Lifespan Cognitive Reserve—A Secret to Coping With Neurodegenerative Pathology (JAMA Neurology editorial):
Given the limited success of therapeutic interventions for Alzheimer disease, there is increased interest in understanding whether modifiable factors can help cope with or postpone the appearance of brain pathology. It is estimated that about 35% of Alzheimer risk is modifiable. Epidemiologic studies have shown that lifetime exposures to higher education, higher occupational attainment, and cognitively stimulating activities are associated with reduced risk of Alzheimer dementia. Autopsy studies have shown interindividual differences in the amount of brain pathology people can tolerate before manifesting cognitive impairments, and autopsied brains of about one-third of individuals who are cognitively normal meet neuropathological criteria for Alzheimer disease.
About a decade ago, the concept of cognitive reserve was proposed to account for the discrepancy between brain pathology and cognitive status. The broad hypothesis was that individuals with enriched lifelong exposures would be able to better tolerate with brain pathology in late life. Many studies have investigated how one can cope with brain damage using proxies of neurodegeneration or synaptic integrity. However, the gold standard for testing the reserve hypothesis is the direct measurement of brain pathology at autopsy. Keep reading (requires subscription)
Association of Lifespan Cognitive Reserve Indicator With Dementia Risk in the Presence of Brain Pathologies (JAMA Neurology). From the abstract:
- Objective: To examine the association of lifespan CR with dementia risk, taking brain pathologies into account.
- Design, setting, and participants: This study used data from 2022 participants in the Rush Memory and Aging Project, an ongoing community-based cohort study with annual follow-up from 1997 to 2018 (mean follow-up, 6 years; maximum follow-up, 20 years) … During follow-up, 611 died and underwent autopsies. Data were analyzed from May to September 2018.
- Exposures: Information on CR factors (education; early-life, midlife, and late-life cognitive activities; and social activities in late life) was obtained at baseline. Based on these factors, lifespan CR scores were captured using a latent variable from a structural equation model and was divided into tertiles (lowest, middle, and highest).
- Results: … The highest CR score tertile was associated with a reduction in dementia risk, even among participants with high Alzheimer disease pathology (HR, 0.57; 95% CI, 0.37–0.87) and any gross infarcts (HR, 0.34; 95% CI, 0.18–0.62).
- Conclusions and relevance: High lifespan CR is associated with a reduction in dementia risk, even in the presence of high brain pathologies. Our findings highlight the importance of lifespan CR accumulation in dementia prevention.