% IMPORTANT: The following is UTF-8 encoded. This means that in the presence % of non-ASCII characters, it will not work with BibTeX 0.99 or older. % Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or % “biber”. @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}, }