This supplement has two overall goals: 1) To develop a genetic repository that will capitalize on the wealth of longitudinal phenotypic data collected over the past 15 years by the Einstein Aging Study (EAS) and provide a valuable resource for future genetic studies of late onset dementia and cognitive decline with aging in the ongoing cohort. 2) To examine the relation of selected genotypes to cognitive outcomes, and rate of cognitive decline within specific domains of cognition. The EAS program project has established a well characterized longitudinal sample with meticulously defined outcomes including incident dementia and its subtypes (particularly Alzheimer's disease: AD), as well as a number of well characterized intermediate states of cognitive decline. The data base includes extensive annual neuropsychological assessments, neurological evaluations, and assays of biological markers that have been implicated as potential dementia risk factors. The EAS has been storing samples appropriate for genetic analysis since 1992. However, due to budgetary constraints, we have not been able to extract and analyze DNA. Since the time our specimen collections began, our understanding of the human genome has advanced. This creates a tremendous opportunity for the EAS to leverage our specimen bank to establish a genetic repository and to explore genotype and phenotype correlations. We can currently test important hypotheses relating genetic factors and cognition. We propose to test genotypes related to longevity, vascular risk factors, neuronal function and dopamine metabolism, and genes implicated in the etiology of late onset AD. In addition, we will develop an outstanding resource for testing additional hypotheses as they arise. Therefore, this supplement proposes to establish a genetic repository for the EAS cohort and to use this valuable resource to test hypotheses regarding the relationship of selected candidate genes to: cognitive decline in several domains; the incidence of AD (alone or combined with vascular disease (VAD); and to the incidence of intermediate cognitive states, such as amnestic Mild Cognitive Impairment (aMCI). On a long-term basis the repository will allow us to conduct genome scans and to relate any number of genes to the wealth of clinical and biological outcome data obtained in the EAS. ? ? ?
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