Prospective memory performance in veterans with and without histories of mild traumatic brain injury: effect of the apolipoprotein E (APOE) ε4 genotype.

Objective: Identifying factors that moderate cognitive outcomes following mild traumatic brain injury (mTBI) is crucial. Prospective memory (PM) is a cognitive domain of interest in mTBI recovery as it may be especially sensitive to TBI-related changes. Since studies show that genetic status - particularly possession of the apolipoprotein E (APOE) ε4 allele - can modify PM performance, we investigated associations between mTBI status and APOE-ε4 genotype on PM performance in a well-characterized sample of Veterans with neurotrauma histories.

Methods: 59 Veterans (mTBI = 33, Military Controls [MCs] = 26; age range: 24-50; average years post-injury = 10.41) underwent a structured clinical interview, neuropsychological assessment, and genotyping. The Memory for Intentions Test (MIST) measured PM across multiple subscales. ANCOVAs, adjusting for age and posttraumatic stress symptoms, tested the effects of mTBI status (mTBI vs. MC) and ε4 status (ε4+ vs. ε4-) on MIST scores.

Results: Veterans with mTBI history performed more poorly compared to MCs on the MIST 15-min delay (=.002, η =.160), Time Cue ( = .003, η =.157), and PM Total ( = .016, η =.102). Those with at least one copy of the ε4 allele performed more poorly compared to ε4- Veterans on the MIST 15-min delay ( = .011, η =.113) and PM Total ( = .048, η = .071). No significant interactions were observed between mTBI and APOE-ε4 status on MIST outcomes (s>.25). Within the mTBI group, APOE-ε4+ Veterans performed worse than APOE-ε4- Veterans on the MIST 15-min delay subscale ( = .031, η = .150).

Conclusions: mTBI history and APOE-ε4 genotype status were independently associated with worse PM performance compared to those without head injury histories or possession of the APOE-e4 genotype. Performance on the MIST 15-min delay was worse in Veterans with both risk factors (mTBI history and APOE-ε4 positivity). Findings suggest that genetic status may modify outcomes even in relatively young Veterans with mTBI histories. Future research examining longitudinal associations and links to neuroimaging and biomarker data are needed.