Parkinson's disease (PD) is a functionally devastating, common neurodegenerative disorder. There is no clear consensus about the specific etiology(ies) of PD, though there is considerable evidence that the disease has important environmental risk factors. The applicants recently completed a NIEHS-funded population-based case-control study of occupational and other potential risk factors for PD among 144 PD and 464 control men and women subjects greater than or equal to 50 years, frequency-matched for sex, race, and age (+/- 5 years), who receive primary medical care at Henry Ford Health System in urban/suburban metropolitan Detroit. The focus of that work was the assessment of occupational exposure to six metals (iron, manganese, copper, lead, mercury, and zinc) and the risk of PD. An industrial hygienist blinded to the case-control status of enrollees, evaluated all jobs held by them for greater than or equal to six months from age 18 years onward using a risk factor questionnaire that detailed actual work site conditions. The investigators found that more than 20 years of occupational exposure to copper, manganese and lead, individually or dual combinations of lead-copper, lead-iron, or iron-copper was associated with PD. Lead was one of the most prevalent exposures in the population. These findings suggest that these metal exposures were risk factors for PD. What is needed now is an objective measure of metal-exposure and a means of modeling all sources of such exposure to arrive at a net cumulative exposure dose over time. K-Xray fluorescence measurement of bone can provide a measure of cumulative, chronic, lead exposure non-invasively as detailed in our preliminary studies. Moreover, sophisticated physiologically-based pharmacokinetic modeling of lead exposure and dynamics have also been developed, as we have demonstrated. Therefore, these investigators propose to assess lead exposures as a risk factor for PD: 1) by integrating exposure information from several sources (i.e., questionnaire-derived on occupational and nonoccupational lead exposure as well as current measurement of cortical and trabecular bone lead and blood lead) to reconstruct the lead exposure history using physiologically-based phamacokinetic modeling and 2) by using the resultant estimate of net body lead burden over time (dose) to calculate whether a quantitative relationship exist for the acquisition of PD, as reflected in a defined population of cases and controls, men and women greater than or equal to 50 years of age, frequency-matched for sex, race, and age (+/- five years). If it can be established that lead exposure is a significant risk factor for PD, it will provide further validation of our earlier analytical epidemiological work and encourage continued, vigorous measures to minimize contact with the metal. Moreover, future research in chelation chemotherapy may then be considered as a means of reducing the body burden of lead. This proposed work will be the most systematic study of lead as a risk factor for PD yet done, and can help in the understanding of the etiopathogenesis of the disease.
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| Gorell, Jay M; Peterson, Edward L; Rybicki, Benjamin A et al. (2004) Multiple risk factors for Parkinson's disease. J Neurol Sci 217:169-74 |
| Johnson, C C; Gorell, J M; Rybicki, B A et al. (1999) Adult nutrient intake as a risk factor for Parkinson's disease. Int J Epidemiol 28:1102-9 |
| Rybicki, B A; Johnson, C C; Peterson, E L et al. (1999) A family history of Parkinson's disease and its effect on other PD risk factors. Neuroepidemiology 18:270-8 |
| Gorell, J M; Rybicki, B A; Cole Johnson, C et al. (1999) Occupational metal exposures and the risk of Parkinson's disease. Neuroepidemiology 18:303-8 |
| Gorell, J M; Rybicki, B A; Johnson, C C et al. (1999) Smoking and Parkinson's disease: a dose-response relationship. Neurology 52:115-9 |
| Gorell, J M; Johnson, C C; Rybicki, B A et al. (1999) Occupational exposure to manganese, copper, lead, iron, mercury and zinc and the risk of Parkinson's disease. Neurotoxicology 20:239-47 |
| Rybicki, B A; Peterson, E L; Johnson, C C et al. (1998) Intra- and inter-rater agreement in the assessment of occupational exposure to metals. Int J Epidemiol 27:269-73 |
| Gorell, J M; Johnson, C C; Rybicki, B A et al. (1998) The risk of Parkinson's disease with exposure to pesticides, farming, well water, and rural living. Neurology 50:1346-50 |
| Rybicki, B A; Johnson, C C; Peterson, E L et al. (1997) Comparability of different methods of retrospective exposure assessment of metals in manufacturing industries. Am J Ind Med 31:36-43 |
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