Blood-brain barrier disruption and increased free water are associated with worse cognitive performance in patients with chronic cerebrovascular disease

Progression of cerebral small vessel disease (CSVD) is associated with cognitive decline. Blood-brain barrier disruption (BBBD) and fluid extravasation to the interstitial space may contribute to progression of white matter hyperintensities (WMH). We hypothesized that increased free water (FW) would...

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Main Authors: Kyle C. Kern, Marwah S. Zagzoug, Rebecca F. Gottesman, Clinton B. Wright, Richard Leigh
Format: Article
Language:English
Published: Elsevier 2024-01-01
Series:NeuroImage: Clinical
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Online Access:http://www.sciencedirect.com/science/article/pii/S2213158224001475
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author Kyle C. Kern
Marwah S. Zagzoug
Rebecca F. Gottesman
Clinton B. Wright
Richard Leigh
author_facet Kyle C. Kern
Marwah S. Zagzoug
Rebecca F. Gottesman
Clinton B. Wright
Richard Leigh
author_sort Kyle C. Kern
collection DOAJ
description Progression of cerebral small vessel disease (CSVD) is associated with cognitive decline. Blood-brain barrier disruption (BBBD) and fluid extravasation to the interstitial space may contribute to progression of white matter hyperintensities (WMH). We hypothesized that increased free water (FW) would colocalize with BBBD and relate to cognitive performance. Patients with ischemic stroke/TIA at least 3 months prior with at least early confluent WMH were studied cross-sectionally with the Montreal Cognitive Assessment (MoCA), diffusion tensor imaging, and dynamic susceptibility contrast imaging. White matter (WM) was segmented into WMH, WMH penumbra, and normal appearing white matter (NAWM). Colocalization of elevated FW and BBBD and their associations with MoCA performance were evaluated. 58 patients were included (mean age 69, 36 % female). Higher BBBD colocalized with elevated FW. Elevated FW in all white matter, NAWM, WMH penumbra, and WMH lesions was associated with lower MoCA score. Increased BBBD in all WM, NAWM, and WMH penumbra was associated with lower MoCA. In WMH penumbra, both elevated FW and increased BBBD were independently associated with lower MoCA. We found agreement between 2 different biomarkers implicated in the pathogenesis of CSVD that independently demonstrated association with cognitive performance when measured in the area of postulated disease activity.
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spelling doaj-art-c6357c498f8c403e8320f648cbf8a49d2025-08-20T02:06:57ZengElsevierNeuroImage: Clinical2213-15822024-01-014410370610.1016/j.nicl.2024.103706Blood-brain barrier disruption and increased free water are associated with worse cognitive performance in patients with chronic cerebrovascular diseaseKyle C. Kern0Marwah S. Zagzoug1Rebecca F. Gottesman2Clinton B. Wright3Richard Leigh4National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United States; Department of Neurology, University of California Los Angeles David Geffen School of Medicine, Los Angeles, CA, United StatesNational Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United StatesNational Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United StatesNational Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United StatesNational Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United States; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, United States; Corresponding author at: 600 N. Wolfe Street, Phipps 4, Suite 446, Baltimore, MD 21287, United StatesProgression of cerebral small vessel disease (CSVD) is associated with cognitive decline. Blood-brain barrier disruption (BBBD) and fluid extravasation to the interstitial space may contribute to progression of white matter hyperintensities (WMH). We hypothesized that increased free water (FW) would colocalize with BBBD and relate to cognitive performance. Patients with ischemic stroke/TIA at least 3 months prior with at least early confluent WMH were studied cross-sectionally with the Montreal Cognitive Assessment (MoCA), diffusion tensor imaging, and dynamic susceptibility contrast imaging. White matter (WM) was segmented into WMH, WMH penumbra, and normal appearing white matter (NAWM). Colocalization of elevated FW and BBBD and their associations with MoCA performance were evaluated. 58 patients were included (mean age 69, 36 % female). Higher BBBD colocalized with elevated FW. Elevated FW in all white matter, NAWM, WMH penumbra, and WMH lesions was associated with lower MoCA score. Increased BBBD in all WM, NAWM, and WMH penumbra was associated with lower MoCA. In WMH penumbra, both elevated FW and increased BBBD were independently associated with lower MoCA. We found agreement between 2 different biomarkers implicated in the pathogenesis of CSVD that independently demonstrated association with cognitive performance when measured in the area of postulated disease activity.http://www.sciencedirect.com/science/article/pii/S2213158224001475Magnetic resonance imagingBlood-brain barrierDiffusion tensor imagingFree waterDementiaVascular
spellingShingle Kyle C. Kern
Marwah S. Zagzoug
Rebecca F. Gottesman
Clinton B. Wright
Richard Leigh
Blood-brain barrier disruption and increased free water are associated with worse cognitive performance in patients with chronic cerebrovascular disease
NeuroImage: Clinical
Magnetic resonance imaging
Blood-brain barrier
Diffusion tensor imaging
Free water
Dementia
Vascular
title Blood-brain barrier disruption and increased free water are associated with worse cognitive performance in patients with chronic cerebrovascular disease
title_full Blood-brain barrier disruption and increased free water are associated with worse cognitive performance in patients with chronic cerebrovascular disease
title_fullStr Blood-brain barrier disruption and increased free water are associated with worse cognitive performance in patients with chronic cerebrovascular disease
title_full_unstemmed Blood-brain barrier disruption and increased free water are associated with worse cognitive performance in patients with chronic cerebrovascular disease
title_short Blood-brain barrier disruption and increased free water are associated with worse cognitive performance in patients with chronic cerebrovascular disease
title_sort blood brain barrier disruption and increased free water are associated with worse cognitive performance in patients with chronic cerebrovascular disease
topic Magnetic resonance imaging
Blood-brain barrier
Diffusion tensor imaging
Free water
Dementia
Vascular
url http://www.sciencedirect.com/science/article/pii/S2213158224001475
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