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

Area of Science:

• Neuroscience
• Vascular Biology
• Cardiology

Background:

• Cardiovascular risk factors (CRFs) are increasingly associated with cognitive decline and dementia, particularly in cerebral small vessel disease (cSVD).
• White matter hyperintensities (WMH) are linked to cognitive impairment, but the underlying mechanisms, potentially involving blood-brain barrier (BBB) dysfunction, are not fully understood.
• BBB integrity is crucial for brain health, and its disruption may play a significant role in cSVD pathogenesis.

Purpose of the Study:

• To investigate the relationship between CRFs, BBB integrity, and WMH burden in individuals with cSVD.
• To determine if CRFs contribute to BBB disruption, which in turn is associated with WMH.
• To explore the potential mechanisms linking vascular health to brain structure and cognitive function.

Main Methods:

• The study analyzed data from 155 participants in the Biomarkers and Cognition Study (BIOCIS).
• Cardiovascular risk factors (hypertension, high cholesterol, diabetes) were assessed via blood tests and blood pressure measurements.
• White matter hyperintensity (WMH) volumes were quantified using MRI, and BBB integrity was evaluated using a Transendothelial Electrical Resistance (TEER) assay with human brain microvascular endothelial cells (hBMEC) exposed to participant plasma.

Main Results:

• Plasma from individuals with higher WMH burden showed increased BBB disruption in hBMEC.
• Higher systolic blood pressure, diastolic blood pressure, and body mass index correlated with greater BBB disruption.
• Elevated blood glucose and lipid levels were linked to increased BBB disruption, affecting both periventricular and subcortical WMH.

Conclusions:

• Cardiovascular risk factors are associated with impaired BBB integrity.
• BBB disruption may be a key mechanism linking CRFs to WMH burden in cSVD.
• These findings suggest that managing CRFs could be crucial for preventing BBB dysfunction and subsequent cognitive decline in cSVD.