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Structural connectome and cognitive performance in young stroke survivors
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  • Article
  • Open access
  • Published: 28 May 2026

Structural connectome and cognitive performance in young stroke survivors

  • Esther M. Boot1,
  • Mijntje M. I. Schellekens1,
  • Hao Li1,
  • Merel S. Ekker1,
  • Jamie I. Verhoeven1,
  • E. Verburgt1,
  • M. Immens1,
  • Nina A. Hilkens1,
  • F. J. A. Meijer3,
  • R. P. C. Kessels2,4,5,
  • Frank-Erik de Leeuw1,
  • Anil M. Tuladhar1 &
  • the ODYSSEY Investigators

Scientific Reports (2026) Cite this article

We are providing an unedited version of this manuscript to give early access to its findings. Before final publication, the manuscript will undergo further editing. Please note there may be errors present which affect the content, and all legal disclaimers apply.

Subjects

  • Diseases
  • Medical research
  • Neurology
  • Neuroscience

Abstract

We aimed to study the relationship between brain network measures and cognitive performance in this population, focusing on hub regions. A sub-cohort of young stroke survivors (ages 18–49) with confirmed cerebral ischemia from the ODYSSEY study underwent MRI and neuropsychological assessments at baseline (n = 60) and follow-up (n = 46) up to 2 years, the discovery cohort. Additionally, a validation cohort of young stroke survivors with confirmed cerebral ischemia who had baseline standard MRI protocol and neuropsychological assessment (n = 423), as well as follow-up neuropsychological assessment (n = 288), was included for validation analysis. We used diffusion tensor imaging (DTI) based connectivity matrices for graph analysis. Lesion impact scores (combining affected voxel percentage and mean betweenness centrality) and rich club scores (quantifying affected voxels in rich club areas) were calculated using a normative brain atlas derived from DTI data from 23 stroke-free controls. Participants were categorized having no/mild or major vascular cognitive disorder (VCD) and group differences were examined. Among 60 participants (median age: 39.2 years (IQR 27.9–46.2) and 52% women), 20 were classified as having major VCD. The major VCD group exhibited larger lesion volumes (p = 0.01), lower global efficiency (p = 0.03) and local efficiency (p = 0.05) compared to the no/mild VCD group at baseline and follow-up. However, after adjusting for network density in sensitivity analyses, these differences in global and local efficiency were no longer statistically significant. Univariable logistic regression analyses revealed that the Lesion Impact Score were a significant predictor for VCD at follow-up and the Rich Club Score predicted VCD at baseline and follow-up. However, in multivariable logistic regression, both the Lesion Impact Score and the Rich Club Score did not retain predictive significance. Following validation analysis, no predictive values were observed for any of these scores. Our findings indicate a significant association between brain network measures and cognitive function in young stroke survivors, indicating a role of network disruption in post-stroke cognitive impairment. However, our study did not reveal specific associations with hub regions.

Funding

Dr. AM Tuladhar is a junior staff member of the Dutch Heart Foundation (grant number 2016T044). Professor Dr. FE de Leeuw has received the Innovational Research Incentive grant (016-126-351) and the clinical established investigator Dutch Heart Foundation grant (2014 T060).

Author information

Author notes
  1. A list of authors and their affiliations appears at the end of the paper.

Authors and Affiliations

  1. Department of Neurology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Reinier Postlaan 4, PO-Box 9101, 6500 HB, Nijmegen, The Netherlands

    Esther M. Boot, Mijntje M. I. Schellekens, Hao Li, Merel S. Ekker, Jamie I. Verhoeven, E. Verburgt, M. Immens, Nina A. Hilkens, Frank-Erik de Leeuw & Anil M. Tuladhar

  2. Cognition and Behaviour, Center for Cognition, Donders Institute for Brain, Radboud University, Postbus 9104, 6500 HE, Nijmegen, The Netherlands

    R. P. C. Kessels

  3. Department of Radiology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, Nijmegen, The Netherlands

    F. J. A. Meijer

  4. Vincent Van Gogh Institute for Psychiatry, Postbus 5, 5800 AA, Venray, The Netherlands

    R. P. C. Kessels

  5. Department of Medical Psychology and Radboudumc Alzheimer Center, Radboud University Medical Center, PO box 9101, 6500 HB, Nijmegen, The Netherlands

    R. P. C. Kessels

  6. Department of Neurology, Gelre Hospitals, Apeldoorn, The Netherlands

    Mayte E. van Alebeek

  7. Department of Neurology, Medisch Spectrum Twente, Enschede, The Netherlands

    Paul J. A. M. Brouwers & Renate M. Arntz

  8. Department of Neurology, Canisius-Wilhelmina Hospital, Nijmegen, The Netherlands

    Gert W. van Dijk

  9. Department of Neurology, Catharina Hospital, Eindhoven, The Netherlands

    Rob A. R. Gons & Inge W. M. van Uden

  10. Department of Neurology, Franciscus Gasthuis and Vlietland, Rotterdam, The Netherlands

    Tom den Heijer

  11. Department of Neurology, Elisabeth-TweeSteden Hospital, Tilburg, The Netherlands

    Julia H. van Tuijl & Paul L. M. de Kort

  12. Department of Neurology, Haga Hospital, Den Haag, The Netherlands

    Karlijn F. de Laat

  13. Department of Neurology, Amphia Hospital, Breda, The Netherlands

    Anouk G. W. van Norden

  14. Department of Neurology, Rijnstate Hospital, Arnhem, The Netherlands

    Sarah E. Vermeer

  15. Department of Neurology, Jeroen Bosch Hospital, ’s-Hertogenbosch, The Netherlands

    Marian S. G. van Zagten

  16. Department of Neurology, School for Mental Health and Neuroscience (MHeNs), Maastricht University Medical Centre, Maastricht, The Netherlands

    Robert J. van Oostenbrugge

  17. Department of Neurology, University Medical Centre Groningen, Groningen, The Netherlands

    Marieke J. H. Wermer

  18. Department of Neurology, Amsterdam University Medical Centre, Location AMC, Amsterdam, the Netherlands

    Paul J. Nederkoorn

  19. Department of Neurology, Frisius Medical Centre, Leeuwarden, The Netherlands

    Frank G. van Rooij

  20. Department of Neurology, Haaglanden Medical Center, Den Haag, The Netherlands

    Ido R. van den Wijngaard

Authors
  1. Esther M. Boot
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  2. Mijntje M. I. Schellekens
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  3. Hao Li
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  4. Merel S. Ekker
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  5. Jamie I. Verhoeven
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  6. E. Verburgt
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  7. M. Immens
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  8. Nina A. Hilkens
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  9. F. J. A. Meijer
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  10. R. P. C. Kessels
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  11. Frank-Erik de Leeuw
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  12. Anil M. Tuladhar
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Consortia

the ODYSSEY Investigators

  • Mayte E. van Alebeek
  • , Paul J. A. M. Brouwers
  • , Renate M. Arntz
  • , Gert W. van Dijk
  • , Rob A. R. Gons
  • , Inge W. M. van Uden
  • , Tom den Heijer
  • , Julia H. van Tuijl
  • , Karlijn F. de Laat
  • , Anouk G. W. van Norden
  • , Sarah E. Vermeer
  • , Marian S. G. van Zagten
  • , Robert J. van Oostenbrugge
  • , Marieke J. H. Wermer
  • , Paul J. Nederkoorn
  • , Frank G. van Rooij
  • , Ido R. van den Wijngaard
  •  & Paul L. M. de Kort

Corresponding author

Correspondence to Anil M. Tuladhar.

Ethics declarations

Competing interests

The authors declare no competing interests.

Declaration of Generative AI and AI-assisted technologies in the writing process

During the preparation of this manuscript, the author(s) utilized ChatGPT to enhance the language. Following the use of this tool, the author(s) reviewed and edited the content as necessary and assume full responsibility for the content of the published article.

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Supplementary Information 2. (download XLSX )

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Cite this article

Boot, E.M., Schellekens, M.M.I., Li, H. et al. Structural connectome and cognitive performance in young stroke survivors. Sci Rep (2026). https://doi.org/10.1038/s41598-026-54404-4

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  • Received: 04 July 2025

  • Accepted: 19 May 2026

  • Published: 28 May 2026

  • DOI: https://doi.org/10.1038/s41598-026-54404-4

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