The role of apolipoprotein E episilon (ε)-4 allele on outcome following traumatic brain injury: A systematic review

Background: The apolipoprotein E gene (APOE) has emerged as a candidate for prognosticating traumatic brain injury (TBI) recovery, with APOE epsilon 4 identified as a susceptibility marker for poor outcome, despite large discrepancy in its reported influence post-TBI. Methods: A systematic review was conducted, including all primary articles investigating the role of APOE epsilon 4 on TBI outcome. A total of 65 studies were included, including 24 predominantly investigating mild (mTBI), seven moderate (modTBI) and 33 severe (sTBI); severity was not reported in one study. Results: In mTBI studies, the association between APOE epsilon 4 and post-TBI outcome was concluded as non-contributory in 14 studies (58.3%), hazardous in nine (37.5%) and protective in one (4.2%). In sTBI studies, the role of APOE epsilon 4 was hazardous in 21 (63.6%), non-contributory in nine (27.3%) and protective in three (9.1%). Of the seven studies investigating dementia outcomes, four observed a hazardous association with APOE epsilon 4, while three reported no association. Six studies examined Alzheimer's dementia pathology, of which three reported a hazardous influence of APOE epsilon 4. Conclusions: The influence of APOE epsilon 4 on neuropsychological testing, functional outcome and in paediatric populations was incongruous. This review supports the majority of research indicating APOE epsilon 4 adversely influences recovery following TBI, particularly with respect to dementia-related outcomes and outcomes following sTBI.