Apolipoprotein E epsilon 4 (APOE- ε 4) 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.