The APOE ε4 variant confers an increased risk of Alzheimer's disease. Longitudinal modeling of cognitive aging showed that memory decline in subjects with one or two APOE ε4 alleles diverged from that of noncarriers before the age of 60 years. The APOE ε4 variant confers an increased risk of Alzheimer's disease. Longitudinal modeling of cognitive aging showed that memory decline in subjects with one or two APOE ε4 alleles diverged from that of noncarriers before the age of 60 years. Cognitive profiles of normal aging emphasize a decline in skills mediated by the frontal lobe, including learning efficiency, working memory, and psychomotor speed. 1 – 3 Although memory loss is the earliest cognitive change in Alzheimer's disease, 4 – 9 distinguishing early disease from normal aging can be difficult. 10 , 11 The apolipoprotein E ( APOE ) ε4 allele, the most prevalent known genetic risk factor for Alzheimer's disease, may account for up to half of all sporadic and familial late-onset cases of Alzheimer's disease. 12 , 13 Carriers of the APOE ε4 allele have more rapidly progressive memory loss and reduced learning efficiency in their 50s . . .