DESCRIPTION: (Verbatim from the Applicant's Abstract) In the United States, nearly 650,000 patients undergo coronary artery bypass grafting (CABG) each year. This procedure, although extraordinarily successful in relieving the symptoms of coronary disease, is also associated with a variety of neurologic problems, ranging from stroke to cognitive changes and depression, which remains a major cause of morbidity after surgery. Not only has it been estimated that from 30 and 79 percent of patients show cognitive decline from 2 weeks to 2 months after CABG, but our prior (separately funded) studies showed late decline in certain cognitive domains 1 to 4 years later. The cause of these cognitive changes is unclear: it is generally thought to be related to the use of the cardiopulmonary bypass machine in the operating room, but lack of appropriate control groups has precluded ruling out other causes including the effects of general anesthesia, Alzheimer's disease (AD) or depression. Therefore, newer techniques of "off-pump" coronary artery bypass surgery (OPAL), that are similar to CABG but do not use the cardiopulmonary bypass machine, provide a unique opportunity to determine the role of the bypass machine in the development of cognitive problems. The present proposal prospectively compares cognitive outcome in 3 groups of patients with coronary artery disease:-CABG patients (general anesthesia, use of the cardiopulmonary bypass machine)-OPCAB patients (general anesthesia)-Nonsurgical control patients (no surgery or general anesthesia) To address our overall hypothesis that patients undergoing CABG will show cognitive decline that differs in nature and time course from decline in surgical and nonsurgical controls, the following specific aims are proposed. By examining patients with neuropsychological tests chosen to assess different cognitive domains, and measures of depression preoperatively, at 3 months, at 1 year, at 3 years, aim 1 will compare the incidence of cognitive change up to 1 year in the three groups, to determine if decline is specific to CABG. Aim 2 will determine the incidence of change at 3 years after surgery. Aim 3 will clarify the role of depression on cognitive changes and the development of angina after surgery. Aim 4 will evaluate demographic, medical and genetic risk factors associated with cognitive change. The long-term objective of this proposal is to determine the role of the cardiopulmonary bypass machine in cognitive change after CABG with the ultimate purpose of proposing interventions to overcome these adverse effects.