Effects of mixed metal exposures on MRI diffusion features in the medial temporal lobe

Abstract

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.