ADAMTS13 and von Willebrand Factor in relation to vascular cognitive impairment and cerebral small vessel disease: the heart-brain connection study

Amos C Pomp; Mathijs T Rosbergen; Moniek P M de Maat; Paul S de Vries; M Arfan Ikram; Mat J A P Daemen; Imo E Hoefer; Wiro J Niessen; Jeroen de Bresser; Esther E Bron; Charlotte E Teunissen; Geert Jan Biessels; Robert J van Oostenbrugge; Frank J Wolters; Heart-Brain Connection Consortium

doi:10.1016/j.jtha.2026.04.022

ADAMTS13 and von Willebrand Factor in relation to vascular cognitive impairment and cerebral small vessel disease: the heart-brain connection study

J Thromb Haemost. 2026 May 7:S1538-7836(26)00272-2. doi: 10.1016/j.jtha.2026.04.022. Online ahead of print.

Authors

Affiliations

¹ Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.
² Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands; Department of Radiology & Nuclear Medicine, Erasmus Medical Center Rotterdam, the Netherlands.
³ Department of Hematology, Erasmus Medical Center, Rotterdam, the Netherlands.
⁴ Department of Epidemiology, Human Genetics, and Environmental Sciences, Human Genetics Center, School of Public Health, The University of Texas Health Science Center at Houston, Houston, Texas, USA.
⁵ Department of Pathology, Amsterdam University Medical Center, Locations AMC and VUmc, University of Amsterdam, Amsterdam, the Netherlands.
⁶ Central Diagnostic Laboratory, University Medical Center Utrecht, Utrecht, the Netherlands.
⁷ Department of Radiology & Nuclear Medicine, Erasmus Medical Center Rotterdam, the Netherlands; Department of Imaging Science and Technology, Faculty of Applied Sciences, Delft University of Technology, the Netherlands.
⁸ Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands.
⁹ Department of Radiology & Nuclear Medicine, Erasmus Medical Center Rotterdam, the Netherlands.
¹⁰ Neurochemistry Laboratory, Department of Clinical Chemistry, Amsterdam Neuroscience, Neurodegeneration, Amsterdam University Medical Centers, Vrije Universiteit, Amsterdam, the Netherlands.
¹¹ Department of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht, the Netherlands.
¹² Department of Neurology, Maastricht University Medical Center+, the Netherlands; School for Cardiovascular Diseases Maastricht (CARIM), Maastricht University, the Netherlands.
¹³ Department of Radiology & Nuclear Medicine, Erasmus Medical Center Rotterdam, the Netherlands. Electronic address: f.j.wolters@erasmusmc.nl.

PMID: 42106011
DOI: 10.1016/j.jtha.2026.04.022

Abstract

Background: Reduced activity of a disintegrin-like and metalloprotease with thrombospondin type 1 repeats 13 (ADAMTS13) is associated with an increased risk of dementia, independent of Von Willebrand factor (VWF) levels. Pathways underlying this association remain poorly understood.

Objectives: Investigate the associations of VWF levels and ADAMTS13 activity with vascular cognitive impairment (VCI) and cerebral small vessel disease (CSVD).

Methods: In this cross-sectional study, we included 147 participants with VCI and 120 reference subjects (mean age: 67.5 years, 41% women). Using multivariable logistic regression, we determined the cross-sectional association of ADAMTS13 activity and VWF levels in plasma with VCI. Additionally, across cases and reference subjects combined, we determined the cross-sectional association of VWF and ADAMTS13 with markers of CSVD on 3T brain magnetic resonance imaging (MRI) scan.

Results: Participants with lower ADAMTS13 activity had a higher odds of VCI (odds ratio [OR] per 1-SD decrease: 1.46 [95% CI, 1.04-2.04]), whereas participants with higher VWF levels did not (OR per 1-SD increase: 1.15 [95% CI, 0.85-1.56]). Overall, lower ADAMTS13 and higher VWF levels were similarly associated with higher white matter hyperintensity volume (mean difference per 1-SD change in ADAMTS13: 0.12 [95% CI, -0.01 to 0.25] and for VWF: 0.13 [95% CI, 0.01-0.26]). For microbleeds, lacunes, and microinfarcts, low ADAMTS13 and high VWF showed ORs of around 2 for the uppermost quartiles, which were statistically significant only for VWF and lacunes. We found no evidence of synergistic effects of ADAMTS13 and VWF.

Conclusions: Low ADAMTS13 activity is associated with VCI, independent of concurrently measured VWF. Low ADAMTS13 activity and high VWF levels are associated with markers of CSVD.

Keywords: ADAMTS13 protein; Von Willebrand factor; cerebral small vessel diseases; dementia; vascular cognitive impairment.