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Apolipoprotein E (APOE) ε4 Status Moderates the Relationship Between Close-Range Blast Exposure and Cognitive Functioning

Published online by Cambridge University Press:  03 November 2020

Thomas Wooten Open the ORCID record for Thomas Wooten [Opens in a new window] ,
Danielle R. Sullivan Open the ORCID record for Danielle R. Sullivan [Opens in a new window] ,
Mark W. Logue ,
Jennifer R. Fonda ,
Catherine B. Fortier ,
Joseph DeGutis ,
Regina McGlinchey ,
William Milberg  and
Michael Esterman Open the ORCID record for Michael Esterman [Opens in a new window]
Thomas Wooten*
Affiliation:
Tufts University, Boston, MA02155, USA Translational Research Center for TBI and Stress Disorders (TRACTS) and Geriatric Research, Educational and Clinical Center (GRECC), VA Boston Healthcare System, Boston, MA02130, USA Boston Attention and Learning Laboratory, VA Boston Healthcare System, Boston, MA02130, USA
Danielle R. Sullivan
Affiliation:
National Center for PTSD, VA Boston Healthcare System, Boston, MA02130, USA Department of Psychiatry, Boston University School of Medicine, Boston, MA02118, USA
Mark W. Logue
Affiliation:
National Center for PTSD, VA Boston Healthcare System, Boston, MA02130, USA Department of Psychiatry, Boston University School of Medicine, Boston, MA02118, USA Biomedical Genetics, Boston University School of Medicine, Boston, MA02118, USA Department of Biostatistics, Boston University School of Public Health, Boston, MA02118, USA
Jennifer R. Fonda
Affiliation:
Translational Research Center for TBI and Stress Disorders (TRACTS) and Geriatric Research, Educational and Clinical Center (GRECC), VA Boston Healthcare System, Boston, MA02130, USA Department of Psychiatry, Boston University School of Medicine, Boston, MA02118, USA Department of Psychiatry, Harvard Medical School, Boston, MA02215, USA
Catherine B. Fortier
Affiliation:
Translational Research Center for TBI and Stress Disorders (TRACTS) and Geriatric Research, Educational and Clinical Center (GRECC), VA Boston Healthcare System, Boston, MA02130, USA Department of Psychiatry, Harvard Medical School, Boston, MA02215, USA
Joseph DeGutis
Affiliation:
Translational Research Center for TBI and Stress Disorders (TRACTS) and Geriatric Research, Educational and Clinical Center (GRECC), VA Boston Healthcare System, Boston, MA02130, USA Boston Attention and Learning Laboratory, VA Boston Healthcare System, Boston, MA02130, USA Department of Psychiatry, Harvard Medical School, Boston, MA02215, USA
Regina McGlinchey
Affiliation:
Translational Research Center for TBI and Stress Disorders (TRACTS) and Geriatric Research, Educational and Clinical Center (GRECC), VA Boston Healthcare System, Boston, MA02130, USA Department of Psychiatry, Harvard Medical School, Boston, MA02215, USA
William Milberg
Affiliation:
Translational Research Center for TBI and Stress Disorders (TRACTS) and Geriatric Research, Educational and Clinical Center (GRECC), VA Boston Healthcare System, Boston, MA02130, USA Department of Psychiatry, Harvard Medical School, Boston, MA02215, USA
Michael Esterman
Affiliation:
Translational Research Center for TBI and Stress Disorders (TRACTS) and Geriatric Research, Educational and Clinical Center (GRECC), VA Boston Healthcare System, Boston, MA02130, USA Boston Attention and Learning Laboratory, VA Boston Healthcare System, Boston, MA02130, USA National Center for PTSD, VA Boston Healthcare System, Boston, MA02130, USA Department of Psychiatry, Boston University School of Medicine, Boston, MA02118, USA
*
*Correspondence and reprint requests to: Thomas Wooten B.S., Department of Psychology, Tufts University, 490 Boston Ave., Medford, MA02155, USA. E-mail: thomas.wooten@tufts.edu
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Abstract

Objectives:

Recent studies suggest that close-range blast exposure (CBE), regardless of acute concussive symptoms, may have negative long-term effects on brain health and cognition; however, these effects are highly variable across individuals. One potential genetic risk factor that may impact recovery and explain the heterogeneity of blast injury’s long-term cognitive outcomes is the inheritance of an apolipoprotein (APOE) ε4 allele, a well-known genetic risk factor for Alzheimer’s disease. We hypothesized that APOE ε4 carrier status would moderate the impact of CBE on long-term cognitive outcomes.

Methods:

To test this hypothesis, we examined 488 post-9/11 veterans who completed assessments of neuropsychological functioning, psychiatric diagnoses, history of blast exposure, military and non-military mild traumatic brain injuries (mTBIs), and available APOE genotypes. We separately examined the effects of CBE on attention, memory, and executive functioning in individuals with and without the APOE ε4 allele.

Results:

As predicted, we observed a differential impact of CBE status on cognition as a function of APOE ε4 status, in which CBE ε4 carriers displayed significantly worse neuropsychological performance, specifically in the domain of memory. These results persisted after adjusting for clinical, demographic, and genetic factors and were not observed when examining other neurotrauma variables (i.e., lifetime or military mTBI, distant blast exposure), though these variables displayed similar trends.

Conclusions:

These results suggest APOE ε4 carriers are more vulnerable to the impact of CBE on cognition and highlight the importance of considering genetic risk when studying cognitive effects of neurotrauma.

Keywords

APOEBlastMemoryConcussiveGeneticVeteransMild traumatic brain injury
Type
Regular Research
Information
Journal of the International Neuropsychological Society , Volume 27 , Issue 4 , April 2021 , pp. 315 - 328
Copyright
Copyright © INS. Published by Cambridge University Press, 2020

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