The first proof-of-concept studies using the new positron emission tomography (PET) tracer, Pittsburgh compound-B (PIB), showed that PIB-PET imaging detected amyloid deposition in the brains of living AD subjects in a pattern similar to that predicted by autopsy studies. The overall objective of this proposal is to define amyloid deposition in early phases of AD and aid in the characterization of PIB as a surrogate marker of amyloid deposition by examining PIB retention and other metabolic and structural makers. The studies ask 3 major questions: 1) in normal elderly subjects, subjects with mild cognitive impairment (MCI), and mild, moderate, and severe Alzheimer's disease (AD), will deposition of PIB be detectable and correlate quantitatively with the level of severity of overall cognition, or cognitive functions referable to specific areas of the brain? 2) Will these subjects show increases in PIB retention (amount of beta amyloid) in a longitudinal study in which PIB-PET and cognitive assessments are performed annually for up to three years? 3) What is the prevalence of PIB retention across the clinical spectrum of Parkinson's Disease (PD), PD with dementia (PDD) and Dementia with Lewy Bodies (DLB);how much amyloid deposition underlies clinical dementia symptoms observed in these patients? We will also perform fluorodeoxyglucose PET (FDG-PET) and MRI to correlate metabolic and volumetric data, cognition, and PIB deposition. To accomplish these objectives we have established an Administrative Core to oversee &coordinate the projects, budgets, and data transfers;a Clinical Core to identify and assess subjects from the University of Pittsburgh ADRC and the Movement Disorders Clinics in the Department of Neurology and the Pittsburgh VA Health System and an Imaging, Methodology and Statistics (IMS) Core comprised of researchers from the UPMC PET Center and the Department of Radiology. Effective collaborations are assured by the fact that the investigators have worked together closely in research &care in the ADRC and the Parkinson's Center for many years.
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