ABSTRACT: To examine whether exposure to general anesthesia for procedures at age ?40 years is associated with prevalent mild cognitive impairment (MCI) in the elderly.A case-control study nested within a population-based cohort. Olmsted County, Minnesota, residents, aged 70-91 years, underwent baseline evaluations that included the Clinical Dementia Rating scale, a neurologic evaluation, and neuropsychologic testing. Individuals identified with MCI (cases) at enrollment were matched 1:2 on age, sex, education, and apolipoprotein genotype with participants who were cognitively normal at the time of the index visit. Medical records from age 40 years until the index visit were reviewed to determine exposures to general anesthesia. Conditional logistic regression, taking into account the matched set study design and adjusting for MCI risk factors, was used to assess whether exposure to anesthesia after the age of 40 years was associated with prevalent MCI.A total of 387 Mayo Clinic Study of Aging participants (219 males, 168 females) were diagnosed with MCI at enrollment with mean age of 81 ± 5 years. Exposure to general anesthesia after the age of 40 years was not significantly associated with prevalent MCI when analyzed as a dichotomous variable (any versus none, adjusted odds ratio, 0.97 [95% confidence interval, 0.68-1.40]) or the number of exposures (odds ratio, 1.13 [0.74-1.72], 0.81 [0.53-1.22], and 1.03 [0.67-1.58] for 1, 2-3, and ?4 exposures, respectively, with no exposure as the reference). Similar results were obtained for exposure to anesthesia after the age of 60 years and during 5, 10, and 20 years before the first visit.Exposure to general anesthesia for procedures at age ?40 years was not associated with prevalent MCI in the elderly.