ADAMTS13 and von Willebrand Factor in relation to vascular cognitive impairment and cerebral small vessel disease
the heart-brain connection study
Amos C. Pomp (Erasmus MC)
Mathijs T. Rosbergen (Erasmus MC)
Moniek P.M. de Maat (Erasmus MC)
Paul S. de Vries (The University of Texas Health Science Center at Houston, Houston, Texas)
M. Arfan Ikram (Erasmus MC)
Wiro J. Niessen (TU Delft - ImPhys/Computational Imaging, Erasmus MC)
JHP de Bresser (Leiden University Medical Center)
Esther E. Bron (Erasmus MC)
Charlotte E. Teunissen (Amsterdam UMC)
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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.
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