Amyloid Deposition Is Linked to Aberrant Entorhinal Activity among Cognitively Normal Older Adults

Willem Huijbers*, Elizabeth C. Mormino, Sarah E. Wigman, Andrew M. Ward, Patrizia Vannini, Donald G. McLaren, J. Alex Becker, Aaron P. Schultz, Trey Hedden, Keith A. Johnson, Reisa A. Sperling

*Corresponding author for this work

Research output: Contribution to journalArticleScientificpeer-review

50 Citations (Scopus)

Abstract

Normal aging is often difficult to distinguish from the earliest stages of Alzheimer's disease. Years before clinical memory deficits manifest, amyloid-beta deposits in the cortex in many older individuals. Neuroimaging studies indicate that a set of densely connected neocortical regions, referred to as the default network, is especially vulnerable to amyloid-beta deposition. Yet, the impact of amyloid-beta on age-related changes within the medial temporal lobe (MTL) memory system is less clear. Here we demonstrate that cognitively normal older humans, compared with young adults, show reduced ability to modulate hippocampal activations and entorhinal deactivations during an episodic memory task. Among older adults, amyloid-beta deposition was associated with failure to modulate activity in entorhinal cortex, but not hippocampus. Furthermore, we show that entorhinal regions demonstrating amyloid-beta-related dysfunction are directly connected to the neocortical regions of the default network. Together these findings link neocortical amyloid-beta deposition to neuronal dysfunction specifically in entorhinal cortex, while aging is associated with more widespread functional changes across the MTL.

Original languageEnglish
Pages (from-to)5200-5210
Number of pages11
JournalJournal of Neuroscience
Volume34
Issue number15
DOIs
Publication statusPublished - 9 Apr 2014
Externally publishedYes

Keywords

  • amyloid
  • default network
  • entorhinal cortex
  • fMRI
  • memory
  • preclinical Alzheimer's disease
  • INTRINSIC FUNCTIONAL CONNECTIVITY
  • EARLY ALZHEIMERS-DISEASE
  • BRAINS DEFAULT NETWORK
  • ENCODING/RETRIEVAL FLIP
  • MEMORY PERFORMANCE
  • BETA DEPOSITION
  • LIFE-SPAN
  • POSTEROMEDIAL CORTEX
  • CLINICAL DECLINE
  • VERBAL MEMORY

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