| dc.description.abstract | Introduction: Some individuals are able to avoid reaching the threshold for clinical dementia despite the presence of Alzheimer neuropathology. This disparity between the neuropathologic and clinical symptoms required for a diagnosis of AD is often attributed to cognitive resilience, defined in the current study as the combined influence of brain reserve and cognitive reserve. This study assessed how educational attainment (a common measure of cognitive reserve), as well as brain weight and cortical atrophy (measures of brain reserve), may influence the outcome of cognitive resilience independently or through interactions with each other.
Methods: Analyses were based on the Nun Study, a longitudinal study of aging in 678 participants aged 75+ years at baseline. Educational attainment data were available through convent archives while brain weight and cortical atrophy data were collected through post mortem autopsies. Alzheimer neuropathology was assessed through post mortem autopsies and was defined using the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) and National Institute on Aging and Reagan Institute (NIA-RI) neuropathologic criteria. Finally, dementia status was determined through annual cognitive testing using DSM-IV criteria. Logistic regression analyses were conducted to assess all associations between exposures (educational attainment, brain weight and cortical atrophy) and the outcome (cognitive resilience), controlling for participant age at the time of death and the presence of apolipoprotein E-ε4.
Results: Higher educational attainment and brain weight, and the absence of cortical atrophy were all positively associated with cognitive resilience defined using both CERAD and NIA-RI neuropathologic criteria. However, the negative association between cortical atrophy and cognitive resilience was significant only when brain weights were high. When brain weight and educational attainment were assessed in the same models, the influence of educational attainment fell below statistical significance. Finally, when educational attainment was assessed in models stratified by cortical atrophy status, it remained significant only in the presence of mild atrophy.
Discussion: It was hypothesized that higher educational attainment, higher brain weight and the absence of cortical atrophy would all be positively associated with cognitive resilience. These hypotheses were supported by findings in the study. Further, it was hypothesized that the impacts of mild atrophy would be more significant among individuals with lower brain weights than among those with higher brain weights, as higher brain weight would act as a buffer against mild atrophy. However, findings were contrary to this hypothesis, with results suggesting that atrophy was only significant when brain weights were high. This non-significant effect is likely partially related to low statistical power in the low brain weight strata. However, this result may additionally be the result of a floor effect whereby low brain weight depletes brain reserve to such an extent that further loss in tissue (through cortical atrophy) is unlikely to result in further impairment. Finally, it was hypothesized that educational attainment would be most strongly associated with cognitive resilience when brain reserve was low (i.e., in the presence of cortical atrophy or low brain weight). This hypothesis was partially supported by findings indicating that when mild atrophy was present, low educational attainment was associated with reduced odds of resilience. Overall, it appears that cognitive reserve factors (educational attainment) are important in reducing the clinical symptoms of AD in late life; however, these positive effects were only found when threats to brain reserve (cortical atrophy, low brain weight) were absent or of mild severity.
Conclusion: Higher levels of education can improve cognitive reserve and help reduce the risk of dementia symptoms despite AD brain changes. These benefits are only realized, however, when low brain weight and cortical atrophy are avoided. This study and future efforts aimed at better understanding how late-life cognitive resilience is influenced by factors from across the lifespan could inform applications of cognitive resilience theory to clinical and community settings with the goal of offsetting the devastating impacts of AD. | en |
