Non-Genetic Risk Factors for Parkinson's Disease: An Overview of 46 Systematic Reviews

Background: Numerous systematic reviews (SRs) and meta-analyses on non-genetic risk factors for Parkinson's disease (PD) development have been published with inconsistent conclusions. Objective: This overview of SRs aimed to summarize evidence on non-genetic factors for the development of PD from the published SRs, and explore the reasons behind the conflicting results. Methods: Three international databases were searched for SRs with meta-analyses summarized evidence on non-genetic factors for PD development. The Assessing the Methodological Quality of Systematic Reviews 2 tool was used to appraise the methodological quality of included SRs. Pooled effect estimations were extracted from each meta-analysis. Results: Forty-six SRs covered six categories, and more than 80 factors were included in this overview. Thirty-nine SRs (84.7%) were judged to be of critically low methodological quality. Evidence from prospective studies showed that physical activity, smoking, coffee, caffeine, tea, fat intake, ibuprofen use, calcium channel blocker use, statin use, thiazolidinediones, and high serum urate levels significantly reduced the risk of PD, while dairy intake, diabetes, hormone replacement therapy, depression, mood disorder, bipolar disorder, and aspirin use significantly increased the risk of PD. Differences in study designs (e.g., cohort studies, case-control studies) accounted for the conflicting results among included SRs. Conclusion: Modifiable lifestyle factors such as physical activity and tea and coffee drinking may reduce the risk of PD, which may offer PD prevention strategies and hypotheses for future research. However, the designs of primary studies on PD risk factors and related SRs need to be improved and harmonized.