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 withou t 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 delay ed recall, but no significant group differences emerged on attention, langu age, constructional skills, psychomotor speed, or executive function. Signi ficantly more ApoE-epsilon 4 participants developed probable or questionabl e Alzheimer's disease (AD) compared with non-epsilon 4 participants, sugges ting that the group differences resulted from a preponderance of preclinica l AD cases within the epsilon 4 group and not from a direct influence of Ap oE genotype on cognition. Cox proportional hazards analysis, adjusting for age, years of education, and global cognitive status, revealed that ApoE-ep silon 4 allele status and measures of recall performance were significant a nd independent predictors of conversion to AD. Results support the importan ce of specific episodic memory changes and possession of the ApoE-epsilon 4 allele in the preclinical detection of AD.