Enlarged perivascular spaces correlate with blood-brain barrier leakage and cognitive impairment in Alzheimer's disease

BackgroundThe clinical significance of enlarged perivascular spaces (EPVS) in Alzheimer' s disease (AD) was ambiguous.ObjectiveTo investigate whether EPVS contribute to blood-brain barrier (BBB) leakage and cognition in AD.MethodsThe study included a total of 64 participants (26 healthy controls and 38 patients with AD). The evaluation of EPVS and BBB permeability was performed in specific anatomical locations: the centrum semiovale (CSO), basal ganglia, and hippocampus. The EPVS ratings were performed according to Potter's instructions. BBB permeability was evaluated using dynamic contrast-enhanced-MRI. The relationship between EPVS and global cognition (Mini-Mental State Examination and Montreal Cognitive Assessment), cognitive subdomains, and BBB permeability were examined in both groups. Finally, the relationship between CSO BBB permeability and cognition in AD patients was investigated.ResultsHigh-grade CSO EPVS was found associated with AD (OR: 3.40, 95% CI: 1.11-11.90, p = 0.04). In the AD group, a significant correlation was observed between high-grade CSO EPVS and lower MMSE score (r = -0.36, p = 0.03) and verbal fluency (r = -0.44, p = 0.01). High-grade CSO EPVS positively correlated with BBB leakage (r = 0.58, p < 0.001). The BBB permeability of CSO negatively correlated with verbal fluency (r = -0.52, p < 0.001) and attention (r = -0.40, p = 0.01).ConclusionsHigh-grade CSO EPVS is related to BBB leakage, which contributes to cognitive impairment in AD patients, especially verbal frequency. CSO EPVS can function as a convenient AD marker for intervention and therapy.