This revised application is for the competing renewal of a cross-national study whose objective is to compare the distribution of, and risk factors for, the dementing disorders in two rural populations un the United States and in India. The US site is the mid-Monongahela Valley, a community near Pittsburgh, where, since 1987, we have been conducting a prospective community study of dementia, the MoVIES project. The Indian site is Ballabgarh, a defined and enumerated population near New Delhi, where the first (current) phase of the cross-national study is in progress. Of note, the elderly members of this community are exclusively Hindi- speaking, and largely uneducated and illiterate, rendering their cognitive screening a major challenge. In Phase 1, our goal has been to develop for this population, systematically and empirically, suitable cognitive and functional screening instrument which (a) is culturally fair, psychometrically sound, and valid for an uneducated population; (b) is sensitive and specific for dementia; (c) will allow not only the identification of cases of dementia, but also more detailed characterization of dementia and of normal and abnormal aging in this cohort; and (d) will allow meaningful cross-national comparisons with MoVIES project data. Phase 1 data indicate that we are indeed succeeding in developing such an instrument. In the proposed Phase 2, we will use the screening instrument developed in Phase 1 to conduct a full-scale epidemiological study in Ballabgarh, using methods similar to those of the MoVIES project. The revised proposal includes evidence of adequate sample size and also new data about a subgroup with partial education. We will screen the entire population aged 55+ years, numbering nearly 5,000, and perform diagnostic examinations of all screen-positive subjects and a 10% sample of screen- negative subjects; thus, we will identify and describe prevalent cases of dementia and also characterize the entire cohort at baseline with respect to potential risk factors including education and APOE genotype. We will then follow up the cohort, and repeat screening and examination after two years, to identify incident cases of dementia and also to determine the nature and extent of cognitive change over that period in non-demented elderly. Thus, we will estimate age- and gender-specific prevalence and incidence rates of the dementias, identify risk factors, and study the outcome (including mortality) in identified prevalent cases. A new aim is to examine, and compare with MoVIES data, the relationship between the APOE gene and dementia/Alzheimer's disease in this community-based cohort. We will also document the population's cognitive characteristics and change over time. We will then make cross-national comparisons of these data with those from the MoVIES project. Similarities and differences between the two populations will reveal further clues as to true risk factors for Alzheimer's and other dementias.
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