The overall goal of this proposal is to test the hypothesis that preoperative presence of brain beta-amyloid plaques in non-demented subjects increases postoperative cognitive decline in elderly subjects scheduled for hip or knee replacement. Postoperative Cognitive Decline affects up to 50% of non-cardiac surgical patients ¡Ý65 years of age, and adversely affects other patient outcomes including mortality rates. Our hypothesis is that preoperative beta-amyloid plaques predict postoperative cognitive decline. The beta amyloid complexes can now be detected with PET scans of the brain using the amyloid specific tracer AV-45. We propose to examine whether the presence and severity of preoperative beta amyloid brain load (as measured with AV-45 PET scanning) predicts incidence of postoperative cognitive decline.Methods: Preoperatively, 44 patients aged ¡Ý65 years scheduled for knee or hip replacement, will undergo PET imaging with an amyloid specific ligand AV-45, and detailed neuropsychological assessment. During the postoperative in-hospital stay, subjects will undergo daily assessments for delirium. The follow-up neuropsychological assessment will be undertaken one week and 3 months after surgery for diagnosis of postoperative cognitive dysfunction. Analysis: The primary analysis for this pilot study will evaluate the association of preoperative beta amyloid deposition with postoperative cognitive decline, while controlling for potential confounders including age, gender, and co-morbidities. Significance: Sensitive and specific methods to preoperatively detect patients with Alzheimer¡¯s Disease neuropathology may identify patients at risk for postoperative cognitive decline, and will represent the enriched patient population in whom preventative and treatment interventions will be trialed. A successful therapeutic pre-emptive treatment to prevent surgery-induced cognitive decline has been recently reported by members of our group in the murine model.