Neuropsychological function and apolipoprotein E genotype in the preclinical detection of Alzheimer's disease.

Nondemented older adults genotyped for the Apolipoprotein E (ApoE) epsilon4 allele (n = 43) were neuropsychologically compared to participants without a copy of the epsilon4 allele (n = 90). At baseline, the groups did not differ on age, education, gender, or global cognitive status. ApoE-epsilon4 participants demonstrated significantly poorer mean performances on delayed recall, but no significant group differences emerged on attention, language, constructional skills, psychomotor speed, or executive function. Significantly more ApoE-epsilon4 participants developed probable or questionable Alzheimer's disease (AD) compared with non-epsilon4 participants, suggesting that the group differences resulted from a preponderance of preclinical AD cases within the epsilon4 group and not from a direct influence of ApoE genotype on cognition. Cox proportional hazards analysis, adjusting for age, years of education, and global cognitive status, revealed that ApoE-epsilon4 allele status and measures of recall performance were significant and independent predictors of conversion to AD. Results support the importance of specific episodic memory changes and possession of the ApoE-epsilon4 allele in the preclinical detection of AD.