There have been very few community-based studies of progression of Alzheimer's disease (AD). None have used incident dementia patients and the later consequences of disease progression were rarely addressed. In the previous study period, we identified and initiated prospective follow-up of 601 AD patients, including 176 incident cases. We found that AD was associated with increased risk of mortality and hospitalization, and increased lifetime disability and paid service use. Male gender, more severe AD, cachexia, and extrapyramidal signs were each associated with increased risk of death. More rapid cognitive decline and mortality were associated with higher educational and occupational attainment. We also developed new measures of functional competence and quality of life, performance-based tests for functional change, and automated medical record retrieval for documenting in patient care. We propose to continue follow-up of the surviving patients and to initiate follow-up of an additional 150 incident and 200 prevalent 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 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 also characterize rapidity of disease course in AD by applying GEE and random effects models to prospectively obtained measures of cognitive function and ability to perform activities of daily living 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 information, 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 non-demented community patients. We will also identify what level of change in particular cognitive domains is associated with alteration in the functional task performance.
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