The goal of this project is to create a repository of cell lines/DNA from over 500 well-characterized subjects aged 90 or more and to begin investigations of the relationship between specific genes and behavior in this """"""""oldest-old"""""""" population. Specifically, we will investigate the effect of DRD4 allelic variation on the personality trait of novelty-seeking and it's relationship to behavior/quality of life in this cohort. The resource generated by this study will allow us to facilitate genetic research for scientists around the country, working in longevity and the clinical, behavioral and functional status of our oldest citizens. We have assembled a multidisciplinary team, consisting of human molecular geneticists, neurologists/epidemiologists, statistical geneticists and clinical psychologists to address the following:
Specific Aim 1 - Development of a genetic repository of the oldest-old. ]'o develop a cell line/DNA bank of a population-based cohort of individuals aged 90 and older (N=560) who are well characterized with medical history, medication use, neuropsychological testing, and neurological examinations.
Specific Aim 2 - To test the hypothesis that specific non-4R alleles of the DRD4 gene are associated with behaviors that effect quality of life in this cohort. Personality questionnaires and a simplified attentional network test (ANT) will be obtained as adjuncts to the current test battery/histories of this oldest-old cohort. Genotyping/sequencing of the DRD4 locus will be used to test if alleles associated with novelty-seeking and behavioral disorders in younger individuals are associated with improved quality of life in this oldest-old population.
Specific Aim 3 - To obtain detailed pedigree information on this cohort as an adjunct to ongoing evaluations. In order to make this oldest-old cohort of maximum value for future genetic studies, we will obtain multigenerational pedigrees with defined, relevant phenotypic information.
