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@INPROCEEDINGS{Fischer:283067,
      author       = {Fischer, Larissa and Adams, Jenna N and Molloy, Eóin N.
                      and Tremblay-Mercier, Jennifer and Remz, Jordana and
                      Binette, Alexa Pichet and Rajah, Natasha and Villeneuve,
                      Sylvia and Maass, Anne},
      collaboration = {Group, PREVENT-AD Research},
      title        = {{C}hange in functional connectivity strength during rest
                      and encoding is differentially related to {A}lzheimer's
                      pathology and memory depending on {APOE} genotype},
      journal      = {Alzheimer's and dementia},
      volume       = {21},
      number       = {Suppl 2},
      issn         = {1552-5260},
      reportid     = {DZNE-2025-01474},
      pages        = {e100192},
      year         = {2025},
      abstract     = {The medial temporal lobe (MTL) and posteromedial cortex
                      (PMC) are essential for episodic memory and affected early
                      by Alzheimer's pathology, particularly in APOE4 carriers.
                      Functional connectivity (FC) changes within and between MTL
                      and PMC could be detrimental or beneficial for cognition.
                      However, the relation of those changes to Alzheimer's
                      pathology and memory performance is unclear and most studies
                      assess FC only during rest. We hypothesized that increasing
                      FC strength would be associated with higher pathology
                      burden, especially in APOE4 carriers.In this preregistered
                      study, we analysed longitudinal 3-Tesla fMRI over up to 4
                      years and cross-sectional amyloid-beta and tau PET
                      (PREVENT-AD cohort; details in Figure 1). We assessed
                      changes in resting-state FC (RSFC) and task-FC during
                      intentional object-location encoding within (ΔFCPMC,
                      ΔFCMTL) and between MTL and PMC (ΔFCMTL-PMC). The sample
                      included 152 cognitively unimpaired older adults
                      (63±5years, 102 female, 59 APOE4). We investigated
                      associations between ΔFC strength with i) pathology burden
                      and ii) change in delayed memory (RBANS composite score and
                      fMRI-task object recognition), and interactions with APOE
                      genotype. We used multiple regression and linear mixed
                      models including APOE, age, sex and education.We found ΔFC
                      by APOE interactions predicting pathology. Specifically,
                      declining RSFCPMC (p = 0.038; Figure 2a) was related to more
                      global amyloid in APOE4 carriers only. In contrast,
                      increasing encoding-FCMTL was related to more entorhinal tau
                      in APOE4 carriers only (p = 0.032, Figure 2b). Regarding
                      cognition, regardless of APOE status, increasing
                      encoding-FCPMC was related to decreasing RBANS (p = 0.018)
                      performance and object recognition (p = 0.001). Finally,
                      increasing RSFCMTL-PMC was related to increasing RBANS
                      performance (p = 0.032; Figure 3a), but increasing
                      encoding-FCMTL-PMC was related to decreasing object
                      recognition (p = 0.014; Figure 3b).Our study shows
                      APOE-dependent and region-specific associations of ΔFC
                      strength within and between episodic memory areas with
                      pathology burden and memory performance. Notably,
                      associations differed between RSFC and task-FC. In APOE4
                      carriers, longitudinally increasing FC or
                      'hyperconnectivity' within MTL during encoding was related
                      to tau in line with our hypothesis. However, in PMC,
                      longitudinally decreasing FC during rest was related to more
                      amyloid, indicating a disconnection in PMC regions. Our
                      study highlights that pathology-related network changes
                      manifest differentially during rest and task (memory
                      encoding).},
      month         = {Jul},
      date          = {2025-07-27},
      organization  = {Alzheimer’s Association
                       International Conference, Toronto
                       (Canada), 27 Jul 2025 - 31 Jul 2025},
      keywords     = {Humans / Female / Male / Magnetic Resonance Imaging /
                      Middle Aged / Biomarkers: metabolism / Apolipoprotein E4:
                      genetics / Aged / tau Proteins: metabolism /
                      Positron-Emission Tomography / Cross-Sectional Studies /
                      Alzheimer Disease: genetics / Alzheimer Disease: diagnostic
                      imaging / Alzheimer Disease: pathology / Amyloid
                      beta-Peptides: metabolism / Temporal Lobe: diagnostic
                      imaging / Temporal Lobe: pathology / Temporal Lobe:
                      metabolism / Longitudinal Studies / Neuropsychological Tests
                      / Biomarkers (NLM Chemicals) / Apolipoprotein E4 (NLM
                      Chemicals) / tau Proteins (NLM Chemicals) / Amyloid
                      beta-Peptides (NLM Chemicals)},
      cin          = {AG Maaß},
      ddc          = {610},
      cid          = {I:(DE-2719)1311001},
      pnm          = {353 - Clinical and Health Care Research (POF4-353)},
      pid          = {G:(DE-HGF)POF4-353},
      typ          = {PUB:(DE-HGF)1 / PUB:(DE-HGF)16},
      pubmed       = {pmid:41447082},
      pmc          = {pmc:PMC12739621},
      doi          = {10.1002/alz70856_100192},
      url          = {https://pub.dzne.de/record/283067},
}