Apolipoprotein e (APOE) ε4 genotype influences memory performance following remote traumatic brain injury in U.S. military service members and veterans

The purpose of this study was to examine the association between the apolipoprotein E (APOE) ε4 allele and neurocognitive functioning following traumatic brain injury (TBI) in military service members and veterans (SMVs). Participants included 176 SMVs with a history of remote TBI (≥1 year post-injury), categorized into mild (n = 100), moderate (n = 40), and severe (n = 36) TBI groups. Participants completed a neuropsychological assessment and APOE genotyping (n = 46 ε4+, n = 130 ε4-). Neurocognitive composite scores representing memory, executive functioning, and visual processing speed were computed. ANCOVAs adjusting for race, education, combat exposure, and PTSD symptom severity showed a significant main effect of ε4 on the memory composite, such that ε4+ SMVs exhibited poorer memory performance than ε4- SMVs. When ε2 allele carriers were removed from the analyses, associations with memory were strengthened, demonstrating a possible protective effect of the ε2 allele. No main effect of TBI group was identified on any cognitive composite, nor were there any significant TBI group × ε4 status interactions for any cognitive composite. Future studies with larger samples are needed to verify these findings, but our results suggest an important relationship between ε4 status and memory functioning following remote TBI of all severities.