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目的 探讨脑小血管病（CSVD）患者预防性应用不同抗血小板药物治疗方案（阿司匹林与氯吡格雷及其具体剂量）对其认知功能、血液指标及脑影像学标志物的影响。方法 采用随机对照研究方法，纳入160例CSVD患者，随机分为：阿司匹林组（ASA组）、氯吡格雷低量组（CLOP-50组）、氯吡格雷常量组（CLOP-75组）及对照组（HC组）。各在基线及治疗6个月时评估认知功能[听觉词语学习测试即刻（AVLT-IR）、听觉词语学习测试短延迟回忆（AVLT-SDR）、听觉词语学习测试长延迟回忆（AVLT-LDR）、汉密尔顿焦虑量表（HAMA）及汉密尔顿抑郁量表（HAMD）、日常生活能力量表（ADL）、痴呆筛查量表（AD8）等]、血液指标[血小板计数（PLT）和平均血小板体积（MPV）等]及CSVD相关影像标志物[脑白质高信号（WMH）、脑微出血（CMB）]的变化。结果 治疗6个月后，组内比较显示，与基线水平相比，ASA组患者的AVLT即刻（AVLT-IR）、短延迟回忆（AVLT-SDR）及长延迟回忆（AVLT-LDR）得分均升高（P<0.05）;CLOP-75组患者HAMA及HAMD得分均降低（P<0.05），且其AVLT-LDR得分亦升高（P<0.05）;ASA组与CLOP-75组的CMB个数均较基线增加（P<0.05），但两组在血液指标方面与基线相比差异无统计学意义。与基线水平相比，CLOP-50组及HC组在认知功能、血液指标及CSVD相关影像学标志物方面变化差异均无统计学意义（P>0.05）。各组间比较显示，ASA组AVLT-LDR评分及CMB数量上的升高速度均快于HC组（β=-0.187, P=0.040;β=-0.805, P<0.001），且ASA组CMB数量的增加速度亦快于CLOP-50组（β=-0.695, P<0.01）。HC组ADL评分的升高速度快于ASA组（β=0.170, P=0.02）。CLOP-75组AD8评分上的下降速度快于HC组（β=-0.128, P=0.04），但其CMB数量的增加速度也快于HC组（β=0.604, P=0.04）。结论 在CSVD患者中，阿司匹林100 mg或氯吡格雷75 mg虽可改善认知功能，但会增加脑出血风险；而氯吡格雷50 mg短期未见临床获益及影像学改善。
Abstract：Objective To investigate the effects of different antiplatelet therapy regimens(aspirin versus clopido‑grel at specific doses) on cognitive function, blood biomarkers and brain imaging biomarkers when used prophylac‑tically in patients with cerebral small vessel disease(CSVD).Methods A randomized controlled trial was con‑ducted involving 160 CSVD patients who were randomly assigned to four groups: aspirin group(ASA), low-dose clopidogrel group(CLOP-50), standard-dose clopidogrel group(CLOP-75), and control group(HC). Cognitive function [auditory verbal learning test-immediate recall(AVLT-IR), auditory verbal learning test-short-delay re‑call(AVLT-SDR), auditory verbal learning test-long-delay recall(AVLT-LDR), hamilton anxiety rating scale(HAMA), and hamilton depression rating scale(HAMD), ADL(activities of daily living scale),(ascertain de‑mentia 8-item questionnaire,AD8)], blood biomarkers [platelet count(PLT) and mean platelet volume(MPV)], and CSVD-related imaging biomarkers [white matter hyperintensities(WMH) and cerebral microbleeds(CMB)] were assessed in all groups at baseline and at the 6-month follow-up.Results After 6 months of treatment, withingroup comparisons showed that, compared with baseline, the ASA group had significantly increased scores on the AVLT immediate recall(AVLT-IR), short-delay recall(AVLT-SDR), and long-delay recall(AVLT-LDR)(P<0. 05). The CLOP-75 group showed significantly decreased HAMA and HAMD scores(P<0. 05), along with a sig‑nificant increase in AVLT-LDR scores(P<0. 05). The number of CMBs increased from baseline in both the ASA and CLOP-75 groups(P<0. 05), whereas no statistically significant changes in blood biomarkers were observed in either group. By contrast, the CLOP-50 and HC groups showed no significant changes in cognitive function, blood biomarkers, or CSVD-related imaging biomarkers compared with baseline(all P<0. 05). Comparisons between groups showed that the AVLT-LDR scores and the number of CMBs increased faster in the ASA group than in the HC group(β=-0. 187, P=0. 04; β=-0. 805, P<0. 001). In addition, the rate of CMB increase was also faster in the ASA group than in the CLOP-50 group(β=-0. 695, P<0. 01). The ADL scores increased faster in the HC group than in the ASA group(β=0. 170, P=0. 02). The AD8 scores decreased faster in the CLOP-75 group than in the HC group(β=-0. 128, P=0. 04), but the rate of CMB increase in the CLOP-75 group was also faster than that in the HC group(β=0. 604, P=0. 04).Conclusion In CSVD patients, aspirin 100 mg or clopidogrel 75 mg im‑proves cognitive function but increases the risk of cerebral hemorrhage. Clopidogrel 50 mg shows no short-term clinical benefit or imaging improvement.
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基本信息:
DOI：10.19405/j.cnki.issn1000-1492.2026.09.022
中图分类号:R743
引用信息:
[1]王志鑫,王月华,秦佳佳,等.不同抗血小板治疗方案对脑小血管病患者的认知功能及脑影像标志物的影响[J].安徽医科大学学报,2026(09):1679-1687.DOI:10.19405/j.cnki.issn1000-1492.2026.09.022.
基金信息:
安徽省高校科研项目(编号:2022AH040159)
2026-08-07
2026-08-07
2026-08-07