Blood-brain barrier leakage in relation to white matter hyperintensity volume and cognition in small vessel disease and normal aging

Blood-brain barrier (BBB) leakage increases with age and is involved in the pathophysiology of cerebral small vessel disease (cSVD). We examined the relationship between BBB leakage and white matter hyperintensity (WMH) volume and cognition, in cSVD patients and healthy controls. Seventy-seven patients with clinically overt cSVD and thirty-nine age matched healthy controls underwent dynamic contract-enhanced and structural brain MRI and neuropsychological assessment. We quantified BBB leakage volume and rate in normal appearing white matter (NAWM), WMH and cortical grey matter (CGM). Larger leakage volume and lower leakage rate in WMH were associated with larger WMH volume in cSVD but not in controls. Higher leakage rate in NAWM was associated with lower scores on executive function and information processing speed in healthy controls, whereas no relation with cognition was found in cSVD patients. Our findings support the involvement of BBB leakage in cSVD and aging. They also suggest that the mechanism of cognitive dysfunction in cSVD is more complex and multifactorial in cSVD compared with normal aging.