Background Age is a predictor of cognitive dysfunction after cardiac surgery, but the mechanism is unknown.The purpose of our study was to determine whether age-related decrements in cognition are associated with cerebral blood flow (CBF) autoregulation during cardiopulmonary bypass (CPB).Methods and Results Cognitive function testing was completed before surgery and before hospital discharge in 215 patients undergoing elective coronary artery bypass grafting (CABG) surgery.The battery consisted of seven tests with nine measures designed to evaluate memory, mood changes, and visuomotor speed and function. Pressure-flow and metabolic-flow cerebral autoregulation during hypothermic cardiopulmonary bypass were determined using the Xenon-133 clearance CBF method and radial artery and jugular bulb effluent to calculate cerebral metabolic rate (CMRo2) and cerebral AV difference (C(AV)o2=20%. Metabolism-flow autoregulation was tested by varying the temperature (CMRo2) and measuring the coupling of CBF and CMRo2. Individual patient autoregulation was correlated with changes in cognitive measures. Cognitive performance declined in 6 of 9 measures after CABG surgery. Age predicted cognitive decline in 7 of 9 measures; short-term memory showed the greatest effect of age. Pressure-flow autoregulation during hypothermic CPB showed a small but significant (P<.0001) effect of pressure on CBF. There was no effect of age on the slope of CBF response to changes in MAP (pressure-flow autoregulation). There was a major effect of temperature on CBF during CPB (P<.0001). Coupling CBF and CMRo2with changing temperature was unaffected by age. Changes in cognition were not associated with measures of cerebral autoregulation. However, increasing C(AV)o2is associated with cognitive deficits in 5 of 9 measures; these associations were independent of age.Conclusions Increased age predisposes to impaired cognition after cardiac surgery.This decline in cognitive function in the elderly is not associated with age-related changes in cerebral blood flow autoregulation. The association of increased oxygen extraction with decline in some measures of cognitive function suggests that an imbalance in cerebral tissue oxygen supply, which is unrelated to age, contributes to acute cognitive dysfunction after cardiac surgery. Cognitive dysfunction after CPB in the elderly cannot be explained by impaired CBF autoregulation. (Circulation. 1994;90(part 2):II-243-II-249.)