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

Neurology. 2015 Oct 20;85(16):1392-9. doi: 10.1212/WNL.0000000000002034. Epub 2015 Sep 25.


Objective: To examine interactions between years of education and APOE ε4 status on gray matter volume and metabolism in cognitively healthy participants.

Methods: Seventy-two healthy participants (28 APOE ε4 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 ε4 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 ε4 status on frontotemporal FDG-PET metabolism, such that higher education was positively related to frontotemporal metabolism only in APOE ε4 carriers. Complementary analyses revealed that (1) this interaction was independent from amyloid load; (2) increased metabolism in APOE ε4 carriers in this region correlated with episodic memory performances; (3) lower educated APOE ε4 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 ε4 on metabolism independently of amyloid deposition. Higher metabolism in higher (compared to lower) educated APOE ε4 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 ε4 carriers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Apolipoprotein E4 / genetics*
  • Education / trends*
  • Educational Status
  • Female
  • Frontal Lobe / metabolism*
  • Heterozygote*
  • Humans
  • Male
  • Memory, Episodic
  • Middle Aged
  • Temporal Lobe / metabolism*
  • Time Factors
  • Young Adult


  • Apolipoprotein E4