Apolipoprotein ɛ4 Status and Brain Structure 12 Months after Mild Traumatic Injury: Brain Age Prediction Using Brain Morphometry and Diffusion Tensor Imaging

Abstract

Background: Apolipoprotein E (APOE) ɛ4 is associated with poor outcome following moderate to severe traumatic brain injury (TBI). There is a lack of studies investigating the influence of APOE ɛ4 on intracranial pathology following mild traumatic brain injury (MTBI). This study explores the association between APOE ɛ4 and MRI measures of brain age prediction, brain morphometry, and diffusion tensor imaging (DTI). Methods: Patients aged 16 to 65 with acute MTBI admitted to the trauma center were included. Multimodal MRI was performed 12 months after injury and associated with APOE ɛ4 status. Corrections for multiple comparisons were done using false discovery rate (FDR). Results: Of included patients, 123 patients had available APOE, volumetric, and DTI data of sufficient quality. There were no differences between APOE ɛ4 carriers (39%) and non-carriers in demographic and clinical data. Age prediction revealed high accuracy both for the DTI-based and the brain morphometry based model. Group comparisons revealed no significant differences in brain-age gap between ɛ4 carriers and non-carriers, and no significant differences in conventional measures of brain morphometry and volumes. Compared to non-carriers, APOE ɛ4 carriers showed lower fractional anisotropy (FA) in the hippocampal part of the cingulum bundle, which did not remain significant after FDR adjustment. Conclusion: APOE ɛ4 carriers might be vulnerable to reduced neuronal integrity in the cingulum. Larger cohort studies are warranted to replicate this finding.

Association of Alzheimer’s disease polygenic risk score with concussion severity and recovery metrics

“…In general, there have been very few studies examining whether concussion-associated WM damage is exacerbated in individuals with high genetic risk for neurodegenerative disease, and this possibility warrants exploration. One study investigated the effect of APOE genotype on DTI metrics in concussion/mild traumatic brain injury and found limited evidence for altered fractional anisotropy (FA) in the cingulum of APOE ɛ4 carriers [85]. Another analyzed relationships between APOE ɛ4 genotype, blast exposure, and WM in military veterans, observing that ɛ4 carriers may be more vulnerable to WM abnormalities after blast exposure [86].…”