Subcortical Microstructural Changes Associated with Multiple Metal Exposure

Metal exposure has been associated with neurodegenerative disorders including Parkinson's disease (PD). This study examined microstructural changes in subcortical motor areas associated with chronic metal exposure. Subjects with/without a welding history (metal-exposed subjects; n = 23 and controls; n = 24) were examined. Brain microstructural differences were assessed by MRI diffusion metrics [mean (MD), axial (AD), radial diffusivity (RD) and fractional anisotropy (FA)] in subcortical motor areas [nigro-basal ganglia-thalamic circuit: substantia nigra (SN), caudate nucleus (CN), putamen, globus pallidus (GP), and thalamus; dentatorubral circuit: dentate nucleus (DN) and red nucleus (RN)]. Metal exposure was estimated by lifetime welding years, whole blood metal levels, and T1 and R2* (1/T2*) metrics (estimates of brain metal accumulation). Compared to controls, metal-exposed subjects displayed higher diffusivities in the GP and thalamus (p's < 0.033) but lower FA values in the putamen, SN, and thalamus (p's < 0.039) without differences in DN and RN (p's > 0.115). Blood metal mixtures predicted higher GP and SN T1 metrics (p's < 0.05). Higher T1 metrics predicted higher GP and TH diffusivities and lower SN and TH FA values (p's < 0.044). Higher blood vanadium levels predicted lower SN FA values (p = 0.009). Multiple metal exposure may be associated with microstructural compromises within the nigro-basal ganglia-thalamic circuit, while the dentatorubral circuit remains relatively spared, a pattern resembling that of PD at-risk populations.