Apolipoprotein e4 Status and Brain Structure 12 Months after Mild Traumatic Injury: Brain Age Prediction Using Brain Morphometry and Diffusion Tensor Imaging

Background: Apolipoprotein E (APOE) e4 is associated with poor outcome following moderate to severe traumatic brain injury (TBI). There is a lack of studies investigating the influence of APOE e4 on intracranial pathology following mild traumatic brain injury (MTBI). This study explores the association between APOE e4 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 e4 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 e4 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 e4 carriers and non-carriers, and no significant differences in conventional measures of brain morphometry and volumes. Compared to non-carriers, APOE e4 carriers showed lower fractional anisotropy (FA) in the hippocampal part of the cingulum bundle, which did not remain significant after FDR adjustment. Conclusion: APOE e4 carriers might be vulnerable to reduced neuronal integrity in the cingulum. Larger cohort studies are warranted to replicate this finding.

Automated summary

The study found that compared to non-carriers, APOE e4 carriers showed lower fractional anisotropy (FA) in the hippocampal part of the cingulum bundle, but this difference did not remain significant after multiple comparison correction. No significant differences were found in brain age prediction, brain morphometry, and volumes between the two groups.