Twin studies can be one of the most important sources of information about the role of environmental as well as genetic factors in the etiology of Alzheimer's disease and other dementing illnesses. This proposal seeks continued support for the Study of Dementia in Swedish Twins, in order to conduct longitudinal follow-ups of all identified cases and partners in concordant and discordant pairs, to identify incident cases from the same population, and to obtain prospective information from the population about exposure to environmental risks, family history of dementia, and medical history. An estimated 60 cases will be followed longitudinally, with 30 to 40 incident cases anticipated during the period encompassed by the study. Longitudinal measures include a cognitive battery and a Clinical Dementia ]gating. Diagnostic assessment of incident cases includes psychological measures, medical evaluation, neuroimaging, and collateral interview. Longitudinal cases and unaffected partners will be requested to participate in an autopsy. Various threshold or cascade models for the etiology and onset of Alzheimer's disease seem most useful in planning analytic approaches. Data analyses will encompass: determining concordance rates for identical and fraternal twins, application of liability-threshold models to estimating the relative contribution of environmental and genetic factors, extension of case-control models using logistic regression to encompass multiple risks, and using quantitative genetic models to examine the distribution of phenotypes that may be indicators of dementia in their extreme. The Swedish sample provides a special research opportunity to achieve these purposes.
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