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<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 <i>APOE4</i> genotype in 152 cognitively unimpaired older adults from the PREVENT-AD cohort. We found <i>APOE4-</i> 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 <i>APOE4</i> carriers and during retrieval in <i>APOE4</i> non-carriers was related to more amyloid and tau, respectively. Conversely, increasing FC over time, or “hyperconnectivity”, within MTL during encoding in <i>APOE4</i> carriers and between MTL and PMC during retrieval independent of <i>APOE4</i> 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>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年11月4日

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

摘要

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.