Abstract:

Objective  To investigate the correlation of inflammatory factors and cerebrovascular reactivity with cognitive impairment in TIA patients.

Methods  This study prospectively enrolled 35 TIA inpatients in Qinghai University Affiliated Hospital as case group and 35 healthy subjects in health management center of this hospital as control group. The levels of serum soluble vascular cell adhesion molecule 1 (sVCAM-1) and lipoprotein-associated phospholipase A2 (Lp-PLA2) in the two groups were detected. Transcranial Doppler ultrasound (TCD) was used to evaluate cerebrovascular reactivity (CVR), and the main index is the breath-holding index (BHI). In addition, the Cambridge neuropsychological test automated battery (CANTAB) was used to evaluate cognitive function such as working memory, executive function and attention. The above indexes of the two groups were compared, and the correlation of two inflammatory factors and CVR with cognitive function in TIA patients were further analyzed.
Results  (1) The levels of sVCAM-1 (310.04±38.34 ng/mL vs. 208.12±31.10 ng/mL, P<0.001)and Lp-PLA2 (174.90±16.37 μg/L vs. 132.48±14.90 μg/L, P<0.001) in TIA group were higher than those in control group. (2) BHI in TIA group was lower than that in control group (1.08±0.65 vs. 1.40±0.42, P=0.024). (3) Compared with the control group, delayed matching to sample (DMS) total correct (DTC) and DTC in the patter of delay (DTCdelay) of working memory in TIA group were lower than those in control group [DTC: 28.00 (23.75-32.00) vs. 30.00 (28.00-33.00), P=0.041; DTCdelay: 18.63±4.81 vs. 21.23±3.10, P=0.016], DMS errors (DE) and DMS prob error given error (DPEGE) of working memory in TIA group were higher than that in control group [DE: 6.90±2.59 vs. 5.67±2.14, P=0.049; DPEGE: 0.34%±0.16% vs.0.26%±0.10%, P=0.038]. The stockings of cambridge (SOC) mean initial thinking time (SMITT) and SOC mean moves (SMM) of executive function in TIA group were higher than those in control group [SMITT: 2505.22±1031.03 ms vs. 1306.93.1±719.74 ms, P<0.001; SMM: 4.0 (3.0-5.0) vs. 3.0 (2.0-4.0), P=0.008]; the simple reaction time (SRT) mean latency (SML) in attention was higher than that in control group (606.83±222.34 ms vs. 483.18±130.52 ms, P=0.012). (4) DMS mean choices to correct (DMCTC) and DPEGE of working memory in TIA group were positively correlated with sVCAM-1 level; DTC, DTCdelay and DMS percent correct (DPC) of working memory in TIA group were negatively correlated with sVCAM-1 level. In TIA group, SMITT of executive function was positively correlated with the levels of sVCAM-1and Lp-PLA2, SRT total omission errors (STOE) in attention was positively correlated with Lp-PLA2 level; SMITT of executive function, STOE and SML in attention were negatively correlated with BHI; BHI was negatively correlated with the levels of sVCAM-1 and Lp-PLA2 in TIA group.
Conclusions  TIA patients have attention deficit, and declined working memory and executive function. For TIA patients, the cognitive impairment including working memory, attention and executive function is associated with the higher levels of inflammatory factors, and the decreased executive function and attention are associated with poor cerebrovascular reactivity.

Key words: Transient ischemic attack; Soluble vascular cell adhesion molecule 1; Lipoprotein-associated phospholipase A2; Cognitive function; Cerebrovascular reactivity

摘要：

目的 探讨TIA患者血清炎症因子、脑血管反应性（cerebrovascular reactivity，CVR）与认知障碍的关系。 

方法 前瞻性连续入组在青海大学附属医院住院治疗的TIA患者和体检中心健康体检者各35例，检测两组研究对象血清中可溶性血管细胞黏附分子-1（soluble vascular cell adhesion molecule 1，sVCAM-1）和脂蛋白相关磷脂酶A2（lipoprotein-associated phospholipase A2，Lp-PLA2）的水平；使用TCD检查评估CVR，主要指标为屏气指数（breath holding index，BHI）；使用剑桥神经心理学自动测试仪（Cambridge neuropsychological test automated battery,CANTAB）进行视觉工作记忆、执行功能、注意力等认知功能的评估。比较两组间sVCAM-1和Lp-PLA2两种炎症因子水平、CVR及认知功能的差异，进一步分析TIA组中认知功能、sVCAM-1和Lp-PLA2两种炎症因子、CVR指标之间的相关性。 

结果 ①与对照组相比，TIA组sVCAM-1水平（310.04±38.34 ng/mL vs. 208.12±31.10 ng/mL，P<0.001）和Lp-PLA2水平（174.90±16.37 μg/L vs. 132.48±14.90 μg/L，P<0.001）较高。②TIA组的BHI（1.08±0.65 vs. 1.40±0.42，P＝0.024）低于对照组。③TIA组视觉工作记忆评估指标中的样本延迟匹配（delayed matching to sample，DMS）总正确次数（DMS total correct，DTC）[28.00（23.75～32.00）次 vs. 30.00（28.00～33.00）次，P=0.041]、延迟选择模式下DTC（DTC延迟）（18.63±4.81次 vs. 21.23±3.10次，P=0.016）低于对照组，DMS选择错误次数（DMS errors，DE）（6.90±2.59次 vs. 5.67±2.14次，P=0.049）、DMS错误率（DMS prob error given error，DPEGE）（0.34%±0.16% vs. 0.26%±0.10%，P=0.038）高于对照组；执行功能指标中的空间规划能力测试（stockings of cambridge，SOC）平均初始思考时间（SOC mean initial thinking time，SMITT）（2505.22±1031.03 ms vs. 1306.93.1±719.74 ms，P<0.001）和SOC平均移动次数（SOC mean moves，SMM）[4.0（3.0～5.0）次 vs. 3.0（2.0～4.0）次，P=0.008]高于对照组；注意力指标中的简单反应时间（simple reaction time，SRT）平均延迟时间（SRT mean latency，SML）高于对照组（606.83±222.34 ms vs. 483.18±130.52 ms，P=0.012）。④TIA组视觉工作记忆评估指标中的DMS平均纠正次数（DMS mean choices to correct，DMCTC）、DPEGE与sVCAM-1水平呈正相关，DTC、DTC延迟及DMS正确率（DMS Percent correct，DPC）与sVCAM-1水平呈负相关；执行功能中的SMITT与sVCAM-1、Lp-PLA2水平均呈正相关；注意力中的SRT总遗漏数（SRT total omission errors，STOE）与Lp-PLA2水平呈正相关；执行功能中的SMITT、注意力中的SML和STOE与BHI呈负相关；BHI与sVCAM-1、Lp-PLA2水平呈负相关。 

结论 TIA患者存在注意力缺陷以及工作记忆、执行功能下降；TIA患者的工作记忆下降、执行功能下降、注意力缺陷与其较高的炎症因子水平有关；TIA患者的执行功能、注意力下降与CVR受损相关。

关键词: 短暂性脑缺血发作; 可溶性血管细胞黏附分子-1; 脂蛋白相关磷脂酶A2; 认知功能; 脑血管反应性