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Aging and Alzheimer's disease have dissociable effects on local and regional medial temporal lobe connectivity

Hrybouski, Stanislau ; Das, Sandhitsu R. ; Xie, Long ; Wisse, Laura E.M. LU orcid ; Kelley, Melissa ; Lane, Jacqueline ; Sherin, Monica ; Dicalogero, Michael ; Nasrallah, Ilya and Detre, John , et al. (2023) In Brain Communications 5(5).
Abstract

Functional disruption of the medial temporal lobe-dependent networks is thought to underlie episodic memory deficits in aging and Alzheimer's disease. Previous studies revealed that the anterior medial temporal lobe is more vulnerable to pathological and neurodegenerative processes in Alzheimer's disease. In contrast, cognitive and structural imaging literature indicates posterior, as opposed to anterior, medial temporal lobe vulnerability in normal aging. However, the extent to which Alzheimer's and aging-related pathological processes relate to functional disruption of the medial temporal lobe-dependent brain networks is poorly understood. To address this knowledge gap, we examined functional connectivity alterations in the medial... (More)

Functional disruption of the medial temporal lobe-dependent networks is thought to underlie episodic memory deficits in aging and Alzheimer's disease. Previous studies revealed that the anterior medial temporal lobe is more vulnerable to pathological and neurodegenerative processes in Alzheimer's disease. In contrast, cognitive and structural imaging literature indicates posterior, as opposed to anterior, medial temporal lobe vulnerability in normal aging. However, the extent to which Alzheimer's and aging-related pathological processes relate to functional disruption of the medial temporal lobe-dependent brain networks is poorly understood. To address this knowledge gap, we examined functional connectivity alterations in the medial temporal lobe and its immediate functional neighbourhood-the Anterior-Temporal and Posterior-Medial brain networks-in normal agers, individuals with preclinical Alzheimer's disease and patients with Mild Cognitive Impairment or mild dementia due to Alzheimer's disease. In the Anterior-Temporal network and in the perirhinal cortex, in particular, we observed an inverted 'U-shaped' relationship between functional connectivity and Alzheimer's stage. According to our results, the preclinical phase of Alzheimer's disease is characterized by increased functional connectivity between the perirhinal cortex and other regions of the medial temporal lobe, as well as between the anterior medial temporal lobe and its one-hop neighbours in the Anterior-Temporal system. This effect is no longer present in symptomatic Alzheimer's disease. Instead, patients with symptomatic Alzheimer's disease displayed reduced hippocampal connectivity within the medial temporal lobe as well as hypoconnectivity within the Posterior-Medial system. For normal aging, our results led to three main conclusions: (i) intra-network connectivity of both the Anterior-Temporal and Posterior-Medial networks declines with age; (ii) the anterior and posterior segments of the medial temporal lobe become increasingly decoupled from each other with advancing age; and (iii) the posterior subregions of the medial temporal lobe, especially the parahippocampal cortex, are more vulnerable to age-associated loss of function than their anterior counterparts. Together, the current results highlight evolving medial temporal lobe dysfunction in Alzheimer's disease and indicate different neurobiological mechanisms of the medial temporal lobe network disruption in aging versus Alzheimer's disease.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
aging, Alzheimer's disease, AT network, medial temporal lobe connectivity, PM network
in
Brain Communications
volume
5
issue
5
article number
fcad245
publisher
Oxford University Press
external identifiers
  • scopus:85174387010
  • pmid:37767219
ISSN
2632-1297
DOI
10.1093/braincomms/fcad245
language
English
LU publication?
yes
additional info
Publisher Copyright: © 2023 The Author(s). Published by Oxford University Press on behalf of the Guarantors of Brain.
id
2700358a-3eda-4014-9d03-aec0e1267b51
date added to LUP
2023-12-18 15:06:19
date last changed
2024-06-12 08:32:17
@article{2700358a-3eda-4014-9d03-aec0e1267b51,
  abstract     = {{<p>Functional disruption of the medial temporal lobe-dependent networks is thought to underlie episodic memory deficits in aging and Alzheimer's disease. Previous studies revealed that the anterior medial temporal lobe is more vulnerable to pathological and neurodegenerative processes in Alzheimer's disease. In contrast, cognitive and structural imaging literature indicates posterior, as opposed to anterior, medial temporal lobe vulnerability in normal aging. However, the extent to which Alzheimer's and aging-related pathological processes relate to functional disruption of the medial temporal lobe-dependent brain networks is poorly understood. To address this knowledge gap, we examined functional connectivity alterations in the medial temporal lobe and its immediate functional neighbourhood-the Anterior-Temporal and Posterior-Medial brain networks-in normal agers, individuals with preclinical Alzheimer's disease and patients with Mild Cognitive Impairment or mild dementia due to Alzheimer's disease. In the Anterior-Temporal network and in the perirhinal cortex, in particular, we observed an inverted 'U-shaped' relationship between functional connectivity and Alzheimer's stage. According to our results, the preclinical phase of Alzheimer's disease is characterized by increased functional connectivity between the perirhinal cortex and other regions of the medial temporal lobe, as well as between the anterior medial temporal lobe and its one-hop neighbours in the Anterior-Temporal system. This effect is no longer present in symptomatic Alzheimer's disease. Instead, patients with symptomatic Alzheimer's disease displayed reduced hippocampal connectivity within the medial temporal lobe as well as hypoconnectivity within the Posterior-Medial system. For normal aging, our results led to three main conclusions: (i) intra-network connectivity of both the Anterior-Temporal and Posterior-Medial networks declines with age; (ii) the anterior and posterior segments of the medial temporal lobe become increasingly decoupled from each other with advancing age; and (iii) the posterior subregions of the medial temporal lobe, especially the parahippocampal cortex, are more vulnerable to age-associated loss of function than their anterior counterparts. Together, the current results highlight evolving medial temporal lobe dysfunction in Alzheimer's disease and indicate different neurobiological mechanisms of the medial temporal lobe network disruption in aging versus Alzheimer's disease.</p>}},
  author       = {{Hrybouski, Stanislau and Das, Sandhitsu R. and Xie, Long and Wisse, Laura E.M. and Kelley, Melissa and Lane, Jacqueline and Sherin, Monica and Dicalogero, Michael and Nasrallah, Ilya and Detre, John and Yushkevich, Paul A. and Wolk, David A.}},
  issn         = {{2632-1297}},
  keywords     = {{aging; Alzheimer's disease; AT network; medial temporal lobe connectivity; PM network}},
  language     = {{eng}},
  number       = {{5}},
  publisher    = {{Oxford University Press}},
  series       = {{Brain Communications}},
  title        = {{Aging and Alzheimer's disease have dissociable effects on local and regional medial temporal lobe connectivity}},
  url          = {{http://dx.doi.org/10.1093/braincomms/fcad245}},
  doi          = {{10.1093/braincomms/fcad245}},
  volume       = {{5}},
  year         = {{2023}},
}