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@INPROCEEDINGS{Tsvetanov:283069,
      author       = {Tsvetanov, Kamen A and Jones, P Simon and Malpetti, Maura
                      and Rittman, Timothy and Bouzigues, Arabella and van
                      Swieten, John and Jiskoot, Lize and Seelaar, Harro and
                      Borroni, Barbara and Premi, Enrico and Sanchez-Valle, Raquel
                      and Moreno, Fermin and Laforce, Robert and Graff, Caroline
                      and Synofzik, Matthis and Galimberti, Daniela and Masellis,
                      Mario and Tartaglia, Carmela and Finger, Elizabeth and
                      Vandenberghe, Rik and de Mendonça, Alexandre and
                      Tagliavini, Fabrizio and Santana, Isabel and Ducharme, Simon
                      and Butler, Christopher and Gerhard, Alexander and Levin,
                      Johannes and Otto, Markus and Sorbi, Sandro and Russell,
                      Lucy L and Rohrer, Jonathan D and Rowe, James B},
      collaboration = {Genetic FTD Initiative, GENFI},
      title        = {{S}tructure‐function decoupling in genetic frontotemporal
                      dementia},
      journal      = {Alzheimer's and dementia},
      volume       = {21},
      number       = {Suppl 2},
      issn         = {1552-5260},
      reportid     = {DZNE-2025-01476},
      pages        = {e100438},
      year         = {2025},
      abstract     = {Functional network integrity is important for maintaining
                      cognitive performance during the 10-20 year presymptomatic
                      period of frontotemporal dementia (FTD), conferring
                      resilience to advancing neuropathology and atrophy. The
                      extent to which functional integrity relies on preserved
                      structural connectivity is unclear. Here, we test the
                      relationship between functional connectivity and structural
                      connectivity, termed structure-function coupling, against
                      genetic risk for FTD and disease progression.We studied 56
                      symptomatic and 165 pre-symptomatic FTD-mutation carriers,
                      and 141 family members without mutations, from the GENFI
                      cohort. Diffusion weighted imaging and functional magnetic
                      resonance imaging (Siemens MR platforms) were acquired and
                      analysed using established approaches to quantify
                      participant-level structural and functional connectomes
                      (Figure 1-(1)). Connectomes were defined in the Brainnetome
                      Atlas and re-mapped onto a subcortical network and seven
                      resting-state networks based on the Yeo Networks (Figure
                      1-(2)). An inter-subject regularized canonical correlation
                      analysis (CCA) with permutation-based cross-validation was
                      used to jointly analyse the structural and functional
                      connectomes (Figure 1-(3-4)). Second-level analysis with
                      robust multiple linear regression models tested for
                      differences between non-carriers, pre-symptomatic carriers
                      and symptomatic carriers in the strength of association
                      between structural and functional CCA subject scores. Age,
                      sex, head motion and scanner site were included as
                      covariates.Canonical correlation analysis identified
                      significant components linking structural and functional
                      connectivity. The first component (r=0.656, p <0.001)
                      reflected a structural connectivity pattern with high
                      within- and between-networks loadings (Figure 1-(5)) with
                      strong within-networks functional connectivity and
                      weak-to-negative between-network functional connectivity
                      (Figure 1-(6)). This component associated structural
                      integrity with function segregation, whereby individuals
                      with high structural connectivity within and between
                      networks exhibit greater functional network segregation as
                      shown by strong within-network functional connectivity and
                      weak between network connectivity. The strength of this
                      structure-function coupling was greater for non-carriers
                      compared to pre-symptomatic carriers (Figure 1-(7)).
                      Symptomatic carriers showed minimal relationship between
                      structural and functional scores, indicating
                      structure-function decoupling, consistent with the
                      hypothesis that cognitive decline is triggered by critical
                      decoupling of previously synergistic neural systems.Our
                      findings demonstrate progressive de-coupling between
                      structural connectivity and functional segregation over the
                      course of genetic frontotemporal dementia. These results
                      have implications for designing pre-symptomatic
                      disease-modifying 'preventative' trials, supported by
                      imaging-based surrogate markers of neural system dynamics.},
      month         = {Jul},
      date          = {2025-07-27},
      organization  = {Alzheimer’s Association
                       International Conference, Toronto
                       (Canada), 27 Jul 2025 - 31 Jul 2025},
      keywords     = {Humans / Male / Female / Frontotemporal Dementia: genetics
                      / Frontotemporal Dementia: diagnostic imaging /
                      Frontotemporal Dementia: physiopathology / Frontotemporal
                      Dementia: pathology / Middle Aged / Magnetic Resonance
                      Imaging / Connectome / Biomarkers / Brain: physiopathology /
                      Brain: diagnostic imaging / Brain: pathology / Aged /
                      Disease Progression / Mutation: genetics / Adult / Cohort
                      Studies / Neural Pathways: physiopathology / Neural
                      Pathways: diagnostic imaging / Diffusion Magnetic Resonance
                      Imaging / Biomarkers (NLM Chemicals)},
      cin          = {AG Gasser / Clinical Research (Munich) / AG Levin},
      ddc          = {610},
      cid          = {I:(DE-2719)1210000 / I:(DE-2719)1111015 /
                      I:(DE-2719)1111016},
      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:41447690},
      pmc          = {pmc:PMC12740290},
      doi          = {10.1002/alz70856_100438},
      url          = {https://pub.dzne.de/record/283069},
}