症状性颅内动脉粥样硬化性狭窄患者的认知功能及脑结构改变 Cognitive Function and Brain Structure Changes in Patients with Symptomatic Intracranial Atherosclerotic Stenosis

目的 探索症状性颅内动脉粥样硬化性狭窄（intracranial atherosclerotic stenosis，ICAS）患者的认知功能和脑结构改变，为症状性ICAS相关的认知障碍防治提供依据。 方法 本研究连续入组2021年12月—2022年12月就诊于北京协和医院神经科门诊诊断为ICAS相关的卒中或TIA患者。同时纳入年龄、受教育年限一致符合入组标准并连续入组的健康对照组。进行临床资料收集、成套认知功能测评（整体认知以及记忆、执行、语言、视空间结构功能4个认知域）和3D结构T1 MRI检查。使用DPABISurf软件进行脑影像数据预处理，获得各脑区（总脑皮质、总脑白质、丘脑、壳核、尾状核、苍白球、海马、杏仁核）体积和总脑容积。比较组间认知功能差异、脑结构差异及其与认知功能的相关性。 结果 共纳入60例症状性ICAS患者[男性40例，平均年龄（57.68±10.95）岁]，包括48例卒中（其中13例梗死灶在认知关键部位即丘脑或基底节，35例梗死灶不在认知关键部位）和12例TIA。同时纳入51例健康对照[男性36例，平均年龄（59.33±6.87）岁]。其中34例症状性ICAS患者和51例健康对照完善了3D结构T1 MRI检查。①认知功能状况：校正年龄、受教育年限、性别、脑血管病危险因素的影响，发现症状性ICAS组MMSE、MoCA评分以及记忆、执行、语言、视空间结构功能Z分均低于对照组（P<0.05）。亚组分析显示，梗死灶在认知关键部位组MMSE、MoCA评分以及执行、语言功能Z分低于对照组，梗死灶不在认知关键部位组MMSE、MoCA评分以及语言功能Z分低于对照组，TIA组语言功能Z分低于对照组（多重比较校正P<0.05）。②脑结构改变：校正混杂因素后，症状性ICAS组双侧脑皮质、脑白质、丘脑、壳核、苍白球、海马和杏仁核体积均低于对照组（P<0.05）。③脑结构与认知功能的相关性：左脑皮质体积与MMSE评分（r=0.784，P<0.001）、MoCA评分（r=0.649，P=0.001）和视空间结构功能Z分（r=0.761，P<0.001）呈正相关；左脑白质体积与MMSE评分（r=0.593，P=0.004）和视空间结构功能Z分（r=0.655，P=0.001）呈正相关；左丘脑体积与视空间结构功能Z分呈正相关（r=0.574，P=0.007）；左苍白球体积与MMSE评分呈正相关（r=0.562，P=0.006）；左海马体积与MMSE评分（r=0.744，P<0.001）、MoCA评分（r=0.632，P=0.002）、执行功能Z分（r=0.574，P=0.008）和视空间结构功能Z分（r=0.790，P<0.001）呈正相关。 结论 症状性ICAS患者存在不同程度的认知功能受损，呈现出广泛的双侧皮质、白质及皮质下脑结构改变，左侧脑萎缩与认知功能明显下降有关。 Abstract: Objective This study was aimed to evaluate the cognitive function and brain structure changes in patients with symptomatic intracranial atherosclerotic stenosis (ICAS), and to provide reference for the prevention and treatment of symptomatic ICAS related cognitive impairment. Methods Patients diagnosed with ICAS related stroke or TIA were consecutively recruited in Department of Neurology of Peking Union Medical College Hospital from December 2021 to December 2022. A control group with matching age and educational background was also recruited. Participants went through clinical data collection, packaged cognitive function assessment (including global cognition and four cognitive domains: memory, executive, language and visuospatial structure function), and 3D structural T1 MRI examination. Software DPABISurf was used to preprocess the brain imaging data. The volume of each brain region (including total cortex, total white matter, thalamus, putamen, caudate nucleus, globus pallidus, hippocampus, amygdala) and estimated total intracranial volume were obtained. The inter-group differences of cognitive function, brain structure and its correlation with cognitive function were compared. Results A total of 60 patients with symptomatic ICAS [40 males, mean age of (57.68±10.95) years], including 48 patients with stroke [13 patients had infarcts in the key areas of cognition (i.e., thalamus or the basal ganglia), and 35 patients had infarcts not in the key areas of cognition] and 12 patients with TIA were recruited. 51 normal controls [36 males, mean age of (59.33±6.87) years] were recruited. Among the participants, 34 patients with symptomatic ICAS and 51 normal controls completed 3D structural T1 MRI examination. The result of comparation were the following. ①Cognitive function status: after adjusting age, educational background, gender and cerebrovascular disease risk factors, it was found that the MMSE, MoCA scores and Z scores of memory, executive, language and visuospatial structure function of the symptomatic ICAS group were lower compared with the controls (P<0.05). Subgroup analysis showed that the MMSE, MoCA scores and Z scores of executive, language function of the group with infarction at the key areas of cognition were lower compared with the controls; the MMSE, MoCA scores and Z score of language function of the group with infarction not at the key areas of cognition were lower compared with the controls; the Z score of language function of the TIA group was lower compared with the controls (multiple comparison corrected, P<0.05). ②Brain structures changes: after adjusting for confounding factors, it was found that patients with symptomatic ICAS showed brain volume reduction of bilateral cortex, white matter, thalamus, putamen, globus pallidus, hippocampus and amygdala compared with the controls (P<0.05). ③Correlations between brain structures and cognitive function: left cortex volume had a positive correlation with MMSE score (r=0.784, P<0.001), MoCA score (r=0.649, P=0.001) and Z score of visuospatial structure function (r=0.761, P<0.001); left white matter volume was positively correlated with MMSE score (r=0.593, P=0.004) and Z score of visuospatial structure function (r=0.655, P=0.001); left thalamus volume was positively correlated with Z score of visuospatial structure function (r=0.574, P=0.007); left globus pallidus volume was positively correlated with MMSE score (r=0.562, P=0.006); left hippocampus volume had a positive correlation with MMSE score (r=0.744, P<0.001), MoCA score (r=0.632, P=0.002), Z score of executive function (r=0.574, P=0.008) and visuospatial structure function (r=0.790, P<0.001). Conclusions Patients with symptomatic ICAS had different degrees of declined cognitive function. Symptomatic ICAS patients showed extensive bilateral cortical, white matter, and subcortical brain structural changes. The left brain atrophy was correlated with significant decline in cognitive function.

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