Dementia is a major public health problem with several unanswered questions. Limited data exist on the trajectory of cognitive, functional, and behavioral decline, their longitudinal interaction, and the variables that modify their expression. Population-based incident cohorts of dementia can best answer these questions. The Cache County Study on Memory in Aging (The Cache County Study) provides such cases for study. Established in 1994, the Cache County Study is a population-based longitudinal investigation of the risk factors for dementia. The entire cohort has been followed for six years, with careful identification of prevalent and incident cases of dementia, and characterization of genetic and environmental risk factors for each individual. Not an aim of the original or recently submitted renewal applications, the present application intends to follow the incident cases of dementia until death. Using existing and new data, we will characterize the clinical trajectories of three important domains in dementia: cognitive, functional, and behavioral. The role of genetic and environmental variables on these trajectories and on survival will be examined. With this unique cohort of incident cases of dementia, available in few other settings worldwide, we will build upon the rich antecedent information gathered prior to the onset of dementia. The cohort is ideal for study as cases are population-based (and not subject to referral bias), have lower rates of medical co-morbidities, and, on average, are longer lived. There are three major specific aims of the project, which are as follows: 1. In a population panel of incident cases of dementia, model the cognitive, functional, and behavioral trajectories to characterize the natural progression of dementia as a continuum from its prodrome to end-stage disease. Models will examine the inter-relatedness of the individual domains. 2. Test in this same cohort a series of hypotheses regarding genetic and environmental variables that modify decline in each trajectory. Along with environmental risk factors such as medical history, key features of the care environment will also be studied. 3. Test in this same cohort a series of hypotheses regarding genetic, social, and environmental variables that modify survival in dementia.
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