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

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    Rights statement: (c) 2016 The Authors. Published by Elsevier Inc. on behalf of the Alzheimer’s Association. This is an open access article under the CC BY license

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Original languageEnglish
JournalAlzheimer's & Dementia
Issue number6
Early online date27 Oct 2016
Publication statusPublished - Jun 2017


INTRODUCTION: Small vessel disease (SVD) is a common contributor to dementia. Subtle blood-brain barrier (BBB) leakage may be important in SVD –induced brain damage. METHODS: We assessed imaging, clinical variables and cognition in patients with mild (i.e. non-disabling) ischemic lacunar or cortical stroke. We analysed BBB leakage, interstitial fluid and white matter integrity using multimodal tissue-specific spatial analysis around white matter hyperintensities (WMH). We assessed predictors of one year cognition, recurrent stroke and dependency. RESULTS: In 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<0.0001), with WMH severity (P=0.033), age (P=0.03) and hypertension (P<0.0001). BBB leakage in WMH predicted declining cognition at one year. DISCUSSION: BBB leakage increases in normal-appearing white matter with WMH and predicts worsening cognition. Interventions to reduce BBB leakage may prevent SVD-associated dementia.

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