Introduction: Welding fumes contain a mixture of metals and are an epitype for environmental metal-related neurotoxicity. Past studies of welders focused largely on basal ganglia regions and their association with parkinsonism. This study evaluated medial temporal lobe (MTL) structures that play a key role in Alzheimer's disease-like pathology. Methods: Exposure history and whole blood metal levels were obtained from subjects with/without a history of welding (42 welders; 31 controls). MTL regions of interest (ROI) (hippocampus, entorhinal and parahippocampal cortices) were assessed by morphologic (volume and cortical thickness) and diffusion tensor imaging [mean (MD), axial (AD), radial diffusivity (RD) and fractional anisotropy (FA)] metrics. Cognition was evaluated using standard neuropsychological tests. Results: Welders had higher blood levels of Cu, Fe, K, Mn, Pb, Se, and Zn (p's<0.026) than controls. Welders had higher MD, AD, and RD in all MTL ROIs (p's<0.040) and lower FA in the entorhinal and parahippocampal cortices (p's<0.033) without significant morphologic differences. Welders also exhibited lower performance on processing/psychomotor speed, executive, and visuospatial function domains (p's<0.046). Greater welding years predicted lower parahippocampal FA (p=0.011), where greater short-term welding intensity (E90) predicted worse Symbol coding digit scores (p=0.019). Blood Mn and Cu levels demonstrated robust relationships with entorhinal diffusivity (p's<0.009) and story recall performance (p=0.003), respectively, throughout correlation, semi-parametric regression, and Bayesian kernel machine regression analyses. Discussion: Welding fumes and related metal exposures are associated with MTL features of early Alzheimer's disease. Given the ubiquitous nature of metal exposure, future studies are warranted and may have public health implications.
Introduction: Metal exposure has been associated with higher risk of neurodegenerative disorders such as Alzheimer's disease (AD). We examined the potential link between welding-related metal co-exposure (e.g., Fe, Mn, Pb) and AD-related structural and neurobehavioral metrics. Methods: Subjects with (welders; n=42) or without (controls; n=31) a history of welding were examined. Metal exposure was estimated by exposure questionnaires and whole blood metal levels. Brain metal accumulations were estimated by MRI R1 (Mn) and R2* (Fe) in the caudate, putamen, globus pallidus, red nucleus (RN), and hippocampus. AD-related structural differences were assessed by volume and diffusion tensor imaging metrics in the hippocampus, and neurobehavioral aspects by learning/memory task scores. Results: Compared to controls, welders displayed higher blood metal levels (p values <0.004) and R2* values in the caudate and RN (p values <0.024). Caudate R2* values were associated with blood Fe (p=0.043), whereas RN R2* values were correlated with blood Pb (p=0.003). Welders had higher hippocampal mean diffusivity (MD; p=0.011) and lower Story Recall scores (p=0.049), but no difference in volume or domain-wise learning/memory performance (p values >0.117). Group differences in hippocampal MD and Story Recall scores were greater with higher RN R2* values (p values <0.016). Moreover, RN R2* values reflected an indirect link between blood Pb and hippocampal MD (p=0.036) across both groups. Discussion: Welders had hippocampal structural and learning/memory performance differences similar to those in AD-at-risk populations. These AD-like differences in welders may, in part, be linked to Pb exposure reflected by higher RN R2* levels at the brain level.
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