Blood-brain barrier integrity disruption is associated with both chronic vascular risk factors and white matter hyperintensities

Cardiovascular risk factors (CRFs) like hypertension, high cholesterol, and diabetes mellitus are increasingly linked to cognitive decline and dementia, especially in cerebral small vessel disease (cSVD). White matter hyperintensities (WMH) are closely associated with cognitive impairment, but the mechanisms behind their development remain unclear. Blood-brain barrier (BBB) dysfunction may be a key factor, particularly in cSVD. This study explores the relationship between CRFs, BBB integrity, and WMH burden. The study included 155 participants from the Biomarkers and Cognition Study, Singapore (BIOCIS). CRFs were assessed through blood tests for glucose and lipid profiles, and blood pressure measurements. WMH volumes were quantified using MRI. BBB integrity was evaluated using a Transendothelial Electrical Resistance (TEER) assay with human brain microvascular endothelial cells (hBMEC) exposed to participant plasma. Plasma from individuals with a higher WMH burden was associated with increased BBB disruption in hBMEC. Higher systolic and diastolic blood pressure, as well as body mass index, were correlated with greater BBB disruption. Regression analyses revealed that elevated blood glucose and lipid levels were linked to increased BBB disruption. Both periventricular and subcortical WMH burdens were associated with increased BBB disruption. This study highlights a relationship between CRFs, BBB disruption, and WMH burden, suggesting that CRFs may impair BBB integrity and contribute to WMH and cognitive decline in cSVD.