APOE ɛ4 constrains engagement of encoding‐related compensatory networks in amnestic mild cognitive impairment

People with amnestic mild cognitive impairment (aMCI), compared to healthy older adults (HO), benefit less from semantic congruent cues during episodic encoding. The presence of the apolipoprotein E (APOE) ?4 makes this congruency benefit smaller, but the neural correlates of this deficit are unknown. Here, we estimated the source generators of EEG oscillatory activity associated with successful encoding of face‐location associations preceded by semantically congruent and incongruent cues in HO (N = 26) and aMCI subjects (N = 34), 16 of which were ?4 carriers (?4⁺) and 18 ?4 noncarriers (?4^?). Source estimation was performed in those spectrotemporal windows where the power of low‐alpha, high‐alpha, and beta oscillatory activity differed either between congruent and incongruent faces or between groups. Differences in high‐alpha and beta‐oscillatory dynamics indicated that aMCI ?4⁺ are unable to activate lateral regions of the temporal lobe involved in associative memory and congruency benefit in HO. Interestingly, and regardless of APOE genotype, aMCI activated additional regions relative to HO, through alpha oscillations. However, only activation in a distributed fronto‐temporo‐parietal network in ?4 noncarriers was paralleled by enhanced memory. On the contrary, the redundant prefrontal activation shown by aMCI ?4⁺ did not prevent performance from decreasing. These results indicate that the effect of aMCI‐related degeneracy on functional networks is constrained by the presence of APOE ?4. Whereas individuals with aMCI ?4^? activate attentional, perceptual and semantic compensatory networks, aMCI ?4⁺ show reduced processing efficiency and capacity. © 2015 Wiley Periodicals, Inc.