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

Background: Environmental exposure to metal mixtures is common and may be associated with increased risk for neurodegenerative disorders including Alzheimer's disease. This study examined associations of mixed metal exposures with medial temporal lobe (MTL) MRI structural metrics and neuropsychological performance. Methods: Metal exposure history, whole blood metal, MRI R1 (1/T1) and R2* (1/T2*) metrics (estimates of brain Mn and Fe, respectively), and neuropsychological tests were obtained from subjects with/without a history of mixed metal exposure from welding fumes (42 exposed subjects; 31 controls). MTL structures (hippocampus, entorhinal and parahippocampal cortices) were assessed by morphologic (volume or cortical thickness) and diffusion tensor imaging [mean (MD), axial (AxD), radial diffusivity (RD), and fractional anisotropy (FA)] metrics. In exposed subjects, effects of mixed metal exposure on MTL structural and neuropsychological metrics were examined. Results: Compared to controls, exposed subjects displayed higher MD, AxD, and RD throughout all MTL ROIs (p's<0.001) with no morphological differences. They also had poorer performance in processing/psychomotor speed, executive, and visuospatial domains (p's<0.046). Long-term mixed metal exposure history indirectly predicted lower processing speed performance via lower parahippocampal FA (p's<0.023). Higher entorhinal R1 and whole blood Mn and Cu levels predicted higher entorhinal diffusivity (p's<0.043) and lower Delayed Story Recall performance (p=0.007). Discussion: Mixed metal exposure predicted certain MTL structural and neuropsychological features that are similar to those detected in Alzheimer's disease at-risk populations. These data warrant follow-up as they may illuminate a potential path for environmental exposure to brain changes associated with Alzheimer's disease-related health outcomes.