Environmental risk factors of young onset Parkinson's disease: a case-control study

Abstract

While the cause of Parkinson's disease (PD) remains unknown, recent evidence suggests certain environmental factors, such as well water drinking, herbicides and pesticides exposure, and neurotoxins, may trigger the chain of oxidative reactions culminating in the death of dopaminergic neurons in substantia nigra to cause parkinsonism. Most studies to date focused on PD with old age onset. However, there is a peculiar group of parkinsonian patients, the young onset Parkinson's disease (YOPD), in whom the age of onset is before 40. It is intriguing to know whether earlier exposure to the putative neurotoxin(s) may contribute to the earlier onset. We therefore conducted this case-control study in which 60 PD patients, 30 YOPD patients and the same number of age- and sex-matched young controls were included. Using logistic regression, we found well water drinking and head injury were risk factors for the development of YOPD. When YOPD patients were compared with PD, we found head injury and exercise were the significant predictors. Keeping all other variables constant, head injury was a risk factor and exercise appeared to be a protective factor. We conclude early exposure to well water drinking and head trauma may trigger and expedite the appearance of parkinsonian features, but such acceleration may be prevented through regular exercise.

Introduction

Since the description in 1817, the etiology of Parkinson's Disease (PD) remains unknown. No single factor has been definitely attributed to the cause of PD. Nevertheless, cumulative pieces of evidence have implicated rural living [9], [12], [22], [24], [26], [28], [32], [38] well water drinking [12], [22], [24], [32], [38] herbicides and pesticides exposure [6], [9], [12], [14], [22], [26], and proximity to industry [30], [31] as risk factors for the disease. The discovery of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism further suggests a similar neurotoxin might cause PD [2], [4]. These findings lend credence to the notion that certain sorts of environmental agents can trigger the chain of reactions resulting in the death of dopaminergic neurons in substantia nigra to cause parkinsonism.

As PD incidence varies greatly with age, which begins to rise after the age of 50 and reaches the maximum at about 75, most epidemiological surveys focused on this age range [9], [26]. However, there is a peculiar group of parkinsonian patients, the Young Onset Parkinson's Disease (YOPD), in whom the age of onset is before 40. Some of them even presented the first symptoms in their teens. These YOPD patients constitute about 3–10% of total patients with PD on hospital-based data [7], [23], [34], [35], [39]. From pathological and clinical view points, parkinsonism with age of onset before and after 40 years are probably the same [8], [16]. Thus, it is intriguing to know whether risk factors found in classical PD might also be implicated in the occurrence of YOPD. With all other considerations being equal, it is wondered how exposure to similar environment risk factors could cause such a great discrepancy in the disease onset age. Would it presumably indicate an earlier or more intensive exposure to the causative agents in YOPD as compared with typical late onset cases? The main objective of this study is to investigate the risk factors implicated in the occurrence of YOPD. We are also keen to examine the differences, if any, in these factors between YOPD and PD patients.