From the Centre for Clinical Brain Sciences (E.S., M.S.S., U.C., C.A.-R., D.J.G., A.C.C.J., S.W., M.V.H., F.M.C., F.N.D., I.M., M.T., J.M.W.) and UK Dementia Research Institute (E.S., M.S.S., U.C., C.A.-R., D.J.G., A.C.C.J., S.W., M.V.H., F.M.C., F.N.D., I.M., M.T., J.M.W.), University of Edinburgh, United Kingdom. Michael Thrippleton and Joanna Wardlaw are currently at Edinburgh Imaging Facility, Royal Infirmary of Edinburgh, University of Edinburgh, United Kingdom.
Neurology. 2024 Dec 10;103(11):e210008. doi: 10.1212/WNL.0000000000210008. Epub 2024 Nov 5.
In patients with cerebral small vessel disease (SVD), impaired cerebrovascular reactivity (CVR) is related to worse concurrent SVD burden, but less is known about cerebrovascular reactivity and long-term SVD lesion progression and clinical outcomes. We investigated associations between cerebrovascular reactivity and 1-year progression of SVD features and clinical outcomes.
Between 2018 and 2021, we recruited patients from the Edinburgh/Lothian stroke services presenting with minor ischemic stroke and SVD features as part of the Mild Stroke Study 3, a prospective observational cohort study (ISRCTN 12113543). We acquired 3T brain MRI at baseline and 1 year. At baseline, we measured cerebrovascular reactivity to 6% inhaled CO in subcortical gray matter, normal-appearing white matter, and white matter hyperintensities (WMH). At baseline and 1 year, we quantified SVD MRI features, incident infarcts, assessed stroke severity (NIH Stroke Scale), recurrent stroke, functional outcome (modified Rankin Scale), and cognition (Montreal Cognitive Assessment). We performed linear and logistic regressions adjusted for age, sex, and vascular risk factors, reporting the regression coefficients and odds ratios with 95% CIs.
We recruited 208 patients of whom 163 (mean age and SD: 65.8 ± 11.2 years, 32% female) had adequate baseline CVR and completed the follow-up structural MRI. The median increase in WMH volume was 0.32 mL with (Q1, Q3) = (-0.48, 1.78) mL; 29% had a recurrent stroke or incident infarct on MRI. At 1 year, patients with lower baseline cerebrovascular reactivity in normal-appearing tissues had increased WMH (regression coefficient: B = -1.14 [-2.13, -0.14] log (%ICV) per %/mm Hg) and perivascular space volumes (B = -1.90 [-3.21, -0.60] log (%ROIV) per %/mm Hg), with a similar trend in WMH. CVR was not associated with clinical outcomes at 1 year.
Lower baseline cerebrovascular reactivity predicted an increase in WMH and perivascular space volumes after 1 year. CVR should be considered in SVD future research and intervention studies.
在患有脑小血管疾病（SVD）的患者中，脑血管反应性（CVR）受损与更严重的同时 SVD 负担相关，但关于 CVR 与 SVD 病变进展和临床结局的长期关系知之甚少。我们研究了脑血管反应性与 SVD 特征和临床结局的 1 年进展之间的关系。
在 2018 年至 2021 年间，我们从爱丁堡/洛锡安卒中服务中招募了因小缺血性卒中及 SVD 特征而出现的患者，这些患者是轻度卒中研究 3 的一部分，这是一项前瞻性观察队列研究（ISRCTN 12113543）。我们在基线和 1 年时进行了 3T 脑 MRI 检查。在基线时，我们测量了皮质下灰质、正常表现的白质和脑白质高信号（WMH）中对 6%吸入 CO 的脑血管反应性。在基线和 1 年时，我们量化了 SVD MRI 特征、新发梗死、评估卒中严重程度（NIH 卒中量表）、卒中复发、功能结局（改良 Rankin 量表）和认知功能（蒙特利尔认知评估）。我们进行了线性和逻辑回归调整，以年龄、性别和血管危险因素为协变量，报告回归系数和比值比及其 95%置信区间。
我们共招募了 208 名患者，其中 163 名（平均年龄和标准差：65.8 ± 11.2 岁，32%为女性）基线 CVR 充分且完成了随访结构 MRI。WMH 体积的中位数增加了 0.32 mL（Q1，Q3：-0.48，1.78）mL；29%的患者在 MRI 上出现了卒中复发或新发梗死。在 1 年时，正常表现组织中基线脑血管反应性较低的患者 WMH 体积增加（回归系数：B=-1.14[-2.13，-0.14]log（%ICV）/%/mmHg）和血管周围间隙体积增加（B=-1.90[-3.21，-0.60]log（%ROIV）/%/mmHg），WMH 也存在类似趋势。CVR 与 1 年后的临床结局无关。
较低的基线脑血管反应性预测 1 年后 WMH 和血管周围间隙体积的增加。CVR 应在未来的 SVD 研究和干预研究中加以考虑。
