Parkinson's disease (PD) is a neurodegenerative disorder affecting one million people in North America. There is no known cause for most cases of PD although environmental factors have been implicated in the majority of cases. We have preliminary evidence that parkinsonism is three to ten times more common in career welders than the general population. The purpose of this grant is to establish welding as a risk-factor for parkinsonism in a population based cohort and to establish a dose-response relationship between welding and parkinsonism. For our first specific aim we will perform a population based epidemiological study of the prevalence of parkinsonism in career welders and controls. We will assemble a cohort of 600 welders (boilermakers) and a non-exposed reference cohort of workers from the same union and same-sex, nearest age, sibling controls. Movement disorders specialists will perform all evaluations and ratings will be verified by a movement disorders specialist who will review each videotaped examination. Prevalence of parkinsonism will be compared between welders and the non-welder reference cohort For the second specific aim of this study, an industrial hygienist will reconstruct subject welding exposure from a detailed exposure questionnaire in all exposed subjects and subjects will be grouped into tertiles of exposure using a Job ExposureMatrix to determine if there is a dose-response relationship between welding exposure and parkinsonism. The team conducting this research represents a unique collaboration of movement disorders specialists, epidemiologists, industrial hygienists, and industry leaders. Demonstrating a definitive relationship between welding and parkinsonism will have substantial public health impact since the majority of these cases should be preventable through worksite modifications. The cohort assembled will provide unique opportunities for future research projects into specific toxins associated with parkinsonism in welders, gene-environment interactions, and exposure related neuroimaging changes. ExpandCollapse Abstract