Risk factors of Parkinson’s disease: Simultaneous assessment, interactions and etiological subtypes

Objective: To perform a simultaneous evaluation of potential risk/protective factors of Parkinson’s disease (PD) in order to identify independent risk/protective factors, assess interaction among factors and determine whether identified risk factors predict etiological subtypes of PD. Methods: We designed a large case-control study assessing 31 protective/risk factors of PD, including environmental and lifestyle factors, comorbidities, and drugs. The study enrolled 694 PD patients and 640 healthy controls from six neurological centers. Data were analyzed by logistic regression models, additive interaction models, and cluster analysis. Results: The simultaneous assessment of 31 putative risk/protective factors of PD showed that only coffee consumption (odds ratio [OR]: 0.6; 95% confidence interval [CI]: 0.4-0.9), smoking (OR: 0.7; 95% CI: 0.6-0.9), physical activity (OR: 0.8; 95% CI: 0.7-0.9), family history of PD (OR: 3.2; 95% CI: 2.2- 4.8), dyspepsia (OR: 1.8; 95% CI:1.3-2.4), exposure to pesticides (OR: 2.3; 95% CI:1.3- 4.2), oils (OR: 5.6; 95% CI: 2.3-13.7), metals (OR: 2.8; 95% CI: 1.5-5.4), and general anesthesia (OR: 6.1; 95% CI: 2.9-12.7) were independently associated with PD. There was no evidence of interaction among risk/protective factors, but cluster analysis identified four subtypes with different risk factor profiles. In Group 1, all patients had a family history of PD, while dyspepsia or exposure to toxic agents were present in 30% of patients. In Group 2 and 3, a family history of PD was lacking, while exposure to toxic agents (Group 2) and dyspepsia (Group 3) played major roles. Group 4 consisted of patients with no risk factors. Conclusions: This study demonstrated that nine factors independently modify PD risk by coexisting in the same patient rather than interacting with others. Our study suggests the need for future preventive strategies aimed at reducing the coexistence of different risk factors within the same subject.