Is cognitive reserve accumulation associated with reduced dementia risk?

Written by Ilana Landau, Editor

A new study, following 1602 dementia-free individuals, has observed high lifespan cognitive reserve to be associated with reduced risk of developing dementia.

The association between individuals’ lifespan cognitive reserve and their risk of developing dementia is poorly understood. This study aimed to examine this relationship and determine if/how it is affected by the presence of dementia-related brain pathologies. Researchers observed lifespan cognitive reserve accumulation to be associated with reduced dementia risk, regardless of the presence of neuropathological brain changes.

The cognitive reserve hypothesis suggests that individuals’ cognitive reserve buffers age-related brain changes and cognitive decline. Cognitive reserve has commonly been estimated from individuals’ education, occupation and social activities. However, more recently, an understanding that cognitive reserve is a dynamic measurement that is impacted by cumulative life experiences has emerged.

The study evaluated data on 2022 individuals from the Rush University Memory and Aging Project (IL, USA); this project is an ongoing cohort study — initiated in 1997 — that annually assesses participants for dementia risk over a follow-up period of 6–20 years.

420 patients were excluded from study analysis due to their incomplete cognitive reserve records, their presentation with prevalent dementia or their dropping out of the study.

1602 individuals were terminally included in the study; all were free of dementia at the start of the study. 747 of these participants died during the course of the study. 611 of these 747 individuals underwent autopsies; these evaluated pathophysiological indicators for Alzheimer’s disease (AD) and other brain pathologies.

Lifespan cognitive reserve scores were calculated from data on participants education, early-, middle- and late-life cognitive activities and late-life social activities at the start of the study, by employing a latent variable from a structural equation model. Participants were grouped into tertiles (low, medium and high) according to their cognitive reserve score.

Diagnosis of dementia during the study was according to international criteria.

Cox or logistic regression models were employed to evaluate the association between lifespan cognitive reserve measurements and incidence of dementia or brain pathology prevalence.

386 of the 1602 included individuals were diagnosed with dementia during the study; 357 of these individuals were diagnosed with AD-related dementia.

Patients in the high lifespan cognitive reserve score tertile had multi-adjusted hazard ratios for their risk of dementia development of 0.61, compared with individuals in the lowest tertile.

For patients in the middle cognitive reserve score tertile, dementia hazard ratio was 0.77 compared with individuals from the lowest tertile.

Even after adjusting for brain pathology prevalence, the association between lifespan cognitive reserve score and dementia risk remained significant; individuals with high lifespan cognitive reserve scores had reduced risk of developing dementia.

In the study, the authors concluded: “This study provides evidence that high lifespan cognitive reserve (CR) indicator, encompassing education, early-life, midlife, and late-life cognitive activities, and social activities in late life, is associated with a reduction in dementia risk, even in people with high AD and vascular pathologies.”

“Our findings suggest that accumulative educational and mentally stimulating activities enhancing CR throughout life might be a feasible strategy to prevent dementia, even in people with high AD or vascular pathologies.”


Xu H, Yang R, Xiuying Q et al. Association of Lifespan Cognitive Reserve Indicator With Dementia Risk in the Presence of Brain Pathologies. JAMA Neurol. doi: 10.1001/jamaneurol.2019.2455 (2019)(Epub ahead of print)