A review of epidemiological evidence for general anesthesia as a risk factor for Alzheimer's disease

Exposure to surgery and general anesthesia (GA) has been hypothesized to be a potential risk factor for the development of Alzheimer's disease (AD). Some basic science research studies have demonstrated AD pathology in animals following exposure to inhalational anesthetics. However, controversy exists as to whether GA is associated with an elevated risk of developing AD in human populations. While randomized controlled clinical trials would provide the strongest evidence for a causal relationship between exposure to surgery under GA and the subsequent development of AD, to date there have not been any trials to address this important question. Therefore, a potential relationship between GA and AD must currently be examined using observational methods. A recent meta-analysis of case-control studies (N = 15) did not find that AD was associated with prior exposure to GA (OR = 1.05, 95% CI: 0.93-1.19, p = 0.4). A limited number of retrospective cohort studies have likewise not provided definitive information supporting an association. Therefore, at the present time there is limited information to support the hypothesis of AD developing as a consequence of GA, although there are few high quality studies in this area. Given the high prevalence and impact of AD, and the relatively frequent exposure of large populations to surgical procedures, the association between AD and GA requires further study.