There have been very few studies of progression of Alzheimer's disease (AD) that have been based in community populations. Typical studies, including some of our owaa previous reports, use clinical populations, often recruited at psychiatric or AD centers. Clinical populations are not representative of the true distribution of the disease and these studies are necessarily biased by the nature of the referral and recruitment patterns particular to the clinical setting. In addition, it is not known what proportion of patients with AD actually is seen in clinical settings. In this project we are conducting a prospective, community based study of a representative sample of patients with AD to investigate determinants of disease course and outcomes. In the previous study period, we identified and initiated prospective follow-up of 903 AD patients, including 356 incident cases. We propose to continue follow-up of the surviving patients and to initiate follow-up of an additional group of incident cases in order to test specific hypotheses regarding determinants of disease course and outcomes. We will have the unprecedented opportunity to test all of our major hypotheses in a multi-ethnic cohort of incident dementia patients. We will characterize rapidity of disease course in AD by applying generalized estimating equations and random effects models to prospectively obtained measures of cognitive function and ability to perform activities of daily living. We will also determine the timing and occurrence of specific disease endpoints: change in CDR stage, use of paraprofessional care, increase in hours of ADL care, admission to nursing home, need for the equivalent of institutional care, and mortality. We will explore factors hypothesized to be associated with increased relative risk for the occurrence of the disease endpoints or with more rapid disease course: demographic features, particularly ethnicity, comorbid medical and sociocultural factors, behavioral manifestations, genetic and molecular data, as well as the rate of cognitive and functional decline and estrogen use information acquired prior to the incident dementia. We will compare hospitalization and mortality in demented patients to that observed in nondemented community patients. We will also identify what level of change in particular cognitive domains is associated with alteration in the functional task performance.