Enhancing Cognitive Performance Prediction through White Matter Hyperintensity Connectivity Assessment: A Multicenter Lesion Network Mapping Analysis of 3,485 Memory Clinic Patients.

Autor:	Petersen M; Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Coenen M; University Medical Center Utrecht Brain Center, Utrecht, The Netherlands., DeCarli C; University of California at Davis, USA., De Luca A; University Medical Center Utrecht Brain Center, Utrecht, The Netherlands.; Image Sciences Institute, Division Imaging and Oncology, UMC Utrecht., van der Lelij E; University Medical Center Utrecht Brain Center, Utrecht, The Netherlands., Barkhof F; Department of Radiology & Nuclear Medicine, Amsterdam UMC, Vrije Universiteit, the Netherlands.; Queen Square Institute of Neurology and Centre for Medical Image Computing, University College London, UK., Benke T; Clinic of Neurology, Medical University Innsbruck, Austria., Chen CPLH; Departments of Pharmacology and Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.; Memory, Aging and Cognition Center, National University Health System, Singapore., Dal-Bianco P; Medical University Vienna, Austria., Dewenter A; Institute for Stroke and Dementia Research (ISD), LMU University Hospital, LMU Munich, Munich, Germany., Duering M; Institute for Stroke and Dementia Research (ISD), LMU University Hospital, LMU Munich, Munich, Germany.; Medical Image Analysis Center (MIAC) and Department of Biomedical Engineering, University of Basel, Basel, Switzerland., Enzinger C; Division of General Neurology, Department of Neurology, Medical University Graz, Austria.; Division of Neuroradiology, Interventional and Vascular Radiology, Department of Radiology, Medical University of Graz, Austria., Ewers M; Institute for Stroke and Dementia Research (ISD), LMU University Hospital, LMU Munich, Munich, Germany., Exalto LG; University Medical Center Utrecht Brain Center, Utrecht, The Netherlands., Fletcher EF; University of California at Davis, USA., Franzmeier N; Institute for Stroke and Dementia Research (ISD), LMU University Hospital, LMU Munich, Munich, Germany., Hilal S; Memory, Aging and Cognition Center, National University Health System, Singapore.; Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore., Hofer E; Division of Neurogeriatrics, Department of Neurology, Medical University of Graz, Austria.; Institute for Medical Informatics, Statistics and Documentation, Medical University of Graz, Austria., Koek HL; University Medical Center Utrecht Brain Center, Utrecht, The Netherlands.; Department of Geriatric Medicine, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands., Maier AB; Departments of Pharmacology and Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.; Memory, Aging and Cognition Center, National University Health System, Singapore., Maillard PM; University of California at Davis, USA., McCreary CR; Department of Clinical Neurosciences and Radiology and Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada., Papma JM; Alzheimer Center Erasmus MC, Erasmus MC University Medical Center, Rotterdam, The Netherlands.; Department of Neurology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.; Department of Internal Medicine, Erasmus MC University Medical Center, Rotterdam, The Netherlands., Pijnenburg YAL; Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands., Schmidt R; Division of Neurogeriatrics, Department of Neurology, Medical University of Graz, Austria.; Institute for Medical Informatics, Statistics and Documentation, Medical University of Graz, Austria., Smith EE; Department of Clinical Neurosciences and Radiology and Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada., Steketee RME; Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands.; Amsterdam Neuroscience, Neurodegeneration, Amsterdam, The Netherlands., van den Berg E; Alzheimer Center Erasmus MC, Erasmus MC University Medical Center, Rotterdam, The Netherlands.; Department of Neurology, Erasmus MC University Medical Center, Rotterdam, The Netherlands., van der Flier WM; Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands.; Amsterdam Neuroscience, Neurodegeneration, Amsterdam, The Netherlands., Venkatraghavan V; Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands.; Amsterdam Neuroscience, Neurodegeneration, Amsterdam, The Netherlands., Venketasubramanian N; Memory, Aging and Cognition Center, National University Health System, Singapore.; Raffles Neuroscience Center, Raffles Hospital, Singapore, Singapore., Vernooij MW; Alzheimer Center Erasmus MC, Erasmus MC University Medical Center, Rotterdam, The Netherlands.; Department of Radiology & Nuclear Medicine, Erasmus MC University Medical Center, Rotterdam, The Netherlands.; Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands., Wolters FJ; Department of Radiology & Nuclear Medicine, Erasmus MC University Medical Center, Rotterdam, The Netherlands.; Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands., Xu X; Memory, Aging and Cognition Center, National University Health System, Singapore.; School of Public Health and the Second Affiliated Hospital of School of Medicine, Zhejiang University, China., Horn A; Charité - Universitätsmedizin Berlin, Movement Disorders and Neuromodulation Unit, Department of Neurology with Experimental Neurology, 10117 Berlin, Germany.; Center for Brain Circuit Therapeutics, Department of Neurology, Psychiatry, and Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, USA., Patil KR; Institute for Systems Neuroscience, Medical Faculty, Heinrich-Heine University Düsseldorf, Düsseldorf, Germany.; Institute of Neuroscience and Medicine, Brain and Behaviour (INM-7), Research Center Jülich, Germany., Eickhoff SB; Institute for Systems Neuroscience, Medical Faculty, Heinrich-Heine University Düsseldorf, Düsseldorf, Germany.; Institute of Neuroscience and Medicine, Brain and Behaviour (INM-7), Research Center Jülich, Germany., Thomalla G; Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Biesbroek JM; University Medical Center Utrecht Brain Center, Utrecht, The Netherlands.; Department of Neurology, Diakonessenhuis Hospital, Utrecht, The Netherlands., Biessels GJ; University Medical Center Utrecht Brain Center, Utrecht, The Netherlands., Cheng B; Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Jazyk:	angličtina
Zdroj:	MedRxiv : the preprint server for health sciences [medRxiv] 2024 Apr 11. Date of Electronic Publication: 2024 Apr 11.
DOI:	10.1101/2024.03.28.24305007
Abstrakt:	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), enables to infer if brain networks are connected to lesions, and could be 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: Measures of WMH-related brain network connectivity significantly improve 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 attentionrelated 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. Competing Interests: F.B. is supported by the NIHR biomedical research center at UCLH. M.D. received honoraria for lectures from Bayer Vital and Sanofi Genzyme, Consultant for Hovid Berhad and Roche Pharma. G.T. has received fees as consultant or lecturer from Acandis, Alexion, Amarin, Bayer, Boehringer Ingelheim, BristolMyersSquibb/Pfizer, Daichi Sankyo, Portola, and Stryker outside the submitted work.
Databáze:	MEDLINE
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