ABSTRACT
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. (PsycINFO Database Record
Subject(s)
Apolipoprotein E4/genetics , Brain Damage, Chronic/diagnosis , Brain Damage, Chronic/genetics , Brain Injuries, Traumatic/diagnosis , Brain Injuries, Traumatic/genetics , Cognition Disorders/diagnosis , Cognition Disorders/genetics , Neuropsychological Tests/statistics & numerical data , Adult , Brain Damage, Chronic/psychology , Brain Injuries, Traumatic/psychology , Cognition Disorders/psychology , Female , Genetic Carrier Screening , Genotype , Humans , Male , Middle Aged , PsychometricsABSTRACT
INTRODUCTION: There is evidence that the e4 allele of the apolipoprotein E (APOE) gene is detrimental to cognitive function, but results from traumatic brain injury (TBI) populations are mixed. A possible explanation is that APOEe2 carriers have routinely been incorporated into APOEe4 and non-e4 groups, despite APOEe2 being proposed to have an ameliorative effect. Our primary aim was to investigate the influence of APOEe4 on cognitive impairment during early recovery following TBI, excluding the potential confound of APOEe2 possession. A secondary objective was to explore whether APOEe4 displays more pronounced effects in moderate to severe TBI and to consider the potential postinjury protective influence of the APOEe2 allele. METHOD: Participants who recently sustained a TBI (posttraumatic amnesia > 5 minutes) were assessed on measures of information processing speed, executive function, and working memory upon remission of posttraumatic amnesia. APOE genotype was determined by buccal saliva DNA extraction (APOEe4 n = 37, APOEe3 n = 92, APOEe2 n = 13). RESULTS: Stepwise multiple regressions were performed to compare APOEe4 carriers to APOEe3 homozygotes, with injury severity, age, and estimated premorbid IQ included in the first step. This model was found to significantly predict performance on all tasks, accounting for 17.3-24.3% of the variance. When APOEe4 status was added for the second step, there were no significant changes on any tasks (additional variance <1%). The effect of APOEe4 in moderate to severe TBI and the effect of APOEe2 were explored by analysis of covariance (ANCOVA), with no significant effects revealed. CONCLUSIONS: It is unlikely that APOE genotype influences cognitive function in the initial recovery period following TBI, regardless of injury severity. However, a more nuanced and long-term exploration of the effect of APOE genotype in the TBI population is warranted.
