General anesthesia exposure and risk of dementia: a meta-analysis of epidemiological studies

The association between exposure to general anesthesia and dementia risk has been inconsistently reported across epidemiological studies. To better understand the association, we conducted a meta-analysis of epidemiological studies. PubMed and Embase were searched through April 2017. Random-effects models were used to pool association estimates. We further evaluated potential dose-response relationship. Based on literature search, seven prospective/cohort studies, 11 case-control studies, and a pooled analysis of six case-control studies were identified. Sixteen of these studies were with high quality. After pooling available risk estimates, overall no significant association between exposure to general anesthesia (yes versus no) and dementia risk was detected (odds ratio (OR) = 1.03, 95% confidence interval (CI) 0.90–1.19, p for heterogeneity < 0.001). The null association persisted in the majority of subgroup analyses, although a significant positive association was detected in studies collecting anesthesia exposure using records (OR = 1.22, 95% CI 1.01–1.47, p for heterogeneity < 0.001), a method that is less prone to bias compared with interview or questionnaire using proxy reporters. Based on the dose-response analysis of three studies, a significant nonlinear relationship between times of exposure to general anesthesia and increased risk of dementia was suggested (p < 0.0001). Overall, this meta-analysis suggests that overall the evidence from epidemiological studies supporting a link between general anesthesia exposure and an increased dementia risk is not very strong, while an association was suggested in the studies collecting anesthesia exposure using records and those providing anesthesia exposure frequency data. Further well-designed studies are warranted to better characterize the relationship of interest.