Apolipoprotein E ε4 affects new learning in cognitively normal individuals at risk for Alzheimer's disease

The Apolipoprotein E (APOE) ε4 allele is an important risk factor for Alzheimer's disease (AD). Given the interest in early identification of at-risk individuals, we examined memory decline as a function of APOE status and age in cognitively intact participants aged 48-77 years old (yo). Participants were grouped by age (<60 versus ≥60) and APOE (ε4+/-). Longitudinal analysis of several components of memory over a 2-year interval showed a significant Age-by-APOE interaction reflecting a decline in new learning for the ≥60 ε4+ group only. Among ε4+, 76% of the ≥60 participants showed a decline versus 32% of the <60, but the amount of decline in new learning over the 2-year interval within the ≥60 group was not further influenced by age. That is, the size of the 2-year change was the same for 60 and 70yo participants. This suggests that longitudinal study of new learning is a sensitive measure for detecting early cognitive changes in at-risk individuals that precede the symptomatic onset of mild cognitive impairment and AD.