Metal Exposure and Risk of Parkinson Disease: A Systematic Review and Meta-Analysis

Abstract

Metal exposure has been suggested as a possible environmental risk factor for Parkinson disease (PD). We searched the PubMed, EMBASE, and Cochrane databases to systematically review the literature on the relationship between metal exposure and PD risk and to examine the overall quality of each study and the exposure assessment method. A total of 83 case-control studies and 5 cohort studies published during the period 1963-July 2021 were included, of which 73 were graded as being of low or moderate overall quality. Investigators in 69 studies adopted self-reported exposure and biomonitoring after disease diagnosis for exposure assessment approaches. The meta-analyses showed that concentrations of copper and iron in serum and concentrations of zinc in either serum or plasma were lower, while concentrations of magnesium in CSF and zinc in hair were higher, among PD cases as compared with controls. Cumulative lead levels in bone were found to be associated with increased risk of PD. We did not find associations between other metals and PD. The current level of evidence for associations between metals and PD risk is limited, as biases from methodological limitations cannot be ruled out. High-quality studies assessing metal levels before disease onset are needed to improve our understanding of the role of metals in the etiology of PD.

Keywords: Parkinson disease; meta-analysis; metals; systematic reviews.

Figure 1

Selection of studies for inclusion in a systematic review and meta-analysis on associations between metal exposure and risk of Parkinson disease (PD), 1963–2020.

Figure 2

Forest plot for the associations of copper levels (plasma, serum, and overall) with Parkinson disease, 1992–2020. All included studies were rated as moderate-quality. The dashed line represents the referent (standardized mean difference (SMD) = 0). Bars show 95% confidence intervals (CIs).

Figure 3

Forest plot for the associations of iron levels (plasma, serum, and overall) with Parkinson disease, 1992–2020. The 2017 study by Costa-Mallen et al. (89) was rated high-quality, and the rest of the studies were rated moderate-quality. The dashed line represents the referent (standardized mean difference (SMD) = 0). Bars show 95% confidence intervals (CIs).

Figure 4

Forest plot for the associations of zinc levels (plasma, serum, and overall) with Parkinson disease, 1992–2020. All included studies were rated as moderate-quality. The dashed line represents the referent (standardized mean difference (SMD) = 0). Bars show 95% confidence intervals (CIs).