Pattern and progression of cognitive decline in Alzheimer's disease:role of premorbid intelligence and ApoE genotype

Background/Aims: Because of controversial results across studies, we evaluated the predictive value of premorbid intelligence and the apolipoprotein E (ApoE) genotype on baseline and progression of cognitive performance in Alzheimer's disease (AD). Methods: Eighty-five mild AD cases, ApoE genotyped and included in a longitudinal cliniconeuropsychological-genetic study, underwent a premorbid intelligence test and up to 11 (average 5) neuropsychological assessments. We applied linear- and logistic-regression models for cross-sectional data and mixed models for longitudinal ones. Results: Higher premorbid intelligence was associated with higher global, executive and memory performance, while the ApoE ε4 allele was specifically related to poorer memory performance. The premorbid intelligence-ApoE ε4/ε4 interaction was significant, with higher premorbid intelligence scores reducing the detrimental effect of ApoE ε4 homozygosity on memory performance. Higher premorbid intelligence, but not the ApoE ε4 allele, was related to faster memory deficit progression. Conclusion: The association of higher premorbid intelligence with better baseline cognitive performance and faster memory decline, as well as its interaction with the ApoE genotype, strengthens the role of cognitive reserve in shaping the disease's clinical expression. Our findings confirm that the ε4 allele affects memory deficit at baseline but does not exert any influence on the rate of cognitive decline.