postacute sequelae of COVID-19 has been predominantly from a younger population, and many of the patients had been hospitalized,” Dr. Cohen noted. “This was the first study to focus on a large population of seniors, most of whom did not require hospitalization.”

Dr. Cohen and colleagues reviewed the health insurance records of more than 133,000 Medicare beneficiaries aged 65 or older who were diagnosed with COVID-19 before April 2020. They also matched individuals by age, race, sex, hospitalization status, and other factors to comparison groups without COVID-19 (one from 2020 and one from 2019), and to a group diagnosed with other lower respiratory tract viral infections before the pandemic.
 

Risk of developing new conditions was higher in hospitalized

After acute COVID-19 infection, 32% of seniors sought medical care for at least one new medical condition in 2020, compared with 21% of uninfected people in the same year.

The most commonly observed conditions included:

• Respiratory failure (7.55% higher risk).
• Fatigue (5.66% higher risk).
• High blood pressure (4.43% higher risk).
• Memory problems (2.63% higher risk).
• Kidney injury (2.59% higher risk).
• Mental health diagnoses (2.5% higher risk).
• Blood-clotting disorders (1.47 % higher risk).
• Heart rhythm disorders (2.9% higher risk).

The risk of developing new conditions was even higher among those 23,486 who were hospitalized in 2020. Those individuals showed a 23.6% higher risk for developing at least one new condition, compared with uninfected seniors in the same year. Also, patients older than 75 had a higher risk for neurological disorders, including dementia, encephalopathy, and memory problems. The researchers also found that respiratory failure and kidney injury were significantly more likely to affect men and Black patients.

When those who had COVID were compared with the group with other lower respiratory viral infections before the pandemic, only the risks of respiratory failure (2.39% higher), dementia (0.71% higher), and fatigue (0.18% higher) were higher.

Primary care providers can learn from these data to better evaluate and manage their geriatric patients with COVID-19 infection, said Amit Shah, MD, a geriatrician with the Mayo Clinic in Phoenix, in an interview.

“We must assess older patients who have had COVID-19 for more than just improvement from the respiratory symptoms of COVID-19 in post-COVID follow-up visits,” he said. “Older individuals with frailty have vulnerability to subsequent complications from severe illnesses and it is common to see post-illness diagnoses, such as new diagnosis of delirium; dementia; or renal, respiratory, or cardiac issues that is precipitated by the original illness. This study confirms that this is likely the case with COVID-19 as well.

“Primary care physicians should be vigilant for these complications, including attention to the rehabilitation needs of older patients with longer-term postviral fatigue from COVID-19,” Dr. Shah added.
 

Data predates ‘Omicron wave’

It remains uncertain whether sequelae will differ with the Omicron variant, but the findings remain applicable, Dr. Cohen said.

“We know that illness from the Omicron variant is on average less severe in those that have been vaccinated. However, throughout the Omicron wave, individuals who have not been vaccinated continue to have significant rates of serious illness and hospitalization,” he said.

“Our findings showed that serious illness with hospitalization was associated with a higher rate of sequelae. It can therefore be inferred that the rates of sequelae seen in our study would continue to occur in unvaccinated individuals who contract Omicron, but might occur less frequently in vaccinated individuals who contract Omicron and have less severe illness.”

Dr. Cohen serves as a consultant for Pfizer. Dr. Shah has disclosed no relevant financial relationships.

Nearly one-third of adults over age 65 developed one or more new medical conditions in the weeks following a COVID-19 infection, according to new research.

The findings of the observational study, which were published in the BMJ, show the risk of a new condition being triggered by COVID is more than twice as high in seniors, compared with younger patients. Plus, the researchers observed an even higher risk among those who were hospitalized, with nearly half (46%) of patients having developed new conditions after the acute COVID-19 infection period.

Respiratory failure with shortness of breath was the most common postacute sequela, but a wide range of heart, kidney, lung, liver, cognitive, mental health, and other conditions were diagnosed at least 3 weeks after initial infection and persisted beyond 30 days.

This is one of the first studies to specifically describe the incidence and severity of new conditions triggered by COVID-19 infection in a general sample of older adults, said study author Ken Cohen MD, FACP, executive director of translational research at Optum Labs and national senior medical director at Optum Care.

“Much of what has been published on the postacute sequelae of COVID-19 has been predominantly from a younger population, and many of the patients had been hospitalized,” Dr. Cohen noted. “This was the first study to focus on a large population of seniors, most of whom did not require hospitalization.”

Dr. Cohen and colleagues reviewed the health insurance records of more than 133,000 Medicare beneficiaries aged 65 or older who were diagnosed with COVID-19 before April 2020. They also matched individuals by age, race, sex, hospitalization status, and other factors to comparison groups without COVID-19 (one from 2020 and one from 2019), and to a group diagnosed with other lower respiratory tract viral infections before the pandemic.
 

Risk of developing new conditions was higher in hospitalized

After acute COVID-19 infection, 32% of seniors sought medical care for at least one new medical condition in 2020, compared with 21% of uninfected people in the same year.

The most commonly observed conditions included:

• Respiratory failure (7.55% higher risk).
• Fatigue (5.66% higher risk).
• High blood pressure (4.43% higher risk).
• Memory problems (2.63% higher risk).
• Kidney injury (2.59% higher risk).
• Mental health diagnoses (2.5% higher risk).
• Blood-clotting disorders (1.47 % higher risk).
• Heart rhythm disorders (2.9% higher risk).

The risk of developing new conditions was even higher among those 23,486 who were hospitalized in 2020. Those individuals showed a 23.6% higher risk for developing at least one new condition, compared with uninfected seniors in the same year. Also, patients older than 75 had a higher risk for neurological disorders, including dementia, encephalopathy, and memory problems. The researchers also found that respiratory failure and kidney injury were significantly more likely to affect men and Black patients.

When those who had COVID were compared with the group with other lower respiratory viral infections before the pandemic, only the risks of respiratory failure (2.39% higher), dementia (0.71% higher), and fatigue (0.18% higher) were higher.

Primary care providers can learn from these data to better evaluate and manage their geriatric patients with COVID-19 infection, said Amit Shah, MD, a geriatrician with the Mayo Clinic in Phoenix, in an interview.

“We must assess older patients who have had COVID-19 for more than just improvement from the respiratory symptoms of COVID-19 in post-COVID follow-up visits,” he said. “Older individuals with frailty have vulnerability to subsequent complications from severe illnesses and it is common to see post-illness diagnoses, such as new diagnosis of delirium; dementia; or renal, respiratory, or cardiac issues that is precipitated by the original illness. This study confirms that this is likely the case with COVID-19 as well.

“Primary care physicians should be vigilant for these complications, including attention to the rehabilitation needs of older patients with longer-term postviral fatigue from COVID-19,” Dr. Shah added.
 

Data predates ‘Omicron wave’

It remains uncertain whether sequelae will differ with the Omicron variant, but the findings remain applicable, Dr. Cohen said.

“We know that illness from the Omicron variant is on average less severe in those that have been vaccinated. However, throughout the Omicron wave, individuals who have not been vaccinated continue to have significant rates of serious illness and hospitalization,” he said.

“Our findings showed that serious illness with hospitalization was associated with a higher rate of sequelae. It can therefore be inferred that the rates of sequelae seen in our study would continue to occur in unvaccinated individuals who contract Omicron, but might occur less frequently in vaccinated individuals who contract Omicron and have less severe illness.”

Dr. Cohen serves as a consultant for Pfizer. Dr. Shah has disclosed no relevant financial relationships.

Dietary intake of polyunsaturated fatty acids (PUFA), particularly omega 6, is associated with improved cognitive function in older adults, new research suggests.

The study provides important “pieces of the puzzle” of the diet and cognition connection, but the results aren’t “ready for prime time,” study investigator Roger S. McIntyre, MD, professor of psychiatry and pharmacology, University of Toronto, said in an interview.

“I don’t think we’re there yet when it comes to recommending supplementation to the general public,” said Dr. McIntyre, adding a larger “more compelling study” is needed.

The study was published online Jan. 14 in The American Journal of Geriatric Psychiatry.
 

Clinically meaningful?

Research shows that 25%-50% of community-dwelling adults aged 65-85 years have some cognitive impairment. Other evidence indicates cognition is affected by dietary fat intake.

Many lines of research show that alterations in lipid homeostasis can cause brain dysfunction, said Dr. McIntyre. “This shouldn’t surprise us because our brain is made up of protein, water, and fat.”

This new analysis used combined data from the 2011-2012 and 2013-2014 cycles of the National Health and Nutrition Examination Survey (NHANES), a series of ongoing cross-sectional surveys conducted by the Centers for Disease Control and Prevention. The data are collected in two phases, an in-home face-to-face interview and a physical examination.

Researchers obtained dietary intake information through two 24-hour dietary recall interviews. Dietary information included total energy (kcal/d), intakes in grams per day (g/d) of total fat, saturated fatty acid (SFAT), monounsaturated fatty acid (MUFA), PUFA, total omega-3 and total omega-6 fatty acids, and milligrams per day (mg/d) of cholesterol.

For cognitive function, the researchers used total and delayed recall scores of the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD), the animal fluency test, and the digit symbol substitution test (DSST).

The study included 2,253 adults aged 60 years and older (mean age, 69.4 years) and 51% were non-Hispanic White individuals.

After adjustment for age, sex, race/ethnicity, educational attainment, smoking status, alcohol consumption, income, and total energy, dietary intake of PUFA and omega-6 fatty acid was positively associated with DSST.

The DSST score increased about 0.06 standard deviation (SD) (about 1 score) with each SD increase in these fatty acids (8.8 g/d for PUFA and 7.9 g/d for omega-6) (P values were .02 for PUFA and .01 for omega-6).

However, it’s unclear what an improvement of 1 DSST score means clinically, said Dr. McIntyre. “The P value is significant, but how does that translate? Does this mean a person can now think more clearly or function better?”
 

‘Million dollar question’ remains unanswered

The fact that omega-6, considered neuroinflammatory, was associated with improved DSST score illustrates the complexity of this field, said Dr. McIntyre.

“We’re learning that when it comes to inflammation, many of the molecules in our brain that are implicated as anti-inflammatory can also be pro-inflammatory, so bad guys can be good guys and good guys can be bad guys.”

It speaks to the notion of homeostasis, he added. “Just like a seesaw; when you push this part down, that part goes up.”

The analysis showed the animal fluency score increased about 0.05 SD (around 0.3 score) with each SD (1.1 g/d) increase in dietary intake of omega-3.

There were no significant associations between other dietary fat intake and cognitive performance.

The researchers investigated the role of oxidative stress and antioxidant biomarkers (gamma glutamyl transpeptidase [GGT], bilirubin, uric acid, and vitamin D).

Cells produce oxidative radicals that are normally “mopped up” by our “innate antioxidant capability,” said Dr. McIntyre. “But in states of cognitive impairment, these oxidative stress markers accumulate and they exceed what the normal innate response is able to manage.”

The study showed GGT levels decreased with increased PUFA and omega-6 fatty acid intakes; levels of bilirubin decreased with increase in most dietary fat intakes; uric acid levels decreased with MUFA intake and omega-6/omega-3 ratio; and vitamin D levels increased with omega-3 fatty acid intake but decreased with SFAT intake.

Causal mediation analysis showed the association between dietary intake of fatty acids and DSST performance was partially mediated by GGT levels. However, Dr. McIntyre emphasized that this does not prove causality.

“The million dollar question is, is this the sole explanation for the association? In other words, is it the oxidative stress that caused the cognitive impairment and therefore correcting it improved it, or is it the case that oxidative stress is a proxy of other activities that are also taking place?”
 

A ‘plausible’ link

In an editorial, Candida Rebello, PhD, of the department of integrated physiology and molecular medicine at Pennington Biomedical Research Center, Baton Rouge, La., said the finding that omega-3 and omega-6 fatty acids are positively associated with cognition in older adults makes some sense.

She noted that aging is associated with an overt inflammatory phenotype, and evidence shows these fatty acids are precursors for bioactive molecules that play a role in self-limiting the acute inflammatory response.

Dr. Rebello said the positive association of omega-6 fatty acid with cognition shown in this study contrasts with the “common belief” that increasing dietary intake of these fatty acids enhances inflammation, but agreed the association is “plausible.”

She said it’s “essential” to determine “the underlying mechanisms that regulate the diverse features of inflammation and sort out the processes that protect from neuronal damage and those that contribute towards it.”

She noted the ratio of omega-6 to omega-3 is about 15:1 in the present day Western diet, as opposed to a 1:1 ratio in diets of the past. Omega-3 fatty acids are found in fish oil supplements and fatty fish like mackerel and salmon, while cereal, grains, and vegetable oil are sources of omega-6.

Attaining a measure of balance of fatty acids in the diet may be a “prudent approach,” said Dr. Rebello. “Substituting some meat entrées with fatty fish and polyunsaturated vegetable oils with monounsaturated fats such as olive oil are small changes that are likely to garner adherence.”

Dr. Rebello noted that the study used NHANES food intake data, which rely on participant self-report and so may not be accurate.

The study received funding from the MOE (Ministry of Education in China) Project of Humanities and Social Sciences and the Research Startup Fund of Southwest University. Dr. McIntyre has received research grant support from CIHR/GACD/Chinese National Natural Research Foundation and speaker/consultation fees from Lundbeck, Janssen, Purdue, Pfizer, Otsuka, Takeda, Neurocrine, Sunovion, Bausch Health, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular, NewBridge Pharmaceuticals, and AbbVie. He is a CEO of Braxia Scientific Corp.

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

Dietary intake of polyunsaturated fatty acids (PUFA), particularly omega 6, is associated with improved cognitive function in older adults, new research suggests.

The study provides important “pieces of the puzzle” of the diet and cognition connection, but the results aren’t “ready for prime time,” study investigator Roger S. McIntyre, MD, professor of psychiatry and pharmacology, University of Toronto, said in an interview.

“I don’t think we’re there yet when it comes to recommending supplementation to the general public,” said Dr. McIntyre, adding a larger “more compelling study” is needed.

The study was published online Jan. 14 in The American Journal of Geriatric Psychiatry.
 

Clinically meaningful?

Research shows that 25%-50% of community-dwelling adults aged 65-85 years have some cognitive impairment. Other evidence indicates cognition is affected by dietary fat intake.

Many lines of research show that alterations in lipid homeostasis can cause brain dysfunction, said Dr. McIntyre. “This shouldn’t surprise us because our brain is made up of protein, water, and fat.”

This new analysis used combined data from the 2011-2012 and 2013-2014 cycles of the National Health and Nutrition Examination Survey (NHANES), a series of ongoing cross-sectional surveys conducted by the Centers for Disease Control and Prevention. The data are collected in two phases, an in-home face-to-face interview and a physical examination.

Researchers obtained dietary intake information through two 24-hour dietary recall interviews. Dietary information included total energy (kcal/d), intakes in grams per day (g/d) of total fat, saturated fatty acid (SFAT), monounsaturated fatty acid (MUFA), PUFA, total omega-3 and total omega-6 fatty acids, and milligrams per day (mg/d) of cholesterol.

For cognitive function, the researchers used total and delayed recall scores of the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD), the animal fluency test, and the digit symbol substitution test (DSST).

The study included 2,253 adults aged 60 years and older (mean age, 69.4 years) and 51% were non-Hispanic White individuals.

After adjustment for age, sex, race/ethnicity, educational attainment, smoking status, alcohol consumption, income, and total energy, dietary intake of PUFA and omega-6 fatty acid was positively associated with DSST.

The DSST score increased about 0.06 standard deviation (SD) (about 1 score) with each SD increase in these fatty acids (8.8 g/d for PUFA and 7.9 g/d for omega-6) (P values were .02 for PUFA and .01 for omega-6).

However, it’s unclear what an improvement of 1 DSST score means clinically, said Dr. McIntyre. “The P value is significant, but how does that translate? Does this mean a person can now think more clearly or function better?”
 

‘Million dollar question’ remains unanswered

The fact that omega-6, considered neuroinflammatory, was associated with improved DSST score illustrates the complexity of this field, said Dr. McIntyre.

“We’re learning that when it comes to inflammation, many of the molecules in our brain that are implicated as anti-inflammatory can also be pro-inflammatory, so bad guys can be good guys and good guys can be bad guys.”

It speaks to the notion of homeostasis, he added. “Just like a seesaw; when you push this part down, that part goes up.”

The analysis showed the animal fluency score increased about 0.05 SD (around 0.3 score) with each SD (1.1 g/d) increase in dietary intake of omega-3.

There were no significant associations between other dietary fat intake and cognitive performance.

The researchers investigated the role of oxidative stress and antioxidant biomarkers (gamma glutamyl transpeptidase [GGT], bilirubin, uric acid, and vitamin D).

Cells produce oxidative radicals that are normally “mopped up” by our “innate antioxidant capability,” said Dr. McIntyre. “But in states of cognitive impairment, these oxidative stress markers accumulate and they exceed what the normal innate response is able to manage.”

The study showed GGT levels decreased with increased PUFA and omega-6 fatty acid intakes; levels of bilirubin decreased with increase in most dietary fat intakes; uric acid levels decreased with MUFA intake and omega-6/omega-3 ratio; and vitamin D levels increased with omega-3 fatty acid intake but decreased with SFAT intake.

Causal mediation analysis showed the association between dietary intake of fatty acids and DSST performance was partially mediated by GGT levels. However, Dr. McIntyre emphasized that this does not prove causality.

“The million dollar question is, is this the sole explanation for the association? In other words, is it the oxidative stress that caused the cognitive impairment and therefore correcting it improved it, or is it the case that oxidative stress is a proxy of other activities that are also taking place?”
 

A ‘plausible’ link

In an editorial, Candida Rebello, PhD, of the department of integrated physiology and molecular medicine at Pennington Biomedical Research Center, Baton Rouge, La., said the finding that omega-3 and omega-6 fatty acids are positively associated with cognition in older adults makes some sense.

She noted that aging is associated with an overt inflammatory phenotype, and evidence shows these fatty acids are precursors for bioactive molecules that play a role in self-limiting the acute inflammatory response.

Dr. Rebello said the positive association of omega-6 fatty acid with cognition shown in this study contrasts with the “common belief” that increasing dietary intake of these fatty acids enhances inflammation, but agreed the association is “plausible.”

She said it’s “essential” to determine “the underlying mechanisms that regulate the diverse features of inflammation and sort out the processes that protect from neuronal damage and those that contribute towards it.”

She noted the ratio of omega-6 to omega-3 is about 15:1 in the present day Western diet, as opposed to a 1:1 ratio in diets of the past. Omega-3 fatty acids are found in fish oil supplements and fatty fish like mackerel and salmon, while cereal, grains, and vegetable oil are sources of omega-6.

Attaining a measure of balance of fatty acids in the diet may be a “prudent approach,” said Dr. Rebello. “Substituting some meat entrées with fatty fish and polyunsaturated vegetable oils with monounsaturated fats such as olive oil are small changes that are likely to garner adherence.”

Dr. Rebello noted that the study used NHANES food intake data, which rely on participant self-report and so may not be accurate.

The study received funding from the MOE (Ministry of Education in China) Project of Humanities and Social Sciences and the Research Startup Fund of Southwest University. Dr. McIntyre has received research grant support from CIHR/GACD/Chinese National Natural Research Foundation and speaker/consultation fees from Lundbeck, Janssen, Purdue, Pfizer, Otsuka, Takeda, Neurocrine, Sunovion, Bausch Health, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular, NewBridge Pharmaceuticals, and AbbVie. He is a CEO of Braxia Scientific Corp.

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

Dietary intake of polyunsaturated fatty acids (PUFA), particularly omega 6, is associated with improved cognitive function in older adults, new research suggests.

The study provides important “pieces of the puzzle” of the diet and cognition connection, but the results aren’t “ready for prime time,” study investigator Roger S. McIntyre, MD, professor of psychiatry and pharmacology, University of Toronto, said in an interview.

“I don’t think we’re there yet when it comes to recommending supplementation to the general public,” said Dr. McIntyre, adding a larger “more compelling study” is needed.

The study was published online Jan. 14 in The American Journal of Geriatric Psychiatry.
 

Clinically meaningful?

Research shows that 25%-50% of community-dwelling adults aged 65-85 years have some cognitive impairment. Other evidence indicates cognition is affected by dietary fat intake.

Many lines of research show that alterations in lipid homeostasis can cause brain dysfunction, said Dr. McIntyre. “This shouldn’t surprise us because our brain is made up of protein, water, and fat.”

This new analysis used combined data from the 2011-2012 and 2013-2014 cycles of the National Health and Nutrition Examination Survey (NHANES), a series of ongoing cross-sectional surveys conducted by the Centers for Disease Control and Prevention. The data are collected in two phases, an in-home face-to-face interview and a physical examination.

Researchers obtained dietary intake information through two 24-hour dietary recall interviews. Dietary information included total energy (kcal/d), intakes in grams per day (g/d) of total fat, saturated fatty acid (SFAT), monounsaturated fatty acid (MUFA), PUFA, total omega-3 and total omega-6 fatty acids, and milligrams per day (mg/d) of cholesterol.

For cognitive function, the researchers used total and delayed recall scores of the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD), the animal fluency test, and the digit symbol substitution test (DSST).

The study included 2,253 adults aged 60 years and older (mean age, 69.4 years) and 51% were non-Hispanic White individuals.

After adjustment for age, sex, race/ethnicity, educational attainment, smoking status, alcohol consumption, income, and total energy, dietary intake of PUFA and omega-6 fatty acid was positively associated with DSST.

The DSST score increased about 0.06 standard deviation (SD) (about 1 score) with each SD increase in these fatty acids (8.8 g/d for PUFA and 7.9 g/d for omega-6) (P values were .02 for PUFA and .01 for omega-6).

However, it’s unclear what an improvement of 1 DSST score means clinically, said Dr. McIntyre. “The P value is significant, but how does that translate? Does this mean a person can now think more clearly or function better?”
 

‘Million dollar question’ remains unanswered

The fact that omega-6, considered neuroinflammatory, was associated with improved DSST score illustrates the complexity of this field, said Dr. McIntyre.

“We’re learning that when it comes to inflammation, many of the molecules in our brain that are implicated as anti-inflammatory can also be pro-inflammatory, so bad guys can be good guys and good guys can be bad guys.”

It speaks to the notion of homeostasis, he added. “Just like a seesaw; when you push this part down, that part goes up.”

The analysis showed the animal fluency score increased about 0.05 SD (around 0.3 score) with each SD (1.1 g/d) increase in dietary intake of omega-3.

There were no significant associations between other dietary fat intake and cognitive performance.

The researchers investigated the role of oxidative stress and antioxidant biomarkers (gamma glutamyl transpeptidase [GGT], bilirubin, uric acid, and vitamin D).

Cells produce oxidative radicals that are normally “mopped up” by our “innate antioxidant capability,” said Dr. McIntyre. “But in states of cognitive impairment, these oxidative stress markers accumulate and they exceed what the normal innate response is able to manage.”

The study showed GGT levels decreased with increased PUFA and omega-6 fatty acid intakes; levels of bilirubin decreased with increase in most dietary fat intakes; uric acid levels decreased with MUFA intake and omega-6/omega-3 ratio; and vitamin D levels increased with omega-3 fatty acid intake but decreased with SFAT intake.

Causal mediation analysis showed the association between dietary intake of fatty acids and DSST performance was partially mediated by GGT levels. However, Dr. McIntyre emphasized that this does not prove causality.

“The million dollar question is, is this the sole explanation for the association? In other words, is it the oxidative stress that caused the cognitive impairment and therefore correcting it improved it, or is it the case that oxidative stress is a proxy of other activities that are also taking place?”
 

A ‘plausible’ link

In an editorial, Candida Rebello, PhD, of the department of integrated physiology and molecular medicine at Pennington Biomedical Research Center, Baton Rouge, La., said the finding that omega-3 and omega-6 fatty acids are positively associated with cognition in older adults makes some sense.

She noted that aging is associated with an overt inflammatory phenotype, and evidence shows these fatty acids are precursors for bioactive molecules that play a role in self-limiting the acute inflammatory response.

Dr. Rebello said the positive association of omega-6 fatty acid with cognition shown in this study contrasts with the “common belief” that increasing dietary intake of these fatty acids enhances inflammation, but agreed the association is “plausible.”

She said it’s “essential” to determine “the underlying mechanisms that regulate the diverse features of inflammation and sort out the processes that protect from neuronal damage and those that contribute towards it.”

She noted the ratio of omega-6 to omega-3 is about 15:1 in the present day Western diet, as opposed to a 1:1 ratio in diets of the past. Omega-3 fatty acids are found in fish oil supplements and fatty fish like mackerel and salmon, while cereal, grains, and vegetable oil are sources of omega-6.

Attaining a measure of balance of fatty acids in the diet may be a “prudent approach,” said Dr. Rebello. “Substituting some meat entrées with fatty fish and polyunsaturated vegetable oils with monounsaturated fats such as olive oil are small changes that are likely to garner adherence.”

Dr. Rebello noted that the study used NHANES food intake data, which rely on participant self-report and so may not be accurate.

The study received funding from the MOE (Ministry of Education in China) Project of Humanities and Social Sciences and the Research Startup Fund of Southwest University. Dr. McIntyre has received research grant support from CIHR/GACD/Chinese National Natural Research Foundation and speaker/consultation fees from Lundbeck, Janssen, Purdue, Pfizer, Otsuka, Takeda, Neurocrine, Sunovion, Bausch Health, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular, NewBridge Pharmaceuticals, and AbbVie. He is a CEO of Braxia Scientific Corp.

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

The American Heart Association (AHA) draws attention to the important bidirectional link between cardiovascular health and brain health in its annual statistical update on heart disease and stroke.

“For several years now, the AHA and the scientific community have increasingly recognized the connections between cardiovascular health and brain health, so it was time for us to cement this into its own chapter, which we highlight as the brain health chapter,” Connie W. Tsao, MD, MPH, chair of the statistical update writing group, with Harvard Medical School, Boston, said in an AHA podcast.

“The global rate of brain disease is quickly outpacing heart disease,” Mitchell S. V. Elkind, MD, immediate past president of the AHA, added in a news release.

“The rate of deaths from Alzheimer’s disease and other dementias rose more than twice as much in the past decade compared to the rate of deaths from heart disease, and that is something we must address,” said Dr. Elkind, with Columbia University Vagelos College of Physicians and Surgeons in New York.

“It’s becoming more evident that reducing vascular disease risk factors can make a real difference in helping people live longer, healthier lives, free of heart disease and brain disease,” Dr. Elkind added.

The AHA’s Heart Disease and Stroke Statistics – 2022 Update was published online January 26 in Circulation).

The report highlights some of the research connecting heart and brain health, including the following:

• A meta-analysis of 139 studies showed that people with midlife hypertension were five times more likely to experience impairment on global cognition and about twice as likely to experience reduced executive function, dementia, and Alzheimer’s disease.
• A meta-analysis of four longitudinal studies found that the risk for dementia associated with heart failure was increased nearly twofold.
• In the large prospective Atherosclerosis Risk in Communities (ARIC) Neurocognitive Study, atrial fibrillation was associated with greater cognitive decline and dementia over 20 years.
• A meta-analysis of 10 prospective studies (including 24,801 participants) showed that coronary heart disease (CHD) was associated with a 40% increased risk of poor cognitive outcomes, including dementia, cognitive impairment, or cognitive decline.

“This new chapter on brain health was a critical one to add,” Dr. Tsao said in the news release.

“The data we’ve collected brings to light the strong correlations between heart health and brain health and makes it an easy story to tell -- what’s good for the heart is good for the brain,” Dr. Tsao added.

Along with the new chapter on brain health, the 2022 statistical update provides the latest statistics and heart disease and stroke. Among the highlights:

• Cardiovascular disease (CVD) remains the leading cause of death worldwide. In the United States in 2019, CVD, listed as the underlying cause of death, accounted for 874,613 deaths, about 2,396 deaths each day. On average, someone dies of CVD every 36 seconds.
• CVD claims more lives each year in the United States than all forms of cancer and chronic lower respiratory disease combined.
• In 2019, CHD was the leading cause (41.3%) of deaths attributable to CVD, followed by other CVD (17.3%), stroke (17.2%), hypertension (11.7%), heart failure (9.9%), and diseases of the arteries (2.8%).
• In 2019, stroke accounted for roughly 1 in every 19 deaths in the United States. On average, someone in the United States has a stroke every 40 seconds and someone dies of stroke every 3 minutes 30 seconds. When considered separately from other CVD, stroke ranks number five among all causes of death in the United States.

While the annual statistics update aims to be a contemporary update of annual heart disease and stroke statistics over the past year, it also examines trends over time, Dr. Tsao explains in the podcast.

“One noteworthy point is that we saw a decline in the rate of cardiovascular mortality over the past three decades or so until about 2010. But over the past decade now, we’re also seeing a rise in these numbers,” she said.

This could be due to rising rates of obesity, diabetes, and poor hypertension control, as well as other lifestyle behaviors, Tsao said.
 

Key risk factor data

Each year, the statistical update gauges the cardiovascular health of Americans by tracking seven key health factors and behaviors that increase risk for heart disease and stroke. Below is a snapshot of the latest risk factor data.

Smoking

In 2019, smoking was the leading risk factor for years of life lost to premature death and the third leading risk factor for years of life lived with disability or injury.

According to the 2020 surgeon general’s report on smoking cessation, more than 480,000 Americans die as a result of cigarette smoking, and more than 41,000 die of secondhand smoke exposure each year (roughly 1 in 5 deaths annually).

One in 7 adults are current smokers, 1 in 6 female adults are current smokers, and 1 in 5 high school students use e-cigarettes.
 

Physical inactivity

In 2018, 25.4% of U.S. adults did not engage in leisure-time physical activity, and only 24.0% met the 2018 Physical Activity Guidelines for Americans for both aerobic and muscle strengthening.

Among U.S. high school students in 2019, only 44.1% were physically active for 60 minutes or more on at least 5 days of the week.
 

Nutrition

While there is some evidence that Americans are improving their diet, fewer than 10% of U.S. adults met guidelines for whole grain, whole fruit, and nonstarchy vegetable consumption each day in 2017–2018.

Overweight/obesity

The prevalence of obesity among adults increased from 1999–2000 through 2017–2018 from 30.5% to 42.4%. Overall prevalence of obesity and severe obesity in U.S. youth 2 to 19 years of age increased from 13.9% to 19.3% and 2.6% to 6.1% between 1999–2000 and 2017–2018.

Cholesterol

Close to 94 million (38.1%) U.S. adults have total cholesterol of 200 mg/dL or higher, according to 2015–2018 data; about 28.0 million (11.5%) have total cholesterol of 240 mg/dL or higher; and 27.8% have high levels of low-density lipoprotein cholesterol (130 mg/dL or higher).

Diabetes

In 2019, 87,647 U.S. deaths were attributed to diabetes; data show that 9.8 million U.S. adults have undiagnosed diabetes, 28.2 million have diagnosed diabetes, and 113.6 million have prediabetes.

Hypertension

A total of 121.5 million (47.3%) U.S. adults have hypertension, based on 2015–2018 data. In 2019, 102,072 U.S. deaths were primarily attributable to hypertension.

This statistical update was prepared by a volunteer writing group on behalf of the American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee. Disclosures for the writing committee are listed with the original article.



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

The American Heart Association (AHA) draws attention to the important bidirectional link between cardiovascular health and brain health in its annual statistical update on heart disease and stroke.

“For several years now, the AHA and the scientific community have increasingly recognized the connections between cardiovascular health and brain health, so it was time for us to cement this into its own chapter, which we highlight as the brain health chapter,” Connie W. Tsao, MD, MPH, chair of the statistical update writing group, with Harvard Medical School, Boston, said in an AHA podcast.

“The global rate of brain disease is quickly outpacing heart disease,” Mitchell S. V. Elkind, MD, immediate past president of the AHA, added in a news release.

“The rate of deaths from Alzheimer’s disease and other dementias rose more than twice as much in the past decade compared to the rate of deaths from heart disease, and that is something we must address,” said Dr. Elkind, with Columbia University Vagelos College of Physicians and Surgeons in New York.

“It’s becoming more evident that reducing vascular disease risk factors can make a real difference in helping people live longer, healthier lives, free of heart disease and brain disease,” Dr. Elkind added.

The AHA’s Heart Disease and Stroke Statistics – 2022 Update was published online January 26 in Circulation).

The report highlights some of the research connecting heart and brain health, including the following:

• A meta-analysis of 139 studies showed that people with midlife hypertension were five times more likely to experience impairment on global cognition and about twice as likely to experience reduced executive function, dementia, and Alzheimer’s disease.
• A meta-analysis of four longitudinal studies found that the risk for dementia associated with heart failure was increased nearly twofold.
• In the large prospective Atherosclerosis Risk in Communities (ARIC) Neurocognitive Study, atrial fibrillation was associated with greater cognitive decline and dementia over 20 years.
• A meta-analysis of 10 prospective studies (including 24,801 participants) showed that coronary heart disease (CHD) was associated with a 40% increased risk of poor cognitive outcomes, including dementia, cognitive impairment, or cognitive decline.

“This new chapter on brain health was a critical one to add,” Dr. Tsao said in the news release.

“The data we’ve collected brings to light the strong correlations between heart health and brain health and makes it an easy story to tell -- what’s good for the heart is good for the brain,” Dr. Tsao added.

Along with the new chapter on brain health, the 2022 statistical update provides the latest statistics and heart disease and stroke. Among the highlights:

• Cardiovascular disease (CVD) remains the leading cause of death worldwide. In the United States in 2019, CVD, listed as the underlying cause of death, accounted for 874,613 deaths, about 2,396 deaths each day. On average, someone dies of CVD every 36 seconds.
• CVD claims more lives each year in the United States than all forms of cancer and chronic lower respiratory disease combined.
• In 2019, CHD was the leading cause (41.3%) of deaths attributable to CVD, followed by other CVD (17.3%), stroke (17.2%), hypertension (11.7%), heart failure (9.9%), and diseases of the arteries (2.8%).
• In 2019, stroke accounted for roughly 1 in every 19 deaths in the United States. On average, someone in the United States has a stroke every 40 seconds and someone dies of stroke every 3 minutes 30 seconds. When considered separately from other CVD, stroke ranks number five among all causes of death in the United States.

While the annual statistics update aims to be a contemporary update of annual heart disease and stroke statistics over the past year, it also examines trends over time, Dr. Tsao explains in the podcast.

“One noteworthy point is that we saw a decline in the rate of cardiovascular mortality over the past three decades or so until about 2010. But over the past decade now, we’re also seeing a rise in these numbers,” she said.

This could be due to rising rates of obesity, diabetes, and poor hypertension control, as well as other lifestyle behaviors, Tsao said.
 

Key risk factor data

Each year, the statistical update gauges the cardiovascular health of Americans by tracking seven key health factors and behaviors that increase risk for heart disease and stroke. Below is a snapshot of the latest risk factor data.

Smoking

In 2019, smoking was the leading risk factor for years of life lost to premature death and the third leading risk factor for years of life lived with disability or injury.

According to the 2020 surgeon general’s report on smoking cessation, more than 480,000 Americans die as a result of cigarette smoking, and more than 41,000 die of secondhand smoke exposure each year (roughly 1 in 5 deaths annually).

One in 7 adults are current smokers, 1 in 6 female adults are current smokers, and 1 in 5 high school students use e-cigarettes.
 

Physical inactivity

In 2018, 25.4% of U.S. adults did not engage in leisure-time physical activity, and only 24.0% met the 2018 Physical Activity Guidelines for Americans for both aerobic and muscle strengthening.

Among U.S. high school students in 2019, only 44.1% were physically active for 60 minutes or more on at least 5 days of the week.
 

Nutrition

While there is some evidence that Americans are improving their diet, fewer than 10% of U.S. adults met guidelines for whole grain, whole fruit, and nonstarchy vegetable consumption each day in 2017–2018.

Overweight/obesity

The prevalence of obesity among adults increased from 1999–2000 through 2017–2018 from 30.5% to 42.4%. Overall prevalence of obesity and severe obesity in U.S. youth 2 to 19 years of age increased from 13.9% to 19.3% and 2.6% to 6.1% between 1999–2000 and 2017–2018.

Cholesterol

Close to 94 million (38.1%) U.S. adults have total cholesterol of 200 mg/dL or higher, according to 2015–2018 data; about 28.0 million (11.5%) have total cholesterol of 240 mg/dL or higher; and 27.8% have high levels of low-density lipoprotein cholesterol (130 mg/dL or higher).

Diabetes

In 2019, 87,647 U.S. deaths were attributed to diabetes; data show that 9.8 million U.S. adults have undiagnosed diabetes, 28.2 million have diagnosed diabetes, and 113.6 million have prediabetes.

Hypertension

A total of 121.5 million (47.3%) U.S. adults have hypertension, based on 2015–2018 data. In 2019, 102,072 U.S. deaths were primarily attributable to hypertension.

This statistical update was prepared by a volunteer writing group on behalf of the American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee. Disclosures for the writing committee are listed with the original article.



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

The American Heart Association (AHA) draws attention to the important bidirectional link between cardiovascular health and brain health in its annual statistical update on heart disease and stroke.

“For several years now, the AHA and the scientific community have increasingly recognized the connections between cardiovascular health and brain health, so it was time for us to cement this into its own chapter, which we highlight as the brain health chapter,” Connie W. Tsao, MD, MPH, chair of the statistical update writing group, with Harvard Medical School, Boston, said in an AHA podcast.

“The global rate of brain disease is quickly outpacing heart disease,” Mitchell S. V. Elkind, MD, immediate past president of the AHA, added in a news release.

“The rate of deaths from Alzheimer’s disease and other dementias rose more than twice as much in the past decade compared to the rate of deaths from heart disease, and that is something we must address,” said Dr. Elkind, with Columbia University Vagelos College of Physicians and Surgeons in New York.

“It’s becoming more evident that reducing vascular disease risk factors can make a real difference in helping people live longer, healthier lives, free of heart disease and brain disease,” Dr. Elkind added.

The AHA’s Heart Disease and Stroke Statistics – 2022 Update was published online January 26 in Circulation).

The report highlights some of the research connecting heart and brain health, including the following:

• A meta-analysis of 139 studies showed that people with midlife hypertension were five times more likely to experience impairment on global cognition and about twice as likely to experience reduced executive function, dementia, and Alzheimer’s disease.
• A meta-analysis of four longitudinal studies found that the risk for dementia associated with heart failure was increased nearly twofold.
• In the large prospective Atherosclerosis Risk in Communities (ARIC) Neurocognitive Study, atrial fibrillation was associated with greater cognitive decline and dementia over 20 years.
• A meta-analysis of 10 prospective studies (including 24,801 participants) showed that coronary heart disease (CHD) was associated with a 40% increased risk of poor cognitive outcomes, including dementia, cognitive impairment, or cognitive decline.

“This new chapter on brain health was a critical one to add,” Dr. Tsao said in the news release.

“The data we’ve collected brings to light the strong correlations between heart health and brain health and makes it an easy story to tell -- what’s good for the heart is good for the brain,” Dr. Tsao added.

Along with the new chapter on brain health, the 2022 statistical update provides the latest statistics and heart disease and stroke. Among the highlights:

• Cardiovascular disease (CVD) remains the leading cause of death worldwide. In the United States in 2019, CVD, listed as the underlying cause of death, accounted for 874,613 deaths, about 2,396 deaths each day. On average, someone dies of CVD every 36 seconds.
• CVD claims more lives each year in the United States than all forms of cancer and chronic lower respiratory disease combined.
• In 2019, CHD was the leading cause (41.3%) of deaths attributable to CVD, followed by other CVD (17.3%), stroke (17.2%), hypertension (11.7%), heart failure (9.9%), and diseases of the arteries (2.8%).
• In 2019, stroke accounted for roughly 1 in every 19 deaths in the United States. On average, someone in the United States has a stroke every 40 seconds and someone dies of stroke every 3 minutes 30 seconds. When considered separately from other CVD, stroke ranks number five among all causes of death in the United States.

While the annual statistics update aims to be a contemporary update of annual heart disease and stroke statistics over the past year, it also examines trends over time, Dr. Tsao explains in the podcast.

“One noteworthy point is that we saw a decline in the rate of cardiovascular mortality over the past three decades or so until about 2010. But over the past decade now, we’re also seeing a rise in these numbers,” she said.

This could be due to rising rates of obesity, diabetes, and poor hypertension control, as well as other lifestyle behaviors, Tsao said.
 

Key risk factor data

Each year, the statistical update gauges the cardiovascular health of Americans by tracking seven key health factors and behaviors that increase risk for heart disease and stroke. Below is a snapshot of the latest risk factor data.

Smoking

In 2019, smoking was the leading risk factor for years of life lost to premature death and the third leading risk factor for years of life lived with disability or injury.

According to the 2020 surgeon general’s report on smoking cessation, more than 480,000 Americans die as a result of cigarette smoking, and more than 41,000 die of secondhand smoke exposure each year (roughly 1 in 5 deaths annually).

One in 7 adults are current smokers, 1 in 6 female adults are current smokers, and 1 in 5 high school students use e-cigarettes.
 

Physical inactivity

In 2018, 25.4% of U.S. adults did not engage in leisure-time physical activity, and only 24.0% met the 2018 Physical Activity Guidelines for Americans for both aerobic and muscle strengthening.

Among U.S. high school students in 2019, only 44.1% were physically active for 60 minutes or more on at least 5 days of the week.
 

Nutrition

While there is some evidence that Americans are improving their diet, fewer than 10% of U.S. adults met guidelines for whole grain, whole fruit, and nonstarchy vegetable consumption each day in 2017–2018.

Overweight/obesity

The prevalence of obesity among adults increased from 1999–2000 through 2017–2018 from 30.5% to 42.4%. Overall prevalence of obesity and severe obesity in U.S. youth 2 to 19 years of age increased from 13.9% to 19.3% and 2.6% to 6.1% between 1999–2000 and 2017–2018.

Cholesterol

Close to 94 million (38.1%) U.S. adults have total cholesterol of 200 mg/dL or higher, according to 2015–2018 data; about 28.0 million (11.5%) have total cholesterol of 240 mg/dL or higher; and 27.8% have high levels of low-density lipoprotein cholesterol (130 mg/dL or higher).

Diabetes

In 2019, 87,647 U.S. deaths were attributed to diabetes; data show that 9.8 million U.S. adults have undiagnosed diabetes, 28.2 million have diagnosed diabetes, and 113.6 million have prediabetes.

Hypertension

A total of 121.5 million (47.3%) U.S. adults have hypertension, based on 2015–2018 data. In 2019, 102,072 U.S. deaths were primarily attributable to hypertension.

This statistical update was prepared by a volunteer writing group on behalf of the American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee. Disclosures for the writing committee are listed with the original article.



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

It all started with genetic data. A gene here, a gene there. Eventually the story became clearer: If scientists are to one day find a cure for Alzheimer’s disease, they should look to the immune system.

Over the past couple decades, researchers have identified numerous genes involved in various immune system functions that may also contribute to Alzheimer’s disease. Some of the prime suspects are genes that control microglia, now the focus of intense research in developing new Alzheimer’s drugs.

Microglia are amoeba-like cells that scour the brain for injuries and invaders. They help clear dead or impaired brain cells and literally gobble up invading microbes. Without them, we’d be in trouble.

In a normal brain, a protein called beta-amyloid is cleared away through our lymphatic system by microglia as molecular junk. But sometimes it builds up. Certain gene mutations are one culprit in this toxic accumulation. Traumatic brain injury is another, and, perhaps, impaired microglial function.

One thing everyone agrees on is that in people with Alzheimer’s disease, too much amyloid accumulates between their brain cells and in the vessels that supply the brain with blood. Once amyloid begins to clog networks of neurons, it triggers the accumulation of another protein, called tau, inside of these brain cells. The presence of tau sends microglia and other immune mechanisms into overdrive, resulting in the inflammatory immune response that many experts believe ultimately saps brain vitality in Alzheimer’s disease.
 

The gene scene

To date, nearly a dozen genes involved in immune and microglial function have been tied to Alzheimer’s disease. The first was CD33, identified in 2008.

“When we got the results, I literally ran to my colleague’s office next door and said, you gotta see this!” said Harvard neuroscientist Rudolph Tanzi. Dr. Tanzi, who goes by Rudy, led the CD33 research. The discovery was quickly named a top medical breakthrough of 2008 by Time magazine.

“We were laughing because what they didn’t know is we had no idea what this gene did,” he joked. But over time, research by Dr. Tanzi and his group revealed that CD33 is a kind of microglial on-off switch, activating the cells as part of an inflammatory pathway.

“We kind of got it all going when it came to the genetics,” he said.

Microglia normally recognize molecular patterns associated with microbes and cellular damage as unwanted. This is how they know to take action – to devour unfamiliar pathogens and dead tissue. Dr. Tanzi believes microglia sense any sign of brain damage as an infection, which causes them to become hyperactive.

Much of our modern human immune system, he explained, evolved many hundreds of thousands of years ago. Our lifespans at the time were far shorter than they are today, and the majority of people didn’t live long enough to develop dementia or the withered brain cells that come with it. So our immune system, he said, assumes any faulty brain tissue is due to a microbe, not dementia. Microglia react aggressively, clearing the area to prevent the spread of infection.

“They say, ‘We better wipe out this part of the brain that’s infected, even if it’s not.’ They don’t know,” quipped Dr. Tanzi. “That’s what causes neuroinflammation. And CD33 turns this response on. The microglia become killers, not just janitors.”
 

A brake on overactive microglia

If CD33 is the yin, a gene called TREM2 is the yang. Discovered a few years after CD33, TREM2 reins in microglial activation, returning them to their role as cellular housekeepers.

Neurologist David Holtzman, MD, of Washington University in St. Louis, who studies TREM2, agrees that wherever you find amyloid, tau, or dead brain cells, there are microglia raring to go and ready to scavenge.

“I think at first a lot of people thought these cells were reacting to Alzheimer’s pathology, and not necessarily a cause of the disease,” he said.

It was the discovery of TREM2 on the heels of CD33 that really shifted the thinking, in part because it produces a protein that in the brain is only found in microglia. “Many of us [in the field] immediately said, ‘Look, there’s now a risk factor that is only expressed in microglia. It must be that innate immune cells are important in some way in the pathogenesis of the disease,’ “ he added.

Dr. Holtzman sees microglial activation in impending dementia as a double-edged sword. In the beginning, microglia clear unwanted amyloid to maintain brain health. But once accumulated amyloid and tau have done enough damage, the neuroinflammation that comes with microglial activation does more harm than good. Neurons die en masse and dementia sets in.

But not all researchers are convinced.

Serge Revist, PhD, is a professor in the department of molecular medicine at the Laval University Medical School in Quebec. Based on his lab’s research, he believes that while impaired immune activity is involved in Alzheimer’s disease, it is not the root cause. “I don’t think it is the immune cells that do the damage, I still think it is the beta-amyloid itself,” he said, “In my lab, in mouse studies, we’ve never found that immune cells were directly responsible for killing neurons.”

He does believe that in some patients with Alzheimer’s disease, microglia may not be able to handle the excess amyloid that accumulates in the disease and that developing treatments that improve the ability of microglia and the immune system to clear the protein could be effective.
 

Microglial medicines

The biological cascade leading to Alzheimer’s disease is a tangled one. Gene variants influencing the accumulation and clearance of amyloid are likely a major contributor. But immune activity caused by early life infection might also be involved, at least in some cases. This infectious theory of Alzheimer’s disease was first proposed by Dr. Tanzi’s now-deceased colleague Robert Moir, PhD. Dr. Tanzi’s group even has evidence that amyloid itself is antimicrobial and evolved to protect us from pathogens, only to become a problem when overactive and aggregated.

And the same goes for microglia, cells whose over-ambition might cause much of the brain degeneration seen in Alzheimer’s disease.

In theory, if a treatment could decrease CD33 activity or increase that of TREM2, doctors might one day may be able to slow or even stop the progression of dementia. Instead of going after amyloid itself – the mechanism behind so many failed investigational Alzheimer’s drugs – a therapy that quells the immune response to amyloid might be the answer in treating dementia.

“There are a number of scientists and companies trying to figure out how to influence genes like TREM2 and CD33 and to both decrease amyloid and act on the downstream consequences of the protein,” said Dr. Holtzman. “All of this is to say that somewhere in the biology that causes Alzheimer’s disease, the immune system is involved.”

It seems that in many cases, the most common form of a dementia might be due to a well-intentioned immune cell going rogue. “I think you’d hear this from basically any researcher worth their salt,” said Dr. Tanzi. “I feel strongly that without microglial activation, you will not get Alzheimer’s disease.”

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

It all started with genetic data. A gene here, a gene there. Eventually the story became clearer: If scientists are to one day find a cure for Alzheimer’s disease, they should look to the immune system.

Over the past couple decades, researchers have identified numerous genes involved in various immune system functions that may also contribute to Alzheimer’s disease. Some of the prime suspects are genes that control microglia, now the focus of intense research in developing new Alzheimer’s drugs.

Microglia are amoeba-like cells that scour the brain for injuries and invaders. They help clear dead or impaired brain cells and literally gobble up invading microbes. Without them, we’d be in trouble.

In a normal brain, a protein called beta-amyloid is cleared away through our lymphatic system by microglia as molecular junk. But sometimes it builds up. Certain gene mutations are one culprit in this toxic accumulation. Traumatic brain injury is another, and, perhaps, impaired microglial function.

One thing everyone agrees on is that in people with Alzheimer’s disease, too much amyloid accumulates between their brain cells and in the vessels that supply the brain with blood. Once amyloid begins to clog networks of neurons, it triggers the accumulation of another protein, called tau, inside of these brain cells. The presence of tau sends microglia and other immune mechanisms into overdrive, resulting in the inflammatory immune response that many experts believe ultimately saps brain vitality in Alzheimer’s disease.
 

The gene scene

To date, nearly a dozen genes involved in immune and microglial function have been tied to Alzheimer’s disease. The first was CD33, identified in 2008.

“When we got the results, I literally ran to my colleague’s office next door and said, you gotta see this!” said Harvard neuroscientist Rudolph Tanzi. Dr. Tanzi, who goes by Rudy, led the CD33 research. The discovery was quickly named a top medical breakthrough of 2008 by Time magazine.

“We were laughing because what they didn’t know is we had no idea what this gene did,” he joked. But over time, research by Dr. Tanzi and his group revealed that CD33 is a kind of microglial on-off switch, activating the cells as part of an inflammatory pathway.

“We kind of got it all going when it came to the genetics,” he said.

Microglia normally recognize molecular patterns associated with microbes and cellular damage as unwanted. This is how they know to take action – to devour unfamiliar pathogens and dead tissue. Dr. Tanzi believes microglia sense any sign of brain damage as an infection, which causes them to become hyperactive.

Much of our modern human immune system, he explained, evolved many hundreds of thousands of years ago. Our lifespans at the time were far shorter than they are today, and the majority of people didn’t live long enough to develop dementia or the withered brain cells that come with it. So our immune system, he said, assumes any faulty brain tissue is due to a microbe, not dementia. Microglia react aggressively, clearing the area to prevent the spread of infection.

“They say, ‘We better wipe out this part of the brain that’s infected, even if it’s not.’ They don’t know,” quipped Dr. Tanzi. “That’s what causes neuroinflammation. And CD33 turns this response on. The microglia become killers, not just janitors.”
 

A brake on overactive microglia

If CD33 is the yin, a gene called TREM2 is the yang. Discovered a few years after CD33, TREM2 reins in microglial activation, returning them to their role as cellular housekeepers.

Neurologist David Holtzman, MD, of Washington University in St. Louis, who studies TREM2, agrees that wherever you find amyloid, tau, or dead brain cells, there are microglia raring to go and ready to scavenge.

“I think at first a lot of people thought these cells were reacting to Alzheimer’s pathology, and not necessarily a cause of the disease,” he said.

It was the discovery of TREM2 on the heels of CD33 that really shifted the thinking, in part because it produces a protein that in the brain is only found in microglia. “Many of us [in the field] immediately said, ‘Look, there’s now a risk factor that is only expressed in microglia. It must be that innate immune cells are important in some way in the pathogenesis of the disease,’ “ he added.

Dr. Holtzman sees microglial activation in impending dementia as a double-edged sword. In the beginning, microglia clear unwanted amyloid to maintain brain health. But once accumulated amyloid and tau have done enough damage, the neuroinflammation that comes with microglial activation does more harm than good. Neurons die en masse and dementia sets in.

But not all researchers are convinced.

Serge Revist, PhD, is a professor in the department of molecular medicine at the Laval University Medical School in Quebec. Based on his lab’s research, he believes that while impaired immune activity is involved in Alzheimer’s disease, it is not the root cause. “I don’t think it is the immune cells that do the damage, I still think it is the beta-amyloid itself,” he said, “In my lab, in mouse studies, we’ve never found that immune cells were directly responsible for killing neurons.”

He does believe that in some patients with Alzheimer’s disease, microglia may not be able to handle the excess amyloid that accumulates in the disease and that developing treatments that improve the ability of microglia and the immune system to clear the protein could be effective.
 

Microglial medicines

The biological cascade leading to Alzheimer’s disease is a tangled one. Gene variants influencing the accumulation and clearance of amyloid are likely a major contributor. But immune activity caused by early life infection might also be involved, at least in some cases. This infectious theory of Alzheimer’s disease was first proposed by Dr. Tanzi’s now-deceased colleague Robert Moir, PhD. Dr. Tanzi’s group even has evidence that amyloid itself is antimicrobial and evolved to protect us from pathogens, only to become a problem when overactive and aggregated.

And the same goes for microglia, cells whose over-ambition might cause much of the brain degeneration seen in Alzheimer’s disease.

In theory, if a treatment could decrease CD33 activity or increase that of TREM2, doctors might one day may be able to slow or even stop the progression of dementia. Instead of going after amyloid itself – the mechanism behind so many failed investigational Alzheimer’s drugs – a therapy that quells the immune response to amyloid might be the answer in treating dementia.

“There are a number of scientists and companies trying to figure out how to influence genes like TREM2 and CD33 and to both decrease amyloid and act on the downstream consequences of the protein,” said Dr. Holtzman. “All of this is to say that somewhere in the biology that causes Alzheimer’s disease, the immune system is involved.”

It seems that in many cases, the most common form of a dementia might be due to a well-intentioned immune cell going rogue. “I think you’d hear this from basically any researcher worth their salt,” said Dr. Tanzi. “I feel strongly that without microglial activation, you will not get Alzheimer’s disease.”

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

It all started with genetic data. A gene here, a gene there. Eventually the story became clearer: If scientists are to one day find a cure for Alzheimer’s disease, they should look to the immune system.

Over the past couple decades, researchers have identified numerous genes involved in various immune system functions that may also contribute to Alzheimer’s disease. Some of the prime suspects are genes that control microglia, now the focus of intense research in developing new Alzheimer’s drugs.

Microglia are amoeba-like cells that scour the brain for injuries and invaders. They help clear dead or impaired brain cells and literally gobble up invading microbes. Without them, we’d be in trouble.

In a normal brain, a protein called beta-amyloid is cleared away through our lymphatic system by microglia as molecular junk. But sometimes it builds up. Certain gene mutations are one culprit in this toxic accumulation. Traumatic brain injury is another, and, perhaps, impaired microglial function.

One thing everyone agrees on is that in people with Alzheimer’s disease, too much amyloid accumulates between their brain cells and in the vessels that supply the brain with blood. Once amyloid begins to clog networks of neurons, it triggers the accumulation of another protein, called tau, inside of these brain cells. The presence of tau sends microglia and other immune mechanisms into overdrive, resulting in the inflammatory immune response that many experts believe ultimately saps brain vitality in Alzheimer’s disease.
 

The gene scene

To date, nearly a dozen genes involved in immune and microglial function have been tied to Alzheimer’s disease. The first was CD33, identified in 2008.

“When we got the results, I literally ran to my colleague’s office next door and said, you gotta see this!” said Harvard neuroscientist Rudolph Tanzi. Dr. Tanzi, who goes by Rudy, led the CD33 research. The discovery was quickly named a top medical breakthrough of 2008 by Time magazine.

“We were laughing because what they didn’t know is we had no idea what this gene did,” he joked. But over time, research by Dr. Tanzi and his group revealed that CD33 is a kind of microglial on-off switch, activating the cells as part of an inflammatory pathway.

“We kind of got it all going when it came to the genetics,” he said.

Microglia normally recognize molecular patterns associated with microbes and cellular damage as unwanted. This is how they know to take action – to devour unfamiliar pathogens and dead tissue. Dr. Tanzi believes microglia sense any sign of brain damage as an infection, which causes them to become hyperactive.

Much of our modern human immune system, he explained, evolved many hundreds of thousands of years ago. Our lifespans at the time were far shorter than they are today, and the majority of people didn’t live long enough to develop dementia or the withered brain cells that come with it. So our immune system, he said, assumes any faulty brain tissue is due to a microbe, not dementia. Microglia react aggressively, clearing the area to prevent the spread of infection.

“They say, ‘We better wipe out this part of the brain that’s infected, even if it’s not.’ They don’t know,” quipped Dr. Tanzi. “That’s what causes neuroinflammation. And CD33 turns this response on. The microglia become killers, not just janitors.”
 

A brake on overactive microglia

If CD33 is the yin, a gene called TREM2 is the yang. Discovered a few years after CD33, TREM2 reins in microglial activation, returning them to their role as cellular housekeepers.

Neurologist David Holtzman, MD, of Washington University in St. Louis, who studies TREM2, agrees that wherever you find amyloid, tau, or dead brain cells, there are microglia raring to go and ready to scavenge.

“I think at first a lot of people thought these cells were reacting to Alzheimer’s pathology, and not necessarily a cause of the disease,” he said.

It was the discovery of TREM2 on the heels of CD33 that really shifted the thinking, in part because it produces a protein that in the brain is only found in microglia. “Many of us [in the field] immediately said, ‘Look, there’s now a risk factor that is only expressed in microglia. It must be that innate immune cells are important in some way in the pathogenesis of the disease,’ “ he added.

Dr. Holtzman sees microglial activation in impending dementia as a double-edged sword. In the beginning, microglia clear unwanted amyloid to maintain brain health. But once accumulated amyloid and tau have done enough damage, the neuroinflammation that comes with microglial activation does more harm than good. Neurons die en masse and dementia sets in.

But not all researchers are convinced.

Serge Revist, PhD, is a professor in the department of molecular medicine at the Laval University Medical School in Quebec. Based on his lab’s research, he believes that while impaired immune activity is involved in Alzheimer’s disease, it is not the root cause. “I don’t think it is the immune cells that do the damage, I still think it is the beta-amyloid itself,” he said, “In my lab, in mouse studies, we’ve never found that immune cells were directly responsible for killing neurons.”

He does believe that in some patients with Alzheimer’s disease, microglia may not be able to handle the excess amyloid that accumulates in the disease and that developing treatments that improve the ability of microglia and the immune system to clear the protein could be effective.
 

Microglial medicines

The biological cascade leading to Alzheimer’s disease is a tangled one. Gene variants influencing the accumulation and clearance of amyloid are likely a major contributor. But immune activity caused by early life infection might also be involved, at least in some cases. This infectious theory of Alzheimer’s disease was first proposed by Dr. Tanzi’s now-deceased colleague Robert Moir, PhD. Dr. Tanzi’s group even has evidence that amyloid itself is antimicrobial and evolved to protect us from pathogens, only to become a problem when overactive and aggregated.

And the same goes for microglia, cells whose over-ambition might cause much of the brain degeneration seen in Alzheimer’s disease.

In theory, if a treatment could decrease CD33 activity or increase that of TREM2, doctors might one day may be able to slow or even stop the progression of dementia. Instead of going after amyloid itself – the mechanism behind so many failed investigational Alzheimer’s drugs – a therapy that quells the immune response to amyloid might be the answer in treating dementia.

“There are a number of scientists and companies trying to figure out how to influence genes like TREM2 and CD33 and to both decrease amyloid and act on the downstream consequences of the protein,” said Dr. Holtzman. “All of this is to say that somewhere in the biology that causes Alzheimer’s disease, the immune system is involved.”

It seems that in many cases, the most common form of a dementia might be due to a well-intentioned immune cell going rogue. “I think you’d hear this from basically any researcher worth their salt,” said Dr. Tanzi. “I feel strongly that without microglial activation, you will not get Alzheimer’s disease.”

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

Subclinical changes in cardiac structure and diastolic function in early adulthood may serve as risk markers for cognitive decline in midlife, new research suggests.

Cardiovascular disease risk factors such as high blood pressure, high cholesterol, and diabetes have been associated with an increased risk for cognitive impairment, but much less is known about heart structure and function and the risks for cognition.

“We showed for the first time that, even before the occurrence of cardiovascular disease, people with abnormalities in cardiac structure and function as early as in young adulthood have lower midlife cognition,” investigators Laure Rouch, PharmD, PhD, and Kristine Yaffe, MD, both with the department of psychiatry, University of California, San Francisco, said in a joint email.

“This study reminds us that heart health is key to brain health and that the overlap and interplay between the two is not limited to patients with end-stage heart disease,” Dr. Rouch and Dr. Yaffe said.

The findings were published online Jan. 26, 2022, in Neurology.
 

Heart/brain connection

The analysis included 2,653 participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study.

Echocardiograms were obtained at year 5, 25, and 30 study visits – at mean ages of 30, 50, and 55 years, respectively. At year 30, participants underwent a standard battery of tests measuring global cognition, processing speed, executive function, delayed verbal memory, and verbal fluency.

Over 25 years, there was an average increase in left ventricular mass of 0.27 g/m2 per year – from a mean of 80.5 g/m² in year 5 to 86.0 g/m² in year 30.

Left atrial volume increased by an average of 0.42 mL/m2 per year, from 16 mL/m² in year 5 to 26 mL/m² in year 30.

Left ventricular ejection fraction (LVEF) decreased by 0.11% per year, from 63.3% in year 5 to 59.7% in year 30.

After adjustment for demographics and education, an increase in left ventricular mass of at least 1 standard deviation over 25 years was associated with lower cognition on most tests (P ≤ .02).

An increase in left atrial volume over the study period was associated with lower global cognition (P = .04), whereas a decrease in LVEF was not associated with cognition. Further adjustment for cardiovascular risk factors yielded similar results.

“A more effective collaboration is needed between cardiologists and neurologists to promote healthy brain aging,” Dr. Rouch and Dr. Yaffe said.

“Echocardiography is a widely available, relatively inexpensive, and noninvasive imaging method that could be integrated into a risk assessment for cognitive impairment,” they added.

Looking ahead, the investigators noted there is a need for further research to determine whether interventions to improve cardiac structure and diastolic function could also benefit brain health.

They should also investigate the role of arterial stiffness and cerebral small vessel disease in the relationship between cardiac structure, function, and cognition, the researchers added.
 

First structural biomarker

Commenting on the study, Shaheen E. Lakhan, MD, PhD, a neurologist in Newton, Mass., said the study is important because, “thus far, the connections have really been physiological parameters,” such as blood pressure and cognitive health.

“This is really strong evidence of a structural cardiac biomarker that can be measured before and independent of changes in physiology or diseased state,” said Dr. Lakhan, who was not involved with the research.

As more and more interventions are being introduced for addressing disorders of cognition, “this potential structural finding may serve as a solid biomarker to determine” what lifestyle or drug therapy should be taken, he added.

Also weighing in on the findings, Pierre Fayad, MD, professor in the department of neurological sciences and director of the Nebraska Stroke Center, University of Nebraska Medical Center, Omaha, said CARDIA is “an important study” providing “precious data.”

The reported changes in cardiac structure and function “precede the clinical symptomatology, as the follow-up stops before they enter into later adulthood, where the risk of clinical events dramatically rises. Meaning these patients still have not had stroke, congestive heart failure, heart attack or dementia, but some of them could be on that trajectory later in their life,” Dr. Fayad told this news organization.

Documenting such changes over time is “valuable to give an insight into what leads us to such progression,” he noted.

How reliably predictive the findings are for eventual clinical cognitive impairment “will need to be confirmed and verified” in future studies, he added.

“If verified, it could be helpful to provide interventions to those with the left atrial volume enlargement marker and see their effectiveness at preventing eventual clinical cognitive impairment,” said Dr. Fayad.

The CARDIA study is supported by the National Heart, Lung, and Blood Institute in collaboration with the University of Alabama at Birmingham, Northwestern University, the University of Minnesota, and the Kaiser Foundation Research Institute. Rouch, Lakhan, and Dr. Fayad have disclosed no relevant financial relationships.

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

Subclinical changes in cardiac structure and diastolic function in early adulthood may serve as risk markers for cognitive decline in midlife, new research suggests.

Cardiovascular disease risk factors such as high blood pressure, high cholesterol, and diabetes have been associated with an increased risk for cognitive impairment, but much less is known about heart structure and function and the risks for cognition.

“We showed for the first time that, even before the occurrence of cardiovascular disease, people with abnormalities in cardiac structure and function as early as in young adulthood have lower midlife cognition,” investigators Laure Rouch, PharmD, PhD, and Kristine Yaffe, MD, both with the department of psychiatry, University of California, San Francisco, said in a joint email.

“This study reminds us that heart health is key to brain health and that the overlap and interplay between the two is not limited to patients with end-stage heart disease,” Dr. Rouch and Dr. Yaffe said.

The findings were published online Jan. 26, 2022, in Neurology.
 

Heart/brain connection

The analysis included 2,653 participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study.

Echocardiograms were obtained at year 5, 25, and 30 study visits – at mean ages of 30, 50, and 55 years, respectively. At year 30, participants underwent a standard battery of tests measuring global cognition, processing speed, executive function, delayed verbal memory, and verbal fluency.

Over 25 years, there was an average increase in left ventricular mass of 0.27 g/m2 per year – from a mean of 80.5 g/m² in year 5 to 86.0 g/m² in year 30.

Left atrial volume increased by an average of 0.42 mL/m2 per year, from 16 mL/m² in year 5 to 26 mL/m² in year 30.

Left ventricular ejection fraction (LVEF) decreased by 0.11% per year, from 63.3% in year 5 to 59.7% in year 30.

After adjustment for demographics and education, an increase in left ventricular mass of at least 1 standard deviation over 25 years was associated with lower cognition on most tests (P ≤ .02).

An increase in left atrial volume over the study period was associated with lower global cognition (P = .04), whereas a decrease in LVEF was not associated with cognition. Further adjustment for cardiovascular risk factors yielded similar results.

“A more effective collaboration is needed between cardiologists and neurologists to promote healthy brain aging,” Dr. Rouch and Dr. Yaffe said.

“Echocardiography is a widely available, relatively inexpensive, and noninvasive imaging method that could be integrated into a risk assessment for cognitive impairment,” they added.

Looking ahead, the investigators noted there is a need for further research to determine whether interventions to improve cardiac structure and diastolic function could also benefit brain health.

They should also investigate the role of arterial stiffness and cerebral small vessel disease in the relationship between cardiac structure, function, and cognition, the researchers added.
 

First structural biomarker

Commenting on the study, Shaheen E. Lakhan, MD, PhD, a neurologist in Newton, Mass., said the study is important because, “thus far, the connections have really been physiological parameters,” such as blood pressure and cognitive health.

“This is really strong evidence of a structural cardiac biomarker that can be measured before and independent of changes in physiology or diseased state,” said Dr. Lakhan, who was not involved with the research.

As more and more interventions are being introduced for addressing disorders of cognition, “this potential structural finding may serve as a solid biomarker to determine” what lifestyle or drug therapy should be taken, he added.

Also weighing in on the findings, Pierre Fayad, MD, professor in the department of neurological sciences and director of the Nebraska Stroke Center, University of Nebraska Medical Center, Omaha, said CARDIA is “an important study” providing “precious data.”

The reported changes in cardiac structure and function “precede the clinical symptomatology, as the follow-up stops before they enter into later adulthood, where the risk of clinical events dramatically rises. Meaning these patients still have not had stroke, congestive heart failure, heart attack or dementia, but some of them could be on that trajectory later in their life,” Dr. Fayad told this news organization.

Documenting such changes over time is “valuable to give an insight into what leads us to such progression,” he noted.

How reliably predictive the findings are for eventual clinical cognitive impairment “will need to be confirmed and verified” in future studies, he added.

“If verified, it could be helpful to provide interventions to those with the left atrial volume enlargement marker and see their effectiveness at preventing eventual clinical cognitive impairment,” said Dr. Fayad.

The CARDIA study is supported by the National Heart, Lung, and Blood Institute in collaboration with the University of Alabama at Birmingham, Northwestern University, the University of Minnesota, and the Kaiser Foundation Research Institute. Rouch, Lakhan, and Dr. Fayad have disclosed no relevant financial relationships.

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

Subclinical changes in cardiac structure and diastolic function in early adulthood may serve as risk markers for cognitive decline in midlife, new research suggests.

Cardiovascular disease risk factors such as high blood pressure, high cholesterol, and diabetes have been associated with an increased risk for cognitive impairment, but much less is known about heart structure and function and the risks for cognition.

“We showed for the first time that, even before the occurrence of cardiovascular disease, people with abnormalities in cardiac structure and function as early as in young adulthood have lower midlife cognition,” investigators Laure Rouch, PharmD, PhD, and Kristine Yaffe, MD, both with the department of psychiatry, University of California, San Francisco, said in a joint email.

“This study reminds us that heart health is key to brain health and that the overlap and interplay between the two is not limited to patients with end-stage heart disease,” Dr. Rouch and Dr. Yaffe said.

The findings were published online Jan. 26, 2022, in Neurology.
 

Heart/brain connection

The analysis included 2,653 participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study.

Echocardiograms were obtained at year 5, 25, and 30 study visits – at mean ages of 30, 50, and 55 years, respectively. At year 30, participants underwent a standard battery of tests measuring global cognition, processing speed, executive function, delayed verbal memory, and verbal fluency.

Over 25 years, there was an average increase in left ventricular mass of 0.27 g/m2 per year – from a mean of 80.5 g/m² in year 5 to 86.0 g/m² in year 30.

Left atrial volume increased by an average of 0.42 mL/m2 per year, from 16 mL/m² in year 5 to 26 mL/m² in year 30.

Left ventricular ejection fraction (LVEF) decreased by 0.11% per year, from 63.3% in year 5 to 59.7% in year 30.

After adjustment for demographics and education, an increase in left ventricular mass of at least 1 standard deviation over 25 years was associated with lower cognition on most tests (P ≤ .02).

An increase in left atrial volume over the study period was associated with lower global cognition (P = .04), whereas a decrease in LVEF was not associated with cognition. Further adjustment for cardiovascular risk factors yielded similar results.

“A more effective collaboration is needed between cardiologists and neurologists to promote healthy brain aging,” Dr. Rouch and Dr. Yaffe said.

“Echocardiography is a widely available, relatively inexpensive, and noninvasive imaging method that could be integrated into a risk assessment for cognitive impairment,” they added.

Looking ahead, the investigators noted there is a need for further research to determine whether interventions to improve cardiac structure and diastolic function could also benefit brain health.

They should also investigate the role of arterial stiffness and cerebral small vessel disease in the relationship between cardiac structure, function, and cognition, the researchers added.
 

First structural biomarker

Commenting on the study, Shaheen E. Lakhan, MD, PhD, a neurologist in Newton, Mass., said the study is important because, “thus far, the connections have really been physiological parameters,” such as blood pressure and cognitive health.

“This is really strong evidence of a structural cardiac biomarker that can be measured before and independent of changes in physiology or diseased state,” said Dr. Lakhan, who was not involved with the research.

As more and more interventions are being introduced for addressing disorders of cognition, “this potential structural finding may serve as a solid biomarker to determine” what lifestyle or drug therapy should be taken, he added.

Also weighing in on the findings, Pierre Fayad, MD, professor in the department of neurological sciences and director of the Nebraska Stroke Center, University of Nebraska Medical Center, Omaha, said CARDIA is “an important study” providing “precious data.”

The reported changes in cardiac structure and function “precede the clinical symptomatology, as the follow-up stops before they enter into later adulthood, where the risk of clinical events dramatically rises. Meaning these patients still have not had stroke, congestive heart failure, heart attack or dementia, but some of them could be on that trajectory later in their life,” Dr. Fayad told this news organization.

Documenting such changes over time is “valuable to give an insight into what leads us to such progression,” he noted.

How reliably predictive the findings are for eventual clinical cognitive impairment “will need to be confirmed and verified” in future studies, he added.

“If verified, it could be helpful to provide interventions to those with the left atrial volume enlargement marker and see their effectiveness at preventing eventual clinical cognitive impairment,” said Dr. Fayad.

The CARDIA study is supported by the National Heart, Lung, and Blood Institute in collaboration with the University of Alabama at Birmingham, Northwestern University, the University of Minnesota, and the Kaiser Foundation Research Institute. Rouch, Lakhan, and Dr. Fayad have disclosed no relevant financial relationships.

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

The study covered in this summary was published in medRxiv.org as a preprint and has not yet been peer reviewed.

Key takeaways

• Measurement of the rate of cellular amyloid uptake and metabolic production of toxic amyloid species could be used as novel biomarkers for early and/or differential diagnosis of Alzheimer’s disease (AD).
• Estimated beta-amyloid (Aβ42) cellular uptake can be more than two times greater in AD patients compared to cognitively normal subjects. A less pronounced yet increased uptake rate was also observed in patients with late-onset mild cognitive impairment (MCI). This increased uptake may prove to be a key mechanism defining age-related AD progression.
• The increased cellular amyloid uptake in AD and LMCI may lead to quicker disease progression, but early-onset MCI may result from increased production of toxic amyloid metabolites.

Why this matters

• Additional biomarkers for AD could greatly aid diagnosis and course prediction, as they are currently limited to PET scan analysis of amyloid plaque deposits and concentration of Aβ42 in cerebrospinal fluid (CSF).
• Amyloid deposits found by PET have a positive correlation with AD diagnosis. In contrast, CSF-Aβ42 and AD diagnosis or cognitive decline are negatively correlated. Normal cognition (NC) is associated with higher CSF beta-amyloid levels, but previous research has not explained why CSF-Aβ42 levels can be equivalent in patients with NC but high amyloid load and patients with AD and low amyloid load.

Study design

• The authors of this retrospective study used anonymized data obtained from the Alzheimer’s’s Disease Neuroimaging Initiative (ADNI). ADNI’s goal has been to test whether serial MRI scans, PET scans, biomarkers, and clinical/neuropsychological assessment can be combined to measure the progression of MCI and AD.
• Study subjects had either an AD diagnosis or NC and were divided into two groups: low amyloid load and high amyloid load. The fraction of patients with an AD diagnosis was calculated as a function of CSF-Aβ42.
• Calculations and statistical comparisons were performed using Microsoft Excel and custom-written C++ programs.

Key results

• The lowest levels of CSF-Aβ42 correlated with the highest percentage of AD-diagnosed patients, estimated to be 27% in subjects with low amyloid deposit density and 65% in those with high deposit density.
• The relationship between CSF-Aβ42 levels and amyloid load can be described using a simple mathematical model: Amyloid concentration in the interstitial cells is equal to the synthesis rate divided by the density of amyloid deposits plus the sum of the rate of amyloid removal through the CSF and the cellular amyloid uptake rate.
• AD and late-onset MCI patients had a significantly higher amyloid removal rate compared to NC subjects.
• Early-onset MCI patients had Aβ42 turnover similar to that of NC subjects, pointing to a different underlying mechanism such as enzymatic disbalance.

Limitations

• The model used to explain amyloid exchange between the interstitial space and the CSF is oversimplified; the actual process is more complex.
• Synthesis and uptake rates of Aβ42 vary throughout areas of the brain. The model assumes a homogeneous distribution within the interstitial compartment.

Study disclosures

• Research reported in this publication was not supported by any external funding. Data collection and sharing for this project were funded by ADNI.

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

The study covered in this summary was published in medRxiv.org as a preprint and has not yet been peer reviewed.

Key takeaways

• Measurement of the rate of cellular amyloid uptake and metabolic production of toxic amyloid species could be used as novel biomarkers for early and/or differential diagnosis of Alzheimer’s disease (AD).
• Estimated beta-amyloid (Aβ42) cellular uptake can be more than two times greater in AD patients compared to cognitively normal subjects. A less pronounced yet increased uptake rate was also observed in patients with late-onset mild cognitive impairment (MCI). This increased uptake may prove to be a key mechanism defining age-related AD progression.
• The increased cellular amyloid uptake in AD and LMCI may lead to quicker disease progression, but early-onset MCI may result from increased production of toxic amyloid metabolites.

Why this matters

• Additional biomarkers for AD could greatly aid diagnosis and course prediction, as they are currently limited to PET scan analysis of amyloid plaque deposits and concentration of Aβ42 in cerebrospinal fluid (CSF).
• Amyloid deposits found by PET have a positive correlation with AD diagnosis. In contrast, CSF-Aβ42 and AD diagnosis or cognitive decline are negatively correlated. Normal cognition (NC) is associated with higher CSF beta-amyloid levels, but previous research has not explained why CSF-Aβ42 levels can be equivalent in patients with NC but high amyloid load and patients with AD and low amyloid load.

Study design

• The authors of this retrospective study used anonymized data obtained from the Alzheimer’s’s Disease Neuroimaging Initiative (ADNI). ADNI’s goal has been to test whether serial MRI scans, PET scans, biomarkers, and clinical/neuropsychological assessment can be combined to measure the progression of MCI and AD.
• Study subjects had either an AD diagnosis or NC and were divided into two groups: low amyloid load and high amyloid load. The fraction of patients with an AD diagnosis was calculated as a function of CSF-Aβ42.
• Calculations and statistical comparisons were performed using Microsoft Excel and custom-written C++ programs.

Key results

• The lowest levels of CSF-Aβ42 correlated with the highest percentage of AD-diagnosed patients, estimated to be 27% in subjects with low amyloid deposit density and 65% in those with high deposit density.
• The relationship between CSF-Aβ42 levels and amyloid load can be described using a simple mathematical model: Amyloid concentration in the interstitial cells is equal to the synthesis rate divided by the density of amyloid deposits plus the sum of the rate of amyloid removal through the CSF and the cellular amyloid uptake rate.
• AD and late-onset MCI patients had a significantly higher amyloid removal rate compared to NC subjects.
• Early-onset MCI patients had Aβ42 turnover similar to that of NC subjects, pointing to a different underlying mechanism such as enzymatic disbalance.

Limitations

• The model used to explain amyloid exchange between the interstitial space and the CSF is oversimplified; the actual process is more complex.
• Synthesis and uptake rates of Aβ42 vary throughout areas of the brain. The model assumes a homogeneous distribution within the interstitial compartment.

Study disclosures

• Research reported in this publication was not supported by any external funding. Data collection and sharing for this project were funded by ADNI.

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

The study covered in this summary was published in medRxiv.org as a preprint and has not yet been peer reviewed.

Key takeaways

• Measurement of the rate of cellular amyloid uptake and metabolic production of toxic amyloid species could be used as novel biomarkers for early and/or differential diagnosis of Alzheimer’s disease (AD).
• Estimated beta-amyloid (Aβ42) cellular uptake can be more than two times greater in AD patients compared to cognitively normal subjects. A less pronounced yet increased uptake rate was also observed in patients with late-onset mild cognitive impairment (MCI). This increased uptake may prove to be a key mechanism defining age-related AD progression.
• The increased cellular amyloid uptake in AD and LMCI may lead to quicker disease progression, but early-onset MCI may result from increased production of toxic amyloid metabolites.

Why this matters

• Additional biomarkers for AD could greatly aid diagnosis and course prediction, as they are currently limited to PET scan analysis of amyloid plaque deposits and concentration of Aβ42 in cerebrospinal fluid (CSF).
• Amyloid deposits found by PET have a positive correlation with AD diagnosis. In contrast, CSF-Aβ42 and AD diagnosis or cognitive decline are negatively correlated. Normal cognition (NC) is associated with higher CSF beta-amyloid levels, but previous research has not explained why CSF-Aβ42 levels can be equivalent in patients with NC but high amyloid load and patients with AD and low amyloid load.

Study design

• The authors of this retrospective study used anonymized data obtained from the Alzheimer’s’s Disease Neuroimaging Initiative (ADNI). ADNI’s goal has been to test whether serial MRI scans, PET scans, biomarkers, and clinical/neuropsychological assessment can be combined to measure the progression of MCI and AD.
• Study subjects had either an AD diagnosis or NC and were divided into two groups: low amyloid load and high amyloid load. The fraction of patients with an AD diagnosis was calculated as a function of CSF-Aβ42.
• Calculations and statistical comparisons were performed using Microsoft Excel and custom-written C++ programs.

Key results

• The lowest levels of CSF-Aβ42 correlated with the highest percentage of AD-diagnosed patients, estimated to be 27% in subjects with low amyloid deposit density and 65% in those with high deposit density.
• The relationship between CSF-Aβ42 levels and amyloid load can be described using a simple mathematical model: Amyloid concentration in the interstitial cells is equal to the synthesis rate divided by the density of amyloid deposits plus the sum of the rate of amyloid removal through the CSF and the cellular amyloid uptake rate.
• AD and late-onset MCI patients had a significantly higher amyloid removal rate compared to NC subjects.
• Early-onset MCI patients had Aβ42 turnover similar to that of NC subjects, pointing to a different underlying mechanism such as enzymatic disbalance.

Limitations

• The model used to explain amyloid exchange between the interstitial space and the CSF is oversimplified; the actual process is more complex.
• Synthesis and uptake rates of Aβ42 vary throughout areas of the brain. The model assumes a homogeneous distribution within the interstitial compartment.

Study disclosures

• Research reported in this publication was not supported by any external funding. Data collection and sharing for this project were funded by ADNI.

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

Medicare intends to limit coverage of the controversial Alzheimer’s drug aducanumab (Aduhelm, Biogen) via a special program intended to help assess how well this exorbitantly expensive medication works, federal officials announced Jan. 11.

On Dec. 20, 2021, Biogen announced a plan to reduce the annual U.S. cost of the drug by 50% – from $56,000 to $28,200 – as Centers for Medicare & Medicaid Services officials were deciding on Medicare’s coverage policy for the medication.

In making its proposed coverage decision, the CMS announced it will pay for aducanumab, a monoclonal antibody, under its coverage-with-evidence-development (CED) mechanism. In making its decision, the CMS approached aducanumab as the first of a potential new class of monoclonal antibodies for the treatment of Alzheimer’s disease. Food and Drug Administration–approved drugs in this class would be covered for those with Medicare only if they are enrolled in qualifying clinical trials, the CMS said. The agency will accept public comments on this decision for 30 days.  

In a statement, CMS Administrator Chiquita Brooks-LaSure said the agency is “committed to providing the American public with a clear, trusted, evidence-based decision that is made only after a thorough analysis of public feedback on the benefits and risks of coverage for Medicare patients.”

As previously reported, the FDA approved aducanumab on June 7, 2021, via an accelerated approval process. The approval, which set off a firestorm of controversy that included resignations of three FDA Peripheral and Central Nervous System Drugs Advisory Committee panel members, was granted based on the medication’s ability to reduce beta-amyloid plaque.

Under the accelerated approval mechanism, Biogen still must deliver solid scientific proof that aducanumab has clinically significant disease-modifying effects. However, the final evidence won’t be in any time soon. In its approval letter, the FDA set a 2030 deadline for a final report on this research.

 

‘Unusual but appropriate’ step

The Medicare decision marks something of a shift in the agency’s approach to paying for medications. On a call with reporters, Tamara Syrek Jensen, JD, director of CMS’ Coverage and Analysis Group, admitted that the agency had taken an “unusual but appropriate” step in trying to set a national policy regarding payment for a drug.

On the same call, Lee Fleisher, MD, CMS’ chief medical officer, addressed the challenges presented by aducanumab, given the serious need for treatments for Alzheimer’s disease. “As a practicing physician, I cannot overemphasize the need to understand the risks and benefits of a given treatment in order to better inform patients and their families,” Dr. Fleisher said. “We do know based on some of the evidence that there may be potential promise with this treatment. That’s why it is critical for us to pursue additional scientific evidence.”

The coverage-with-evidence program will allow Medicare to aid in gathering data, while protecting patients, Dr. Fleisher noted.

“CMS is using its authority provided by Congress to determine if the drug is considered reasonable and necessary, meaning that the benefits of improvement of cognition outweigh the harms in the Medicare population,” Dr. Fleisher said.
 

Biogen disappointed

Cambridge, Mass.–based Biogen urged the CMS to reconsider its approach to payment for aducanumab. In a statement, the company said Medicare should cover “the class of amyloid-directed therapies with the populations studied in the respective clinical trials and guided by expert recommendations for appropriate use.

“We believe Alzheimer’s patients should have access consistent with other therapies with FDA accelerated approval,” Biogen said in the release.

In the company’s view, the CED approach will “significantly limit patient access to an FDA-approved treatment, especially for underserved patients as evidenced in other CED determinations.

“CEDs can take months to years to initiate, and hundreds of Alzheimer’s patients – the majority of whom are Medicare beneficiaries – are progressing each day from mild to moderate disease stages, where treatment may no longer be an option,” Biogen said.

Drug makers had been worried about CMS opting for CED even before the draft decision was unveiled.
 

Others weigh in

BIO, the trade group for biotechnology companies, urged the CMS to provide access to aducanumab without excess restrictions.

There already are concerns among drug makers about CMS efforts “to impose new coverage barriers – and, in particular, coverage with evidence development,” Crystal Kuntz, vice president of policy and research at BIO, and Andy Cosgrove, the organization’s senior director for policy and research, noted in a July 2021 comment about the aducanumab review.

Medicare should instead continue to provide access to medicines for indications that the FDA has approved, with additional flexibility for off-label indications of cancer drugs, they noted. “We believe this should continue to be the case, to ensure that vulnerable Medicare beneficiaries have necessary access to life-altering and lifesaving medications,” the BIO officials wrote.

However, the CMS also received many pleas from physicians asking the agency to limit use of aducanumab at least until there is evidence that it produces a significant clinical benefit.

In a press release, Howard Fillit, MD, cofounder and chief science officer of the Alzheimer’s Drug Discovery Foundation, applauded the decision, describing it as “the right call.

“This decision supports conducting additional clinical trials, which are needed to obtain further insights into the clinical efficacy and safety profile of this drug in real-world populations. This decision has implications for other drugs in this class in late-stage development. If these trials show more clear and robust clinical efficacy, then it is possible the FDA will give these amyloid monoclonal antibodies full approval, and Medicare would be likely to provide full payment,” he added.

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

Medicare intends to limit coverage of the controversial Alzheimer’s drug aducanumab (Aduhelm, Biogen) via a special program intended to help assess how well this exorbitantly expensive medication works, federal officials announced Jan. 11.

On Dec. 20, 2021, Biogen announced a plan to reduce the annual U.S. cost of the drug by 50% – from $56,000 to $28,200 – as Centers for Medicare & Medicaid Services officials were deciding on Medicare’s coverage policy for the medication.

In making its proposed coverage decision, the CMS announced it will pay for aducanumab, a monoclonal antibody, under its coverage-with-evidence-development (CED) mechanism. In making its decision, the CMS approached aducanumab as the first of a potential new class of monoclonal antibodies for the treatment of Alzheimer’s disease. Food and Drug Administration–approved drugs in this class would be covered for those with Medicare only if they are enrolled in qualifying clinical trials, the CMS said. The agency will accept public comments on this decision for 30 days.  

In a statement, CMS Administrator Chiquita Brooks-LaSure said the agency is “committed to providing the American public with a clear, trusted, evidence-based decision that is made only after a thorough analysis of public feedback on the benefits and risks of coverage for Medicare patients.”

As previously reported, the FDA approved aducanumab on June 7, 2021, via an accelerated approval process. The approval, which set off a firestorm of controversy that included resignations of three FDA Peripheral and Central Nervous System Drugs Advisory Committee panel members, was granted based on the medication’s ability to reduce beta-amyloid plaque.

Under the accelerated approval mechanism, Biogen still must deliver solid scientific proof that aducanumab has clinically significant disease-modifying effects. However, the final evidence won’t be in any time soon. In its approval letter, the FDA set a 2030 deadline for a final report on this research.

 

‘Unusual but appropriate’ step

The Medicare decision marks something of a shift in the agency’s approach to paying for medications. On a call with reporters, Tamara Syrek Jensen, JD, director of CMS’ Coverage and Analysis Group, admitted that the agency had taken an “unusual but appropriate” step in trying to set a national policy regarding payment for a drug.

On the same call, Lee Fleisher, MD, CMS’ chief medical officer, addressed the challenges presented by aducanumab, given the serious need for treatments for Alzheimer’s disease. “As a practicing physician, I cannot overemphasize the need to understand the risks and benefits of a given treatment in order to better inform patients and their families,” Dr. Fleisher said. “We do know based on some of the evidence that there may be potential promise with this treatment. That’s why it is critical for us to pursue additional scientific evidence.”

The coverage-with-evidence program will allow Medicare to aid in gathering data, while protecting patients, Dr. Fleisher noted.

“CMS is using its authority provided by Congress to determine if the drug is considered reasonable and necessary, meaning that the benefits of improvement of cognition outweigh the harms in the Medicare population,” Dr. Fleisher said.
 

Biogen disappointed

Cambridge, Mass.–based Biogen urged the CMS to reconsider its approach to payment for aducanumab. In a statement, the company said Medicare should cover “the class of amyloid-directed therapies with the populations studied in the respective clinical trials and guided by expert recommendations for appropriate use.

“We believe Alzheimer’s patients should have access consistent with other therapies with FDA accelerated approval,” Biogen said in the release.

In the company’s view, the CED approach will “significantly limit patient access to an FDA-approved treatment, especially for underserved patients as evidenced in other CED determinations.

“CEDs can take months to years to initiate, and hundreds of Alzheimer’s patients – the majority of whom are Medicare beneficiaries – are progressing each day from mild to moderate disease stages, where treatment may no longer be an option,” Biogen said.

Drug makers had been worried about CMS opting for CED even before the draft decision was unveiled.
 

Others weigh in

BIO, the trade group for biotechnology companies, urged the CMS to provide access to aducanumab without excess restrictions.

There already are concerns among drug makers about CMS efforts “to impose new coverage barriers – and, in particular, coverage with evidence development,” Crystal Kuntz, vice president of policy and research at BIO, and Andy Cosgrove, the organization’s senior director for policy and research, noted in a July 2021 comment about the aducanumab review.

Medicare should instead continue to provide access to medicines for indications that the FDA has approved, with additional flexibility for off-label indications of cancer drugs, they noted. “We believe this should continue to be the case, to ensure that vulnerable Medicare beneficiaries have necessary access to life-altering and lifesaving medications,” the BIO officials wrote.

However, the CMS also received many pleas from physicians asking the agency to limit use of aducanumab at least until there is evidence that it produces a significant clinical benefit.

In a press release, Howard Fillit, MD, cofounder and chief science officer of the Alzheimer’s Drug Discovery Foundation, applauded the decision, describing it as “the right call.

“This decision supports conducting additional clinical trials, which are needed to obtain further insights into the clinical efficacy and safety profile of this drug in real-world populations. This decision has implications for other drugs in this class in late-stage development. If these trials show more clear and robust clinical efficacy, then it is possible the FDA will give these amyloid monoclonal antibodies full approval, and Medicare would be likely to provide full payment,” he added.

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

Medicare intends to limit coverage of the controversial Alzheimer’s drug aducanumab (Aduhelm, Biogen) via a special program intended to help assess how well this exorbitantly expensive medication works, federal officials announced Jan. 11.

On Dec. 20, 2021, Biogen announced a plan to reduce the annual U.S. cost of the drug by 50% – from $56,000 to $28,200 – as Centers for Medicare & Medicaid Services officials were deciding on Medicare’s coverage policy for the medication.

In making its proposed coverage decision, the CMS announced it will pay for aducanumab, a monoclonal antibody, under its coverage-with-evidence-development (CED) mechanism. In making its decision, the CMS approached aducanumab as the first of a potential new class of monoclonal antibodies for the treatment of Alzheimer’s disease. Food and Drug Administration–approved drugs in this class would be covered for those with Medicare only if they are enrolled in qualifying clinical trials, the CMS said. The agency will accept public comments on this decision for 30 days.  

In a statement, CMS Administrator Chiquita Brooks-LaSure said the agency is “committed to providing the American public with a clear, trusted, evidence-based decision that is made only after a thorough analysis of public feedback on the benefits and risks of coverage for Medicare patients.”

As previously reported, the FDA approved aducanumab on June 7, 2021, via an accelerated approval process. The approval, which set off a firestorm of controversy that included resignations of three FDA Peripheral and Central Nervous System Drugs Advisory Committee panel members, was granted based on the medication’s ability to reduce beta-amyloid plaque.

Under the accelerated approval mechanism, Biogen still must deliver solid scientific proof that aducanumab has clinically significant disease-modifying effects. However, the final evidence won’t be in any time soon. In its approval letter, the FDA set a 2030 deadline for a final report on this research.

 

‘Unusual but appropriate’ step

The Medicare decision marks something of a shift in the agency’s approach to paying for medications. On a call with reporters, Tamara Syrek Jensen, JD, director of CMS’ Coverage and Analysis Group, admitted that the agency had taken an “unusual but appropriate” step in trying to set a national policy regarding payment for a drug.

On the same call, Lee Fleisher, MD, CMS’ chief medical officer, addressed the challenges presented by aducanumab, given the serious need for treatments for Alzheimer’s disease. “As a practicing physician, I cannot overemphasize the need to understand the risks and benefits of a given treatment in order to better inform patients and their families,” Dr. Fleisher said. “We do know based on some of the evidence that there may be potential promise with this treatment. That’s why it is critical for us to pursue additional scientific evidence.”

The coverage-with-evidence program will allow Medicare to aid in gathering data, while protecting patients, Dr. Fleisher noted.

“CMS is using its authority provided by Congress to determine if the drug is considered reasonable and necessary, meaning that the benefits of improvement of cognition outweigh the harms in the Medicare population,” Dr. Fleisher said.
 

Biogen disappointed

Cambridge, Mass.–based Biogen urged the CMS to reconsider its approach to payment for aducanumab. In a statement, the company said Medicare should cover “the class of amyloid-directed therapies with the populations studied in the respective clinical trials and guided by expert recommendations for appropriate use.

“We believe Alzheimer’s patients should have access consistent with other therapies with FDA accelerated approval,” Biogen said in the release.

In the company’s view, the CED approach will “significantly limit patient access to an FDA-approved treatment, especially for underserved patients as evidenced in other CED determinations.

“CEDs can take months to years to initiate, and hundreds of Alzheimer’s patients – the majority of whom are Medicare beneficiaries – are progressing each day from mild to moderate disease stages, where treatment may no longer be an option,” Biogen said.

Drug makers had been worried about CMS opting for CED even before the draft decision was unveiled.
 

Others weigh in

BIO, the trade group for biotechnology companies, urged the CMS to provide access to aducanumab without excess restrictions.

There already are concerns among drug makers about CMS efforts “to impose new coverage barriers – and, in particular, coverage with evidence development,” Crystal Kuntz, vice president of policy and research at BIO, and Andy Cosgrove, the organization’s senior director for policy and research, noted in a July 2021 comment about the aducanumab review.

Medicare should instead continue to provide access to medicines for indications that the FDA has approved, with additional flexibility for off-label indications of cancer drugs, they noted. “We believe this should continue to be the case, to ensure that vulnerable Medicare beneficiaries have necessary access to life-altering and lifesaving medications,” the BIO officials wrote.

However, the CMS also received many pleas from physicians asking the agency to limit use of aducanumab at least until there is evidence that it produces a significant clinical benefit.

In a press release, Howard Fillit, MD, cofounder and chief science officer of the Alzheimer’s Drug Discovery Foundation, applauded the decision, describing it as “the right call.

“This decision supports conducting additional clinical trials, which are needed to obtain further insights into the clinical efficacy and safety profile of this drug in real-world populations. This decision has implications for other drugs in this class in late-stage development. If these trials show more clear and robust clinical efficacy, then it is possible the FDA will give these amyloid monoclonal antibodies full approval, and Medicare would be likely to provide full payment,” he added.

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

The number of individuals older than 40 with dementia will nearly triple worldwide and double in the United States by 2050 unless steps are taken to address risk factors, new research suggests.

Results from a study of 195 countries and territories estimates that by 2050, 153 million people are expected to have dementia worldwide – up from 57 million in 2019. In the United States, the number is expected to increase 100%, from an estimated 5.3 million in 2019 to 10.5 million in 2050.

The increase is largely driven by population growth and population aging, but researchers noted that expanding access to education and addressing risk factors such as obesity, high blood sugar, and smoking could blunt the rise in cases.

The study predicts increases in dementia in every country included in the analysis. The sharpest rise is expected in north Africa and the Middle East (367%) and sub-Saharan Africa (357%). The smallest increases will be in high-income countries in Asia Pacific (53%) and western Europe (74%).

Although the United States had the 37th lowest percentage increase across all countries considered, “this expected increase is still large and requires attention from policy and decision-makers,” said coinvestigator Emma Nichols, MPH, a researcher with the Institute for Health Metrics and Evaluation at the University of Washington, Seattle.

The findings were published online Jan. 6, 2022, in The Lancet Public Health (doi: 10.1016/S2468-2667[21]00249-8).
 

Dementia prevalence

For the study, researchers used country-specific estimates of dementia prevalence from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 study to project dementia prevalence globally, by world region, and at the country level.

They also used information on projected trends in four important dementia risk factors (high body mass index, high fasting plasma glucose, smoking, and education) to estimate how changes in these risk factors might impact dementia prevalence between 2019 and 2050.

Despite large increases in the projected number of people living with dementia, age-standardized both-sex prevalence remained stable between 2019 and 2050, with a global percentage change of 0.1% (95% uncertainty interval, –7.5 to 10.8).

Dementia prevalence was higher in women than in men and increased with age, doubling about every 5 years until 85 years of age in both 2019 and 2050 (female-to-male ratio, 1.67; 95% UI, 1.52-1.85).

Projected increases in cases could largely be attributed to population growth and population aging, although their relative importance varied by world region. Population growth contributed most to the increases in sub-Saharan Africa and population aging contributed most to the increases in east Asia.

The countries with the highest expected percentage change in total number of dementia cases between 2019 and 2050 were: Qatar (1,926%), United Arab Emirates (1,795%), Bahrain (1,084%), Oman (943%), Saudi Arabia (898%), Kuwait (850%), Iraq (559%), Maldives (554%), Jordan (522%), and Equatorial Guinea (498%).

The countries with the lowest expected percentage change in total number of dementia cases between 2019 and 2050 were Japan (27%), Bulgaria (37%), Serbia (38%), Lithuania (44%), Greece (45%), Latvia (47%), Croatia (55%), Ukraine (55%), Italy (56%), and Finland (58%).
 

Modifiable risk factors

Researchers also calculated how changes in risk factors might affect dementia prevalence. They found that improvements in global education access would reduce dementia prevalence by an estimated 6.2 million cases worldwide by 2050. However, that decrease would be offset by expected increases in obesity, high blood sugar, and smoking, which investigators estimate will result in an additional 6.8 million dementia cases.

The projections are based on expected trends in population aging, population growth, and risk factor trajectories, but “projections could change if effective interventions for modifiable risk factors are developed and deployed,” Ms. Nichols said.

In 2020, the Lancet Commission on Dementia Prevention, Intervention, and Care issued an update of its 2017 report, identifying 12 modifiable risk factors that could delay or prevent 40% of dementia cases. The risk factors were low education, hypertension, hearing impairment, smoking, midlife obesity, depression, physical inactivity, diabetes, social isolation, excessive alcohol consumption, head injury, and air pollution.

“Countries, including the U.S., should look to develop effective interventions for modifiable risk factors, but also should invest in the resources needed to support those with dementia and their caregivers,” Ms. Nichols said. She added that additional support for research and resources to develop therapeutic interventions is also warranted.
 

Oversimplifying mechanisms?

In an accompanying commentary, Michaël Schwarzinger, MD, and Carole Dufouil, PhD, of Bordeaux (France) University Hospital, noted that the authors’ efforts to build on GBD 2019 oversimplify the underlying mechanisms that cause dementia. The authors “provide somehow apocalyptic projections that do not factor in advisable changes in lifestyle over the lifetime,” they wrote.

“There is a considerable and urgent need to reinforce a public health approach towards dementia to better inform the people and decision-makers about the appropriate means to delay or avoid these dire projections,” the editorialists added.

The study was funded by the Bill and Melinda Gates Foundation and Gates Ventures. Ms. Nichols and the editorialists disclosed no relevant financial relationships.

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

The number of individuals older than 40 with dementia will nearly triple worldwide and double in the United States by 2050 unless steps are taken to address risk factors, new research suggests.

Results from a study of 195 countries and territories estimates that by 2050, 153 million people are expected to have dementia worldwide – up from 57 million in 2019. In the United States, the number is expected to increase 100%, from an estimated 5.3 million in 2019 to 10.5 million in 2050.

The increase is largely driven by population growth and population aging, but researchers noted that expanding access to education and addressing risk factors such as obesity, high blood sugar, and smoking could blunt the rise in cases.

The study predicts increases in dementia in every country included in the analysis. The sharpest rise is expected in north Africa and the Middle East (367%) and sub-Saharan Africa (357%). The smallest increases will be in high-income countries in Asia Pacific (53%) and western Europe (74%).

Although the United States had the 37th lowest percentage increase across all countries considered, “this expected increase is still large and requires attention from policy and decision-makers,” said coinvestigator Emma Nichols, MPH, a researcher with the Institute for Health Metrics and Evaluation at the University of Washington, Seattle.

The findings were published online Jan. 6, 2022, in The Lancet Public Health (doi: 10.1016/S2468-2667[21]00249-8).
 

Dementia prevalence

For the study, researchers used country-specific estimates of dementia prevalence from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 study to project dementia prevalence globally, by world region, and at the country level.

They also used information on projected trends in four important dementia risk factors (high body mass index, high fasting plasma glucose, smoking, and education) to estimate how changes in these risk factors might impact dementia prevalence between 2019 and 2050.

Despite large increases in the projected number of people living with dementia, age-standardized both-sex prevalence remained stable between 2019 and 2050, with a global percentage change of 0.1% (95% uncertainty interval, –7.5 to 10.8).

Dementia prevalence was higher in women than in men and increased with age, doubling about every 5 years until 85 years of age in both 2019 and 2050 (female-to-male ratio, 1.67; 95% UI, 1.52-1.85).

Projected increases in cases could largely be attributed to population growth and population aging, although their relative importance varied by world region. Population growth contributed most to the increases in sub-Saharan Africa and population aging contributed most to the increases in east Asia.

The countries with the highest expected percentage change in total number of dementia cases between 2019 and 2050 were: Qatar (1,926%), United Arab Emirates (1,795%), Bahrain (1,084%), Oman (943%), Saudi Arabia (898%), Kuwait (850%), Iraq (559%), Maldives (554%), Jordan (522%), and Equatorial Guinea (498%).

The countries with the lowest expected percentage change in total number of dementia cases between 2019 and 2050 were Japan (27%), Bulgaria (37%), Serbia (38%), Lithuania (44%), Greece (45%), Latvia (47%), Croatia (55%), Ukraine (55%), Italy (56%), and Finland (58%).
 

Modifiable risk factors

Researchers also calculated how changes in risk factors might affect dementia prevalence. They found that improvements in global education access would reduce dementia prevalence by an estimated 6.2 million cases worldwide by 2050. However, that decrease would be offset by expected increases in obesity, high blood sugar, and smoking, which investigators estimate will result in an additional 6.8 million dementia cases.

The projections are based on expected trends in population aging, population growth, and risk factor trajectories, but “projections could change if effective interventions for modifiable risk factors are developed and deployed,” Ms. Nichols said.

In 2020, the Lancet Commission on Dementia Prevention, Intervention, and Care issued an update of its 2017 report, identifying 12 modifiable risk factors that could delay or prevent 40% of dementia cases. The risk factors were low education, hypertension, hearing impairment, smoking, midlife obesity, depression, physical inactivity, diabetes, social isolation, excessive alcohol consumption, head injury, and air pollution.

“Countries, including the U.S., should look to develop effective interventions for modifiable risk factors, but also should invest in the resources needed to support those with dementia and their caregivers,” Ms. Nichols said. She added that additional support for research and resources to develop therapeutic interventions is also warranted.
 

Oversimplifying mechanisms?

In an accompanying commentary, Michaël Schwarzinger, MD, and Carole Dufouil, PhD, of Bordeaux (France) University Hospital, noted that the authors’ efforts to build on GBD 2019 oversimplify the underlying mechanisms that cause dementia. The authors “provide somehow apocalyptic projections that do not factor in advisable changes in lifestyle over the lifetime,” they wrote.

“There is a considerable and urgent need to reinforce a public health approach towards dementia to better inform the people and decision-makers about the appropriate means to delay or avoid these dire projections,” the editorialists added.

The study was funded by the Bill and Melinda Gates Foundation and Gates Ventures. Ms. Nichols and the editorialists disclosed no relevant financial relationships.

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

The number of individuals older than 40 with dementia will nearly triple worldwide and double in the United States by 2050 unless steps are taken to address risk factors, new research suggests.

Results from a study of 195 countries and territories estimates that by 2050, 153 million people are expected to have dementia worldwide – up from 57 million in 2019. In the United States, the number is expected to increase 100%, from an estimated 5.3 million in 2019 to 10.5 million in 2050.

The increase is largely driven by population growth and population aging, but researchers noted that expanding access to education and addressing risk factors such as obesity, high blood sugar, and smoking could blunt the rise in cases.

The study predicts increases in dementia in every country included in the analysis. The sharpest rise is expected in north Africa and the Middle East (367%) and sub-Saharan Africa (357%). The smallest increases will be in high-income countries in Asia Pacific (53%) and western Europe (74%).

Although the United States had the 37th lowest percentage increase across all countries considered, “this expected increase is still large and requires attention from policy and decision-makers,” said coinvestigator Emma Nichols, MPH, a researcher with the Institute for Health Metrics and Evaluation at the University of Washington, Seattle.

The findings were published online Jan. 6, 2022, in The Lancet Public Health (doi: 10.1016/S2468-2667[21]00249-8).
 

Dementia prevalence

For the study, researchers used country-specific estimates of dementia prevalence from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 study to project dementia prevalence globally, by world region, and at the country level.

They also used information on projected trends in four important dementia risk factors (high body mass index, high fasting plasma glucose, smoking, and education) to estimate how changes in these risk factors might impact dementia prevalence between 2019 and 2050.

Despite large increases in the projected number of people living with dementia, age-standardized both-sex prevalence remained stable between 2019 and 2050, with a global percentage change of 0.1% (95% uncertainty interval, –7.5 to 10.8).

Dementia prevalence was higher in women than in men and increased with age, doubling about every 5 years until 85 years of age in both 2019 and 2050 (female-to-male ratio, 1.67; 95% UI, 1.52-1.85).

Projected increases in cases could largely be attributed to population growth and population aging, although their relative importance varied by world region. Population growth contributed most to the increases in sub-Saharan Africa and population aging contributed most to the increases in east Asia.

The countries with the highest expected percentage change in total number of dementia cases between 2019 and 2050 were: Qatar (1,926%), United Arab Emirates (1,795%), Bahrain (1,084%), Oman (943%), Saudi Arabia (898%), Kuwait (850%), Iraq (559%), Maldives (554%), Jordan (522%), and Equatorial Guinea (498%).

The countries with the lowest expected percentage change in total number of dementia cases between 2019 and 2050 were Japan (27%), Bulgaria (37%), Serbia (38%), Lithuania (44%), Greece (45%), Latvia (47%), Croatia (55%), Ukraine (55%), Italy (56%), and Finland (58%).
 

Modifiable risk factors

Researchers also calculated how changes in risk factors might affect dementia prevalence. They found that improvements in global education access would reduce dementia prevalence by an estimated 6.2 million cases worldwide by 2050. However, that decrease would be offset by expected increases in obesity, high blood sugar, and smoking, which investigators estimate will result in an additional 6.8 million dementia cases.

The projections are based on expected trends in population aging, population growth, and risk factor trajectories, but “projections could change if effective interventions for modifiable risk factors are developed and deployed,” Ms. Nichols said.

In 2020, the Lancet Commission on Dementia Prevention, Intervention, and Care issued an update of its 2017 report, identifying 12 modifiable risk factors that could delay or prevent 40% of dementia cases. The risk factors were low education, hypertension, hearing impairment, smoking, midlife obesity, depression, physical inactivity, diabetes, social isolation, excessive alcohol consumption, head injury, and air pollution.

“Countries, including the U.S., should look to develop effective interventions for modifiable risk factors, but also should invest in the resources needed to support those with dementia and their caregivers,” Ms. Nichols said. She added that additional support for research and resources to develop therapeutic interventions is also warranted.
 

Oversimplifying mechanisms?

In an accompanying commentary, Michaël Schwarzinger, MD, and Carole Dufouil, PhD, of Bordeaux (France) University Hospital, noted that the authors’ efforts to build on GBD 2019 oversimplify the underlying mechanisms that cause dementia. The authors “provide somehow apocalyptic projections that do not factor in advisable changes in lifestyle over the lifetime,” they wrote.

“There is a considerable and urgent need to reinforce a public health approach towards dementia to better inform the people and decision-makers about the appropriate means to delay or avoid these dire projections,” the editorialists added.

The study was funded by the Bill and Melinda Gates Foundation and Gates Ventures. Ms. Nichols and the editorialists disclosed no relevant financial relationships.

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