APOE and Alzheimer disease: Besides old age, APOE ε4 allele and chromosomal female sex are two well-established unmodifiable factors that increase the risk of late-onset AD.11,12 Consistent with that finding, evidence indicates that among patients with cognitive impairment, regional cerebral perfusion deficits differ by sex and APOE ε4 status.13, –15 Nevertheless, it remains unknown, whether APOE ε4 allele and female sex could, independently or synergistically, modify cerebral perfusion trajectories with increasing age in asymptomatic middle-aged and older adults.