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.
Objective:To assess factors associated with white matter hyperintensity (WMH) change in a large cohort after observing obvious WMH shrinkage 1 year after minor stroke in several participants in a longitudinal study.Methods:We recruited participants with minor ischemic stroke and performed clinical assessments and brain MRI. At 1 year, we assessed recurrent cerebrovascular events and dependency and repeated the MRI. We assessed change in WMH volume from baseline to 1 year (normalized to percent intracranial volume [ICV]) and associations with baseline variables, clinical outcomes, and imaging parameters using multivariable analysis of covariance, model of changes, and multinomial logistic regression.Results:Among 190 participants (mean age 65.3 years, range 34.3–96.9 years, 112 [59%] male), WMH decreased in 71 participants by 1 year. At baseline, participants whose WMH decreased had similar WMH volumes but higher blood pressure (p = 0.0064) compared with participants whose WMH increased. At 1 year, participants with WMH decrease (expressed as percent ICV) had larger reductions in blood pressure (β = 0.0053, 95% confidence interval [CI] 0.00099–0.0097 fewer WMH per 1–mm Hg decrease, p = 0.017) and in mean diffusivity in normal-appearing white matter (β = 0.075, 95% CI 0.0025–0.15 fewer WMH per 1-unit mean diffusivity decrease, p = 0.043) than participants with WMH increase; those with WMH increase experienced more recurrent cerebrovascular events (32%, vs 16% with WMH decrease, β = 0.27, 95% CI 0.047–0.50 more WMH per event, p = 0.018).Conclusions:Some WMH may regress after minor stroke, with potentially better clinical and brain tissue outcomes. The role of risk factor control requires verification. Interstitial fluid alterations may account for some WMH reversibility, offering potential intervention targets.
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