Cumulative Cognitive Reserve Tied to Dementia Risk

LOS ANGELES — Higher scores on a measure of cumulative lifetime cognitive reserve reduced dementia risk even in the presence of brain pathologies, researchers reported here.

Older adults with the highest levels of lifespan cognitive reserve had a 39% lower risk of dementia than those with the lowest levels — and dementia risk was less for these people even if they had Alzheimer’s or vascular pathology, reported Xiuying Qi, PhD, and Weili Xu, MD, PhD, of Tianjin Medical University in China, and colleagues at the Alzheimer’s Association International Conference (AAIC). The study was published simultaneously in JAMA Neurology.

Cognitive reserve has been proposed as a compensatory mechanism to explain why some people maintain better cognitive function with age-related brain changes or disease-related pathologies, noted co-author Hui Wu, also of Tianjin Medical University.

In much research, “one reserve-enhancing factor during a certain time period alone — such as education, social, or cognitive activities — has been considered as a proxy measure of cognitive reserve,” Wu told MedPage Today. “However, emerging evidence has suggested that cognitive reserve is an active construct which develops from continued life experiences.”

“Our findings suggest that accumulative educational and mentally-stimulating activities enhancing cognitive reserve might be a feasible strategy to prevent dementia, even in people with high Alzheimer’s disease or vascular pathologies,” she added.

To create a cumulative cognitive reserve measurement that spanned a lifetime, the researchers collected data about mental and social activities from 1,602 participants in the Rush University Memory and Aging Project, an ongoing community-based prospective cohort study. The average age of participants was nearly 80 and most participants (75.9%) were women.

The researchers constructed a lifespan cognitive reserve score that incorporated education, cognitive activities in early, mid-, and late life, social activity in late life, and social networks late in life. Participant scores were divided into tertiles — lowest, middle, and highest.

Participants were dementia-free at baseline and were followed annually from 1997 to 2018 for a mean of 6 years. Over the follow-up period, 747 participants died and 611 underwent autopsy.

During follow-up, 386 participants developed dementia (24.1%), including 357 participants with Alzheimer’s disease dementia (22.3%). Compared with people in the lowest tertile of lifespan cognitive reserve scores, people in the middle tertile had an adjusted HR of dementia of 0.77 (95% CI 0.59-0.99), and people in the highest tertile had an HR of 0.61 (95% CI 0.47-0.81).

Cognitive reserve was not associated with most brain pathologies on autopsy, and links between cognitive reserve and dementia remained significant after adjusting for brain pathologies (HR 0.60, 95% CI 0.42-0.86). The highest tertile of lifespan cognitive reserve scores had lower dementia risk even in the presence of high Alzheimer’s disease pathology (HR 0.57, 95% CI 0.37-0.87) and any gross infarcts (HR 0.34, 95% CI 0.18-0.62).

“Lifespan cognitive reserve is a derived entity,” noted Yonas Geda, MD, of the Mayo Clinic in Scottsdale, Arizona, who was not involved with the study. “Whenever you create a new construct by relying on other constructs, it can increase the risk of measurement error,” he told MedPage Today.

But overall, “their finding makes sense and confirms what Mayo Clinic and others have reported — that mentally stimulating activities decrease the risk of mild cognitive or dementia, possibly via the mechanism of cognitive reserve,” Geda observed.

The study has several limitations: participants were volunteers and findings may not apply to other populations. Lifespan cognitive reserve factors were assessed by retrospective self-report, and unmeasured confounders also may have influenced results. And because brain changes occur many years before clinical diagnosis of dementia, reverse causality may be a factor.