This dissertation explores the role of biologic factors and a novel method of measuring cognitive function in investigating mechanisms and risk factors of cognitive aging. With a rapidly increasing aging population, the public health burden of dementia is expected to rise in the future. Therefore, it is important to both better understand the etiology and identify novel risk factors, in order to reduce the incidence of new cases and develop effective treatments. Blood-based biomarkers, such as amyloid-beta and sex hormones, can provide an objective measure of factors likely associated with dementia risk. Additionally, computerized cognitive testing can provide efficient and accurate measurement of cognitive function, yet is seldom used in epidemiologic studies.
Our first chapter involves the first systematic review and meta-analysis of prospective studies exploring the association between plasma amyloid-beta and incident Alzheimer’s disease or dementia. While preclinical prediction of Alzheimer’s disease is important for effective intervention, studies have considerably varied in design, assays and sample size, making it difficult to interpret the overall data and thus necessitating a systematic review and meta-analysis.
The second chapter explores the association between endogenous hormone levels and cognitive function in a population of older women. While many studies have investigated the role of hormone therapy in cognitive aging, fewer studies have investigated endogenous hormones, which may provide a more objective measure of hormonal status. We therefore present a prospective cohort study investigating the association between several endogenous sex hormones and their prohormones at baseline, and cognitive function over 20 years later.
The third chapter evaluates the feasibility and performance of a self-administered computerized cognitive battery. Although most epidemiologic studies of cognitive aging rely on traditional neuropsychological testing to measure cognitive outcomes, such methods can be prone to error, interviewer bias, and demand substantial time and cost. Therefore, we present results demonstrating for the first time the feasibility and performance of an unsupervised self-administered computerized cognitive battery in a population of older men.Epidemiolog
