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 ) ε 4 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 ‐ ε 4(+/−) 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 ‐ ε 4(−) =79; APOE ‐ ε 4(+) =35), ApoE‐ ε 4(+) 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 ‐ ε 4 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 .