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

Abstract

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.

Keywords: Parkinson’s disease; Risk factors; meta-analysis; systematic review.

Fig. 1

PRISMA flowchart: the screening and selection process. Note: PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses.

Fig. 2

The methodological quality of the 46 included systematic reviews based on AMSTAR-2 tool. Note: AMSTAR-2 tool: Assessing the Methodological Quality of Systematic Reviews 2 tool. Item 1: Did the research questions and inclusion criteria for the review include the components of PICO? Item 2: Did the report of the review contain an explicit statement that the review methods were established prior to the conduct of the review and did the report justify any significant deviations from the protocol? Item 3: Did the review authors explain their selection of the study designs for inclusion in the review? Item 4: Did the review authors use a comprehensive literature search strategy? Item 5: Did the review authors perform study selection in duplicate? Item 6: Did the review authors perform data extraction in duplicate? Item 7: Did the review authors provide a list of excluded studies and justify the exclusions? Item 8: Did the review authors describe the included studies in adequate detail? Item 9: Did the review authors use a satisfactory technique for assessing the risk of bias (RoB) in individual studies that were included in the review? Item 10: Did the review authors report on the sources of funding for the studies included in the review? Item 11: If meta-analysis was performed did the review authors use appropriate methods for statistical combination of results? Item 12: If meta-analysis was performed, did the review authors assess the potential impact of RoB in individual studies on the results of the meta-analysis or other evidence synthesis? Item 13: Did the review authors account for RoB in individual studies when interpreting/discussing the results of the review? Item 14: Did the review authors provide a satisfactory explanation for, and discussion of, any heterogeneity observed in the results of the review? Item 15: If they performed quantitative synthesis did the review authors carry out an adequate investigation of publication bias (small study bias) and discuss its likely impact on the results of the review? Item 16: Did the review authors report any potential sources of conflict of interest, including any funding they received for conducting the review?