Episodic memory changes are associated with the APOE-epsilon 4 allele in nondemented older adults

Objective: To compare the memory performances of nondemented older adults with and without the epsilon 4 allele of the apolipoprotein E (APOE-epsilon 4). Background: Few studies have examined the cognitive status of subjects at high risk for the development of dementia of the Alzheimer type (DAT). A newly reported risk factor for DAT allows for an examination of the cognitive performances of nondemented subjects who are at risk by virtue of being either heterozygous or homozygous for the APOE-epsilon 4 allele. Methods: The California Verbal Learning Test (CVLT) was administered to 52 nondemented older adults. Subjects were divided into two groups on the basis of the presence (n = 17) or absence (n = 35) of one or two APOE-epsilon 4 alleles. Results: APOE-epsilon 4 and non-epsilon 4 groups did not significantly differ in demographic, mental status, and functional characteristics. APOE-epsilon 4 subjects demonstrated significantly poorer mean performances than non-epsilon 4 subjects on nine CVLT variables. Seven group differences remained significant, and three approached significance (0.05 < p < 0.10), after the effects of age and gender were taken into account. Six of the 14 APOE-epsilon 4 subjects who completed annual follow-up evaluations developed either DAT or questionable DAT, whereas none of the 26 non-epsilon 4 subjects who received follow-up demonstrated any cognitive decline. Conclusions: Results suggest that episodic memory changes in older adults are associated with APOE-epsilon 4 allele; sensitive cognitive markers such as those of the CVLT may precede the subsequent development of DAT.