Evaluating Longitudinal Outcomes of Cognition by Environment, Genes, and Sleep in Aging Individuals

Dementia and neurodegenerative diseases including Alzheimer’s dementia (AD), which increase in prevalence with age, greatly impact the health and quality of life of older adults, as well as their families and support systems. At a population level, as the “Baby Boomer” generation enters older age, both the number and the proportion of older adults will continue to grow and along with it, the number of people with dementia and Alzheimer’s disease. Some estimates project that by 2050, the prevalence of AD could grow three fold from levels in 2000 to as much as 13 million affected individuals1,2 Identification of both preventable risk factors for dementia and Alzheimer’s disease and for early indicators of decline is critical in intervention planning and in preparing healthcare and care infrastructures. Both level of cognition and rate of cognitive decline in mid and late life are predictive of the development of dementia. Prior research has identified behavioral, environmental, and genetic, namely the APOE e4 allele, risk factors for cognitive function and decline and described pathophysiologic processes. Early indicators and many risk factors for cognitive decline are measured and represent temporally concurrent circumstances, but researchers have advocated for a life-course approach to studying cognitive aging3,4 In this dissertation we used data from three cohorts to look at predictors of cognitive level, rate of decline, and of neuropathology associated with cognitive decline. Specifically, we aimed to 1) evaluate the association of actigraph and self-reported sleep with cognitive function and 5-year cognitive decline, 2) evaluate whether the genetic penetrance of the APOE e4 risk allele varies by early life environment operationalized as birth-year cohort in one study and Adverse Childhood Experiences (ACEs) in another.