The goal of the project is to clarify the cognitive transitions that lead from normality to well-defined intermediate states and from intermediate states to Alzheimer's Disease (AD) or AD and Vascular Dementia (AD/VaD) as well as the risk factors and protective factors that influence those transitions. AD and AD/VaD develop in 3 stages which can be retrospectively identified using change point models: a stage of relative cognitive stability, a stage of accelerated cognitive decline and a stage of clinical dementia. Based on theoretical considerations, we have developed and tested two prospective operational definitions for intermediate states of Cognitive Impairment. The first, Anmestic Cognitive Impairment (ACI) has a prevalence of 21%, more than 4 times the prevalence of amnestic Mild Cognitive Impairment (MCI) in our sample, and is associated with a 10% annual conversion rate to dementia. A second, less well characterized intermediate stage, Nonamnestic Cognitive Impairment (NACI) has a prevalence of 15%. These constructs expand the pool of potential subjects for preventive interventions. In addition, emerging evidence suggests that the influence of risk factors on AD and AD/VaD may depend upon the stage of illness. This project proposes to assess five categories of risk factors in the context of a stage of illness model. Risk factor categories include modifiable cardiovascular risk factors, clinical and neuropsychological measures, sociodemographic and selected behavioral measures, biological markers (inflammation, thrombosis, lipid profiles and plasma Abeta) as well as neuroimaging. Ultimately, this research should facilitate the translation of epidemiologic research into clinical trials and public health practice by better defining the intermediate states that lead to dementia and assessing risk factors in a framework tied to models of primary and secondary prevention.
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