Reduced Hippocampal Activity During Encoding in Cognitively Normal Adults Carrying the Apoe ɛ4 Allele

Abstract

Apolipoprotein (APOE) ε4-related differences in memory performance can be detected before age 65. The hippocampus and the surrounding medial temporal lobe (MTL) structures are the first site affected by Alzheimer's Disease (AD) and the MTL is the seat of episodic and visuospatial memory. However, reports on APOE ε4-related differences in these brain structures are not consistent in either cross-sectional or longitudinal studies. Results from functional magnetic resonance imaging (fMRI) studies using various episodic memory paradigms involving the MTL structures are inconsistent in regard to determining the amount of increased risk for AD associated with APOE ε4. In addition, there is increasing evidence that the brain activity at baseline (defined as the activity during fixation or rest) may be different in APOE ε4 carriers compared to non-carriers. In this fMRI study, cognitively normal APOE ε4 carriers and non-carriers engaged in a perspective-dependent learning task (Shelton & Gabrieli, 2002) previously shown to activate MTL structures in older participants (Borghesani et al., 2008). A low-level, visually engaging dot-control task was used for comparison to provide non-MTL-based activity, in addition to fixation. Route vs. survey perspectives were not different in ε4 carriers compared to non-carriers (F (1, 19) = 1.56, p > .1) and there was no Genotype x Perspective interaction, F (1, 19) = 0.02, p > .1. When the encoding of the two perspectives was contrasted against the dot-control task the encoding-related activation was significantly higher than the dot-control (F (2, 33.74) = 9.63, p < .001) and there was a Genotype x Task interaction, F (2, 33.74) = 4.92, p < .05. No ε4-related differences in the hippocampus were found when encoding during the two perspective tasks was compared with fixation. The present study illustrates APOE ε4-related differences during encoding in the hippocampus proper and elaborates on the role of low level control contrast for a complex encoding task. The results of this study have implications for fMRI studies that investigate the task-positive network (TPN) and default-mode network (DMN) in APOE ε4 carriers to help evaluate AD risk in the otherwise cognitively normal population.