Elderly patients who undergo anesthesia and non-cardiac surgery are subject to deterioration of brain function including the development of postoperative delirium (PD) and postoperative cognitive dysfunction (POCD). These disorders cause disability, distress for both patients and their families, are associated with other medical complications and account for significant additional health care costs. We currently use relatively primative approaches to preventing and treating PD and POCD. The proposed project expands on previous work exploring PD and POCD to propose a randomized controlled trial of perioperative dexmedetomidine to prevent PD and, potentially, POCD. Seven hundred and six patients will be enrolled at seven centers representing both academic and community hospitals. Participants will undergo preoperative cognitive testing and provide saliva samples for cortisol. Patients will be randomized to either dexmedetomidine or placebo which will be started prior to surgery and continued for 24 hours postoperatively. Follow up studies will include surveillance for delirium while in the hospital and cognitive testing at 3 and 6 months following surgery. Part of the neuropsychologic evaluation will include an assessment for mild cognitive impairment(MCI). Dexmedetomidine is a drug used for sedation in critically ill patients that provides some pain relief and controls the bodies response to stress. The sedation produced by dexmedetomidine appears more similar to natural sleep than any other drug used for anesthesia and postoperative sedation. Data indicating that dexmedetomidine can prevent delirium following cardiac surgery and the developing understanding of the causes of PD and POCD suggest that dexmedetomidine will be particularly effective. The proposed project includes important efforts to further define POCD and understand the pathophysiology of these problems. The evaluation of patients for MCI represents a particularly important and challenging innovation in the study of PD and POCD. PUBLIC HEALTH: Almost eight million elderly patients had surgery in 2004. Perhaps 10% of those patients suffer from problems that can be thought of as postoperative brain failure. These problems are extremely expensive in terms of health care dollars and cause significant disability - representing the next challenge for physicians as they confront the increasing surgical burden of the baby boom generation.