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Microvascular Dysfunction and Whole-Brain White Matter Connectivity: The Maastricht Study
Magdalena Beran1,2,3, April C E van Gennip1,2, Coen D A Stehouwer1,2
1Department of Internal Medicine Maastricht University Medical Centre+ (MUMC+) Maastricht The Netherlands.
Background:
Microvascular dysfunction is involved in the development of various cerebral disorders. It may contribute to these disorders by disrupting white matter tracts and altering brain connectivity, but evidence is scarce. We investigated the association between multiple biomarkers of microvascular function and whole-brain white matter connectivity.
Methods And Results:
Cross-sectional data from The Maastricht Study, a Dutch population-based cohort (n=4326; age, 59.4±8.6 years; 49.7% women). Measures of microvascular function included urinary albumin excretion, central retinal arteriolar and venular calibers, composite scores of flicker light-induced retinal arteriolar and venular dilation, and plasma biomarkers of endothelial dysfunction (intercellular adhesion molecule-1, vascular cell adhesion molecule-1, E-selectin, and von Willebrand factor). White matter connectivity was calculated from 3T diffusion magnetic resonance imaging to quantify the number (average node degree) and organization (characteristic path length, global efficiency, clustering coefficient, and local efficiency) of white matter connections. A higher plasma biomarkers of endothelial dysfunction composite score was associated with a longer characteristic path length (β per SD, 0.066 [95% CI, 0.017-0.114]) after adjustment for sociodemographic, lifestyle, and cardiovascular factors but not with any of the other white matter connectivity measures. After multiple comparison correction, this association was nonsignificant. None of the other microvascular function measures were associated with any of the connectivity measures.
Conclusions:
These findings suggest that microvascular dysfunction as measured by indirect markers is not associated with whole-brain white matter connectivity.
Insights
Microvascular dysfunction, indicated by indirect markers, does not appear to impact overall white matter connectivity in the brain. This study found no significant associations between various microvascular measures and brain connectivity metrics.
Area of Science:
- Neuroscience
- Vascular Biology
- Medical Imaging
Background:
- Microvascular dysfunction is implicated in cerebral disorders.
- Its role in disrupting white matter tracts and brain connectivity requires further investigation.
- This study explores the link between microvascular function biomarkers and brain connectivity.
Purpose of the Study:
- To investigate the association between multiple microvascular function biomarkers and whole-brain white matter connectivity.
- To determine if markers of endothelial dysfunction correlate with white matter network organization.
Main Methods:
- Utilized cross-sectional data from The Maastricht Study (n=4326).
- Assessed microvascular function via urinary albumin excretion, retinal vessel calibers, dilation responses, and plasma endothelial dysfunction biomarkers.
- Quantified white matter connectivity using 3T diffusion MRI, analyzing measures like characteristic path length and global efficiency.
Main Results:
- A composite score of endothelial dysfunction biomarkers showed a nonsignificant association with longer characteristic path length after multiple comparison correction.
- No significant associations were found between other microvascular function measures and any white matter connectivity metrics.
- The study adjusted for sociodemographic, lifestyle, and cardiovascular factors.
Conclusions:
- Indirect markers of microvascular dysfunction are not associated with whole-brain white matter connectivity.
- These findings suggest a lack of a direct link between the measured microvascular health and the structural organization of white matter networks.
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