Investigation of risk of Alzheimer’s disease diagnosis and survival based on variation to life experiences used to operationalize cognitive reserve

BackgroundAlzheimer's disease dementia (AD) is a debilitating progressive neurodegenerative disease. Life experiences are hypothesized to build cognitive reserve (CR), a theoretical construct associated with delayed onset of AD symptoms. While CR is a key moderator of cognitive decline, operationalization of CR is varied resulting in inconsistencies within the literature.ObjectiveThis study explored the relationship between life experiences used as proxies of CR and risk of AD diagnosis and death following diagnosis.MethodsWe explored results based on 30 different published CR operationalizations, including two standardized questionnaires and an investigator-developed lifecourse indicator. Using data from the Memory and Aging Project, we applied Cox proportional hazard models to evaluate the impact of operationalization on time to outcomes.ResultsHazard ratios, indicating instantaneous risk of AD or death for a standard deviation increase in the CR proxy utilized as a predictor, ranged from 0.80-1.40 for AD diagnosis and 0.80-1.29 for death following diagnosis. Among nine predictors that showed a significant reduction in risk of AD, there was a decrease of between 12% and 20%. Two predictors were associated with reduced risk of death, with 13%-20% reduction, while three predictors were associated with 18%-22% heightened risk of death following diagnosis.ConclusionsModel results were highly sensitive to CR operationalization. Based on the variation in results, composite measures that incorporate multiple lifecourse variables may still be the most comprehensive and faithful representation of CR. Attention to methodology and refining of measurement are needed to make use of CR and promote healthy aging.