This application is for the 5-year renewal of the program project, Healthy Aging and Senile Dementia (HASD), now in its 19th year. In this renewal there is a continued focus on the clinical, psychometric, and neuropathologic correlates of DAT in comparison with healthy aging with a new thrust addressing preclinical Alzheimer's disease. Six 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. Core F: Neuroimaging is a new core to collect structural imaging data on our cohort to visualize change in anatomy associated with cognitive decline. Two new projects replace the current Projects 1 and 2 which are being absorbed by appropriate cores. The new Project 1 (""""""""Dementia Assessment in the Community"""""""" JC Morris) evaluates a modified version of our informant-based research assessment in two community settings. The new Project 2 (""""""""Novel Biomarkers to predict Alzheimer disease"""""""" DM Holtzman) examines potential novel biomarkers (Abeta40/Abeta42 ratio, CSF sulfatides) and other variables to predict presence and progression of AD. Two current projects continue in new directions. Prelect 3 (""""""""Attention Profiles in Healthy Aging and Early Stage DAT,"""""""" D Balota) will explore the subcomponents of attention as early indicators of DAT and individual attentional profiles in both variability in performance, and personality characteristics. Project 4 (""""""""Predicting Cognitive Decline in Healthy Elders,"""""""" JG Csernansky) 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 issue of detecting preclinical disease.
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