Whole-Body Lifetime Occupational Lead Exposure and Risk of Parkinson’s Disease

BACKGROUND: Several epidemiologic studies have suggested an association between Parkinson’s disease (PD) and exposure to heavy metals using subjective exposure measurements. OBJECTIVES: We investigated the association between objective chronic occupational lead exposure and the risk of PD. METHODS: We enrolled 121 PD patients and 414 age-, sex-, and race-, frequency-matched controls in a case–control study. As an indicator of chronic Pb exposure, we measured concentrations of tibial and calcaneal bone Pb stores using (109)Cadmium excited K-series X-ray fluorescence. As an indicator of recent exposure, we measured blood Pb concentration. We collected occupational data on participants from 18 years of age until the age at enrollment, and an industrial hygienist determined the duration and intensity of environmental Pb exposure. We employed physiologically based pharmacokinetic modeling to combine these data, and we estimated whole-body lifetime Pb exposures for each individual. Logistic regression analysis produced estimates of PD risk by quartile of lifetime Pb exposure. RESULTS: Risk of PD was elevated by > 2-fold [odds ratio = 2.27 (95% confidence interval, 1.13–4.55); p = 0.021] for individuals in the highest quartile for lifetime lead exposure relative to the lowest quartile, adjusting for age, sex, race, smoking history, and coffee and alcohol consumption. The associated risk of PD for the second and third quartiles were elevated but not statistically significant at the α = 0.05 level. CONCLUSIONS: These results provide an objective measure of chronic Pb exposure and confirm our earlier findings that occupational exposure to Pb is a risk factor for PD.