Resilient brain aging: characterization of discordance between Alzheimer's disease pathology and cognition.
Level 3 - non-randomized controlled study
Prospective longitudinal cohort study with post-mortem clinicopathological analysis
PubMed 23919768 · doi:10.2174/15672050113109990157
What was done
Analyzed 966 deceased participants from two prospective cohort studies (the Religious Orders Study and the Rush Memory and Aging Project) who underwent annual evaluations, completed comprehensive cognitive testing proximate to death, and had post-mortem brain autopsy. Cognitive resilience was quantified as a continuous metric using studentized residuals from a linear regression of global cognition on global Alzheimer's disease pathology. Multivariate and stepwise linear regression models adjusting for demographic variables were used to evaluate associations between resilience and early-life socioeconomic status, reading ability, APOE-ε4 status, and past cognitive activity.
What was found
Multivariate regression models adjusting for demographics showed significant associations between resilience and early-life socioeconomic status, reading ability, APOE-ε4 status, and past cognitive activity. In a stepwise regression model, reading level (estimate = 0.10, SE = 0.02, p < 0.0001) and past cognitive activity (estimate = 0.27, SE = 0.09, p = 0.002) were independently retained as significant predictors of resilience.
Why it matters
This study provides an empirical regression-residual framework to quantify resilience against Alzheimer's pathology and demonstrates that literacy and lifelong cognitive activity are significant predictors of preserved cognitive function despite neuropathological burden.
Limits
The observational design cannot establish a causal link between cognitive activity and resilience. The cohort comprised selected older volunteers, including religious clergy, which may limit generalizability to more diverse populations. Past cognitive activity and early-life factors relied on retrospective self-report, introducing potential recall bias.
Cited by
- supports In the Religious Orders Study, autopsy examinations showed that some Catholic nuns had physical Alzheimer's pathology in their brains without having exhibited cognitive deficits during life.