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

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

Cite this

Huijbers, W., Mormino, E. C., Wigman, S. E., Ward, A. M., Vannini, P., McLaren, D. G., ... Sperling, R. A. (2014). Amyloid Deposition Is Linked to Aberrant Entorhinal Activity among Cognitively Normal Older Adults. Journal of Neuroscience, 34(15), 5200-5210. https://doi.org/10.1523/JNEUROSCI.3579-13.014
Huijbers, Willem ; Mormino, Elizabeth C. ; Wigman, Sarah E. ; Ward, Andrew M. ; Vannini, Patrizia ; McLaren, Donald G. ; Becker, J. Alex ; Schultz, Aaron P. ; Hedden, Trey ; Johnson, Keith A. ; Sperling, Reisa A. / Amyloid Deposition Is Linked to Aberrant Entorhinal Activity among Cognitively Normal Older Adults. In: Journal of Neuroscience. 2014 ; Vol. 34, No. 15. pp. 5200-5210.
@article{b2ff800d6e9448458ad197197fa46f01,
title = "Amyloid Deposition Is Linked to Aberrant Entorhinal Activity among Cognitively Normal Older Adults",
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.",
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",
author = "Willem Huijbers and Mormino, {Elizabeth C.} and Wigman, {Sarah E.} and Ward, {Andrew M.} and Patrizia Vannini and McLaren, {Donald G.} and Becker, {J. Alex} and Schultz, {Aaron P.} and Trey Hedden and Johnson, {Keith A.} and Sperling, {Reisa A.}",
year = "2014",
month = "4",
day = "9",
doi = "10.1523/JNEUROSCI.3579-13.014",
language = "English",
volume = "34",
pages = "5200--5210",
journal = "Journal of Neuroscience",
issn = "0270-6474",
publisher = "SOC NEUROSCIENCE",
number = "15",

}

Huijbers, W, Mormino, EC, Wigman, SE, Ward, AM, Vannini, P, McLaren, DG, Becker, JA, Schultz, AP, Hedden, T, Johnson, KA & Sperling, RA 2014, 'Amyloid Deposition Is Linked to Aberrant Entorhinal Activity among Cognitively Normal Older Adults', Journal of Neuroscience, vol. 34, no. 15, pp. 5200-5210. https://doi.org/10.1523/JNEUROSCI.3579-13.014

Amyloid Deposition Is Linked to Aberrant Entorhinal Activity among Cognitively Normal Older Adults. / Huijbers, Willem; Mormino, Elizabeth C.; Wigman, Sarah E.; Ward, Andrew M.; Vannini, Patrizia; McLaren, Donald G.; Becker, J. Alex; Schultz, Aaron P.; Hedden, Trey; Johnson, Keith A.; Sperling, Reisa A.

In: Journal of Neuroscience, Vol. 34, No. 15, 09.04.2014, p. 5200-5210.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - Amyloid Deposition Is Linked to Aberrant Entorhinal Activity among Cognitively Normal Older Adults

AU - Huijbers, Willem

AU - Mormino, Elizabeth C.

AU - Wigman, Sarah E.

AU - Ward, Andrew M.

AU - Vannini, Patrizia

AU - McLaren, Donald G.

AU - Becker, J. Alex

AU - Schultz, Aaron P.

AU - Hedden, Trey

AU - Johnson, Keith A.

AU - Sperling, Reisa A.

PY - 2014/4/9

Y1 - 2014/4/9

N2 - 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.

AB - 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.

KW - amyloid

KW - default network

KW - entorhinal cortex

KW - fMRI

KW - memory

KW - preclinical Alzheimer's disease

KW - INTRINSIC FUNCTIONAL CONNECTIVITY

KW - EARLY ALZHEIMERS-DISEASE

KW - BRAINS DEFAULT NETWORK

KW - ENCODING/RETRIEVAL FLIP

KW - MEMORY PERFORMANCE

KW - BETA DEPOSITION

KW - LIFE-SPAN

KW - POSTEROMEDIAL CORTEX

KW - CLINICAL DECLINE

KW - VERBAL MEMORY

U2 - 10.1523/JNEUROSCI.3579-13.014

DO - 10.1523/JNEUROSCI.3579-13.014

M3 - Article

VL - 34

SP - 5200

EP - 5210

JO - Journal of Neuroscience

JF - Journal of Neuroscience

SN - 0270-6474

IS - 15

ER -