大脑中动脉闭塞患者的认知障碍与血流动力学异常相关：一项基于 TCD 的研究

抽象：

背景： 颅内动脉粥样硬化性狭窄 （ICAS） 是世界范围内中风的常见原因，与认知障碍密切相关。 方法： 本研究共纳入 66 例单侧 MCA 闭塞患者，其中症状组 （sICAS） 42 例，无症状组 （AsICAS） 24 例，匹配健康对照者 （HC） 23 例。所有受试者均完成全套神经心理学测试和 TCD 评估，并收集双侧大脑前动脉 （arteria cerebri anterior， ACA） 和 MCA。大脑后动脉 （PCA） EDV 的峰值收缩速度 （PSV） 和舒张末期速度 （EDV） 和平均流速 （MFV） 用于反映每个受试者的血流动力学状态和侧支循环的补偿。部分受试者完成 MRI 扫描以获得脑血灌注 （CBF）。 分析3组被试认知功能和血流动力学指标的差异，分析两者之间的相关性。 结果s： 症状组高血压患病率显著高于其他两组 （P<0.001）。MMSE、MoCA、CAVLT （即时记忆/延迟记忆/记忆识别）、DS、VFT、Stroop 和 CTT 测试的评分表明，MCA 闭塞患者的认知功能明显受损，HC、AsICAS 和 sICAS 三组之间存在显着的梯度效应。此外，除病灶侧的 MCA 流速外，在病灶侧 ACA 和 PCA 的流速比较中，AsICAS 组和 sICAS 组显著快于 HC 组。病灶对侧流速比较中，AsICAS 组流速明显快于其他两组。AsICAS 组病灶对侧 MCA-PSV 、 MCA-EDV 和 MCA-MFV 与执行功能 （Stroop-CW） 显著相关 （R=-0.526，P=0.008;R=-0.441，P=0.031;R=-0.471，P=0.020）。 结论： MCA 闭塞患者的认知功能明显受损。血流动力学状态可能与认知功能有关。

关键词 ： 颅内动脉粥样硬化性狭窄， 认知障碍， 经颅多普勒超声， 大脑中动脉闭塞

1.引言

颅内动脉粥样硬化性狭窄是世界范围内中风的常见原因之一。发病显示出显着的种族差异，在东亚、西班牙裔和非白人美国人中更为普遍^1-3.ICAS 的患病率在亚洲国家最高，从 9% 到 65% 不等¹.在中国，约 46.6% 的缺血性卒中患者合并 ICAS⁴.一项涉及 1,089 名脑卒中的研究表明，有 ICAS 的脑卒中患者 90 天的脑卒中复发率高达 11.9%，远高于没有 ICAS 的脑卒中患者（1.3%）⁵，给家庭和社会带来了沉重的负担。

颅内动脉粥样硬化性疾病除了导致中风引起的身体残疾外，还与血管性认知障碍密切相关^6-8.一项涉及 1,701 名受试者的研究发现，41.1% 的 ICAS 受试者存在不同程度的认知障碍，其中 ICAS>50% 与认知障碍显著相关，痴呆⁹。ICAS 引起的血管性认知障碍通常表现为智力低下和执行功能问题，包括高级认知功能，如计划和组织活动¹⁰.然而，目前，ICAS 导致认知障碍的机制尚不完全清楚。目前，关于其机制的研究大多集中在慢性脑灌注不足¹¹，对其血流动力学机制仍缺乏探索。

目前，大多数研究都是基于颈动脉粥样硬化性狭窄和认知功能^12-14，目前还缺乏对前循环血管颅内段和认知功能的研究。MCA 作为 ICAS 的常见部位和颅内前循环的重要组成部分¹⁵，供应整个大脑半球的大部分上外侧区域，并影响多个大脑区域，包括记忆和执行等功能。因此，有必要关注 MCA 闭塞患者认知功能的变化。

Aaslid 的研究表明，通过颞骨的经颅入路，2MHz 探头可以检测到颅内主要血管流速的变化¹⁶。 经颅多普勒超声 （TCD） 是一种基于多普勒原理的无创检查方法（超声探头发出的信号被红细胞反射，反射信号的频率与移动物体的速度成正比），通过测量颅内动脉的血流速度来评估颅内动脉的血流动力学¹⁷.先前的多项研究表明，在执行认知任务的过程中，颅内血管的血流速度增加^18-20，表明认知功能和颅内血流速度之间可能存在某种关系。TCD 作为一种有效、快速的工具，对 MCA 闭塞的诊断和排除有很好的效果^21-23.它还可以通过监测血流速度来反映 ACA 和 PCA 的侧支循环状态^{24 25}.

综上所述，MCA 闭塞对认知功能和血流动力学的影响值得关注。在这项横断面研究中，我们对动脉粥样硬化引起的 MCA 闭塞患者进行了认知功能评估和血流动力学监测，旨在从血流动力学角度探讨 MCA 闭塞患者认知功能变化的机制。

材料和方法：

2.1： 参与者

在这项研究中，我们纳入了 66 例大脑中动脉 M1 段单侧动脉粥样硬化闭塞患者和 23 例健康对照者。既往有缺血事件的患者定义为有症状，没有自我报告的中枢神经系统功能障碍症状和体征且头颅 CT 或 MRI 上脑实质或腔隙性梗死正常的患者被定义为无症状。纳入标准包括： （1） 年龄在 30 至 80 岁之间;（2） 由 CTA、MRA 或 DSA 确定的单侧大脑中动脉（M1 段）闭塞;（3） 非残疾，NIHSS<4;（4） 近 14 天内无脑梗死或短暂性脑缺血发作等新发缺血性脑血管事件;（5） 右撇子。排除标准： （1）存在其他影响认知功能的疾病和因素，如颅内出血、脑瘤、脑积水、抑郁症、精神疾病、药物滥用引起的阿尔茨海默病、帕金森病、脑外伤等;（2） 严重的视觉、听觉、语言和躯体功能障碍，无法完成相应的测试量表;（3） 神经心理学量表的评价过程协调性差;（4） 大面积脑梗死或皮质梗死;（5） 非动脉粥样硬化性狭窄（包括但不限于烟雾病和血管炎）;（6） 支架置入术、球囊扩张术、颈内动脉内膜切除术、动脉瘤栓塞术、动静脉畸形栓塞术或开腹头颈手术史。2021 年至 2024 年，所有患者均在安徽医科大学第一附属医院神经内科门诊或神经内科病房住院。对照组的参与者是在年龄、性别和受教育年限方面与患者组匹配的健康个体。

2.2 Demographic and general clinical data
2.2 人口统计学和一般临床数据

The basic information of the subjects, including gender, age, years of education, etc., was collected, and the past medical history of the subjects was recorded. The imaging data of the subjects were judged by neurologists after reviewing films or examination reports from professional medical institutions.
收集受试者的基本信息，包括性别、年龄、受教育年限等，并记录受试者的既往病史。受试者的影像学资料由神经内科医生在查阅影像或专业医疗机构的检查报告后进行判断。

2.3 Neuropsychological assessment
2.3 神经心理学评估

After all participants were enrolled, the same evaluator completed a full range of neuropsychological assessments, including global and individual cognitive assessments. Global cognitive function was assessed using MMSE, Montreal Cognitive Assessment (MoCA), and memory function was assessed using the Chinese version of Auditory Verbal Learning Test (CAVLT), which included immediate, delayed, and recognition memory functions. The digit span test was used to assess participants 'attention function, and the language fluency test was used to assess language function. Executive function was assessed using the stroop color word test and color trace test A/B. The assessors did not know the details of the subjects.
在所有参与者都被纳入后，同一位评估员完成了全方位的神经心理学评估，包括整体和个人认知评估。使用 MMSE 、蒙特利尔认知评估 （MoCA） 评估整体认知功能，使用中文版听觉语言学习测试 （CAVLT） 评估记忆功能，包括即时、延迟和识别记忆功能。数字跨度测试用于评估参与者的注意力功能，语言流利度测试用于评估语言功能。使用 stroop 颜色词测试和颜色痕迹测试 A/B 评估执行功能。评估员不知道受试者的细节。

2.4 Transcranial Doppler ultrasound assessment
2.4 经颅多普勒超声评估

TCD was performed using a Delicay device (Multi-Dop X digital, Singen(Germany)). All inspections were performed by the same operator. The following TCD parameters were obtained and recorded: peak systolic velocity (PSV), end-diastolic velocity (EDV), mean blood flow velocity (MBFV). All parameters were recorded 30 seconds after stable recording.
使用 Delicay 设备 （Multi-Dop X digital， Singen（Germany）） 进行 TCD。所有检查均由同一作员执行。获得并记录以下 TCD 参数：峰值收缩速度 （PSV） 、舒张末期速度 （EDV）、平均血流速度 （MBFV）。稳定记录后 30 秒记录所有参数。

2.5 MRI evaluation
2.5 MRI 评估

All subjects completed MRI data acquisition in the MRI Room of Information Center, University of Science and Technology, China. The MRI machine was a 3.0T scanner (GE 750w), and the scanning sequence was fMRI including T1-weighted MRI and pCASL. Sagittal T1-weighted images were obtained using a three-dimensional brain volume (3D-BRAVO) sequence with the following parameters: repetition time (TR) =8.16 ms, echo time (TE)= 3.18 ms, inversion time (TI) =450ms, acquisition time =283 s, flip angle (FA)=12°, matrix size =256×256, field of view (FOV)=256mm×256mm, slice thickness = 1mm, voxel size =1 × 1mm, slice thickness =180°; resting state perfusion images were collected using a pCASL sequence with 3D fast spin echo acquisition and background suppression. Acquisition parameters were as follows:TR=4781ms, TE= 11.12 ms, Delay after labeling =1525ms, Acquisition time =411s, FA=111°, Number of Excitations (NEX)=3, Matrix size =128×128, FOV=220mm×220mm, Voxel size =2 ×2mm, Slice thickness = 3mm, Serial Slice =45. All MRI data were preprocessed using MATLAB(R2013b), the Data Processing Assistant of the Rest-State Functional Magnetic Resonance Imaging Toolkit (DPARSF) and Statistical Parameter Mapping software (SPM8, http://www.fil.ion.ucl.ac.uk/spm). All CBF images were processed through the following steps:(1) data format conversion;(2) registration of CBF data to PET perfusion templates in the Montreal Neurological Institute (MNI) standard space;(3) division of CBF values for each voxel by the average CBF values for the whole brain to reduce the effects of individual differences; and (4) smoothing of normalized CBF images using a 3D Gaussian smoothing kernel with a full width at half maximum of 8 mm.
所有受试者均在中国科学技术大学信息中心 MRI 室完成 MRI 数据采集。MRI 机器为 3.0T 扫描仪 （GE 750w），扫描顺序为 fMRI，包括 T1 加权 MRI 和 pCASL。使用三维脑体积 （3D-BRAVO） 序列获得矢状 T1 加权图像，参数如下：重复时间 （TR） =8.16 ms，回波时间 （TE）= 3.18 ms，反转时间 （TI） =450ms，采集时间 =283 s，翻转角 （FA）=12°，矩阵尺寸 =256×256，视野 （FOV）=256mm×256mm，切片厚度 = 1mm，体素大小 =1 × 1mm，切片厚度 =180°;使用 pCASL 序列收集静息态灌注图像，具有 3D 快速自旋回波采集和背景抑制。采集参数如下：TR=4781ms，TE=11.12 ms，标记后延迟=1525ms，采集时间=411s，FA=111°，激发数（NEX）=3，矩阵大小=128×128，FOV=220mm×220mm，体素大小=2 ×2mm，切片厚度=3mm，序列切片=45。所有 MRI 数据均使用 MATLAB（R2013b）、剩余态功能磁共振成像工具包 （DPARSF） 的数据处理助手和统计参数映射软件 （SPM8， http://www.fil.ion.ucl.ac.uk/spm） 进行预处理。所有 CBF 图像均通过以下步骤处理：（1） 数据格式转换;（2） 在蒙特利尔神经学研究所 （MNI） 标准空间中将 CBF 数据注册到 PET 灌注模板;（3） 将每个体素的 CBF 值除以整个大脑的平均 CBF 值，以减少个体差异的影响;（4） 使用半峰全宽为 8 mm 的 3D 高斯平滑核对归一化 CBF 图像进行平滑处理。

2.6: Statistical analysis
2.6： 统计分析

Measurement data are expressed as mean ± standard deviation, and enumeration data are expressed as numbers. Differences in age, years of education, and cognitive assessments were assessed using one-way ANOVA (normally distributed data) or rank sum tests (non-normally distributed data), and differences in gender distribution, diabetes, and hypertension between control and patient groups were assessed using chi-square tests. The above analyses were performed using Social Science Statistical Package 26(SPSS, Chicago, IL, USA).
测量数据表示为平均值±标准差，计数数据表示为数字。使用单因素方差分析（正态分布数据）或秩和检验（非正态分布数据）评估年龄、教育年限和认知评估的差异，使用卡方检验评估对照组和患者组之间性别分布、糖尿病和高血压的差异。上述分析是使用 Social Science Statistical Package 26 （SPSS， Chicago， IL， USA） 进行的。

Results
结果

3.1: Demographic and clinical characteristics
3.1： 人口统计学和临床特征

Three groups showed no significant differences in gender, age, education and affected side distribution. Patients with sICAS and AsICAS had significantly higher prevalence of hypertension than HC. Demographic and clinical characteristics of the subjects are presented in Table 1.
3 组在性别、年龄、教育程度和患侧分布方面无显著差异。sICAS 和 AsICAS 患者的高血压患病率显著高于 HC。受试者的人口统计学和临床特征见表 1。

TABLE 1 Demographic data and clinical characteristics of the study participants
表 1 研究参与者的人口统计数据和临床特征

Note: ICAS: Intracranial atherosclerotic stenosis, AsICAS: Asymptomatic Intracranial atherosclerotic stenosis, HC: Healthy control; L: left, R: right.
注：ICAS：颅内动脉粥样硬化性狭窄，AsICAS：无症状颅内动脉粥样硬化性狭窄，HC：健康对照; L：左，R：右。

significant at 0.05 level, ** significant at 0.01 level, *** significant at 0.001 level (2-tailed);
在 0.05 水平显著，** 在 0.01 水平显著，*** 在 0.001 水平显著（2 尾）;

^aICAS groups versus AsICAS groups(p<0.05),
^aICAS 组与 AsICAS 组 （p<0.05），

^bICAS groups versus HC groups(p<0.05),
^bICAS 组 vs HC 组 （p<0.05），

^cAsICAS groups versus HC groups(p<0.05).
^cAsICAS 组与 HC 组 （p<0.05）。

3.2：Cognitive performance
3.2： 认知表现

MCA occlusion patients showed significant impairment in global cognition, memory, execution, language and attention, and significant gradient effects among HC, AsICAS and sICAS groups. AsICAS patients showed significant differences in executive function and language function compared with sICAS patients (Stroop-CW: P= 0.016, VFT-1: P= 0.011, VFT-2: P=0.003), and in AsICAS patients, contralateral MCA flow velocity was significantly correlated with executive function (Stroop-CW)(see Figure 2). The cognitive function assessment results of the subjects are shown in Table 2.
MCA 闭塞患者整体认知、记忆、执行、语言和注意力均出现显著受损，HC 、 AsICAS 和 sICAS 组间梯度效应显著。与 sICAS 患者相比，AsICAS 患者的执行功能和语言功能存在显著差异 （Stroop-CW： P= 0.016， VFT-1： P= 0.011， VFT-2： P=0.003），在 AsICAS 患者中，对侧 MCA 流速与执行功能显著相关 （Stroop-CW） （见图 2）。受试者的认知功能评估结果如 表 2 所示。

TABLE 2 Cognitive function assessments of the study participants
表 2 研究参与者的认知功能评估

Note:significant at 0.05 level, ** significant at 0.01 level, *** significant at 0.001 level (2-tailed);
注：在 0.05 水平显著，** 在 0.01 水平显著，*** 在 0.001 水平显著（2 尾）;

^aICAS groups versus AsICAS groups(p<0.05),
^aICAS 组与 AsICAS 组 （p<0.05），

^bICAS groups versus HC groups(p<0.05),
^bICAS 组 vs HC 组 （p<0.05），

^cAsICAS groups versus HC groups(p<0.05).
^cAsICAS 组与 HC 组 （p<0.05）。

3.3 Results of Ultrasound Assessment
3.3 超声评估结果

The flow velocity of ACA and PCA was significantly faster in AsICAS and sICAS than that in HC, but no significant difference was found between AsICAS and sICAS. In the comparison of flow velocity on the healthy side, AsICAS and sICAS groups were also significantly faster than HC group, and AsICAS group flow velocity was significantly faster than sICAS group, as shown in Figure 1.
AsICAS 和 sICAS 中 ACA 和 PCA 的流速显著快于 HC，但 AsICAS 和 sICAS 之间无显著差异。在健康侧流速比较中，AsICAS 和 sICAS 组也显著快于 HC 组，AsICAS 组流速显著快于 sICAS 组，如图 1 所示。

Figure 1: TCD monitoring of blood flow velocity in subjects
图 1：受试者血流速度的 TCD 监测

Note:significant at 0.05 level,* significant at 0.05 level, ** significant at 0.01 level, *** significant at 0.001 level (2-tailed);
注：在 0.05 水平显著，* 在 0.05 水平显著，** 在 0.01 水平显著，*** 在 0.001 水平显著（2 尾）;

i: ipsilateral side c: contrast side
I：同侧 C：造影剂侧

ACA: anterior cerebral artery MCA: middle cerebral artery PCA: posterior cerebral artery
ACA： 大脑前动脉 MCA： 大脑中动脉 PCA ： 大脑后动脉

vs: systolic peak velocity vd: diastolic end velocity vm: mean blood flow velocity
VS：收缩期峰值速度 VD：舒张期终末速度 VM：平均血流速度

Figure 2: Correlation between contralateral MCA velocity and Stroop-CW in AsICAS patients
图 2：AsICAS 患者对侧 MCA 速度与 Stroop-CW 的相关性

Note:i: ipsilateral side c: contrast side
注：i：同侧 c：造影剂侧

MCA: middle cerebral artery
MCA：大脑中动脉

vs: systolic peak velocity vd: diastolic end velocity vm: mean blood flow velocity
VS：收缩期峰值速度 VD：舒张期终末速度 VM：平均血流速度

Finally, 9 sICAS patients, 12 AsICAS patients, and 17 HC patients completed MRI scans. CBF was significantly lower than HC in sICAS group. See Table 3 for details.
最后，9 例 sICAS 患者、12 例 AsICAS 患者和 17 例 HC 患者完成了 MRI 扫描。sICAS 组 CBF 显著低于 HC。具体请参见表 3。

TABLE 3 CBF assessments of the study participants
表 3 研究参与者的 CBF 评估

Note:significant at 0.05 level, ** significant at 0.01 level, *** significant at 0.001 level (2-tailed);
注：在 0.05 水平显著，** 在 0.01 水平显著，*** 在 0.001 水平显著（2 尾）;

i: ipsilateral side c: contrast side b:bilateral
I：同侧 C：造影剂侧 B：双侧

^aICAS groups versus AsICAS groups(p<0.05),
^aICAS 组与 AsICAS 组 （p<0.05），

^bICAS groups versus HC groups(p<0.05),
^bICAS 组 vs HC 组 （p<0.05），

^cAsICAS groups versus HC groups(p<0.05).
^cAsICAS 组与 HC 组 （p<0.05）。

Discussion:
讨论：

In this study, we included patients with unilateral MCA occlusion and divided them into sICAS and AsICAS based on whether ischemic events occurred in the past. The blood flow velocities of bilateral ACA, MCA, and PCA were monitored by TCD to reflect their hemodynamic status, and the relationship between hemodynamic status and cognitive function was further explored. It was found that patients with MCA occlusion had significant impairments in overall cognition, memory, language, and execution, and showed a significant gradient effect among the three groups of HC, AsICAS, and sICAS. Moreover, a significant correlation between executive function (Stroop-CW) and the flow velocity of the healthy MCA was found in the AsICAS patient group. In terms of hemodynamics, except for the flow velocity of the MCA on the affected side, the flow velocities of the other major intracranial vessels in patients with MCA occlusion all showed significant increases. Among them, the contralateral flow velocity of patients with AsICAS was significantly faster than that of patients with sICAS, and significant differences were reflected in the comparison of flow velocities of ACA, MCA, and PCA on the healthy side. Furthermore, we quantitatively evaluated the cerebral blood perfusion of the subjects using ASL. In the comparison of perfusion on the affected side, the CBF on the affected side of patients with MCA occlusion was significantly decreased, among which the sICAS group was the lowest and significantly lower than HC. In the comparison of CBF on the healthy side, the sICAS group was the highest, and AsICAS was similar to HC, showing no significant difference.
在本研究中，我们纳入了单侧 MCA 闭塞患者，并根据过去是否发生过缺血事件将其分为 sICAS 和 AsICAS。TCD 监测双侧 ACA 、 MCA 和 PCA 的血流速度，以反映其血流动力学状态，并进一步探讨血流动力学状态与认知功能之间的关系。结果发现，MCA 闭塞患者在整体认知、记忆、语言和执行方面存在显著损害，并且在 HC 、 AsICAS 和 sICAS 三组之间表现出显着的梯度效应。此外，在 AsICAS 患者组中发现执行功能 （Stroop-CW） 与健康 MCA 的流速之间存在显着相关性。在血流动力学方面，除患侧 MCA 的流速外，MCA 闭塞患者其他主要颅内血管的流速均表现出显著增加。其中，AsICAS 患者的对侧流速显著快于 sICAS 患者，健康侧 ACA 、 MCA 和 PCA 的流速比较反映出显著差异。此外，我们使用 ASL 定量评估了受试者的脑血灌注。在患侧灌注比较中，MCA 闭塞患者患侧 CBF 显著降低，其中 sICAS 组最低，显著低于 HC。在健康侧 CBF 的比较中，sICAS 组最高，AsICAS 与 HC 相似，差异无统计学意义。

Previous studies have shown that ICAS is closely related to cognitive impairment^{26 27}. Our research found that patients with MCA occlusion had significant impairments in overall cognition, memory, language, execution, etc., and showed a significant gradient effect among the HC, AsICAS, and sICAS groups, further supporting the close connection between ICAS and cognitive impairment. The possible mechanisms of cognitive impairment caused by ICAS include chronic cerebral insufficiency, chronic inflammatory response, endothelial dysfunction, etc^28-30. Some studies have pointed out that atherosclerosis, on the one hand, can lead to lumen stenosis and occlusion of perforating arteries, resulting in progressive reduction of local blood flow and chronic hypoxia, and ultimately leading to metabolic failure^{31 32}. On the other hand, endothelial dysfunction leads to lipid accumulation and becomes an inflammatory precursor, which further activates the endothelium and causes the migration of adhesion molecules and chemokines, aggravating endothelial cell damage⁸. Furthermore, cognitive impairment caused by ICAS is often mixed with the effects of Alzheimer's disease and cerebral small vessel disease. Autopsy studies have shown that compared with subjects without dementia, patients clinically diagnosed with Alzheimer's disease before death have a higher burden of ICAS³³.
以前的研究表明，ICAS 与认知障碍密切相关 ^{26 27}。我们的研究发现，MCA 闭塞患者在整体认知、记忆、语言、执行等方面存在显著损害，并在 HC 、 AsICAS 和 sICAS 组中表现出显著的梯度效应，进一步支持 ICAS 与认知障碍之间的密切联系。ICAS 引起的认知障碍的可能机制包括慢性脑功能不全、慢性炎症反应、内皮功能障碍等 ^28-30。有研究指出，动脉粥样硬化一方面可导致肠腔狭窄和穿孔动脉闭塞，导致局部血流进行性减少和慢性缺氧，最终导致代谢衰竭 ^{31 32}。另一方面，内皮功能障碍导致脂质积累并成为炎症前体，进一步激活内皮并导致粘附分子和趋化因子的迁移，加重内皮细胞损伤 ⁸。 此外，ICAS 引起的认知障碍通常与阿尔茨海默病和脑小血管病的影响混合在一起。尸检研究表明，与没有痴呆的受试者相比，临床诊断为阿尔茨海默病的患者在死前具有更高的 ICAS³³ 负担 。

In addition to the above mechanisms, hemodynamic disorders caused by vascular stenosis due to atherosclerosis may also be one of the mechanisms leading to cognitive impairment
除上述机制外，动脉粥样硬化引起的血管狭窄引起的血流动力学障碍也可能是导致认知障碍的机制之一^34-37. Previous studies have suggested that endovascular treatment may improve patients' cognitive function
先前的研究表明，血管内治疗可能会改善患者的认知功能^{38 39}, and during the execution of cognitive tasks, the blood flow velocity of intracranial vessels will increase
，在执行认知任务的过程中，颅内血管的血流速度会增加¹⁸, suggesting that there may be a certain connection between cognitive function and hemodynamics
，表明认知功能和血流动力学之间可能存在某种联系. Our study included patients with unilateral occlusion of the M1 segment of the MCA.
.我们的研究包括 MCA M1 段单侧闭塞的患者。As the terminal artery of the internal carotid artery, when the M1 segment of the MCA is occluded, the forward blood flow at the lesion vessel significantly decreases. The low perfusion in the blood supply area of the MCA forms a pressure gradient, mainly providing blood supply through the compensatory formation of the lateral branches of the pia mater, resulting in a significant increase in the flow velocity of the remaining intracranial vessels 重试    错误原因 ^{25 40}. In our study, it was also observed that, except for the occluded MCA, the flow velocities of the remaining intracranial vessels increased significantly compared with HC. Meanwhile, we found a significant correlation between executive function (Stroop-CW) and the flow velocity of the healthy MCA in patients of the AsICAS group, suggesting that cognitive impairment in patients with MCA occlusion may be related to their hemodynamic impairment to some extent. We did not find the correlation between cognitive function in other dimensions and intracranial vascular velocity, possibly because executive function is the dimension that is most commonly impaired in patients with cognitive impairment caused by ICAS. Furthermore, we found that the cognitive function of patients in the AsICAS group was generally better than that of patients in the sICAS group, and the intracranial vascular flow velocity was generally faster than that of patients in the sICAS group. This suggests that the hemodynamic compensation of patients in the AsICAS group may be better than that of patients in the sICAS group, which might be one of the reasons for the better cognitive performance of patients in the AsICAS group. However, in the comparison of CBF on the healthy side, patients in the sICAS group had the highest rate. AsICAS was similar to HC and did not show significant differences. On the one hand, it might be that the number of subjects we included is relatively small, which may affect the results to a certain extent. On the one hand, it may be because ischemic events have occurred in patients with sICAS in the past, and the proportion of patients with incomplete wills arterial ring and hypertension in the sICAS group is the highest. This is related to cerebral hyperperfusion and simultaneously affects the redistribution
.在我们的研究中，还观察到，除了闭塞的 MCA 外，与 HC 相比，其余颅内血管的流速显着增加。同时，我们发现 AsICAS 组患者的执行功能 （Stroop-CW） 与健康 MCA 的流速之间存在显着相关性，表明 MCA 闭塞患者的认知障碍可能与他们的血流动力学障碍有一定程度的关系。我们没有发现其他维度的认知功能与颅内血管速度之间的相关性，可能是因为执行功能是 ICAS 引起的认知障碍患者最常受损的维度。此外，我们发现 AsICAS 组患者的认知功能普遍优于 sICAS 组患者，颅内血管流速普遍快于 sICAS 组患者。这表明 AsICAS 组患者的血流动力学代偿可能优于 sICAS 组患者，这可能是 AsICAS 组患者认知表现更好的原因之一。然而，在健康侧 CBF 的比较中，sICAS 组患者的发生率最高。AsICAS 与 HC 相似，无显著差异。一方面，可能是我们纳入的受试者数量比较少，这可能会在一定程度上影响结果。一方面，可能是因为 sICAS 患者既往曾发生过缺血事件，而 sICAS 组动脉环不完全和高血压患者比例最高。 这与脑高灌注有关，同时影响再分布 of intracranial blood flow.
颅内血流。

Endovascular treatment has been suggested to potentially improve cognitive function. However, given the risks of intracranial vascular interventional therapy, currently, it mostly relies on whether ischemic events occur, the degree of vascular stenosis, and perfusion status as the basis for surgical treatment. Our study focuses on two perspectives: cognitive function and hemodynamics. For patients with severely impaired cognitive function and poor hemodynamic status, A more aggressive treatment plan might need to be considered.
血管内治疗被认为有可能改善认知功能。但鉴于颅内血管介入治疗的风险，目前主要依靠是否发生缺血事件、血管狭窄程度和灌注状态作为手术治疗的依据。我们的研究侧重于两个角度：认知功能和血流动力学。对于认知功能严重受损和血流动力学状态不佳的患者，可能需要考虑更积极的治疗计划。

Despite careful recruitment of participants and data analysis, this study still has some limitations. Firstly, the sample size is relatively small, which may affect the results to a certain extent. Secondly, this study is a cross-sectional one, and it is difficult to obtain a strong causal relationship from the study itself. Thirdly, we failed to rule out the possible influence of stenosis of ACA and PCA in the enrolled patients. Fourth: We failed to rule out the damage to cognitively related brain regions caused by previous ischemic events in patients with sICAS, although we have chosen mild strokes and avoided the acute phase of cerebral infarction to minimize this impact as much as possible. In view of the above limitations, a larger sample size and corresponding follow-up observations are needed in the future.
尽管仔细招募了参与者并进行了数据分析，但这项研究仍然存在一些局限性。首先，样本量相对较小，这可能会在一定程度上影响结果。其次，这项研究是一项横断面研究，很难从研究本身获得很强的因果关系。第三，我们未能排除 ACA 和 PCA 狭窄对入组患者的可能影响。第四：我们未能排除 sICAS 患者既往缺血事件对认知相关脑区造成的损害，尽管我们选择了轻度卒中并避免了脑梗死的急性期，以尽可能减少这种影响。鉴于上述限制，未来需要更大的样本量和相应的后续观察。

Conclusion: The cognitive function of patients with MCA occlusion is significantly impaired. The executive function of patients with AsICAS is significantly better than that of patients with sICAS, which may be related to the better hemodynamics and collateral circulation status of patients with AsICAS. For patients with MCA occlusion who have experienced cognitive decline and poor blood flow compensation, a more aggressive treatment plan may need to be considered.
结论： MCA 闭塞患者的认知功能明显受损。AsICAS 患者的执行功能明显优于 sICAS 患者，这可能与 AsICAS 患者更好的血流动力学和侧支循环状态有关。对于经历认知能力下降和血流代偿不良的 MCA 闭塞患者，可能需要考虑更积极的治疗计划。

1. Gutierrez J, Turan TN, Hoh BL, et al. Intracranial atherosclerotic stenosis: risk factors, diagnosis, and treatment. Lancet Neurol 2022;21(4):355-68. doi: 10.1016/s1474-4422(21)00376-8 [published Online First: 20220207]
2022;21(4):355-68.doi： 10.1016/s1474-4422（21）00376-8 [在线首次发布：20220207]

2. Jia B, Zhang X, Ma N, et al. Comparison of Drug-Eluting Stent With Bare-Metal Stent in Patients With Symptomatic High-grade Intracranial Atherosclerotic Stenosis: A Randomized Clinical Trial. JAMA Neurol 2022;79(2):176-84. doi: 10.1001/jamaneurol.2021.4804
2022;79(2):176-84.doi： 10.1001/jamaneurol.2021.4804

3. Wang Y, Zhao X, Liu L, et al. Prevalence and outcomes of symptomatic intracranial large artery stenoses and occlusions in China: the Chinese Intracranial Atherosclerosis (CICAS) Study. Stroke 2014;45(3):663-9. doi: 10.1161/strokeaha.113.003508 [published Online First: 20140130]
2014;45(3):663-9.doi： 10.1161/strokeaha.113.003508 [首次在线发布： 20140130]

4. Levine DA, Galecki AT, Langa KM, et al. Trajectory of Cognitive Decline After Incident Stroke. Jama 2015;314(1):41-51. doi: 10.1001/jama.2015.6968
4. Levine DA， Galecki AT， Langa KM， et al. 中风后认知能力下降的轨迹。 贾马 2015;314(1):41-51.doi： 10.1001/jama.2015.6968

5. Pan Y, Meng X, Jing J, et al. Association of multiple infarctions and ICAS with outcomes of minor stroke and TIA. Neurology 2017;88(11):1081-88. doi: 10.1212/wnl.0000000000003719 [published Online First: 20170215]
2017;88(11):1081-88.doi： 10.1212/wnl.00000000000003719 [在线首次发布：20170215]

6. Si Q, Teng Y, Liu C, et al. Stroke incidence and cognitive outcomes of intracranial atherosclerotic stenosis: study protocol for a multicenter, prospective, observational cohort study. Ann Transl Med 2022;10(16):909. doi: 10.21037/atm-22-3570
2022;10(16):909.doi： 10.21037/atm-22-3570

7. Zwartbol MHT, van der Kolk AG, Ghaznawi R, et al. Intracranial atherosclerosis on 7T MRI and cognitive functioning: The SMART-MR study. Neurology 2020;95(10):e1351-e61. doi: 10.1212/wnl.0000000000010199 [published Online First: 20200706]
2020;95（10）：e1351-e61。doi： 10.1212/wnl.00000000000010199 [在线首次发布：20200706]

8. Zhao D, Guallar E, Qiao Y, et al. Intracranial Atherosclerotic Disease and Incident Dementia: The ARIC Study (Atherosclerosis Risk in Communities). Circulation 2024;150(11):838-47. doi: 10.1161/circulationaha.123.067003 [published Online First: 20240801]
2024;150(11):838-47.doi： 10.1161/circulationaha.123.067003 [在线首次发布：20240801]

9. Suri MFK, Zhou J, Qiao Y, et al. Cognitive impairment and intracranial atherosclerotic stenosis in general population. Neurology 2018;90(14):e1240-e47. doi: 10.1212/wnl.0000000000005250 [published Online First: 20180309]
2018;90（14）：e1240-e47。doi： 10.1212/wnl.00000000000005250 [首次在线发布：20180309]

10. van der Flier WM, Skoog I, Schneider JA, et al. Vascular cognitive impairment. Nat Rev Dis Primers 2018;4:18003. doi: 10.1038/nrdp.2018.3 [published Online First: 20180215]
2018;4:18003.doi： 10.1038/nrdp.2018.3 [首次在线发布：20180215]
10. van der Flier WM， Skoog I， Schneider JA， et al. 血管性认知障碍。 Nat Rev Dis 引物 2018;4：18003. doi： 10.1038/nrdp.2018.3 [在线首次发布：20180215]

11. van Dinther M, Hooghiemstra AM, Bron EE, et al. Lower cerebral blood flow predicts cognitive decline in patients with vascular cognitive impairment. Alzheimers Dement 2024;20(1):136-44. doi: 10.1002/alz.13408 [published Online First: 20230725]
2024;20(1):136-44.doi： 10.1002/alz.13408 [在线首次发布： 20230725]
11. van Dinther M， Hooghiemstra AM， Bron EE， et al. 较低的脑血流量预测血管性认知障碍患者的认知能力下降。 阿尔茨海默病 2024;20(1):136-44.doi： 10.1002/alz.13408 [在线首次发布： 20230725]

12. Hattori Y, Kakino Y, Nakaoku Y, et al. Cerebral hemodynamic severity of asymptomatic carotid artery stenosis/occlusion estimated by neurocognitive domains. J Alzheimers Dis 2025:13872877251344259. doi: 10.1177/13872877251344259 [published Online First: 20250525]
2025：13872877251344259. doi： 10.1177/13872877251344259 [首次在线发布： 20250525]
12. Hattori Y， Kakino Y， Nakaoku Y， et al. 由神经认知领域估计的无症状颈动脉狭窄/闭塞的脑血流动力学严重程度。 阿尔茨海默氏症杂志 2025：13872877251344259. doi： 10.1177/13872877251344259 [在线首次发布：20250525]

13. Williams JR, DeConne TM, Pewowaruk R, et al. Total and Structural Carotid Artery Stiffness Are Associated With Cognitive Decline and Structural Brain Abnormalities Related to Alzheimer Disease and Alzheimer Disease-Related Dementias Pathology: The Multi-Ethnic Study of Atherosclerosis. J Am Heart Assoc 2025;14(9):e039925. doi: 10.1161/jaha.124.039925 [published Online First: 20250502]
2025;14（9）：e039925。doi： 10.1161/jaha.124.039925 [在线首次发布：20250502]
13. Williams JR， DeConne TM， Pewowaruk R， et al. 颈动脉全动脉和结构性动脉僵硬 与认知能力下降和与阿尔茨海默病相关的脑结构异常和阿尔茨海默 病相关痴呆病理学相关： 动脉粥样硬化的 多种族研究。 J Am Heart Assoc 2025;14（9）：e039925。doi： 10.1161/jaha.124.039925 [在线首次发布：20250502]

14. Kakino Y, Hattori Y, Ogata S, et al. Cerebral Hemodynamic Impairment and Cognitive Dysfunction in APOE4 Carriers With Asymptomatic Carotid Artery Stenosis/Occlusion. J Am Heart Assoc 2025;14(6):e039210. doi: 10.1161/jaha.124.039210 [published Online First: 20250313]
2025;14（6）：e039210。doi： 10.1161/jaha.124.039210 [首次在线发布： 20250313]
14. Kakino Y， Hattori Y， Ogata S， et al. 无症状颈动脉狭窄/闭塞的 APOE4 携带者的脑血流动力学障碍和认知功能障碍。 J Am Heart Assoc 2025;14（6）：e039210。doi： 10.1161/jaha.124.039210 [首次在线发布：20250313]

15. Yin S, Zhang Y, Du B, et al. Effects of intracranial artery stenosis of anterior circulation on cognition-A CT perfusion-based study. Brain Behav 2024;14(9):e3521. doi: 10.1002/brb3.3521
2024;14（9）：e3521。doi： 10.1002/brb3.3521
15. Yin S， Zhang Y， Du B， et al.前循环颅内动脉狭窄对认知 A CT 灌注的影响研究。大脑行为 2024;14（9）：e3521。doi： 10.1002/brb3.3521

16. Aaslid R, Markwalder TM, Nornes H. Noninvasive transcranial Doppler ultrasound recording of flow velocity in basal cerebral arteries. J Neurosurg 1982;57(6):769-74. doi: 10.3171/jns.1982.57.6.0769
1982;57(6):769-74.doi： 10.3171/jns.1982.57.6.0769
16. Aaslid R， Markwalder TM， Nornes H. 无创经颅多普勒超声记录基底脑动脉流速。神经外科杂志 1982;57(6):769-74.doi： 10.3171/jns.1982.57.6.0769

17. DeWitt LD, Wechsler LR. Transcranial Doppler. Stroke 1988;19(7):915-21. doi: 10.1161/01.str.19.7.915
17. DeWitt LD，韦氏 LR。经颅多普勒。中风 1988;19(7):915-21.doi： 10.1161/01.str.19.7.915

18. Boban M, Črnac P, Junaković A, et al. Hemodynamic monitoring of middle cerebral arteries during cognitive tasks performance. Psychiatry Clin Neurosci 2014;68(11):795-803. doi: 10.1111/pcn.12191 [published Online First: 20140609]
2014;68(11):795-803.doi： 10.1111/pcn.12191 [在线首次发布： 20140609]
18. Boban M， Črnac P， JunakoviĆ A， et al. 认知任务执行期间大脑中动脉的血流动力学监测。 精神病学 Clin Neurosci 2014;68(11):795-803.doi： 10.1111/pcn.12191 [首次在线发布： 20140609]

19. Kelley RE, Chang JY, Scheinman NJ, et al. Transcranial Doppler assessment of cerebral flow velocity during cognitive tasks. Stroke 1992;23(1):9-14. doi: 10.1161/01.str.23.1.9
1992;23(1):9-14.doi：10.1161/01.str.23.1.9
19. Kelley RE， Chang JY， Scheinman NJ， et al. 认知任务期间脑流速的经颅多普勒评估。中风 1992;23(1):9-14.doi： 10.1161/01.str.23.1.9

20. Vingerhoets G, Stroobant N. Lateralization of cerebral blood flow velocity changes during cognitive tasks. A simultaneous bilateral transcranial Doppler study. Stroke 1999;30(10):2152-8. doi: 10.1161/01.str.30.10.2152
1999;30(10):2152-8.doi：10.1161/01.str.30.10.2152
20. Vingerhoets G， Stroobant N. 认知任务期间脑血流速度变化的偏侧化。一项同步双侧经颅多普勒研究。中风 1999;30(10):2152-8.doi： 10.1161/01.str.30.10.2152

21. Wong KS, Li H, Chan YL, et al. Use of transcranial Doppler ultrasound to predict outcome in patients with intracranial large-artery occlusive disease. Stroke 2000;31(11):2641-7. doi: 10.1161/01.str.31.11.2641
2000;31(11):2641-7.doi：10.1161/01.str.31.11.2641
21. Wong KS， Li H， Chan YL 等人。使用经颅多普勒超声预测颅内大动脉闭塞性疾病患者的预后。中风 2000;31(11):2641-7.doi： 10.1161/01.str.31.11.2641

22. Alexandrov AV, Bladin CF, Norris JW. Intracranial blood flow velocities in acute ischemic stroke. Stroke 1994;25(7):1378-83. doi: 10.1161/01.str.25.7.1378
22. 亚历山德罗夫 AV，布拉丁 CF，诺里斯 JW。急性缺血性卒中的颅内血流速度。中风 1994;25(7):1378-83.doi： 10.1161/01.str.25.7.1378

23. Mattioni A, Cenciarelli S, Eusebi P, et al. Transcranial Doppler sonography for detecting stenosis or occlusion of intracranial arteries in people with acute ischaemic stroke. Cochrane Database Syst Rev 2020;2(2):Cd010722. doi: 10.1002/14651858.CD010722.pub2 [published Online First: 20200219]
2020;2（2）：Cd010722. doi： 10.1002/14651858.CD010722.pub2 [在线首次发布：20200219]
23. Mattioni A， Cenciarelli S， Eusebi P， et al. 经颅多普勒超声检测急性缺血性中风患者颅内动脉狭窄或闭塞。 Cochrane 数据库系统修订版 2020;2（2）：Cd010722. doi： 10.1002/14651858.CD010722.pub2 [在线首次发布：20200219]

24. Kim Y, Sin DS, Park HY, et al. Relationship between flow diversion on transcranial Doppler sonography and leptomeningeal collateral circulation in patients with middle cerebral artery occlusive disorder. J Neuroimaging 2009;19(1):23-6. doi: 10.1111/j.1552-6569.2008.00242.x [published Online First: 20080519]
2009;19(1):23-6.doi： 10.1111/j.1552-6569.2008.00242.x [在线首次发布： 20080519]
24. Kim Y， Sin DS， Park HY， et al. 大脑中动脉闭塞性疾病患者经颅多普勒超声血流分流与软脑膜侧支循环的关系。 神经影像学杂志 2009;19(1):23-6.doi： 10.1111/j.1552-6569.2008.00242.x [在线首次发布： 20080519]

25. Wang N, Chen Z, Zhang S, et al. Leptomeningeal collateral flow in patients with middle cerebral artery occlusion assessed by transcranial Doppler. J Neuroimaging 2022;32(1):179-86. doi: 10.1111/jon.12937 [published Online First: 20211014]
2022;32(1):179-86.doi： 10.1111/jon.12937 [在线首次发布： 20211014]
25. Wang N， Chen Z， Zhang S， et al. 经颅多普勒评估大脑中动脉闭塞患者的软脑膜侧支血流。 神经影像学杂志 2022;32(1):179-86.doi： 10.1111/jon.12937 [在线首次发布： 20211014]

26. Dearborn JL, Zhang Y, Qiao Y, et al. Intracranial atherosclerosis and dementia: The Atherosclerosis Risk in Communities (ARIC) Study. Neurology 2017;88(16):1556-63. doi: 10.1212/wnl.0000000000003837 [published Online First: 20170322]
2017;88(16):1556-63.doi： 10.1212/wnl.00000000000003837 [在线首次发布：20170322]
26. Dearborn JL， Zhang Y， Qiao Y， et al. 颅内动脉粥样硬化和痴呆：社区动脉粥样硬化风险 （ARIC） 研究。 神经病学 2017;88(16):1556-63.doi： 10.1212/wnl.00000000000003837 [在线首次发布：20170322]

27. Gottesman RF, Mosley TH, Knopman DS, et al. Association of Intracranial Atherosclerotic Disease With Brain β-Amyloid Deposition: Secondary Analysis of the ARIC Study. JAMA Neurol 2020;77(3):350-57. doi: 10.1001/jamaneurol.2019.4339
2020;77(3):350-57.doi： 10.1001/jamaneurol.2019.4339
27. Gottesman RF、Mosley TH、Knopman DS 等人。颅内动脉粥样硬化疾病与脑 β-淀粉样蛋白沉积的关联：ARIC 研究的二次分析。美国医学会神经学杂志 2020;77(3):350-57.doi： 10.1001/jamaneurol.2019.4339

28. Rundek T, Tolea M, Ariko T, et al. Vascular Cognitive Impairment (VCI). Neurotherapeutics 2022;19(1):68-88. doi: 10.1007/s13311-021-01170-y [published Online First: 20211222]
28. Rundek T， Tolea M， Ariko T， et al. 血管性认知障碍 （VCI）。 神经治疗学 2022;19(1):68-88.doi： 10.1007/s13311-021-01170-y [在线首次发布： 20211222]

29. Mok VCT, Cai Y, Markus HS. Vascular cognitive impairment and dementia: Mechanisms, treatment, and future directions. Int J Stroke 2024;19(8):838-56. doi: 10.1177/17474930241279888
2024;19(8):838-56.doi： 10.1177/17474930241279888
29. 莫 VCT，蔡 Y，马库斯 HS。血管性认知障碍和痴呆：机制、治疗和未来方向。国际 J Stroke 2024;19(8):838-56.doi： 10.1177/17474930241279888

30. Farooq MU, Gorelick PB. Vascular cognitive impairment. Curr Atheroscler Rep 2013;15(6):330. doi: 10.1007/s11883-013-0330-z
30. Farooq MU，Gorelick PB。血管性认知障碍。Curr 动脉粥样硬化代表 2013;15(6):330.doi： 10.1007/s11883-013-0330-z

31. Iadecola C, Duering M, Hachinski V, et al. Vascular Cognitive Impairment and Dementia: JACC Scientific Expert Panel. J Am Coll Cardiol 2019;73(25):3326-44. doi: 10.1016/j.jacc.2019.04.034
2019;73(25):3326-44.doi： 10.1016/j.jacc.2019.04.034
31. Iadecola C， Duering M， Hachinski V， et al. 血管性认知障碍和痴呆症：JACC 科学专家组。J Am Coll 心脏 2019;73(25):3326-44.doi： 10.1016/j.jacc.2019.04.034

32. Yang D, Cherian L, Arfanakis K, et al. Intracranial atherosclerotic disease and neurodegeneration: a narrative review and plausible mechanisms. J Stroke Cerebrovasc Dis 2024;33(12):108015. doi: 10.1016/j.jstrokecerebrovasdis.2024.108015 [published Online First: 20240918]
32. Yang D， Cherian L， Arfanakis K， et al. 颅内动脉粥样硬化疾病和神经退行性变：叙述性回顾和可能的机制。 J Stroke Cerebrovasc Dis 2024;33(12):108015.doi： 10.1016/j.jstrokecerebrovasdis.2024.108015 [在线首次发布：20240918]

33. Sabayan B, Goudarzi R, Ji Y, et al. Intracranial Atherosclerosis Disease Associated With Cognitive Impairment and Dementia: Systematic Review and Meta-Analysis. J Am Heart Assoc 2023;12(22):e032506. doi: 10.1161/jaha.123.032506 [published Online First: 20231120]
2023;12（22）：e032506。doi： 10.1161/jaha.123.032506 [在线首次发布：20231120]
33. Sabayan B， Goudarzi R， Ji Y， et al. 与认知障碍和痴呆相关的颅内动脉粥样硬化疾病：系统评价和荟萃分析。 J Am Heart Assoc 2023;12（22）：e032506。doi： 10.1161/jaha.123.032506 [首次在线发布： 20231120]

34. Li C, Zhu Y, Ma Y, et al. Association of Cumulative Blood Pressure With Cognitive Decline, Dementia, and Mortality. J Am Coll Cardiol 2022;79(14):1321-35. doi: 10.1016/j.jacc.2022.01.045
2022;79(14):1321-35.doi： 10.1016/j.jacc.2022.01.045
34. Li C， Zhu Y， 马 Y， et al.累积血压与认知能力下降、痴呆和死亡率的关联。J Am Coll 心脏 2022;79(14):1321-35.doi： 10.1016/j.jacc.2022.01.045

35. Viticchi G, Falsetti L, Buratti L, et al. Carotid occlusion: Impact of cerebral hemodynamic impairment on cognitive performances. Int J Geriatr Psychiatry 2021;36(1):197-206. doi: 10.1002/gps.5414 [published Online First: 20200911]
2021;36(1):197-206.doi： 10.1002/gps.5414 [在线首次发布：20200911]
35. Viticchi G， Falsetti L， Buratti L， et al. 颈动脉闭塞：脑血流动力学损伤对认知能力的影响。 国际老年精神病学杂志 2021;36(1):197-206.doi： 10.1002/gps.5414 [在线首次发布： 20200911]

36. Lal BK, Dux MC, Sikdar S, et al. Asymptomatic carotid stenosis is associated with cognitive impairment. J Vasc Surg 2017;66(4):1083-92. doi: 10.1016/j.jvs.2017.04.038
2017;66(4):1083-92.doi： 10.1016/j.jvs.2017.04.038 [published Online First: 20170714]
36. Lal BK， Dux MC， Sikdar S， et al. 无症状颈动脉狭窄与认知 障碍有关。 J Vasc 外科杂志 2017;66(4):1083-92.doi： 10.1016/j.jvs.2017.04.038 [在线首次发布：20170714]

37. Balestrini S, Perozzi C, Altamura C, et al. Severe carotid stenosis and impaired cerebral hemodynamics can influence cognitive deterioration. Neurology 2013;80(23):2145-50. doi: 10.1212/WNL.0b013e318295d71a [published Online First: 20130426]
2013;80(23):2145-50.doi： 10.1212/WNL.0b013e318295d71a [在线首次发布：20130426]
37. Balestrini S， Perozzi C， Altamura C， et al. 严重的颈动脉狭窄和脑血流动力学受损会影响认知能力下降。 神经病学 2013;80(23):2145-50.doi： 10.1212/WNL.0b013e318295d71a [首次在线发布：20130426]

38. Ji R, Zhang S, Chen H, et al. Impact of Endovascular Revascularization on Functional Connectivity and Cognition in Symptomatic Chronic Internal Carotid Artery Occlusion Patients: A Preliminary Exploratory Study. J Integr Neurosci 2025;24(4):36330. doi: 10.31083/jin36330
2025;24(4):36330.doi： 10.31083/jin36330
38. Ji R， Zhang S， Chen H， et al.血管内血运重建对有症状的慢性颈内动脉闭塞患者功能连接和认知的影响：一项初步探索性研究。J Integr Neurosci 2025;24(4):36330.doi： 10.31083/jin36330

39. Kaur R, Summers P, Siu W, et al. Carotid Artery Stenting Intervention to Enhance Global Brain Blood Flow and Cognition in Carotid Artery Disease: Preliminary Findings from a Prospective Follow-Up MRI Study. Medicina (Kaunas) 2025;61(5) doi: 10.3390/medicina61050848 [published Online First: 20250505]
2025;61（5） doi： 10.3390/medicina61050848 [在线首次发布：20250505]
39. Kaur R， Summers P， Siu W， et al. 颈动脉支架置入术增强颈动脉疾病的整体脑血流和认知能力：前瞻性随访 MRI 研究的初步结果。 Medicina （Kaunas） 2025 年;61（5） doi： 10.3390/medicina61050848 [在线首次发布：20250505]

40. Zhang X, Zhang M, Ding W, et al. Distinct predictive role of collateral status on clinical outcome in variant stroke subtypes of acute large arterial occlusion. Eur J Neurol 2018;25(2):293-300. doi: 10.1111/ene.13493 [published Online First: 20171211]
2018;25(2):293-300.doi： 10.1111/ene.13493 [在线首次发布： 20171211]
40. Zhang X， Zhang M， Ding W， et al. 侧支状态对急性大动脉闭塞变异卒中亚型临床结果的独特预测作用。 欧洲神经杂志 2018;25(2):293-300.doi： 10.1111/ene.13493 [首次在线发布： 20171211]