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 [18FJFDOPA 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.

Public Health Relevance

None provided.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Midcareer Investigator Award in Patient-Oriented Research (K24)
Project #
5K24ES017765-02
Application #
7822772
Study Section
NST-2 Subcommittee (NST)
Program Officer
Shreffler, Carol K
Project Start
2009-05-01
Project End
2014-04-30
Budget Start
2010-05-01
Budget End
2011-04-30
Support Year
2
Fiscal Year
2010
Total Cost
$129,012
Indirect Cost
Name
Washington University
Department
Neurology
Type
Schools of Medicine
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Al-Lozi, Amal; Nielsen, Susan Searles; Hershey, Tamara et al. (2017) Cognitive control dysfunction in workers exposed to manganese-containing welding fume. Am J Ind Med 60:181-188
Criswell, Susan R; Nielsen, Susan Searles; Warden, Mark et al. (2017) [18F]FDOPA positron emission tomography in manganese-exposed workers. Neurotoxicology :
Racette, Brad A; Gross, Anat; Criswell, Susan R et al. (2017) A screening tool to detect clinical manganese neurotoxicity. Neurotoxicology :
Martin, W R W; Hartlein, J; Racette, B A et al. (2017) Pathologic correlates of supranuclear gaze palsy with parkinsonism. Parkinsonism Relat Disord 38:68-71
Racette, Brad A; Searles Nielsen, Susan; Criswell, Susan R et al. (2017) Dose-dependent progression of parkinsonism in manganese-exposed welders. Neurology 88:344-351
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
Criswell, Susan R; Nelson, Gill; Gonzalez-Cuyar, Luis F et al. (2015) Ex vivo magnetic resonance imaging in South African manganese mine workers. Neurotoxicology 49:8-14
Morris, Marie; Willis, Allison W; Searles Nielsen, Susan et al. (2015) Physician response to a medication alert system in inpatients with levodopa-treated diseases. Neurology 85:420-4
Andruska, Kristin M; Racette, And Brad A (2015) Neuromythology of Manganism. Curr Epidemiol Rep 2:143-148
Safarpour, Delaram; Thibault, Dylan P; DeSanto, Cori L et al. (2015) Nursing home and end-of-life care in Parkinson disease. Neurology 85:413-9

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