Superfund Research Program
Parkinsonism and Metal Exposures Among Welders
Project Leader: Harvey Checkoway (University of California-San Diego)
Grant Number: P42ES004696
Funding Period: 2009-2015
Project Summary (2009-2015)
The Parkinsonism and Metal Exposures Among Welders project is an epidemiologic investigation of the roles of metals as determinants of the risk, severity, and progression of parkinsonism (PS) among professional welders. Previous epidemiologic and experimental research has demonstrated very plausible links between manganese (Mn) and other metals, individually and in combination, and PS. The study population includes 875 Wisconsin shipyard welders (775 actively employed, 100 retired) and 200 non-exposed shipyard workers with no welding exposure history previously enrolled in an ongoing NEIHS-funded R01. The new features of this study are the refinement of exposure assessment to generate quantitative metal-specific levels, and repeated neurological examinations of longitudinal change of PS-related motor function. The scientific objectives of the project are to:
- estimate dose-response relations between Mn and other metal exposures and PS risk and severity;
- test the hypothesis that these metal exposures are associated with PS progression;
- determine the predictive relations of PS proteomic biomarkers, characterized in the Plasma Biomarkers for Parkinsonism in Welders project (Dr. Zhang), with PS risk, severity, and progression;
- test dose-response relations for Mn and other metals with PS proteomic biomarker profiles as indicators of preclinical disease.
To achieve these objectives, project researchers are performing repeated standardized neurological exams of motor function (Unified Parkinson's Disease Rating Scale Motor Subsection 3 [UPDRS3]) 3 years after enrollment exams for as many study subjects as can be enrolled (~75 percent). Additionally, in collaboration with the Plasma Biomarkers for Parkinsonism in Welders project, researchers are collecting plasma samples for assays of proteomics that have been validated as strongly associated with PS for a sample of 150 subjects selected according to baseline UPDRS3 ('normal', borderline PS, probable/definite PS). Data on potentially important confounding factors, especially cigarette smoking and pesticide exposure, are obtained by questionnaire. This project has great potential to quantify the extent of neurological effects of metals, which are widespread environmental contaminants, and thus could contribute to disease prevention strategies.