TY - JOUR
T1 - Cerebrovascular Function in Sporadic and Genetic Cerebral Small Vessel Disease
AU - Stringer, Michael S
AU - Blair, Gordon W
AU - Kopczak, Anna
AU - Kerkhofs, Danielle
AU - Thrippleton, Michael J
AU - Chappell, Francesca M
AU - Maniega, Susana Muñoz
AU - Brown, Rosalind
AU - Shuler, Kirsten
AU - Hamilton, Iona
AU - Garcia, Daniela Jaime
AU - Doubal, Fergus N
AU - Clancy, Una
AU - Sakka, Eleni
AU - Poliakova, Tetiana
AU - Janssen, Esther
AU - Duering, Marco
AU - Ingrisch, Michael
AU - Staals, Julie
AU - Backes, Walter H
AU - van Oostenbrugge, Robert
AU - Biessels, Geert Jan
AU - Dichgans, Martin
AU - Wardlaw, Joanna M
N1 - Publisher Copyright:
© 2024 The Author(s). Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.
PY - 2025/3
Y1 - 2025/3
N2 - Objective: 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. Methods: 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. Results: 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. Interpretation: 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.
AB - Objective: 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. Methods: 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. Results: 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. Interpretation: 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.
UR - http://www.scopus.com/inward/record.url?scp=85210001186&partnerID=8YFLogxK
U2 - 10.1002/ana.27136
DO - 10.1002/ana.27136
M3 - Article
C2 - 39552538
SN - 0364-5134
VL - 97
SP - 483
EP - 498
JO - Annals of Neurology
JF - Annals of Neurology
IS - 3
ER -