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001     276782
005     20250323000832.0
024 7 _ |a 10.1002/ana.27136
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024 7 _ |a 0364-5134
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024 7 _ |a 1531-8249
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037 _ _ |a DZNE-2025-00319
041 _ _ |a English
082 _ _ |a 610
100 1 _ |a Stringer, Michael S
|0 0000-0002-3811-4439
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245 _ _ |a Cerebrovascular Function in Sporadic and Genetic Cerebral Small Vessel Disease.
260 _ _ |a Hoboken, NJ
|c 2025
|b Wiley-Blackwell
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520 _ _ |a Cerebral 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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650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Female
|2 MeSH
650 _ 2 |a Male
|2 MeSH
650 _ 2 |a Middle Aged
|2 MeSH
650 _ 2 |a Cerebral Small Vessel Diseases: genetics
|2 MeSH
650 _ 2 |a Cerebral Small Vessel Diseases: diagnostic imaging
|2 MeSH
650 _ 2 |a Cerebral Small Vessel Diseases: physiopathology
|2 MeSH
650 _ 2 |a Cross-Sectional Studies
|2 MeSH
650 _ 2 |a Aged
|2 MeSH
650 _ 2 |a Magnetic Resonance Imaging
|2 MeSH
650 _ 2 |a Prospective Studies
|2 MeSH
650 _ 2 |a CADASIL: genetics
|2 MeSH
650 _ 2 |a CADASIL: physiopathology
|2 MeSH
650 _ 2 |a CADASIL: diagnostic imaging
|2 MeSH
650 _ 2 |a Cerebrovascular Circulation: physiology
|2 MeSH
650 _ 2 |a White Matter: diagnostic imaging
|2 MeSH
650 _ 2 |a White Matter: pathology
|2 MeSH
650 _ 2 |a Adult
|2 MeSH
700 1 _ |a Blair, Gordon W
|b 1
700 1 _ |a Kopczak, Anna
|b 2
700 1 _ |a Kerkhofs, Danielle
|b 3
700 1 _ |a Thrippleton, Michael J
|b 4
700 1 _ |a Chappell, Francesca M
|b 5
700 1 _ |a Maniega, Susana Muñoz
|b 6
700 1 _ |a Brown, Rosalind
|b 7
700 1 _ |a Shuler, Kirsten
|b 8
700 1 _ |a Hamilton, Iona
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700 1 _ |a Garcia, Daniela Jaime
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700 1 _ |a Doubal, Fergus N
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700 1 _ |a Clancy, Una
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700 1 _ |a Sakka, Eleni
|b 13
700 1 _ |a Poliakova, Tetiana
|b 14
700 1 _ |a Janssen, Esther
|b 15
700 1 _ |a Duering, Marco
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700 1 _ |a Ingrisch, Michael
|b 17
700 1 _ |a Staals, Julie
|b 18
700 1 _ |a Backes, Walter H
|0 0000-0001-7905-0681
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700 1 _ |a van Oostenbrugge, Robert
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700 1 _ |a Biessels, Geert Jan
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700 1 _ |a Dichgans, Martin
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700 1 _ |a Wardlaw, Joanna M
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700 1 _ |a consortium, SVDs@target
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773 _ _ |a 10.1002/ana.27136
|g Vol. 97, no. 3, p. 483 - 498
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910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
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