Working memory deficits in healthy APOE epsilon 4 carriers

Studies on the cognitive effects of APOE allele variation in healthy persons have mainly focused on episodic memory performance as most sensitive to genetic effects. The present study focuses on working memory performance, measured both in an experimental paradigm, the AX-Continuous Performance Task (AX-CPT), and in neuropsychological test paradigms of span capacity and interference control. In a highly functioning healthy group (N=186) of mean age 64.5 years we found evidence of reduced working memory performance in APOE epsilon4 carriers, with sex and epsilon4 dose as modifying variables. Several aspects of capacity and control in working memory were affected, while genetic effects were not present for measures of episodic memory. The pattern of results suggests that response inhibition is sensitive to genetic effects. In healthy individuals the broad range of neurobiological mechanisms associated with APOE is consistent with effects on non-memory cognitive subsystems, and gender effects may be modulated by interaction of APOE with myelination, androgen mechanisms, or broad patterns of age-related changes in gene expression.