Interaction between years of education and APOE ε4 status on frontal and temporal metabolism

Objective:To examine interactions between years of education and APOE epsilon 4 status on gray matter volume and metabolism in cognitively healthy participants.Methods:Seventy-two healthy participants (28 APOE epsilon 4 carriers and 44 noncarriers; from 23 to 84 years of age) with FDG-PET and structural MRI were included. A subgroup also underwent florbetapir-PET. We tested the interaction effect between years of education and APOE epsilon 4 status (carrier vs noncarrier) on FDG-PET and structural MRI within the whole brain (voxel-wise) adjusting for age and sex. Computed florbetapir standardized uptake value ratios were used for complementary analyses.Results:We found an interaction between years of education and APOE epsilon 4 status on frontotemporal FDG-PET metabolism, such that higher education was positively related to frontotemporal metabolism only in APOE epsilon 4 carriers. Complementary analyses revealed that (1) this interaction was independent from amyloid load; (2) increased metabolism in APOE epsilon 4 carriers in this region correlated with episodic memory performances; (3) lower educated APOE epsilon 4 carriers showed decreased metabolism relative to noncarriers in medial temporal and prefrontal areas, while higher educated carriers were comparable to noncarriers in these areas and showed increased metabolism in the middle temporal lobe.Conclusions:Our results showed that education may counteract the effects of APOE epsilon 4 on metabolism independently of amyloid deposition. Higher metabolism in higher (compared to lower) educated APOE epsilon 4 carriers was found in regions that sustain episodic memory. Overall, our results point to education as a protective factor that may help to postpone cognitive changes in APOE epsilon 4 carriers.