Objective. To investigate the association between exposure to general anesthesia and the development of Alzheimer’s disease (AD) and dementia by reviewing and integrating the evidence from epidemiological studies published to date. Methods. We searched MEDLINE, EMBASE, and Google Scholar to identify all relevant articles up to April 2018 reporting the risk of AD/dementia following exposure to general anesthesia and finally updated in February 2020. We included patients older than 60 or 65 years who had not been diagnosed with dementia or AD before the study period. The overall pooled effect size (ES) was evaluated with a random-effect model. Subgroup analyses were conducted and possibility of publication bias was assessed. Results. A total of 23 studies with 412253 patients were included in our analysis. A statistically significant positive association between exposure to general anesthesia and the occurrence of AD was detected in the overall analysis (pooled ,), but with substantial heterogeneity (,). Although the overall analysis revealed a significant association, the results of the subgroup analyses were inconsistent, and the possibility of publication bias was detected. Conclusions. This meta-analysis demonstrated a significant positive association between general anesthesia and AD. However, considering other results, our meta-analysis must be interpreted with caution. Particularly, it should be considered that it was nearly impossible to discriminate the influence of general anesthesia from the effect of surgery itself on the development of AD. Further, large-scale studies devised to reduce the risk of bias are needed to elucidate the evidence of association between general anesthesia and AD. Trial registration. PROSPERO International prospective register of systematic reviews CRD42017073790.
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