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Original research
Role of small acute hyperintense lesions in long-term progression of cerebral small vessel disease and clinical outcome: a 14-year follow-up study
  1. Esmée Verburgt1,2,
  2. Esther Janssen1,2,
  3. Mina A Jacob1,2,
  4. Mengfei Cai3,
  5. Annemieke ter Telgte4,
  6. Kim Wiegertjes1,2,
  7. Roy P C Kessels2,5,
  8. David G Norris6,
  9. Jose Marques6,
  10. Marco Duering7,
  11. Anil M Tuladhar1,2,
  12. Frank-Erik De Leeuw1,2
  1. 1 Department of Neurology, Radboudumc, Nijmegen, Gelderland, The Netherlands
  2. 2 Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, Gelderland, The Netherlands
  3. 3 Department of Neurology, Guangdong Provincial People's Hospital, Guangzhou, Guangdong, China
  4. 4 Research Center on Vascular Ageing and Stroke (VASCage GmbH), Innsbruck, Austria
  5. 5 Vincent Van Gogh Instituut, Venray, Limburg, The Netherlands
  6. 6 Centre for Cognitive Neuroimaging, Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, Gelderland, The Netherlands
  7. 7 Medical Image Analysis Center (MIAC AG) and qbig, Department of Biomedical Engineering, University of Basel, Basel, Basel-Stadt, Switzerland
  1. Correspondence to Dr Frank-Erik De Leeuw, Department of Neurology, Radboudumc Department of Neurology, 6525 GA Nijmegen, Gelderland, The Netherlands; FrankErik.deleeuw{at}


Background Small hyperintense lesions are found on diffusion-weighted imaging (DWI) in patients with sporadic small vessel disease (SVD). Their exact role in SVD progression remains unclear due to their asymptomatic and transient nature. The main objective is to investigate the role of DWI+lesions in the radiological progression of SVD and their relationship with clinical outcomes.

Methods Participants with SVD were included from the Radboud University Nijmegen Diffusion tensor MRI Cohort. DWI+lesions were assessed on four time points over 14 years. Outcome measures included neuroimaging markers of SVD, cognitive performance and clinical outcomes, including stroke, all-cause dementia and all-cause mortality. Linear mixed-effect models and Cox regression models were used to examine the outcome measures in participants with a DWI+lesion (DWI+) and those without a DWI+lesion (DWI−).

Results DWI+lesions were present in 45 out of 503 (8.9%) participants (mean age: 66.7 years (SD=8.3)). Participants with DWI+lesions and at least one follow-up (n=33) had higher white matter hyperintensity progression rates (β=0.36, 95% CI=0.05 to 0.68, p=0.023), more incident lacunes (incidence rate ratio=2.88, 95% CI=1.80 to 4.67, p<0.001) and greater cognitive decline (β=−0.03, 95% CI=−0.05 to −0.01, p=0.006) during a median follow-up of 13.2 (IQR: 8.8–13.8) years compared with DWI− participants. No differences were found in risk of all-cause mortality, stroke or dementia.

Conclusion Presence of a DWI+lesion in patients with SVD is associated with greater radiological progression of SVD and cognitive decline compared with patients without DWI+lesions.

  • MRI

Data availability statement

Data are available upon reasonable request.

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Data availability statement

Data are available upon reasonable request.

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  • EV and EJ contributed equally.

  • Contributors Study concept and design: RPCK, DGN, JM, AMT and F-EDL. Data acquisition and analysis: EV, EJ, MJ, MC, KW, MD, AMT and F-EDL. Drafting the manuscript: EV and EJ. Revised the manuscript for intellectual content: all authors. F-EDL acts as guarantor.

  • Funding F-EDL was supported by a VIDI innovational grant from The Netherlands Organisation for Health Research and Development (ZonMw grant 016.126.351).

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.