Lack of association between appendectomy and Parkinson's disease: a systematic review and meta-analysis

Background Accumulation of aggregated alpha-synuclein from the enteric nervous system is believed to be involved in the pathogenesis of Parkinson's disease (PD). The appendix contains abundant alpha-synuclein and lacks a blood-tissue barrier, suggesting that appendectomy might reduce alpha-synuclein aggregation, and therefore the risk of PD. Studies on this intriguing possibility have not come to consistent conclusions. Methods PubMed, Embase (via Ovid), and the Cochrane Controlled Register of Trials were searched for studies published through February 20, 2019 on the potential relationship between appendectomy and PD. Two reviewers independently screened literature, extracted data and evaluated the quality of included studies. Data were summarized as pooled effect sizes (RRs or SMDs) with 95% confidence intervals (CIs), which were calculated using the inverse variance method and a random-effects model. Heterogeneity was assessed using the I-2 statistic and explored in subgroup analyses. Results Of the 408 references screened, six studies involving 3,554,540 people were included eventually. Appendectomy did not significantly affect PD risk (RR 1.02, 95% CI 0.87-1.20, I-2 = 83.1%, P = 0.789) or delay its onset (SMD 0.21, 95% CI - 0.03 to 0.44, I-2 = 43.4%, P = 0.083). Conclusion The available evidence suggests no protective effect of appendectomy against PD. Future studies should seek to clarify the role of inflammation, alpha-synuclein pathology and the gut-brain axis in PD pathogenesis.