Is APOE ε4 associated with poorer cognitive outcome following traumatic brain injury? a meta-analysis

Objective: Cognitive impairment is a common sequelae of traumatic brain injury (TBI); however, predicting who will experience poorer outcomes remains challenging. A potential risk factor that has gained attention is the APOE gene, with the ε4 allele hypothesized to have a detrimental effect on post-TBI cognitive outcome. The aim of this meta-analysis was to evaluate the effect of APOE ε4 both in terms of general cognitive function and within specific domains known to be prone to impairment following TBI (executive function, working memory, verbal memory and visual memory).

Method: A literature search was undertaken in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA), resulting in the inclusion of 10 studies (ε4-carriers n = 143, noncarriers n = 510). Neuropsychological tasks were identified, and Cohen's d was calculated and pooled. Meta-analyses were conducted on general cognitive functioning and for the specific cognitive domains of interest.

Results: No significant differences were found between APOE ε4-carriers or noncarriers, either in general cognitive function or in the cognitive domains of executive function, working memory, verbal memory, or visual memory.

Conclusions: This meta-analysis indicates that APOE ε4 does not have a detrimental effect on cognitive performance following TBI. We propose that the relationship between APOE and cognitive function following TBI is complex, and a more-nuanced exploration of APOE genotypes is needed.