Appendectomy and risk of Parkinson’s disease: a systematic review and meta-analysis

Braak's hypothesis suggests that α-synuclein may enter the central nervous system through the enteric nervous system and contribute to the pathogenesis of Parkinson's disease (PD). The appendix, enriched in α-synuclein, has been proposed as a possible entry point in PD pathogenesis. This systematic review and meta-analysis aimed to assess the association between appendectomy and PD risk using newly available data. A literature search was conducted in PubMed and Embase through September 10, 2024, to identify studies on appendectomy and PD risk. Two independent reviewers screened and assessed articles for eligibility with a third reviewer involved in cases of disagreement. Study quality was assessed using the Newcastle-Ottawa Scale. Data for meta-analysis were pooled using a random-effects model and analyzed in Review Manager 5.4. Meta-regression, subgroup, and sensitivity analyses were performed. Nine studies met inclusion criteria. Meta-analysis indicated no significant association between appendectomy and PD risk (RR: 1.01, 95% CI: 0.90-1.12, p = 0.89). Subgroup analyses showed similar findings. Sensitivity analyses did not change the estimate. This analysis suggests no association between appendectomy and PD risk.