Background-Virtually all adult studies of APOE genotypes and cognition have included individuals over 60. In older adults, ε4 carriers may manifest greater cognitive asymmetries than non-ε4 carriers even in the absence of overall mean differences. General cognitive ability may also be affected by aging and APOE genotype, but most studies have inadequately addressed this potential confound. The goals of this study were to examine, in middle age, the relationship of APOE genotype with episodic memory and verbal-visuospatial episodic memory asymmetries, after accounting for prior general cognitive ability.