Longitudinal functional connectivity during rest and task is differentially related to Alzheimer’s pathology and episodic memory in older adults

Changes in functional connectivity (FC) strength involving the medial temporal lobe (MTL) and posteromedial cortex (PMC) are related to early Alzheimer's pathology and alterations in episodic memory performance in cognitively unimpaired older adults, but their dynamics remain unclear. We examined how longitudinal changes in FC involving MTL and PMC during resting-state, episodic memory encoding, and retrieval relate to subsequent amyloid- and tau-PET burden, longitudinal episodic memory performance, and the APOE4 genotype in 152 cognitively unimpaired older adults from the PREVENT-AD cohort. We found APOE4- and fMRI paradigm-dependent associations of change in FC strength with pathology burden and change in episodic memory performance. Decreasing FC over time, or "hypoconnectivity", within PMC during rest in APOE4 carriers and during retrieval in APOE4 non-carriers was related to more amyloid and tau, respectively. Conversely, increasing FC over time, or "hyperconnectivity", within MTL during encoding in APOE4 carriers and between MTL and PMC during retrieval independent of APOE4 status was related to more tau. Further, increasing FC between MTL and PMC during rest, unlike during encoding, was beneficial for episodic memory. Our study highlights that pathology-related episodic memory network changes manifest differently during rest and task and have differential implications for episodic memory trajectories.

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Publication Details

Journal
Scientific Reports
Published
2025-11-04
DOI
https://doi.org/10.1038/s41598-025-21596-0
Primary Topic
Functional Brain Connectivity Studies
Type
article
Field-Weighted Citation Impact
0.00

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article

Longitudinal functional connectivity during rest and task is differentially related to Alzheimer’s pathology and episodic memory in older adults

Andrée‐Ann Baril, Christian Bocti, Jennifer Tremblay‐Mercier, Judes Poirier et al.
Scientific Reports
Functional Brain Connectivity Studies
article

Longitudinal functional connectivity during rest and task is differentially related to Alzheimer’s pathology and episodic memory in older adults

Andrée‐Ann Baril, Christian Bocti, Jennifer Tremblay‐Mercier, Judes Poirier, Alan C. Evans, Étienne Vachon‐Presseau, Alexa Pichet Binette, Mohamed Badawy, M. Mallar Chakravarty, Jordana Remz, Anne Maaß, Maiya R. Geddes, Jean‐Paul Soucy, Yasser Ituria‐Medina, Christine Tardif, Sylvain Baillet, Lisa Marie Munter, Maxime Descoteaux, Taylor W. Schmitz, Larissa Fischer, Danilo Bzdok, Mahsa Dadar, M. Natasha Rajah, Rick Hoge, Jenna N. Adams, John C.S. Breitner, D. Louis Collins, Bellec Pierre, Sylvia Villeneuve, Véronique D. Bohbot, Gerhard Multhaup, Robert Laforce, Claudine Joëlle Gauthier, Eóin N. Molloy, Pedro Rosa‐Neto, Simon Ducharme, Nathan Spreng
article en

Abstract

Changes in functional connectivity (FC) strength involving the medial temporal lobe (MTL) and posteromedial cortex (PMC) are related to early Alzheimer's pathology and alterations in episodic memory performance in cognitively unimpaired older adults, but their dynamics remain unclear. We examined how longitudinal changes in FC involving MTL and PMC during resting-state, episodic memory encoding, and retrieval relate to subsequent amyloid- and tau-PET burden, longitudinal episodic memory performance, and the APOE4 genotype in 152 cognitively unimpaired older adults from the PREVENT-AD cohort. We found APOE4- and fMRI paradigm-dependent associations of change in FC strength with pathology burden and change in episodic memory performance. Decreasing FC over time, or "hypoconnectivity", within PMC during rest in APOE4 carriers and during retrieval in APOE4 non-carriers was related to more amyloid and tau, respectively. Conversely, increasing FC over time, or "hyperconnectivity", within MTL during encoding in APOE4 carriers and between MTL and PMC during retrieval independent of APOE4 status was related to more tau. Further, increasing FC between MTL and PMC during rest, unlike during encoding, was beneficial for episodic memory. Our study highlights that pathology-related episodic memory network changes manifest differently during rest and task and have differential implications for episodic memory trajectories.

Scientific ReportsVol. 15(1)
Western University (CA), Université de Sherbrooke (CA), Lund University (SE), University of California, Irvine (US), Douglas Mental Health University Institute (CA), German Center for Neurodegenerative Diseases (DE), Institut Universitaire de Gériatrie de Montréal (CA), Université Laval (CA), McGill University (CA), Toronto Metropolitan University (CA), Concordia University (CA), Université de Montréal (CA), Otto-von-Guericke-Universität Magdeburg (DE)
Deutsche Forschungsgemeinschaft
Openalex Percentile: Top 68%
Functional Brain Connectivity Studies
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