Blood-brain barrier leakage at baseline and cognitive decline in cerebral small vessel disease: a 2-year follow-up study.
Level 3 - non-randomized controlled study
Prospective longitudinal cohort study with 2-year follow-up
PubMed 34160780 · doi:10.1007/s11357-021-00399-x
What was done
Researchers evaluated 51 patients with clinically overt cerebral small vessel disease (cSVD, presenting with lacunar stroke or mild vascular cognitive impairment). At baseline, participants underwent dynamic contrast-enhanced (DCE) MRI to quantify blood-brain barrier (BBB) leakage volume and rate in normal-appearing white matter (NAWM), white matter hyperintensities (WMH), cortical grey matter (CGM), and deep grey matter (DGM). Cognitive performance across executive function, information processing speed, and memory was assessed at baseline and after 2 years. Associations between baseline BBB permeability and 2-year cognitive decline were analyzed via multivariable linear regression adjusting for age, sex, education, baseline WMH volume, and baseline brain volume.
What was found
Higher baseline BBB leakage volume and leakage rate in the NAWM and CGM were significantly associated with greater overall cognitive decline over 2 years. Specifically, higher leakage volume in NAWM and CGM, as well as higher leakage rate in CGM, were significantly associated with greater decline in executive function. Exact regression coefficients, confidence intervals, and p-values were not reported in the abstract.
Why it matters
This study provides longitudinal evidence linking microvascular blood-brain barrier breakdown directly to subsequent cognitive deterioration in cSVD, independent of structural brain volume and white matter hyperintensity burden. It highlights BBB permeability as a potential predictive biomarker and mechanistic target for vascular cognitive impairment.
Limits
The study sample was small (n = 51) and recruited from a specific clinical subset with overt cSVD, limiting generalizability to earlier or asymptomatic stages. The follow-up duration was relatively short (2 years), and numerical effect sizes, test statistics, and attrition rates were omitted from the abstract.
Cited by
- supports Baseline blood-brain barrier breakdown measured by MRI or biofluid biomarkers predicts the rate of future cognitive decline.