Apolipoprotein E (APOE) ε4 genotype is associated with reduced neuropsychological performance in military veterans with a history of mild traumatic brain injury

ABSTRACT

Introduction: The purpose of this study was to investigate the effect of the apolipoprotein E (APOE) ε4 allele on neuropsychological functioning in military Veterans with a remote history of mild traumatic brain injury (mTBI).

Method: This cross-sectional study included 99 Veterans (mTBI = 53; military controls, MC = 46) who underwent neuropsychological assessment and APOE genotyping. Three neurocognitive composite scores—memory (α = .84), speed (α = .85), and executive functioning (α = .76)—were computed from 24 norm-referenced variables, and the total number of impaired scores (>1.5 SDs below mean) for each participant was calculated.

Results: Analyses of covariance adjusting for ethnicity and posttraumatic stress disorder (PTSD) symptoms revealed that although no significant differences were observed between mTBI ε4 allele groups on the executive functioning composite (p > .05), mTBI ε4+ Veterans performed more poorly than ε4− Veterans on the memory (p = .045, η_p² = .083) and speed (p = .023, η_p² = .106) composites. Furthermore, Mann–Whitney U tests showed that ε4+ mTBI Veterans displayed a significantly greater number of impaired scores than did ε4− mTBI Veterans (p = .010, r = .355). In contrast, there were no significant differences across any of the cognitive variables between ε4+ and ε4− MCs (all p > .05).

Conclusions: Results suggest that APOE ε4 genotype is related to reduced memory and processingspeed performance, as well as overall cognitive impairment, in those with a history of mTBI, but does not appear to have the same negative effects on cognition in the absence of neurotrauma. Although results are preliminary, the present study advances understanding of genetic influences on cognitive functioning in Veterans with remote mTBIs. Future longitudinal work is needed to elucidate the underlying brain-based mechanisms of ε4 allelic effects on cognitive and clinical outcomes following TBI.

KEYWORDS:

• Apolipoprotein E gene
• cognitive functioning
• mild traumatic brain injury
• military Veterans
• neuropsychological assessment

Disclosure statement

No potential conflict of interest was reported by the authors.

Notes

1. Participants were excluded if they did not perform adequately on one or both of the validity indices (California Verbal Learning Test–Second Edition, CVLT–II, Forced Choice Recognition and Test of Memory Malingering, TOMM, Trial 2).

Additional information

Funding

This work was supported by Veterans Affairs grants awarded to Lisa Delano-Wood [grant number 829-MR-NB-25860], Dawn Schiehser [grant number CDA-2-065-10S], and Scott Sorg [grant number CDA-2-CX001508]; the National Institute of Neurological Disorders and Stroke of the National Institutes of Health [grant number F31NS09870] to Alexandra Clark; finally, this research was supported by the Department of Veterans Affairs Office of Academic Affiliations Postdoctoral Residency Program in Neuropsychology (VA San Diego Healthcare System) and a grant awarded to Mark Bondi by the National Institutes of Health [grant number K24 AG026431].