This application is a for 5-year renewal of the program project, Healthy Aging and Senile Dementia (HASD), now in its 14th year. In this renewal there is a continued focus on the clinical, psychometric, and neuropathologic correlates of DAT in comparison with healthy aging. Five interactive and supportive Cores are proposed: Core A: Clinical recruits, enrolls, and clinically assesses subjects annually to supply all projects; Core B: Psychometrics provides longitudinal cognitive assessments of subjects; Core C: Neuropathology performs postmortem examinations for clinicopathological correlation for all studies and provides appropriate tissue and data to Projects 2 and 4; Core D: Biostatistics oversees data management and provides statistical input to all Cores and projects; and Core E: Administration provides administrative support to all components and assures progress in accomplishing program project goals. Three current projects continue. Project 1 (""""""""Intellect and Alzheimer changes in the very old"""""""") examines clinical, psychometric, and neuropathologic differences and overlap in nondemented and demented subjects greater than or equal to 85. Project 2 (""""""""Mapping of neuropathology in healthy aging and dementia"""""""") studies preclinical stages of Alzheimer's disease (AD) in comparison with healthy brain aging and mild DAT. Project 3 (""""""""Frontal control systems and memory in aging and DAT"""""""") explores the contributions of medial temporal and frontal systems to cognitive performance in aging and DAT. A new study, Project 4 (""""""""Imaging neuronal loss with MRI/MRS in DAT and controls"""""""") evaluates the ability of sensitive neuroimaging measures to discriminate aging and very mild DAT. Together, these projects and their supporting cores will define very mild DAT in comparison with healthy brain aging and address the critical problem of whether aging and AD are continuous or discrete processes.
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