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. This proposal consists of a cohort study to test the hypothesis that the prevalence of parkinsonism is increased in a dose-dependent manner relative to non-exposed persons of similar age and gender. For our first specific aim we will perform a population based epidemiological study of the prevalence of parkinsonism in career welders and non-exposed referents. We will assemble a a population based cohort of 875 workers and retirees (members of the International Brotherhood of Boilermakers) and 200 same-sex, nearest-age sibling referents with no prior welding history. Movement disorders specialists will perform all evaluations and ratings will be verified by a movement disorders specialist who will review a 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. Subjects will be grouped into tertiles of exposure using a Job Exposure Matrix to determine if there is a dose-response relationship between welding exposure and parkinsonism. The research team represents a 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 gene-environment interactions and exposure related neuroimaging changes.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project (R01)
Project #
5R01ES013743-05
Application #
7992413
Study Section
Neurological, Aging and Musculoskeletal Epidemiology (NAME)
Program Officer
Lawler, Cindy P
Project Start
2007-02-03
Project End
2012-11-30
Budget Start
2010-12-01
Budget End
2012-11-30
Support Year
5
Fiscal Year
2011
Total Cost
$502,477
Indirect Cost
Name
Washington University
Department
Neurology
Type
Schools of Medicine
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Searles Nielsen, Susan; Checkoway, Harvey; Criswell, Susan R et al. (2015) Inducible nitric oxide synthase gene methylation and parkinsonism in manganese-exposed welders. Parkinsonism Relat Disord 21:355-60
Lundin, Jessica I; Checkoway, Harvey; Criswell, Susan R et al. (2014) Screening for early detection of parkinsonism using a self-administered questionnaire: a cross-sectional epidemiologic study. Neurotoxicology 45:232-7
Racette, Brad A (2014) Manganism in the 21st century: the Hanninen lecture. Neurotoxicology 45:201-7
Racette, Brad A; Criswell, Susan R; Lundin, Jessica I et al. (2012) Increased risk of parkinsonism associated with welding exposure. Neurotoxicology 33:1356-61
Criswell, Susan R; Perlmutter, Joel S; Huang, John L et al. (2012) Basal ganglia intensity indices and diffusion weighted imaging in manganese-exposed welders. Occup Environ Med 69:437-43
Racette, Brad A; Aschner, Michael; Guilarte, Tomas R et al. (2012) Pathophysiology of manganese-associated neurotoxicity. Neurotoxicology 33:881-6
Criswell, Susan R; Perlmutter, Joel S; Crippin, Jeffrey S et al. (2012) Reduced uptake of FDOPA PET in end-stage liver disease with elevated manganese levels. Arch Neurol 69:394-7
Criswell, S R; Perlmutter, J S; Videen, T O et al. (2011) Reduced uptake of [¹⁸F]FDOPA PET in asymptomatic welders with occupational manganese exposure. Neurology 76:1296-301
Harris, Rachel C; Lundin, Jessica I; Criswell, Susan R et al. (2011) Effects of parkinsonism on health status in welding exposed workers. Parkinsonism Relat Disord 17:672-6
Hobson, Angela; Seixas, Noah; Sterling, David et al. (2011) Estimation of particulate mass and manganese exposure levels among welders. Ann Occup Hyg 55:113-25

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