Occupational risk factors for Parkinson disease

Abstract

Environmental factors probably play an important role in the etiology of Parkinson disease (PD). However, not many environmental factors have been identified for which unequivocal evidence is available for a relation with PD risk. The main focus of the research described in this thesis was on studying associations between occupational exposures and PD risk. A large case-control study was conducted, for which all patients diagnosed between 2006 and 2011 in five participating hospitals were invited. Two age and sex matched controls per patient were selected from individuals who visited the same hospital for a range of non-neurodegenerative neurological complaints. We observed a strong inverse association of cigarette smoking with PD risk. This is in correspondence with many previous studies. In addition, we applied a novel modeling approach and observed effect modification by time-since-cessation of tobacco smoking with a diminishing protective effect of total smoking after cessation of smoking. A systematic review of the literature published on PD and ever use of pesticides was performed and a significantly increased summary risk ratio of 1.62 was found. We investigated the observed heterogeneity in study outcomes. The results were suggestive for an effect of method of exposure assessment: studies using job-title based exposure assignment resulted in higher risk estimates than studies using self-reported information on pesticide use. For the present case-control study, we tried to improve upon methods for exposure assessment by combining self-reported information, a job-exposure matrix (JEM), an exposure algorithm and a crop-exposure matrix. The results did not show statistically significant associations between occupational pesticide exposure and PD. However, elevated odds ratios in the higher exposure categories for insecticides, herbicides and fungicides were suggestive for a positive association as observed in the systematic review. Analyses on specific active ingredients revealed a significant association with historical exposure to the fungicide benomyl, which is no longer allowed to be applied in the Netherlands We performed the most comprehensive analyses to date on the association between electricity related exposures and PD. JEMs were used to estimate lifetime occupational exposure to extremely low-frequency magnetic fields and electrical shocks. We also analyzed ever having worked in so-called ‘electrical jobs’, self-reported number of electrical shocks and use of selected electric household appliances. No associations with PD were observed and together with the results of previous studies and the absence of any known plausible mechanism, this strongly suggests that no relation exists. Results of previous studies that investigated the associations between metals and organic solvents and PD risk were inconclusive. We estimated exposure to metals and chlorinated and aromatic solvents using JEMs. Although slightly elevated risk estimates for the highest exposure categories for aromatic solvents were observed, we did not observe statistically significant associations. As such, our results do not provide additional evidence for an increased risk of PD after exposure to metals or solvents. New epidemiological studies on occupational risk factors should focus on improving methods to classify exposure to specific pesticides, metals or solvents; both in terms of specification, quantification as well as timing of exposure.