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

Hippocampus. 2015 Sep;25(9):993-1007. doi: 10.1002/hipo.22422. Epub 2015 Feb 9.

Abstract

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) ɛ4 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 ɛ4 carriers (ɛ4(+) ) and 18 ɛ4 noncarriers (ɛ4(-) ). 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 ɛ4(+) 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 ɛ4 noncarriers was paralleled by enhanced memory. On the contrary, the redundant prefrontal activation shown by aMCI ɛ4(+) 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 ɛ4. Whereas individuals with aMCI ɛ4(-) activate attentional, perceptual and semantic compensatory networks, aMCI ɛ4(+) show reduced processing efficiency and capacity.

Keywords: APOE ɛ4; amnestic mild cognitive impairment; associative memory; brain oscillations; semantic memory.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Amnesia / complications*
  • Apolipoprotein E4 / genetics*
  • Association Learning / physiology
  • Brain Mapping
  • Brain Waves / genetics*
  • Cognitive Dysfunction* / etiology
  • Cognitive Dysfunction* / genetics
  • Cognitive Dysfunction* / pathology
  • Electroencephalography
  • Female
  • Fourier Analysis
  • Humans
  • Image Processing, Computer-Assisted
  • Magnetic Resonance Imaging
  • Male
  • Mental Recall
  • Mental Status Schedule
  • Middle Aged
  • Neural Pathways / physiology
  • Neuropsychological Tests
  • Reaction Time / genetics
  • Semantics
  • Statistics, Nonparametric
  • Time Factors
  • Visual Perception / physiology

Substances

  • Apolipoprotein E4