Apolipoprotein E genotype modulates longitudinal atrophy at the temporal lobe after mild traumatic brain injury

BackgroundsModerate or severe traumatic brain injury (TBI) is one of the strongest environmental risks for late-life dementia, especially Alzheimers disease (AD). However, the interaction between genetic factors and environmental exposure to mild TBI triggering neurodegenerative processes is still unclear. We used longitudinal imaging to differentiate spatial patterns of progressive brain volume loss in individual patients with and without carrying apolipoprotein E (APOE) {varepsilon}4 carriers. MethodsFor 59 patients with acute mild TBI (mTBI, age: 36.92 {+/-} 11.91 years; 14 APOE {varepsilon}4 carriers) and 48 matched healthy controls (HCs, age: 37.92 {+/-} 11.72 years; 10 APOE {varepsilon}4 carriers), longitudinal (6-12 months follow-up) brain structure was assessed using voxel-based morphometry on T1-weighted scans. Longitudinal volume changes in the temporal lobe were characterized by the Jacobian determinant (JD) metric, reflecting spatial warping between the baseline and follow-up scans. JD values were regionally calculated and correlated with neuropsychological measures. ResultsMTBI patients lost a mean of 0.27% (SD = 0.43) of GM and 0.27% (SD = 0.50) of WM volume in the temporal lobe over the 6-12 month follow-up. Patients with a high genetic risk for AD (APOE {varepsilon}4 allele carries) were associated with severer atrophy in the left superior temporal gyrus and middle temporal gyrus regions than the controls (P < 0.05). Furthermore, atrophy in these regions of gray matter could predict the performance change ratio of the language fluency in mTBI APOE {varepsilon}4 carriers ({beta} = 0.570, P < 0.05). While, compared with HC APOE {varepsilon}4 non-carriers, mTBI non-carriers exhibited volume loss in the medial temporal lobe. ConclusionsThis prospective study provided evidence that the APOE {varepsilon}4 allele interacting with mTBI increased the risk of AD phenotype development with language dysfunction. Graphic Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=113 SRC="FIGDIR/small/503827v1_ufig1.gif" ALT="Figure 1"> View larger version (56K): org.highwire.dtl.DTLVardef@39af96org.highwire.dtl.DTLVardef@136a0f7org.highwire.dtl.DTLVardef@181deb4org.highwire.dtl.DTLVardef@144349d_HPS_FORMAT_FIGEXP M_FIG C_FIG