{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T07:14:30Z","timestamp":1770794070781,"version":"3.50.0"},"posted":{"date-parts":[[2026,2,4]]},"group-title":"Neurology","reference-count":56,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T00:00:00Z","timestamp":1770163200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,2,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  Following observations from a pilot study that, contrary to expectations, indicated that critical white matter (WM) connections were not more vulnerable to either SVD or AD pathologies than non-critical connections, we set out to systematically evaluate the relation between these pathologies and both connections types. For patients with CADASIL (n=59), Mixed pathology (n=57) and autosomal dominant AD (ADAD; n=50) we reconstructed WM networks based on diffusion tensor imaging and subsequently defined critical and non-critical connections. Associations between AD markers (CSF A\u03b2\n                  <jats:sup>42<\/jats:sup>\n                  , p-tau levels, estimated years of onset (EYO)) and SVD markers (WM hyperintensity (WMH) volume) and both connection types were tested with linear regression analyses. WMH volume showed equally strong associations to the strength of both critical and non-critical connections. A\u03b2-positivity, A\u03b2\n                  <jats:sup>42<\/jats:sup>\n                  levels, p-tau levels and EYO, while less strongly related to the strength of the WM connections, did consistently show similar effect sizes for both connection types. Sensitivity analyses using different definitions of connectivity yielded similar results. SVD burden influenced WM integrity more than AD, but we found no support for critical connections being more vulnerable to these disease effects than non-critical connections.\n                <\/jats:p>","DOI":"10.64898\/2026.02.03.26345446","type":"posted-content","created":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T02:10:35Z","timestamp":1770257435000},"source":"Crossref","is-referenced-by-count":0,"title":["Critical and non-critical connections not differently associated with either Alzheimer\u2019s disease or vascular pathologies"],"prefix":"10.64898","author":[{"given":"Naomi","family":"Vlegels","sequence":"first","affiliation":[{"name":"Department of Neurology and Neurosurgery, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht, the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bruno M.","family":"de Brito Robalo","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurosurgery, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht, the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alberto","family":"de Luca","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurosurgery, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht, the Netherlands"},{"name":"Image Sciences Institute, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wiesje M.","family":"van der Flier","sequence":"additional","affiliation":[{"name":"Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands"},{"name":"Department of Epidemiology and Data Science, VU University Medical Center, Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"Dominantly Inherited Alzheimer Network (DIAN)","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Randall","family":"Bateman","sequence":"additional","affiliation":[{"name":"Department of Neurology, Washington University School of Medicine, St Louis, MO, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tammie L. S.","family":"Benzinger","sequence":"additional","affiliation":[{"name":"Mallinckrodt Institute of Radiology, Washington University School of Medicine, St Louis, MO, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlos","family":"Cruchaga","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA"},{"name":"NeuroGenomics and Informatics Center, Washington University School of Medicine, St. Louis, MO, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dave M.","family":"Cash","sequence":"additional","affiliation":[{"name":"Dementia Research Centre, Institute of Neurology, University College London, London, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroshi","family":"Mori","sequence":"additional","affiliation":[{"name":"Department of Clinical Neuroscience, Medical School, Osaka Metropolitan University, Nagaoka Sutoku University, Abenoku, Osaka, Nagaoka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Igor","family":"Yakushev","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Technical University of Munich, Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco","family":"Duering","sequence":"additional","affiliation":[{"name":"Institute for Stroke and Dementia Research (ISD), University Hospital, LMU Munich, Germany"},{"name":"Medical Image Analysis Center (MIAC AG) and Department of Biomedical Engineering, University of Basel, Basel, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sofia","family":"Finsterwalder","sequence":"additional","affiliation":[{"name":"Institute for Stroke and Dementia Research (ISD), University Hospital, LMU Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benno","family":"Gesierich","sequence":"additional","affiliation":[{"name":"Institute for Stroke and Dementia Research (ISD), University Hospital, LMU Munich, Germany"},{"name":"Medical Image Analysis Center (MIAC AG) and Department of Biomedical Engineering, University of Basel, Basel, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Kopczak","sequence":"additional","affiliation":[{"name":"Institute for Stroke and Dementia Research (ISD), University Hospital, LMU Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yael D.","family":"Reijmer","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurosurgery, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht, the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Geert Jan","family":"Biessels","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurosurgery, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht, the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2026020606504193000_2026.02.03.26345446v1.1","doi-asserted-by":"publisher","DOI":"10.1186\/s12883-014-0254-4"},{"key":"2026020606504193000_2026.02.03.26345446v1.2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1202753"},{"key":"2026020606504193000_2026.02.03.26345446v1.3","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24758"},{"key":"2026020606504193000_2026.02.03.26345446v1.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2019.116443"},{"key":"2026020606504193000_2026.02.03.26345446v1.5","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2575"},{"key":"2026020606504193000_2026.02.03.26345446v1.6","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awy229"},{"key":"2026020606504193000_2026.02.03.26345446v1.7","doi-asserted-by":"publisher","DOI":"10.1002\/hbm.22830"},{"key":"2026020606504193000_2026.02.03.26345446v1.8","doi-asserted-by":"publisher","DOI":"10.1002\/hbm.23069"},{"key":"2026020606504193000_2026.02.03.26345446v1.9","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2021.604119"},{"key":"2026020606504193000_2026.02.03.26345446v1.10","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awt184"},{"key":"2026020606504193000_2026.02.03.26345446v1.11","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2017.12.007"},{"key":"2026020606504193000_2026.02.03.26345446v1.12","doi-asserted-by":"publisher","DOI":"10.1177\/1747493020963387"},{"key":"2026020606504193000_2026.02.03.26345446v1.13","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3007901"},{"key":"2026020606504193000_2026.02.03.26345446v1.14","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12150"},{"key":"2026020606504193000_2026.02.03.26345446v1.15","doi-asserted-by":"publisher","DOI":"10.31887\/DCNS.2018.20.2\/AGRIFFA"},{"key":"2026020606504193000_2026.02.03.26345446v1.16","doi-asserted-by":"publisher","DOI":"10.1016\/j.numecd.2018.07.008"},{"key":"2026020606504193000_2026.02.03.26345446v1.17","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1002582"},{"key":"2026020606504193000_2026.02.03.26345446v1.18","doi-asserted-by":"publisher","DOI":"10.1016\/j.nicl.2018.06.025"},{"key":"2026020606504193000_2026.02.03.26345446v1.19","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1203593109"},{"key":"2026020606504193000_2026.02.03.26345446v1.20","doi-asserted-by":"publisher","DOI":"10.1001\/jamapsychiatry.2013.1328"},{"key":"2026020606504193000_2026.02.03.26345446v1.21","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3539-11.2011"},{"key":"2026020606504193000_2026.02.03.26345446v1.22","doi-asserted-by":"publisher","DOI":"10.1002\/hbm.21032"},{"key":"2026020606504193000_2026.02.03.26345446v1.23","first-page":"4141","article-title":"\u2018NATURE \u00b7 VOL 383 \u00b7 24 OCTOBER 1996 LETTERS TO NATURE 7. Frani;ois\u2019","volume":"92","year":"1987","journal-title":"Earth Planet. Sci. Lett"},{"key":"2026020606504193000_2026.02.03.26345446v1.24","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2014.1482"},{"key":"2026020606504193000_2026.02.03.26345446v1.25","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.26054"},{"key":"2026020606504193000_2026.02.03.26345446v1.26","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000000612"},{"key":"2026020606504193000_2026.02.03.26345446v1.27","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24647"},{"key":"2026020606504193000_2026.02.03.26345446v1.28","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-180027"},{"key":"2026020606504193000_2026.02.03.26345446v1.29","unstructured":"Leemans, A. et al. (2009) \u2018ExploreDTI: a graphical toolbox for processing, analyzing, and visualizing diffusion MR data\u2019, in 17th Annual Meeting of Intl Soc Mag Reson Med. Hawaii, USA, p. 3537."},{"key":"2026020606504193000_2026.02.03.26345446v1.30","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.21890"},{"key":"2026020606504193000_2026.02.03.26345446v1.31","doi-asserted-by":"publisher","DOI":"10.1016\/j.nicl.2019.102048"},{"key":"2026020606504193000_2026.02.03.26345446v1.32","doi-asserted-by":"publisher","DOI":"10.1186\/alzrt213"},{"key":"2026020606504193000_2026.02.03.26345446v1.33","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(15)00463-8"},{"key":"2026020606504193000_2026.02.03.26345446v1.34","first-page":"62","article-title":"\u2018Otsu_1979_otsu_method\u2019, IEEE Transactions on Systems, Man, and Cybernetics","volume":"1","year":"1979","journal-title":"C"},{"key":"2026020606504193000_2026.02.03.26345446v1.35","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.62.7.1091"},{"key":"2026020606504193000_2026.02.03.26345446v1.36","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2017-316603"},{"key":"2026020606504193000_2026.02.03.26345446v1.37","unstructured":"R Core Team (2018) \u2018R: A language and environment for statistical computing. R Foundation for Statistical Computing\u2019. Vienna, Austria: R Foundation for Statistical Computing."},{"key":"2026020606504193000_2026.02.03.26345446v1.38","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e31828c2ee5"},{"key":"2026020606504193000_2026.02.03.26345446v1.39","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awu316"},{"key":"2026020606504193000_2026.02.03.26345446v1.40","doi-asserted-by":"publisher","DOI":"10.1002\/hbm.23186"},{"key":"2026020606504193000_2026.02.03.26345446v1.41","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2012.12.066"},{"key":"2026020606504193000_2026.02.03.26345446v1.42","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.27471"},{"key":"2026020606504193000_2026.02.03.26345446v1.43","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2009.03.024"},{"key":"2026020606504193000_2026.02.03.26345446v1.44","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2023.3618"},{"key":"2026020606504193000_2026.02.03.26345446v1.45","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2018.01178"},{"key":"2026020606504193000_2026.02.03.26345446v1.46","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.25165"},{"issue":"7","key":"2026020606504193000_2026.02.03.26345446v1.47","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1038\/s41582-018-0014-y","article-title":"From a Focal To a Global Perspective","volume":"14","year":"2018","journal-title":"Nature Reviews Neurology"},{"key":"2026020606504193000_2026.02.03.26345446v1.48","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2019.116137"},{"key":"2026020606504193000_2026.02.03.26345446v1.49","doi-asserted-by":"publisher","DOI":"10.1002\/hbm.23032"},{"key":"2026020606504193000_2026.02.03.26345446v1.50","doi-asserted-by":"publisher","DOI":"10.1002\/hbm.23479"},{"key":"2026020606504193000_2026.02.03.26345446v1.51","doi-asserted-by":"publisher","DOI":"10.1006\/nimg.2001.0978"},{"key":"2026020606504193000_2026.02.03.26345446v1.52","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4757-2719-7_14"},{"key":"2026020606504193000_2026.02.03.26345446v1.53","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2013.05.028"},{"key":"2026020606504193000_2026.02.03.26345446v1.54","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.26124"},{"key":"2026020606504193000_2026.02.03.26345446v1.55","doi-asserted-by":"publisher","DOI":"10.1016\/j.dadm.2017.01.003"},{"key":"2026020606504193000_2026.02.03.26345446v1.56","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-132561"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.02.03.26345446","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T14:50:49Z","timestamp":1770389449000},"score":1,"resource":{"primary":{"URL":"http:\/\/medrxiv.org\/lookup\/doi\/10.64898\/2026.02.03.26345446"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,4]]},"references-count":56,"URL":"https:\/\/doi.org\/10.64898\/2026.02.03.26345446","relation":{},"subject":[],"published":{"date-parts":[[2026,2,4]]},"subtype":"preprint"}}