Featured ArticleBlood-brain barrier failure as a core mechanism in cerebral small vessel disease and dementia: evidence from a cohort study

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- In 201 patients with non-disabling stroke and white matter hyperintensities (WMH), we measured blood-brain barrier (BBB) leakage with contrast-enhanced MRI.
- BBB leakage was higher in WMH than in normal appearing white matter.
- BBB leakage increased in both WMH and normal appearing white matter with the burden of small vessel disease, hypertension, and age.
- BBB leakage predicted cognitive decline one year later.
- The leakage pattern supported the hypothesis that BBB leak was pathogenic of diffuse brain damage in cerebral small vessel disease.

IntroductionSmall vessel disease (SVD) is a common contributor to dementia. Subtle blood-brain barrier (BBB) leakage may be important in SVD-induced brain damage.MethodsWe assessed imaging, clinical variables, and cognition in patients with mild (i.e., nondisabling) ischemic lacunar or cortical stroke. We analyzed BBB leakage, interstitial fluid, and white matter integrity using multimodal tissue-specific spatial analysis around white matter hyperintensities (WMH). We assessed predictors of 1 year cognition, recurrent stroke, and dependency.ResultsIn 201 patients, median age 67 (range 34-97), BBB leakage, and interstitial fluid were higher in WMH than normal-appearing white matter; leakage in normal-appearing white matter increased with proximity to WMH (P < .0001), with WMH severity (P = .033), age (P = .03), and hypertension (P < .0001). BBB leakage in WMH predicted declining cognition at 1 year.DiscussionBBB leakage increases in normal-appearing white matter with WMH and predicts worsening cognition. Interventions to reduce BBB leakage may prevent SVD-associated dementia.