APOE ε4 and Cognitive Function in Early Life: A Meta-Analysis

Introduction: Ills well established that the Apolipoprotein E (APOE) epsilon 4 allele is associated with cognitive impairment and Alzheimer's disease in old age. By contrast, several studies have demonstrated cognitive benefits in young epsilon 4 carriers. It is therefore possible that the epsilon 4 allele exhibits a pleiotropic association with cognition across the life span where epsilon 4-related benefits in youth reverse to become risk factors for cognitive impairment and dementia in later life. To date, though, there has been no broad quantitative review of work assessing APOE-cognition associations in children, adolescents and young adults. Method: Based on 20 studies investigating cognitive performance in epsilon 4-carrying young persons and their non-epsilon 4 counterparts, a meta-analytic study was conducted to examine APOE epsilon 4-related differences in cognitive performance. Additionally, we assessed whether the level of executive demands affected the strength of associations between the epsilon 4 allele and cognitive measures. Results: In all analyses, estimated APOE epsilon 4-related population effect sizes did not reliably differ from zero. Furthermore, the level of executive demands of the task did not affect this finding. Conclusion: We found no APOE epsilon 4-related cognitive benefits in young adults, adolescents and children, and findings were not moderated by the level of executive demands in a cognitive task. Given the current empirical evidence therefore, suggestions that APOE epsilon 4 exhibits a pleiotropic association with cognition across the life span should be treated with caution.