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. We have an NIEHS and Michael J. Fox Foundation funded research program to investigate welding as a risk-factor for parkinsonism. For the funded research, we will perform a population based, epidemiology study of the prevalence of parkinsonism in career welders and controls. We will assemble a cohort of 875 active shipyard workers (and retirees) and 200 same-sex, nearest age, sibling controls. Movement disorders specialists will examine all subjects for parkinsonism. Prevalence of parkinsonism will be compared between shipyard welders, non-welder shipyard workers and the non-welder, same-sex, sibling controls. 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 Exposure Matrix (JEM) to determine if there is a dose-response relationship between welding exposure and parkinsonism. New research to be supported by this proposal includes assessment of the relationship between blood manganese levels and increased Tl-weighted signal changes in globus pallidum. In addition, we will determine if lifetime welding exposure reconstructed from a validated questionnaire and categorized by a JEM is associated with a dose dependent decrease in [18F]FDOPA striatal uptake using PET and with greater severity of parkinsonism as measured by clinical examination and timed motor tasks. The team conducting this research represents a unique collaboration of movement disorders specialists, epidemiologists, occupational medicine specialists, 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. This multi-institution and multi-discipline research program, in addition to the numerous educational (institutional K12, extensive lectures/seminar series) and collaborative resources in the Department of Neurology (P30), makes this research proposal an ideal environment to mentor trainees in patient-oriented neurological research. ExpandCollapse Abstract