ADAMTS13 and Von Willebrand Factor in Relation to Vascular Cognitive Impairment and Cerebral Small Vessel Disease: The Heart-Brain Connection Study

Authors

• 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

Language

English

Publication Date

8-1-2026

Journal

Journal of Thrombosis and Haemostasis

DOI

10.1016/j.jtha.2026.04.022

PMID

42106011

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

Humans, ADAMTS13 Protein, von Willebrand Factor, Female, Aged, Cerebral Small Vessel Diseases, Cross-Sectional Studies, Male, Biomarkers, Middle Aged, Logistic Models, Magnetic Resonance Imaging, Risk Factors, Odds Ratio, Cognition, Multivariate Analysis, Dementia, Vascular, Case-Control Studies, Brain, ADAMTS13 protein, Von Willebrand factor, cerebral small vessel diseases, dementia, vascular cognitive impairment

Published Open-Access

yes

Recommended Citation

Pomp, Amos C; Rosbergen, Mathijs T; de Maat, Moniek P M; et al., "ADAMTS13 and Von Willebrand Factor in Relation to Vascular Cognitive Impairment and Cerebral Small Vessel Disease: The Heart-Brain Connection Study" (2026). Faculty, Staff and Student Publications. 1406.
https://digitalcommons.library.tmc.edu/uthsph_docs/1406