Background: The apolipoprotein E gene (APOE) has emerged as a candidate for prognosticating traumatic brain injury (TBI) recovery, with APOEε4 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 APOEε4 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 APOEε4 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 APOEε4 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 APOEε4, while three reported no association. Six studies examined Alzheimer's dementia pathology, of which three reported a hazardous influence of APOEε4.
Conclusions: The influence of APOEε4 on neuropsychological testing, functional outcome and in paediatric populations was incongruous. This review supports the majority of research indicating APOEε4 adversely influences recovery following TBI, particularly with respect to dementia-related outcomes and outcomes following sTBI.
Keywords: APOE; Apolipoprotein E; recovery; traumatic brain injury.