Williams OA, An Y, Armstrong NM, et al. - This investigation was undertaken to determine if the effects of apolipoprotein E (APOE)-ε4 on the cognitive decline are comparable in men and women and how APOE-ε4 and age interact in different cognitive domains to influence decline. Baseline age-dependent connections between APOE-ε4 status and longitudinal cognitive trajectories have been analyzed in cognitively normal Caucasian older adults (631 men, 561 women, baseline age range: 50–93, 6733 assessments) in sex-stratified analyses. In men, older baseline age was linked to higher effects of APOE-ε4 on the longitudinal decline in memory and executive function, respectively, detectable from baseline age 64 and 68. In women, older baseline age has been linked to greater effects of APOE-ε4 on longitudinal attention decline, detectable at 66 years of baseline age. For language, visual-spatial ability, or processing speed, no significant APOE-ε4 effects were discovered. Results emphasize the significance of considering gender and age when evaluating cognitive decline vulnerability associated with APOE-ε4.