Alzheimer's Disease AD, the major cause of dementia in the elderly, islikely to be caused by a combination of aging, genetic and environmentalfactors. While the evidence that AD is at least in part geneticallydetermined, little is known with any certainty about non-genetic riskfactors. A powerful method of determining risk factors for AD would be toidentify populations from the same ethnic group at different levels ofdevelopment and in different environments with varying rates of illness. The Indianapolis-Ibadan Dementia project has now established twopopulation-based cohorts of community-dwelling elderly African AmericansN=2212 and Africans N=2494, carefully evaluated with identicalmethodology. So far two major findings have resulted from this study. The age-adjusted prevalence of AD is significantly lower in Africans thanin African Americans. In pilot studies, the allele of apolipoprotein EAPOE had a strong association with AD in African Americans equal to thatin Caucasian populations. In Africans the APOEepilon4 allele is asignificant risk factor for AD in incidence cases in African Americans butnot in Africans. The secondary aims of the studies are: 3 to identifyrisk factors for incidence cases of AD from data collected prior to theonset of disease; 4 to describe the natural history of cognitive andsocial functioning over a six year period in the two community dwellingcohorts and to identify factors which may predict decline in cognitive andsocial functioning; and 5 to store blood, plasma and DNA samples forfuture genetic and biological studies. In order to accomplish thesegoals, we are proposing a five-year longitudinal study with two incidencephases in years two and four. Subjects who are diagnosed with dementiawill have follow-up clinical assessments in years one, three and five. Weare also planning to determine the APOE genotypes of all subjects whoconsent to this procedure in the two samples and to continue to collectother risk factor data.