Blood-Brain Barrier Integrity Disruption is Associated to both Chronic Vascular Risk Factors and White Matter Hyperintensities

Cardiovascular risk factors (CRFs) such as hypertension, high cholesterol, and diabetes are increasingly implicated in cognitive decline and cerebral small vessel disease (cSVD). White matter hyperintensities (WMH), a hallmark of cSVD, are strongly linked to cognitive impairment, but their underlying mechanisms remain unclear. Blood-brain barrier (BBB) dysfunction has been proposed as a potential contributor to WMH development. This study aimed to explore the relationships between CRFs, BBB integrity, and WMH burden. We analyzed 155 participants from the Biomarkers and Cognition Study, Singapore, assessing CRFs through blood tests for glucose and lipid profiles, alongside blood pressure measurements. WMH volume was quantified using MRI, and an in vitro assay evaluated the impact of plasma on BBB integrity using human brain microvascular endothelial cells. Results showed that plasma from participants with higher WMH burden correlated with increased BBB disruption, which was further associated with higher blood pressure, elevated blood glucose, and lipid levels. Both periventricular and subcortical WMH were linked to BBB disruption. These findings suggest that CRFs contribute to BBB dysfunction, promoting WMH development and cognitive decline in cSVD. Further research is needed to clarify the precise mechanisms driving these associations.