Association Between Rheumatoid Arthritis and Risk of Parkinson's Disease: A Meta-Analysis and Systematic Review

BACKGROUND: Rheumatoid arthritis (RA) and Parkinson's disease (PD) are two common chronic diseases worldwide, and any potential link between the two would significantly impact public health practice. Considering the current inconsistent evidence, we conducted a meta-analysis and systematic review to examine the risk of PD in patients with RA. METHODS: Two investigators (DL and XH) conducted a comprehensive search of PubMed, Embase, and Web of Science using medical subject headings terms combined with free words to identify relevant papers published from inception through December 31, 2021. All studies that explored the relationship between RA and PD were included for quantitative analysis and qualitative review. Random- and fixed-effects models were used to pool the risk ratios (RRs) of PD in patients with RA. The Newcastle-Ottawa scale was used to assess the quality of included studies. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA 2020) guideline. RESULTS: Four population-based studies involving 353,246 patients and one Mendelian randomized study were included in our study. The pooled result showed a significantly reduced risk of PD in patients with RA than in the general population (RR = 0.74, 95% CI: 0.56-0.98, P = 0.034). No apparent effects of gender, age, region, follow-up time, or study design on PD risk were observed. Sensitivity analysis showed that pooled results were relatively stable, and no publication bias was detected. The Mendelian randomization study indicated a significant inverse association between RA and PD (genetic correlation: −0.10, P = 0.0033) and that each one standard deviation increase in the risk of RA was significantly associated with a lower risk of PD. Of note, the current study is limited by the relatively small number of included studies and unmeasured confounding factors, especially for RA-related anti-inflammatory agents. CONCLUSIONS: This study supports that people with RA had a lower PD risk than those without RA. Further studies are needed to explore the underlying molecular mechanisms of the interaction between the two diseases.