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 #
5K24ES017765-04
Application #
8265645
Study Section
NST-2 Subcommittee (NST)
Program Officer
Shreffler, Carol K
Project Start
2009-05-01
Project End
2014-04-30
Budget Start
2012-05-01
Budget End
2013-04-30
Support Year
4
Fiscal Year
2012
Total Cost
$131,911
Indirect Cost
$9,771
Name
Washington University
Department
Neurology
Type
Schools of Medicine
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
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
Willis, Allison W; Schootman, Mario; Kung, Nathan et al. (2014) Disparities in deep brain stimulation surgery among insured elders with Parkinson disease. Neurology 82:163-71
Gonzalez-Cuyar, Luis F; Nelson, Gill; Criswell, Susan R et al. (2014) Quantitative neuropathology associated with chronic manganese exposure in South African mine workers. Neurotoxicology 45:260-6
Harris-Hayes, Marcie; Willis, Allison W; Klein, Sandra E et al. (2014) Relative mortality in U.S. Medicare beneficiaries with Parkinson disease and hip and pelvic fractures. J Bone Joint Surg Am 96:e27
Lundin, Jessica I; Ton, Thanh G N; LaCroix, Andrea Z et al. (2014) Formulations of hormone therapy and risk of Parkinson's disease. Mov Disord 29:1631-6
Czuppon, Sylvia; Racette, Brad A; Klein, Sandra E et al. (2014) Variables associated with return to sport following anterior cruciate ligament reconstruction: a systematic review. Br J Sports Med 48:356-64
Willis, A W; Schootman, M; Kung, N et al. (2013) Epidemiology and neuropsychiatric manifestations of Young Onset Parkinson's Disease in the United States. Parkinsonism Relat Disord 19:202-6
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
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

Showing the most recent 10 out of 18 publications