Longitudinal functional connectivity during rest and task is differentially related to Alzheimer’s pathology and episodic memory in older adults
Open Access
- 4 November 2025
- journal article
- research article
- Published by Springer Nature in Scientific Reports
- Vol. 15 (1) , 1-14
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.Keywords
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Funding Information
- Otto-von-Guericke-Universität Magdeburg
This publication has 98 references indexed in Scilit:
- Reactivation and consolidation of memory traces during post‐encoding rest across the adult lifespanAnnals of Clinical and Translational Neurology, 2025
- Longitudinal blood biomarker trajectories in preclinical Alzheimer's diseaseAlzheimer's & Dementia, 2023
- The relationship between resting‐state amplitude fluctuations and memory‐related deactivations of the default mode network in young and older adultsHuman Brain Mapping, 2023
- A comprehensive score reflecting memory‐related fMRI activations and deactivations as potential biomarker for neurocognitive agingHuman Brain Mapping, 2021
- Diagnosis and Management of Dementia: ReviewJAMA, 2019
- Functional connectivity along the anterior–posterior axis of hippocampal subfields in the ageing human brainHippocampus, 2019
- The retrosplenial cortex: A memory gateway between the cortical default mode network and the medial temporal lobeHuman Brain Mapping, 2018
- Altered memory-related functional connectivity of the anterior and posterior hippocampus in older adults at increased genetic risk for Alzheimer's diseaseHuman Brain Mapping, 2015
- Prevalence of Cerebral Amyloid Pathology in Persons Without DementiaJAMA, 2015
- Functional connectivity with the hippocampus during successful memory formationHippocampus, 2005