Extracerebral microvascular dysfunction is related to brain MRI markers of cerebral small vessel disease: The Maastricht Study

Maud Van Dinther,Casper G Schalkwijk,Coen D A Stehouwer,Jacobus F A Jansen,Julie Staals,Alfons J H M Houben,Robert J Van Oostenbrugge,Walter H Backes,Miranda T Schram,Tos T J M Berendschot

doi:10.1007/s11357-021-00493-0

Maud Van Dinther, Casper G Schalkwijk + Show 8 more

Open Access

https://doi.org/10.1007/s11357-021-00493-0

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Journal: GeroScience	Publication Date: Nov 23, 2021
Citations: 13	License type: open-access

Affiliation: Maastricht University

Abstract

BackgroundCerebral small vessel disease (cSVD) is a late consequence of cerebral microvascular dysfunction (MVD). MVD is hard to measure in the brain due to its limited accessibility. Extracerebral MVD (eMVD) measures can give insights in the etiology of cerebral MVD, as MVD may be a systemic process. We aim to investigate whether a compound score consisting of several eMVD measures is associated with structural cSVD MRI markers.MethodsCross-sectional data of the population-based Maastricht Study was used (n = 1872, mean age 59 ± 8 years, 49% women). Measures of eMVD included flicker light-induced retinal arteriolar and venular dilation response (retina), albuminuria and glomerular filtration rate (kidney), heat-induced skin hyperemia (skin), and plasma biomarkers of endothelial dysfunction (sICAM-1, sVCAM-1, sE-selectin, and von Willebrand factor). These measures were standardized into z scores and summarized into a compound score. Linear and logistic regression analyses were used to investigate the associations between the compound score and white matter hyperintensity (WMH) volume, and the presence of lacunes and microbleeds, as measured by brain MRI.ResultsThe eMVD compound score was associated with WMH volume independent of age, sex, and cardiovascular risk factors (St β 0.057 [95% CI 0.010–0.081], p value 0.01), but not with the presence of lacunes (OR 1.011 [95% CI 0.803–1.273], p value 0.92) or microbleeds (OR 1.055 [95% CI 0.896–1.242], p value 0.52).ConclusionA compound score of eMVD is associated with WMH volume. Further research is needed to expand the knowledge about the role of systemic MVD in the pathophysiology of cSVD.

Highlights

Cerebral small vessel disease is an umbrella term that covers all pathologies of cerebral small vessels
The present study demonstrates that a compound score of extracerebral microvascular dysfunction (eMVD) measures is associated with cerebral white matter hyperintensities (WMH) volume, independent of major cardiovascular eMVD compound score
Point estimates and 95% CIs indicate the mean difference in WMH volume per standard deviation (SD) higher microvascular compound score

Summary

Introduction

Cerebral small vessel disease (cSVD) is an umbrella term that covers all pathologies of cerebral small vessels. The most prevalent form is age- and cardiovascular risk factor associated cSVD [1]. It may cause hemorrhagic stroke, ischemic lacunar stroke, vascular cognitive impairment, and contributes majorly to dementia. Typical cSVD lesions as detected with brain magnetic resonance imaging (MRI) are white matter hyperintensities (WMH), lacunes, perivascular spaces, and microbleeds [2]. These MRI features support the diagnosis of cSVD [3, 4]. These macrostructural MRI visible lesions are assumed to be the ultimate consequence of long-standing microvascular dysfunction [5]. Cerebral small vessel disease (cSVD) is a late consequence of cerebral microvascular dysfunction (MVD).

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