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000276782 1001_ $$00000-0002-3811-4439$$aStringer, Michael S$$b0
000276782 245__ $$aCerebrovascular Function in Sporadic and Genetic Cerebral Small Vessel Disease.
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000276782 520__ $$aCerebral small vessel diseases (SVDs) are associated with cerebrovascular dysfunction, such as increased blood-brain barrier leakage (permeability surface area product), vascular pulsatility, and decreased cerebrovascular reactivity (CVR). No studies assessed all 3 functions concurrently. We assessed 3 key vascular functions in sporadic and genetic SVD to determine associations with SVD severity, subtype, and interrelations.In this prospective, cross-sectional, multicenter INVESTIGATE-SVDs study, we acquired brain magnetic resonance imaging in patients with sporadic SVD/cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), including structural, quantitative microstructural, permeability surface area product, blood plasma volume fraction, vascular pulsatility, and CVR (in response to CO2) scans. We determined vascular function and white matter hyperintensity (WMH) associations, using covariate-adjusted linear regression; normal-appearing white matter and WMH differences, interrelationships between vascular functions, using linear mixed models; and major sources of variance using principal component analyses.We recruited 77 patients (45 sporadic/32 CADASIL) at 3 sites. In adjusted analyses, patients with worse WMH had lower CVR (B = -1.78, 95% CI -3.30, -0.27) and blood plasma volume fraction (B = -0.594, 95% CI -0.987, -0.202). CVR was worse in WMH than normal-appearing white matter (eg, CVR: B = -0.048, 95% CI -0.079, -0.017). Adjusting for WMH severity, SVD subtype had minimal influence on vascular function (eg, CVR in CADASIL vs sporadic: B = 0.0169, 95% CI -0.0247, 0.0584). Different vascular function mechanisms were not generally interrelated (eg, permeability surface area product~CVR: B = -0.85, 95% CI -4.72, 3.02). Principal component analyses identified WMH volume/quantitative microstructural metrics explained most variance in CADASIL and arterial pulsatility in sporadic SVD, but similar main variance sources.Vascular function was worse with higher WMH, and in WMH than normal-appearing white matter. Sporadic SVD-CADASIL differences largely reflect disease severity. Limited vascular function interrelations may suggest disease stage-specific differences. ANN NEUROL 2025;97:483-498.
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000276782 650_2 $$2MeSH$$aHumans
000276782 650_2 $$2MeSH$$aFemale
000276782 650_2 $$2MeSH$$aMale
000276782 650_2 $$2MeSH$$aMiddle Aged
000276782 650_2 $$2MeSH$$aCerebral Small Vessel Diseases: genetics
000276782 650_2 $$2MeSH$$aCerebral Small Vessel Diseases: diagnostic imaging
000276782 650_2 $$2MeSH$$aCerebral Small Vessel Diseases: physiopathology
000276782 650_2 $$2MeSH$$aCross-Sectional Studies
000276782 650_2 $$2MeSH$$aAged
000276782 650_2 $$2MeSH$$aMagnetic Resonance Imaging
000276782 650_2 $$2MeSH$$aProspective Studies
000276782 650_2 $$2MeSH$$aCADASIL: genetics
000276782 650_2 $$2MeSH$$aCADASIL: physiopathology
000276782 650_2 $$2MeSH$$aCADASIL: diagnostic imaging
000276782 650_2 $$2MeSH$$aCerebrovascular Circulation: physiology
000276782 650_2 $$2MeSH$$aWhite Matter: diagnostic imaging
000276782 650_2 $$2MeSH$$aWhite Matter: pathology
000276782 650_2 $$2MeSH$$aAdult
000276782 7001_ $$aBlair, Gordon W$$b1
000276782 7001_ $$aKopczak, Anna$$b2
000276782 7001_ $$aKerkhofs, Danielle$$b3
000276782 7001_ $$aThrippleton, Michael J$$b4
000276782 7001_ $$aChappell, Francesca M$$b5
000276782 7001_ $$aManiega, Susana Muñoz$$b6
000276782 7001_ $$aBrown, Rosalind$$b7
000276782 7001_ $$aShuler, Kirsten$$b8
000276782 7001_ $$aHamilton, Iona$$b9
000276782 7001_ $$aGarcia, Daniela Jaime$$b10
000276782 7001_ $$aDoubal, Fergus N$$b11
000276782 7001_ $$aClancy, Una$$b12
000276782 7001_ $$aSakka, Eleni$$b13
000276782 7001_ $$aPoliakova, Tetiana$$b14
000276782 7001_ $$aJanssen, Esther$$b15
000276782 7001_ $$aDuering, Marco$$b16
000276782 7001_ $$aIngrisch, Michael$$b17
000276782 7001_ $$aStaals, Julie$$b18
000276782 7001_ $$00000-0001-7905-0681$$aBackes, Walter H$$b19
000276782 7001_ $$avan Oostenbrugge, Robert$$b20
000276782 7001_ $$aBiessels, Geert Jan$$b21
000276782 7001_ $$0P:(DE-2719)2000030$$aDichgans, Martin$$b22$$udzne
000276782 7001_ $$00000-0002-9812-6642$$aWardlaw, Joanna M$$b23
000276782 7001_ $$aconsortium, SVDs@target$$b24$$eCollaboration Author
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