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@INPROCEEDINGS{Gatzen:283116,
      author       = {Gatzen, Julia and Fischer, Larissa and Behrenbruch, Niklas
                      and Schumann-Werner, Beate and Schwarck, Svenja and Molloy,
                      Eóin N. and Hochkeppler, Anne and Garcia-Garcia, Berta and
                      Buechel, Anna-Therese and Incesoy, Enise I and Rullmann,
                      Michael and Patt, Marianne and Schildan, Andreas and
                      Stephens, Andrew W. and Behnisch, Gusalija and Morgado,
                      Barbara and Esselmann, Hermann and Seidenbecher, Constanze
                      I. and Schott, Björn H. and Barthel, Henryk and Sabri,
                      Osama and Wiltfang, Jens and Kreissl, Michael C. and Düzel,
                      Emrah and Maass, Anne},
      title        = {{E}pisodic memory network connectivity with aging and
                      {A}lzheimer’s disease pathology in cognitively unimpaired
                      older adults},
      journal      = {Alzheimer's and dementia},
      volume       = {21},
      number       = {S7},
      issn         = {1552-5260},
      reportid     = {DZNE-2026-00012},
      pages        = {e108678},
      year         = {2025},
      abstract     = {Background:Regions of the medial temporal lobe and
                      posteromedial cortex are crucial for episodic memory and are
                      among the first to be affected by Alzheimer´s disease (AD)
                      pathology. Hyperconnectivity in association with amyloid and
                      tau pathology has been found in preclinical stages of AD,
                      and may be compensatory or detrimental to memory function.
                      Aiming to identify distinct connections displaying aberrant
                      resting-state functional connectivity (rsFC), we
                      hypothesized lower rsFC with higher age in non-pathological
                      aging, and higher rsFC with higher pathology burden,
                      especially in APOE4 carriers.Method:In this preregistered
                      study, we analysed cross-sectional resting-state fMRI data
                      and blood- and PET-markers of amyloid, tau and APOE status
                      from an observational aging cohort (SFB1436). RsFC strength
                      was examined between predefined ROIs. The sample included
                      187 cognitively unimpaired older adults (71±7years, 92
                      female, 44 APOE4 carrier). We investigated associations
                      between rsFC, AD pathology burden, and CAG (cognitive age
                      gap) and potential APOE interactions. Multiple regression
                      models and a moderation analysis with rsFC strength were
                      used. An A-T- subcohort was formed to investigate the effect
                      of age on rsFC and to differentiate it from the effect of
                      pathology.Result:We found a significant association between
                      higher blood-based pathology and low rsFC in the right
                      posterior hippocampus to bilateral subgenual medial
                      prefrontal cortex (mPFC). No significant association was
                      observed between rsFC and tau-PET burden, APOE4 status or
                      age (within A-T-subcohort). Additionally, there was no
                      significant effect of pathology on CAG. Furthermore, we
                      found no evidence of rsFC moderating the relationship
                      between pathology and CAG.Conclusion:Our results do not
                      support the initial hypothesis, which predicted
                      hyperconnectivity in distinct brain regions with high
                      pathology. This could be due to relatively low overall
                      pathology burden, consistent with an early preclinical stage
                      of potential disease progression. This interpretation is
                      further supported by the absence of significant associations
                      between pathology or rsFC strength and memory performance.
                      We identified lower rsFC strength in two distinct
                      connections with higher blood-based pathology. These
                      alterations were not observed in the A-T- subcohort,
                      suggesting it to be an early marker differentiating
                      pathological from healthy aging.},
      month         = {Jul},
      date          = {2025-07-27},
      organization  = {Alzheimer’s Association
                       International Conference, Toronto
                       (Canada), 27 Jul 2025 - 31 Jul 2025},
      cin          = {AG Maaß / AG Düzel / AG Wiltfang / AG Fischer / Core MR
                      PET},
      ddc          = {610},
      cid          = {I:(DE-2719)1311001 / I:(DE-2719)5000006 /
                      I:(DE-2719)1410006 / I:(DE-2719)1410002 /
                      I:(DE-2719)1340016},
      pnm          = {353 - Clinical and Health Care Research (POF4-353) / 352 -
                      Disease Mechanisms (POF4-352) / 899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-353 / G:(DE-HGF)POF4-352 /
                      G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)1 / PUB:(DE-HGF)16},
      doi          = {10.1002/alz70861_108678},
      url          = {https://pub.dzne.de/record/283116},
}