Cerebrovascular Reactivity in Patients With Small Vessel Disease: A Cross-Sectional Study

Abstract

BACKGROUND: Cerebrovascular reactivity (CVR) is inversely related to white matter hyperintensity severity, a marker of cerebral small vessel disease (SVD). Less is known about the relationship between CVR and other SVD imaging features or cognition. We aimed to investigate these cross-sectional relationships. METHODS: Between 2018 and 2021 in Edinburgh, we recruited patients presenting with lacunar or cortical ischemic stroke, whom we characterized for SVD features. We measured CVR in subcortical gray matter, normal-appearing white matter, and white matter hyperintensity using 3T magnetic resonance imaging. We assessed cognition using Montreal Cognitive Assessment. Statistical analyses included linear regression models with CVR as outcome, adjusted for age, sex, and vascular risk factors. We reported regression coefficients with 95% CIs. RESULTS: Of 208 patients, 182 had processable CVR data sets (median age, 68.2 years; 68% men). Although the strength of association depended on tissue type, lower CVR in normal-appearing tissues and white matter hyperintensity was associated with larger white matter hyperintensity volume (B NAWM =−0.0073 [95% CI, −0.0133 to −0.0014] %/mm Hg per 10-fold increase in percentage intracranial volume), more lacunes (B NAWM =−0.00129 [95% CI, −0.00215 to −0.00043] %/mm Hg per lacune), more microbleeds (B NAWM =−0.00083 [95% CI, −0.00130 to −0.00036] %/mm Hg per microbleed), higher deep atrophy score (B NAWM =−0.00218 [95% CI, −0.00417 to −0.00020] %/mm Hg per score point increase), higher perivascular space score (B NAWM =−0.0034 [95% CI, −0.0066 to −0.0002] %/mm Hg per score point increase in basal ganglia), and higher SVD score (B NAWM =−0.0048 [95% CI, −0.0075 to −0.0021] %/mm Hg per score point increase). Lower CVR in normal-appearing tissues was related to lower Montreal Cognitive Assessment without reaching convention statistical significance (B NAWM =0.00065 [95% CI, −0.00007 to 0.00137] %/mm Hg per score point increase). CONCLUSIONS: Lower CVR in patients with SVD was related to more severe SVD burden and worse cognition in this cross-sectional analysis. Longitudinal analysis will help determine whether lower CVR predicts worsening SVD severity or vice versa. REGISTRATION: URL: https://www.isrctn.com ; Unique identifier: ISRCTN12113543.

Pathophysiology of cerebral small vessel disease: a journey through recent discoveries

“…CO 2 -induced vasodilation is assessed by measuring cerebral blood flow (CBF) increases in response to breathing CO 2 with functional MRI using blood O 2 level–dependent (BOLD) response or arterial spin labeling, which can directly measure CBF. Two recent, large cross-sectional cohort studies showed that a reduced CO 2 response in the WM or subcortical gray matter is associated with more severe cSVD burden (WMHs, lacunes, microbleeds, enlarged PVSs, and brain atrophy) and impaired cognition ( 78 , 79 ). In a 1-year longitudinal study performed in patients with age-related WMHs, regions of normal-appearing WM that progress to WMHs over time had a lower baseline response to hypercapnia compared with normal-appearing WM ( 80 ).…”

Nimodipine Protects Vascular and Cognitive Function in an Animal Model of Cerebral Small Vessel Disease

“…The vascular dysfunction associated with cSVD has emerged as a promising biomarker of forthcoming cognitive decline. Apart from cerebral hypoperfusion, 6 there are important deficits in dynamic vascular function, namely neurovascular coupling (NVC) 7 and cerebrovascular reactivity (CVR), 8 mainly due to increased arterial stiffness and endothelial dysfunction. 9 In fact, it is the deficit in dynamic function of the vasculature, rather than in cerebral perfusion at resting state, which best predicts clinical outcomes, 10 including poor cognitive performance.…”