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@ARTICLE{Petersen:1024693,
      author       = {Petersen, Marvin and Coenen, Mirthe and DeCarli, Charles
                      and De Luca, Alberto and van der Lelij, Ewoud and Barkhof,
                      Frederik and Benke, Thomas and Chen, Christopher P. L. H.
                      and Dal-Bianco, Peter and Dewenter, Anna and Duering, Marco
                      and Enzinger, Christian and Ewers, Michael and Exalto, Lieza
                      G. and Fletcher, Evan F. and Franzmeier, Nicolai and Hilal,
                      Saima and Hofer, Edith and Koek, Huiberdina L. and Maier,
                      Andrea B. and Maillard, Pauline M. and McCreary, Cheryl R.
                      and Papma, Janne M. and Pijnenburg, Yolande A. L. and
                      Rubinski, Anna and Schmidt, Reinhold and Smith, Eric E. and
                      Steketee, Rebecca M. E. and van den Berg, Esther and van der
                      Flier, Wiesje M. and Venkatraghavan, Vikram and Vernooij,
                      Meike W. and Venketasubramanian, Narayanaswamy and Wolters,
                      Frank J. and Xin, Xu and Horn, Andreas and Patil, Kaustubh
                      R. and Eickhoff, Simon B. and Thomalla, Götz and Biesbroek,
                      J. Matthijs and Biessels, Geert Jan and Cheng, Bastian},
      title        = {{E}nhancing {C}ognitive {P}erformance {P}rediction through
                      {W}hite {M}atter {H}yperintensity {D}isconnectivity
                      {A}ssessment: {A} {M}ulticenter {L}esion {N}etwork {M}apping
                      {A}nalysis of 3,485 {M}emory {C}linic {P}atients},
      reportid     = {FZJ-2024-02366},
      year         = {2024},
      abstract     = {Introduction: White matter hyperintensities of presumed
                      vascular origin (WMH) are associated with cognitive
                      impairment and are a key imaging marker in evaluating
                      cognitive health. However, WMH volume alone does not fully
                      account for the extent of cognitive deficits and the
                      mechanisms linking WMH to these deficits remain unclear. We
                      propose that lesion network mapping (LNM), enabling the
                      inference of brain networks disconnected by lesions,
                      represents a promising technique for enhancing our
                      understanding of the role of WMH in cognitive disorders. Our
                      study employed this approach to test the following
                      hypotheses: (1) LNM-informed markers surpass WMH volumes in
                      predicting cognitive performance, and (2) WMH contributing
                      to cognitive impairment map to specific brain
                      networks.Methods $\&$ results: We analyzed cross-sectional
                      data of 3,485 patients from 10 memory clinic cohorts within
                      the Meta VCI Map Consortium, using harmonized test results
                      in 4 cognitive domains and WMH segmentations. WMH
                      segmentations were registered to a standard space and mapped
                      onto existing normative structural and functional brain
                      connectome data. We employed LNM to quantify WMH
                      connectivity across 480 atlas-based gray and white matter
                      regions of interest (ROI), resulting in ROI-level structural
                      and functional LNM scores. The capacity of total and
                      regional WMH volumes and LNM scores in predicting cognitive
                      function was compared using ridge regression models in a
                      nested cross-validation. LNM scores predicted performance in
                      three cognitive domains (attention and executive function,
                      information processing speed, and verbal memory)
                      significantly better than WMH volumes. LNM scores did not
                      improve prediction for language functions. ROI-level
                      analysis revealed that higher LNM scores, representing
                      greater disruptive effects of WMH on regional connectivity,
                      in gray and white matter regions of the dorsal and ventral
                      attention networks were associated with lower cognitive
                      performance.Conclusion: WMH-related brain network
                      disconnectivity significantly improves the prediction of
                      current cognitive performance in memory clinic patients
                      compared to WMH volume as a traditional imaging marker of
                      cerebrovascular disease. This highlights the crucial role of
                      network effects, particularly in attention-related brain
                      regions, improving our understanding of vascular
                      contributions to cognitive impairment. Moving forward,
                      refining WMH information with connectivity data could
                      contribute to patient-tailored therapeutic interventions and
                      facilitate the identification of subgroups at risk of
                      cognitive disorders.},
      cin          = {INM-7},
      cid          = {I:(DE-Juel1)INM-7-20090406},
      pnm          = {5252 - Brain Dysfunction and Plasticity (POF4-525) / 5253 -
                      Neuroimaging (POF4-525)},
      pid          = {G:(DE-HGF)POF4-5252 / G:(DE-HGF)POF4-5253},
      typ          = {PUB:(DE-HGF)25},
      doi          = {10.1101/2024.03.28.24305007},
      url          = {https://juser.fz-juelich.de/record/1024693},
}