Reduced hippocampal activity during encoding in cognitively normal adults carrying the APOE e{open}4 allele

Maheen M. Adamson, J. Benjamin Hutchinson, Amy L. Shelton, Anthony D. Wagner, Joy L. Taylor

Research output: Contribution to journalArticlepeer-review

25 Scopus citations


Apolipoprotein (APOE) e{open}4-related differences in memory performance have been 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 memory, including visuo-spatial memory. While reports of APOE e{open}4-related differences in these brain structures are not consistent in either cross-sectional or longitudinal structural and functional magnetic resonance imaging (fMRI) studies, there is increasing evidence that brain activity at baseline (defined as activity during fixation or rest) may differ in APOE e{open}4 carriers compared to non-carriers. In this fMRI study, cognitively normal APOE e{open}4 carriers and non-carriers engaged in a perspective-dependent spatial 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, in addition to fixation. APOE e{open}4 carriers showed less activation than non-carriers in the hippocampus proper during encoding. Specifically, when spatial encoding was contrasted against the dot-control task, encoding-related activation was significantly lower in carriers than non-carriers. By contrast, no e{open}4-related differences in the hippocampus were found when spatial encoding was compared with fixation. Lower activation, however, was not global since encoding-related activation in early visual cortex (left lingual gyrus) was not different between APOE e{open}4 carriers and non-carriers. The present data document APOE e{open}4-related differences in the hippocampus proper during encoding and underscore the role of low-level control contrasts for complex encoding tasks. These results have implications for fMRI studies that investigate the default-mode network (DMN) in middle-aged to older APOE e{open}4 carriers to help evaluate AD risk in this otherwise cognitively normal population.

Original languageEnglish (US)
Pages (from-to)2448-2455
Number of pages8
Issue number9
StatePublished - Jul 2011
Externally publishedYes


  • APOE e{open}4
  • Hippocampus
  • Learning
  • Medial temporal lobe
  • Memory
  • Visuo-spatial

ASJC Scopus subject areas

  • Experimental and Cognitive Psychology
  • Cognitive Neuroscience
  • Behavioral Neuroscience


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