Abstract:

Objective HHcy is one of the independent risk factors for either cerebrovascular disease or cognitive impairment. The aim of this study is to investigate the relationship between blood Hcy level and early cognitive impairment in small vessel disease (SVD). Methods The data of SVD patients with no dementia from stroke clinic in our hospital for poststroke follow-up were consecutively collected. The data included demographic information, vascular risk factors (VRFs) spectrum, cognitive assessment results and etc. The fasting blood Hcy was measured within 1 week after enrollment. HHcy was defined as plasma Hcy level higher than 15 μmol/L. According to the Hcy test results, the patients were divided into HHcy group (Hcy>15 μmmol/L) and normal homocysteine (NHcy) group (Hcy≤15 μmol/L). Multimodal MRI was performed in all patients within 2 weeks after enrollment. The cognitive scores and imaging feature between the two groups were compared. The correlations of Hcy level with cognitive assessment results as well as with the imaging indices were analyzed. Results (1) A total of 81 SVD patients were enrolled in this study, with average age (64.3±7.4) years old, 65 male patients (80.2%) and 50 patients (61.7%) with mild cognitive impairment. (2) 30 patients (37.0%) in HHcy group and 51 ones (63.0%) in NHcy group. There were more smoking patients in HHcy than in NHcy group. There were no significant difference in age, gender, education years between the two groups. (3) There were significant difference in the attentionexecutive function assessment such as trail making test B (TMT-B) (P =0.016), digital symbol substitution test (DSST) (P =0.013) and forward digital span test (DS-forward) (P =0.029) scores between the two groups. (4) The proportion of moderate to severe periventricular white matter lesions (PV-WMLs) (63.3% vs 39.2%, P =0.018), deep WMLs (60.0% vs 37.3%, P =0.036) and multiple cerebral microbleedings (CMBs) (36.7% vs 17.3%, P =0.047) in HHcy group were higher than those in NHcy group. The blood Hcy level was correlated with PV-WMLs (r =0.227, P =0.041). (5) After adjusting for PV-WMLs score, Hcy level was positively correlated with TMT-B time (r =0.278, P =0.013), negatively correlated with DSST (r =-0.354, P =0.004) and DS-forward (r =-0.366, P =0.001). Conclusions The blood Hcy level in SVD was significantly correlated with attention-executive function and PV-WMLs. The blood Hcy level might be one of the markers of early cognitive impairment in SVD.

Key words: Small vessel disease; Hyperhomocysteinemia; Cognition; Neuroimaging

摘要：

目的 HHcy是脑血管病和认知功能障碍的危险因素之一。本文拟明确脑小血管病（small vessel disease，SVD）患者外周血Hcy水平与早期认知功能损害的相关性及其机制。 方法 连续入组缺血性卒中后门诊随访的非痴呆SVD患者，登记人口社会学、血管危险因素等资 料，进行全面认知评估。入组1周内采集空腹静脉血检测Hcy，根据血浆Hcy水平将SVD患者分为HHcy组 （Hcy＞15 μmmol/L）和正常Hcy（normal Hcy，NHcy）组（Hcy≤15 μmmol/L）。2周内行多模式头颅MRI检 查。对2组患者的认知评分及影像特点进行比较，并与Hcy水平进行相关性分析。 结果 ①研究共纳入81例SVD患者，平均年龄（64.3±7.4）岁；男性65例，占80.2%；轻度认知障 碍50例，占61.7%。②HHcy组30例（37.0%），NHcy组51例（63.0%）。HHcy组吸烟比例高于NHcy组。 ③HHcy组执行功能中交替连线测验B（trail making test B，TMT-B）耗时数高于NHcy组（P =0.016），数 字符号转换测验（digital symbol substitution test，DSST）（P =0.013）、数字广度测验（digital span test， DS）顺背（P =0.029）得分低于NHcy组。④HHcy组较NHcy组中重度脑室旁白质病变（63.3% vs 39.2%， P =0.018）、深部白质病变（60.0% vs 37.3%，P =0.036）和多发微出血（36.7% vs 17.3%，P =0.047）的 比例更高，且Hcy水平与脑室旁白质病变评分显著相关（r =0.227，P =0.041）。⑤经脑室旁白质病变评 分校正后，Hcy水平与TMT-B耗时数（r =0.278，P =0.013）正相关，与DSST（r =-0.354，P =0.004）和DS 顺背（r =-0.366，P =0.001）得分负相关。 结论 SVD患者外周血Hcy水平与执行注意以及脑室旁白质病变严重程度显著相关，外周血Hcy水平 可能是SVD早期认知功能障碍的生物标志物之一。

关键词: 脑小血管病; 高同型半胱氨酸血症; 认知功能; 神经影像