The University of Pittsburgh ADRC is a multi-disciplinary resource which oversees clinical assessment and care, stimulates dementia research, and trains health professionals in Alzheimer's disease (AD) and other dementias. Centered in the Department of Psychiatry of Western Psychiatry Institute and Clinic, it involves clinicians and investigators from 18 departments in 8 schools at the University. In this competing continuation the ADRC will continue to address its 4 specific aims: to advance research in AD and other dementias, to training physicians and other professionals and to promote understanding of AD and other dementias in the region and nationally. There are 6 cores in the ADRC: the Administrative Core oversees all ADRC functions, and provides scientific initiatives and direction. The Data Management and Analysis Component maintains the ADRC database and provides biostatistical consultation. The Clinical Core performs clinical and research evaluations of patients and controls; follows this cohort longitudinally; and provides clinical data, subjects, and technical and scientific leadership for research for research. It also performs outreach to the African American community via a successful satellite leadership for research. It also performs outreach to the African American community via a successful satellite clinic. The Neuropathology Core provides neuropathologic analyses of all cases, a well catalogued brain bank, and sophisticated image analysis and technical expertise for ADRC investigators. The Training and Information Core provides training in geriatrics and AD, provides outreach to minority groups and rural areas, and systematically evaluates ADRC programs. The Neuroimaging Core provides centralized acquisition, analysis, reporting and archiving of all MR imaging of all MR imaging on ADRC patients, coordinates MR with PET research studies, and provides expertise consultation in design of imaging studies in dementia. The newest core, the Genetics Core, will collect blood and DNA from participants, perform APOE genotyping, and provide genetic material for research collaborations. The projects proposed reflect the broad scientific strengths and resources at the University of Pittsburgh, our ability to attract outstanding researchers to the field, and important domains of inquiry in AD research, with emphasis on genetics, neuroimaging and neuropsychiatry. Project 1 examines functional MRI in semantic memory in AD. Project 2 assesses AChE imaging on PET, in AD patients treated with cholinergic drugs. project 3 studies the role of bleomycin hydrolase, a cysteine protease, on amyloid metabolism and alpha secretase activity. Project 4 will perform the first incidence study of psychosis in AD, and determine the risk of certain neurotransmitter receptor polymorphisms in predisposing to development of psychosis. This proposal illustrates the continuing development of this mature ADRC, and its ability to manage and stimulate productive clinical and basic research, service and training activities.