Epidemiologic studies of environmental exposures in Parkinson's disease

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Abstract

Parkinson's disease (PD) is the most common cause of the parkinsonian syndromes and the most frequent neurodegenerative disease after Alzheimer's disease. Because of the ageing of Western populations, an increasing number of persons will be affected with PD in the future and neither curative treatments nor preventive measures have been identified. PD is considered as a multifactorial disease, resulting from the effect of environmental factors and genetic susceptibility. Increasing age and male sex appear to be associated with an increased risk of PD. In addition, recent epidemiological studies have identified environmental exposures that influence the risk of PD. This review provides an overview of the epidemiologic evidence for environmental etiologies in PD; we will focus on two environmental exposures that have been quite consistently associated with PD – cigarette smoking and pesticide exposure – and will summarize briefly the findings for other exposures. Understanding the mechanisms underlying these epidemiological associations is an essential step for the understanding of the etiology of this neurodegenerative condition and, ideally, to develop neuroprotective drugs.

Introduction

Parkinson's disease (PD) is the most common cause of the parkinsonian syndrome and the most frequent neurodegenerative disease after Alzheimer's disease [1]. PD is the consequence of the degeneration of dopaminergic neurons in the substantia nigra. The pathological hallmark of PD is the presence of intracytoplasmic inclusions, known as Lewy bodies in these neurons. Because PD diagnosis is only based on the clinical examination and its cardinal signs can be observed in other, albeit less frequent, conditions, there is a risk of diagnostic misclassification. In a recent autopsy study, 10% of PD patients referred to autopsy in a movement disorders referral center did not have PD after examination of their brain [2]. It is also recognized that the different diagnostic criteria often used in the context of epidemiologic studies can yield different frequency estimates [3], [4].

Incidence studies have provided estimates ranging between 10 and 15 per 100 000 person years [5]; the lifetime risk of PD is of approximately 1.6% [6]. PD is exceptional before 40 years. The incidence of PD increases with age rising from 17.4 per 100 000 person years between 50 to 59 years to 93.1 per 100 000 person years between 70 to 79 years [1]. The incidence of PD is reported to be approximately 1.5 times higher in men than in women [6]; this finding may be related to risk factors more frequently found in men than in women (e.g., occupational risk factors), or to protective factors in women (e.g., hormonal factors). PD prevalence ranges between 100 and 200 per 100 000 persons overall, and between 1.5% and 2.0% after 65 years [7], [8]. Given the ageing of the western populations, an increase in PD prevalence is expected. There is no cure for the disease and only symptomatic treatments are available; any preventive measure would therefore be useful. Although PD treatment has improved in recent years, PD patients have decreased quality of life [9], and face an increased risk of dementia, institutionalization [10] and death [11], [12].

There is important variation in the estimates of PD frequency in different parts of the world. The interpretation of this finding is, however, difficult, because part of this variability is likely to result from differences in the methods used in the studies (e.g., identification of PD patients, diagnostic criteria) [3]. Some conclusions can still be drawn from studies that used similar methods. There is no important difference in PD prevalence among four European countries (France, Italy, Spain, The Netherlands) [7], [8]. The incidence of PD in African Americans and Asian Americans is similar to that in Caucasians [13], [14], [15]. It has also been shown recently that the prevalence of PD in China is similar to that observed in Western countries [16]. On the contrary, a lower prevalence of PD in Africans compared to African Americans has been reported [17], and this has been interpreted as suggestive of an environmental factor.

Studies of temporal trends in the frequency of PD are difficult due to important changes in the diagnosis and treatment of PD in the last decades and few studies are available [18]. An incidence study did not find evidence of temporal trends in Olmsted County (MN, US) during a short period of time (1976–1990) [19]. In Finland, an increase in prevalence of PD was observed between 1971 and 1992, only among men, and it was more pronounced in rural than in urban areas [20]; incidence also increased in men in this time interval, but it decreased in women.

Section snippets

Environmental exposures and Parkinson's disease

PD is considered a multifactorial disease resulting from the effect of environmental factors and genetic susceptibility [21]. In addition to increasing age and male sex, it is likely that several other exposures influence the risk of PD; their identification is complicated by several issues, including small effects, possible interactions with genetic susceptibility, and etiologic heterogeneity [21]. Our review will focus on two environmental exposures that have been quite consistently

Conclusions

We have summarized the results of studies of the relation between PD and some environmental exposures. The pursuit of their identification and understanding the mechanisms that lead to the destruction of dopaminergic neurons are the essential next steps to better understand the etiology of this neurodegenerative condition and, ideally, to develop neuroprotective drugs. In addition, any preventive measure would be useful. Professional pesticide exposure is a preventable exposure for which

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