Population-based prevalence and incidence studies can provide an indirect indication of potential environmental etiologies of PD, although it is impossible to compare between studies of different populations, given that genetic differences could account for the differing prevalence. Within a population, however, these studies can provide critical clues to environmental risk factors. A higher prevalence of PD in rural environments implicates regional farming practices, including pesticides, herbicides, and rural water sources. A higher prevalence of PD in urban environments potentially implicates byproducts of industrialization. Numerous studies demonstrate a higher risk of PD for individuals living in a rural environment in Alberta, Canada (21), Finland (21), the United States (22,23), and Italy (24). However, this relationship has not been found in all studies (25).
Although the findings are inconsistent, a higher prevalence of PD in urban areas argues for byproducts of industrialization as risk factors for PD. Several studies suggest that increasing industrialization may increase PD risk. Schoenberg et al. compared the prevalence of PD in Copiah County, Mississippi, U.S.A. (341/100,000 over age 39) to Igbo-Ora, Nigeria (67/100,000 over age 39) using similar methodology, and studying genetically similar populations. They concluded that environmental factors may be responsible for the observed higher prevalence in the industrialized U.S. population (26). In contrast, a study (27) of PD in Estonia found a similar prevalence of PD in urban and rural regions, although the definitions of "urban" and "rural" were unclear. A small study (25) conducted in a health district in Canada found a lower risk of PD in industrialized areas of the district. In a population-based mortality study, Rybicki et al. (28) demonstrated that counties in Michigan, U.S.A. with a higher concentration of industries, with potential for heavy-metal exposures (iron, zinc, copper, mercury, magnesium, and manganese), had a higher PD death rate. Using levodopa prescription records as a surrogate for PD, two studies (29) have shown an increased risk of PD in areas with prominent employment in the wood pulp and steel alloy industries. Potential confounds to the surrogate diagnosis and study methodologies include inclusion of non-PD phenocopies and inability to separate working in an environment from living in an environment. Similarly, a study (30) of annual death rates by the state of U.S. World War II veterans found a higher PD death rate in a North-South gradient, with higher disease death rates in the more populated and industrialized Northern cities. Important methodologic limitations include inconsistent definitions of "rural living" and lack of information on timing of rural living, which may be a critical determinant of PD risk.
If increasing world industrialization is a risk factor for PD, the incidence should be increasing throughout the last century. Only one study has addressed the incidence of PD over time. The yearly incidence of PD has not significantly changed between 1967 and 1979 in Rochester, Minnesota, U.S.A. (31). However, it is unlikely that there has been a substantial change in the industrialization of this relatively rural community over that period of time. The population prevalence of PD in the Midlands district of England increased between 1982 and 1992, potentially implicating greater regional industrialization or greater medical and public awareness of the disease (32). No preindustrial epidemiologic studies of PD exist, and many cases of PD likely went unrecognized in the beginning of industrialization in this country. It may be possible to reconcile these contradictory data with more attention to regional differences in industrial pollution and farming practices.
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