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

Nondemented older adults genotyped for the Apolipoprotein E (ApoE) epsilon 4 allele (n = 43) were neuropsychologically compared to participants without a copy of the epsilon 4 allele (n = 90). At baseline, the groups did not differ on age, education, gender, or global cognitive status. ApoE-epsilon 4 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-epsilon 4 participants developed probable or questionable Alzheimer's disease (AD) compared with non-epsilon 4 participants, suggesting that the group differences resulted from a preponderance of preclinical AD cases within the epsilon 4 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-epsilon 4 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-epsilon 4 allele in the preclinical detection of AD.