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

ABSTRACT

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 (p=.002, η_p² =.160), Time Cue (p = .003, η_p² =.157), and PM Total (p = .016, η_p² =.102). Those with at least one copy of the ε4 allele performed more poorly compared to ε4- Veterans on the MIST 15-min delay (p = .011, η_p² =.113) and PM Total (p = .048, η_p² = .071). No significant interactions were observed between mTBI and APOE-ε4 status on MIST outcomes (ps>.25). Within the mTBI group, APOE-ε4+ Veterans performed worse than APOE-ε4− Veterans on the MIST 15-min delay subscale (p = .031, η_p² = .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.

KEYWORDS:

• Apolipoprotein E gene
• mild traumatic brain injury
• military veterans
• prospective memory
• risk factors

Acknowledgments

We want to thank all of the Veterans that volunteered their time to participate in this study.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Author contribution

J. S. Adler contributed to study design, conducted data analysis and interpretation, and drafted the manuscript. E. D. Ozturk contributed to study design, data analysis and interpretation, drafting, and revisions of the manuscript. V. C. Merritt contributed to study design, data interpretation, and revisions of the manuscript. L. Delano-Wood contributed to study design and revisions of the manuscript. D. M. Schiehser contributed to study design and revisions of the manuscript. M. W. Bondi contributed to revisions of the manuscript. M. Ly contributed to revisions of the manuscript. A. Ton-Loy contributed to revisions of the manuscript. S. F. Sorg contributed to study design, data analysis and interpretation, and revisions of the manuscript.

Data availability statement

The data that support the findings of this study are available from the corresponding author, MTL, upon reasonable request.

Additional information

Funding

This work was supported by Veteran Affairs research grants including Career Development Awards to Drs. Sorg (IK2 CX001508) and Delano-Wood (CDA-2-034-07F) and a Merit Award to Dr. Delano-Wood (CX000842-01A2), as well as a Department of Defense Investigator-Initiated Research Grant awarded to Dr. Delano-Wood [W81XWH-10 February 169]. This material is further supported by resources of the Veterans Affairs Center of Excellence for Stress and Mental Health. Dr. Merritt received salary support during this work from a Career Development Award (IK2 CX001952) from the VA Clinical Science Research & Development Service. Ms. Ozturk received salary support during this work from the Graduate Research Fellowship from the National Science Foundation. Dr. Sorg received salary support during this work from a Veterans Affairs Merit Award (CX002246).