Parkinson's Disease: Association of Cumulative Lead Exposure
Background: Research using reconstructed exposure histories has suggested an association between heavy metal exposures, including lead, and Parkinson's disease (PD), but the only study that used bone lead, a biomarker of cumulative lead exposure, found a nonsignificant increase in risk of PD with increasing bone lead.
Objectives: We sought to assess the association between bone lead and PD.
Methods: Bone lead concentrations were measured using Cd excited K-shell X-ray fluorescence from 330 PD patients (216 men, 114 women) and 308 controls (172 men, 136 women) recruited from four clinics for movement disorders and general-community cohorts. Adjusted odds ratios (ORs) for PD were calculated using logistic regression.
Results: The average age of cases and controls at bone lead measurement was 67 (SD = 10) and 69 (SD = 9) years of age, respectively. In primary analyses of cases and controls recruited from the same groups, compared with the lowest quartile of tibia lead, the OR for PD in the highest quartile was 3.21 [95% confidence interval (CI), 1.17–8.83]. Results were similar but slightly weaker in analyses restricted to cases and controls recruited from the movement disorders clinics only (fourth-quartile OR = 2.57; 95% CI, 1.11–5.93) or when we included controls recruited from sites that did not also contribute cases (fourth-quartile OR = 1.91; 95% CI, 1.01–3.60). We found no association with patella bone lead.
Conclusions: These findings, using an objective biological marker of cumulative lead exposure among typical PD patients seen in our movement disorders clinics, strengthen the evidence that cumulative exposure to lead increases the risk of PD.
Parkinson's disease (PD) is a complex disease for which a number of genetic and environmental risks have been identified. Twin studies suggest that environmental risk factors may be particularly important in patients whose illness begins after 50 years of age (Tanner et al. 1999). Although much of the research into environmental contributors to PD has focused on pesticides, other toxicants have been explored as well (Elbaz and Moisan 2008; Lai et al. 2002). Lead is known to disrupt dopaminergic function in experimental studies and can induce oxidative stress (Ercal et al. 2001), which is a candidate hypothesis for the etiology of PD (Jenner 2003). The assessment of exposure to lead, particularly cumulative exposure, however, can be difficult.
Lead can be measured easily in blood, but its half-life is approximately 30 days, rendering this biomarker a better indicator of recent exposure than of cumulative exposure. Cumulative exposure, however, might be more relevant than recent exposure for the development of PD. Prior studies of lead and PD have generally relied on self-reported exposure or on work histories from which cumulative exposures are reconstructed. Although these studies have suggested an association with cumulative exposure to lead, biomarkers of cumulative exposure could provide a more robust exposure measure. Circulating lead is deposited in bone, where it has a half-life on the order of years to decades, making it an excellent biomarker of cumulative lead exposure (Hu et al. 1998). Bone lead can be assessed with the K-shell X-ray fluorescence (KXRF) technique, but only one study has examined the association of this biomarker with PD, finding a suggestive but not quite significant [odds ratio (OR) = 1.62; 95% confidence intervals (CI), 0.83–3.17] association in an analysis involving 121 PD patients and 414 controls (Coon et al. 2006). We examined the association between cumulative exposure to lead—as measured by lead in bone with KXRF—and odds of PD in a case–control study based in Boston, Massachusetts.
Abstract and Introduction
Abstract
Background: Research using reconstructed exposure histories has suggested an association between heavy metal exposures, including lead, and Parkinson's disease (PD), but the only study that used bone lead, a biomarker of cumulative lead exposure, found a nonsignificant increase in risk of PD with increasing bone lead.
Objectives: We sought to assess the association between bone lead and PD.
Methods: Bone lead concentrations were measured using Cd excited K-shell X-ray fluorescence from 330 PD patients (216 men, 114 women) and 308 controls (172 men, 136 women) recruited from four clinics for movement disorders and general-community cohorts. Adjusted odds ratios (ORs) for PD were calculated using logistic regression.
Results: The average age of cases and controls at bone lead measurement was 67 (SD = 10) and 69 (SD = 9) years of age, respectively. In primary analyses of cases and controls recruited from the same groups, compared with the lowest quartile of tibia lead, the OR for PD in the highest quartile was 3.21 [95% confidence interval (CI), 1.17–8.83]. Results were similar but slightly weaker in analyses restricted to cases and controls recruited from the movement disorders clinics only (fourth-quartile OR = 2.57; 95% CI, 1.11–5.93) or when we included controls recruited from sites that did not also contribute cases (fourth-quartile OR = 1.91; 95% CI, 1.01–3.60). We found no association with patella bone lead.
Conclusions: These findings, using an objective biological marker of cumulative lead exposure among typical PD patients seen in our movement disorders clinics, strengthen the evidence that cumulative exposure to lead increases the risk of PD.
Introduction
Parkinson's disease (PD) is a complex disease for which a number of genetic and environmental risks have been identified. Twin studies suggest that environmental risk factors may be particularly important in patients whose illness begins after 50 years of age (Tanner et al. 1999). Although much of the research into environmental contributors to PD has focused on pesticides, other toxicants have been explored as well (Elbaz and Moisan 2008; Lai et al. 2002). Lead is known to disrupt dopaminergic function in experimental studies and can induce oxidative stress (Ercal et al. 2001), which is a candidate hypothesis for the etiology of PD (Jenner 2003). The assessment of exposure to lead, particularly cumulative exposure, however, can be difficult.
Lead can be measured easily in blood, but its half-life is approximately 30 days, rendering this biomarker a better indicator of recent exposure than of cumulative exposure. Cumulative exposure, however, might be more relevant than recent exposure for the development of PD. Prior studies of lead and PD have generally relied on self-reported exposure or on work histories from which cumulative exposures are reconstructed. Although these studies have suggested an association with cumulative exposure to lead, biomarkers of cumulative exposure could provide a more robust exposure measure. Circulating lead is deposited in bone, where it has a half-life on the order of years to decades, making it an excellent biomarker of cumulative lead exposure (Hu et al. 1998). Bone lead can be assessed with the K-shell X-ray fluorescence (KXRF) technique, but only one study has examined the association of this biomarker with PD, finding a suggestive but not quite significant [odds ratio (OR) = 1.62; 95% confidence intervals (CI), 0.83–3.17] association in an analysis involving 121 PD patients and 414 controls (Coon et al. 2006). We examined the association between cumulative exposure to lead—as measured by lead in bone with KXRF—and odds of PD in a case–control study based in Boston, Massachusetts.