TY  - JOUR
AU  - Fischer, Larissa
AU  - Adams, Jenna N
AU  - Molloy, Eóin N.
AU  - Tremblay-Mercier, Jennifer
AU  - Remz, Jordana
AU  - Binette, Alexa Pichet
AU  - Rajah, M Natasha
AU  - Villeneuve, Sylvia
AU  - Maass, Anne
TI  - Longitudinal functional connectivity during rest and task is differentially related to Alzheimer's pathology and episodic memory in older adults.
JO  - Scientific reports
VL  - 15
IS  - 1
SN  - 2045-2322
CY  - [London]
PB  - Springer Nature
M1  - DZNE-2025-01227
SP  - 38499
PY  - 2025
AB  - 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.
KW  - Humans
KW  - Memory, Episodic
KW  - Alzheimer Disease: physiopathology
KW  - Alzheimer Disease: pathology
KW  - Alzheimer Disease: diagnostic imaging
KW  - Alzheimer Disease: metabolism
KW  - Aged
KW  - Female
KW  - Male
KW  - Magnetic Resonance Imaging
KW  - Apolipoprotein E4: genetics
KW  - Rest: physiology
KW  - Temporal Lobe: physiopathology
KW  - Temporal Lobe: diagnostic imaging
KW  - Temporal Lobe: pathology
KW  - tau Proteins: metabolism
KW  - Longitudinal Studies
KW  - Aged, 80 and over
KW  - Positron-Emission Tomography
KW  - Middle Aged
KW  - APOE4 (Other)
KW  - Aging (Other)
KW  - Alzheimer’s disease (Other)
KW  - Episodic memory (Other)
KW  - Functional connectivity (Other)
KW  - fMRI (Other)
KW  - Apolipoprotein E4 (NLM Chemicals)
KW  - tau Proteins (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:41188354
DO  - DOI:10.1038/s41598-025-21596-0
UR  - https://pub.dzne.de/record/281854
ER  -