Longitudinal functional connectivity during rest and task is differentially related to Alzheimer’s pathology and episodic memory in older adults
(2025) In Scientific Reports 15(1).- 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.... (More)
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.
(Less)
- author
- author collaboration
- organization
- publishing date
- 2025-12
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Aging, Alzheimer’s disease, APOE4, Episodic memory, fMRI, Functional connectivity
- in
- Scientific Reports
- volume
- 15
- issue
- 1
- article number
- 38499
- publisher
- Nature Publishing Group
- external identifiers
-
- scopus:105020893963
- pmid:41188354
- ISSN
- 2045-2322
- DOI
- 10.1038/s41598-025-21596-0
- language
- English
- LU publication?
- yes
- additional info
- .
- id
- eb4249d4-d0b1-468e-892c-c6fdb47cad2d
- date added to LUP
- 2025-12-11 13:32:40
- date last changed
- 2025-12-12 03:00:20
@article{eb4249d4-d0b1-468e-892c-c6fdb47cad2d,
abstract = {{<p>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.</p>}},
author = {{Fischer, Larissa and Adams, Jenna N. and Molloy, Eóin N. and Tremblay-Mercier, Jennifer and Remz, Jordana and Binette, Alexa Pichet and Rajah, M. Natasha and Villeneuve, Sylvia and Maass, Anne and Binette, Alexa Pichet and Laforce, Robert and Descoteaux, Maxime and Bocti, Christian and Vachon-Presseau, Etienne and Tardif, Christine and Spreng, Nathan and Soucy, Jean Paul and Schmitz, Taylor and Rosa-Neto, Pedro and Münter, Lisa Marie and Multhaup, Gerhard and Ituria-Medina, Yasser and Hoge, Rick and Geddes, Maiya R. and Gauthier, Claudine and Evans, Alan and Ducharme, Simon and Dadar, Mahsa and Collins, D. Louis and Chakravarty, Mallar and Bzdok, Danilo and Bohbot, Véronique and Bellec, Pierre and Baril, Andrée Ann and Baillet, Sylvain and Badawy, Mohamed and Breitner, John C.S. and Poirier, Judes}},
issn = {{2045-2322}},
keywords = {{Aging; Alzheimer’s disease; APOE4; Episodic memory; fMRI; Functional connectivity}},
language = {{eng}},
number = {{1}},
publisher = {{Nature Publishing Group}},
series = {{Scientific Reports}},
title = {{Longitudinal functional connectivity during rest and task is differentially related to Alzheimer’s pathology and episodic memory in older adults}},
url = {{http://dx.doi.org/10.1038/s41598-025-21596-0}},
doi = {{10.1038/s41598-025-21596-0}},
volume = {{15}},
year = {{2025}},
}