Apolipoprotein E epsilon 4 (APOE-ε4) genotype is associated with decreased 6-month verbal memory performance after mild traumatic brain injury

Introduction: The apolipoprotein E (APOE) ε4 allele associates with memory impairment in neurodegenerative diseases. Its association with memory after mild traumatic brain injury (mTBI) is unclear. Methods: mTBI patients (Glasgow Coma Scale score 13–15, no neurosurgical intervention, extracranial Abbreviated Injury Scale score ≤1) aged ≥18 years with APOE genotyping results were extracted from the Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot (TRACK-TBI Pilot) study. Cohorts determined by APOE-ε4(+/−) were assessed for associations with 6-month verbal memory, measured by California Verbal Learning Test, Second Edition (CVLT-II) subscales: Immediate Recall Trials 1–5 (IRT), Short-Delay Free Recall (SDFR), Short-Delay Cued Recall (SDCR), Long-Delay Free Recall (LDFR), and Long-Delay Cued Recall (LDCR). Multivariable regression controlled for demographic factors, seizure history, loss of consciousness, posttraumatic amnesia, and acute intracranial pathology on computed tomography (CT). Results: In 114 mTBI patients (APOE-ε4(−)=79; APOE-ε4(+)=35), ApoE-ε4(+) was associated with long-delay verbal memory deficits (LDFR: B = −1.17 points, 95% CI [−2.33, −0.01], p =.049; LDCR: B = −1.58 [−2.63, −0.52], p =.004), and a marginal decrease on SDCR (B = −1.02 [−2.05, 0.00], p =.050). CT pathology was the strongest predictor of decreased verbal memory (IRT: B = −8.49, SDFR: B = −2.50, SDCR: B = −1.85, LDFR: B = −2.61, LDCR: B = −2.60; p <.001). Seizure history was associated with decreased short-term memory (SDFR: B = −1.32, p =.037; SDCR: B = −1.44, p =.038). Conclusion: The APOE-ε4 allele may confer an increased risk of impairment of 6-month verbal memory for patients suffering mTBI, with implications for heightened surveillance and targeted therapies. Acute intracranial pathology remains the driver of decreased verbal memory performance at 6 months after mTBI.

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