目的 探讨盐酸多奈哌齐联合尼莫地平片对脑小血管病致认知功能障碍患者认知功能及生活质量的影响。方法 选取郑州大学附属郑州中心医院91例脑小血管病致认知功能障碍患者,按照随机数字表法分组,对照组45例予以盐酸多奈哌齐治疗,观察组46例予以盐酸多奈哌齐+尼莫地平片治疗,观察2组认知功能(MoCA)评分及临床治疗效果,并统计2组不良反应发生情况及生活质量(QOL)评分。结果 观察组用药3个月后MoCA评分较对照组高,差异有统计学意义(P<0.05);观察组治疗总有效率为89.13%(41/46),高于对照组68.89%(31/45),差异有统计学意义(P<0.05);观察组不良反应发生率为15.22%(7/46),对照组为6.67%(3/45),组间比较差异无统计学意义(P>0.05);用药3个月后观察组QOL评分高于对照组,差异有统计学意义(P<0.05)。结论 对脑小血管病致认知功能障碍患者给予盐酸多奈哌齐联合尼莫地平片治疗,效果显著,用药安全性高,可改善患者生活质量及认知功能。
多奈哌齐联合尼莫地平片对脑小血管病患者认知功能的影响
尹刘杰 李世泽△
郑州大学附属郑州中心医院,河南郑州 450000
作者简介:尹刘杰,Email:sunny527xx@sina.com
△通信作者:李世泽,Email:13683812815@163.com
【摘要】 目的 探讨盐酸多奈哌齐联合尼莫地平片对脑小血管病致认知功能障碍患者认知功能及生活质量的影响。方法 选取郑州大学附属郑州中心医院91例脑小血管病致认知功能障碍患者,按照随机数字表法分组,对照组45例予以盐酸多奈哌齐治疗,观察组46例予以盐酸多奈哌齐+尼莫地平片治疗,观察2组认知功能(MoCA)评分及临床治疗效果,并统计2组不良反应发生情况及生活质量(QOL)评分。结果 观察组用药3个月后MoCA评分较对照组高,差异有统计学意义(P<0.05);观察组治疗总有效率为89.13%(41/46),高于对照组68.89%(31/45),差异有统计学意义(P<0.05);观察组不良反应发生率为15.22%(7/46),对照组为6.67%(3/45),组间比较差异无统计学意义(P>0.05);用药3个月后观察组QOL评分高于对照组,差异有统计学意义(P<0.05)。结论 对脑小血管病致认知功能障碍患者给予盐酸多奈哌齐联合尼莫地平片治疗,效果显著,用药安全性高,可改善患者生活质量及认知功能。
【关键词】 脑小血管病;认知功能障碍;盐酸多奈哌齐;尼莫地平片;认知功能;生活质量
【中图分类号】 R743 【文献标识码】 A 【文章编号】 1673-5110(2018)24-2703-05 DOI:10.12083/SYSJ.2018.24.564
Influence of donepezil and nimodipine on cognitive function and life quality of patients with cognitive disorder caused by CSVD
YIN Liujie,LI Shize
Zhengzhou Central Hospital Affiliated of Zhengzhou University,Zhengzhou 450000,China
【Abstract】 Objective To investigate the influence of donepezil and nimodipine on cognitive function,life quality of patients with cognitive disorder caused by CSVD.Methods 91 cases with cognitive disorder caused by CSVD in Zhengzhou Central Hospital Affiliated of Zhengzhou University were selected and divided according to random number table.45 cases in control group and was given donepezil,46 cases in observation group and was given donepezil + nimodipine.The MoCA score and clinic effect of the two groups,record the adverse reactions and QOL of the tow groups were compared.Results 3 months after medicine,MoCA score of observation group was higher than control group,the difference was statistic snigificant (P<0.05);total efficiency of observation group [89.13%(41/46)]was higher than control group [68.89%(31/45)],the difference was statistic snigificant (P<0.05);adverse reaction rate of observation group and control group were 15.22%(7/46)and 6.67%(3/45),the difference between the groups was not statistic snigificant (P>0.05);3 months after medicine,QOL of observation group was higher than control group,the difference was statistic snigificant (P<0.05).Conclusion Donepezil and nimodipine in treating patients with cognitive disorder caused by CSVD has significant effect and higher safety,it can improve life quality and cognitive function of patients.
【Key words】 CSVD;Cognitive function disorder;Donepezil;nimodipine;Cognitive function;Life quality
脑小血管病(cerebral small vessel disease,CSVD)是由颅内微动脉或小动脉病变引发的颅内出血性损害或脑缺血,临床多表现为平衡障碍、认知功能障碍、尿失禁、注意力不集中等,严重者甚至诱发血管性痴呆、阿尔茨海默病,严重影响患者日常生活[1-3]。及早对CSVD所致认知功能障碍患者给予胆碱酯酶抑制剂盐酸多奈哌齐治疗,可缓解患者临床症状,促进其认知功能恢复,但单一用药治疗疗程长,预后效果不理想[4-5]。有学者指出尼莫地平片可改善脑部微循环,保护脑细胞,缓解患者认知功能障碍[6-7]。由此表明盐酸多奈哌齐与尼莫地平在治疗血管性痴呆以及改善患者认知功能及日常生活活动能力方面均具有显著效果,但二者联合治疗CSVD致认知功能障碍效果如何,临床鲜有研究。本研究将盐酸多奈哌齐与尼莫地平片联合应用于CSVD致认知功能障碍患者,探讨其对生活质量及认知功能的影响。
1 对象和方法
1.1 研究对象 选取2014-10—2016-11在郑州大学附属郑州中心医院接受治疗的91例CSVD致认知功能障碍患者,按照随机数字表法分组,对照组45例,男24例,女21例,年龄50~80(63.38±4.72)岁,病程2~11(6.40±4.10)a,受教育年限6~15(11.48±3.39)a;并发症:高血压25例,糖尿病20例。观察组46例,男26例,女20例,年龄51~79(62.44±4.67)岁,病程2~13(6.71±4.23)a,受教育年限6~17(12.56±3.28)a;并发症:高血压27例,糖尿病19例。2组临床资料对比无显著差异(P>0.05)。本研究经院伦理委员会审核通过。
1.2 入选与排除标准 (1)入选标准:均经头颅MRI或脑CT检查确诊为CSVD[8-10];患者或家属知晓本研究并签署书面知情同意书。(2)排除标准:伴恶性肿瘤患者;心、肾、肝功能严重不全者;对本研究所用药物成分过敏者;缺氧性脑病或一氧化碳中毒、低血糖、脑积水等造成的脑白质异常;变性疾患或全身性疾病引发的认知功能减退。
1.3 方法 对照组口服5 mg盐酸多奈哌齐(山东罗欣药业集团股份有限公司,国药准字H20080381)治疗,1次/d,持续治疗3个月。观察组于以上基础上口服尼莫地平片(湖南绅泰春药业有限公司,国药准字H43020833)治疗,30 mg/次,3次/d,持续治疗3个月。
1.4 观察指标 (1)采用蒙特利尔认知评定量表(MoCA)对2组用药前及用药3个月后认知功能进行评估对比。得分越高,认知功能恢复越好,MoCA评分不足26分为认知功能障碍[11-13]。(2)依据MoCA评分提高率评估临床治疗效果,MoCA评分提高率=(治疗后评分-治疗前评分)/治疗前评分×100%。MoCA评分提高率不足12%为无效;MoCA评分提高率为12%及以上但不足20%为好转;MoCA评分提高率为20%及以上为显著好转。总有效率为好转率与显著好转率之和。(3)统计比较2组血压下降、面部潮红、嗜睡、心动过缓、头晕等不良反应发生情况。(4)以生活质量评定量表(QOL)对2组用药前及用药后3个月生活质量进行评估比较,得分与生活质量呈正相关即分数越高生活质量越好[14-16]。
1.5 统计学分析 以SPSS 20.0进行数据分析,计量资料以均数±标准差(x±s)表示,采用t检验,计数资料以百分数(%)表示,采用χ2检验,P<0.05为差异有统计学意义。
2 结果
2.1 2组MoCA评分对比 用药3个月后相比于对照组,观察组MoCA评分较高,差异有统计学意义(P<0.05)。见表1。
2.2 2组治疗效果对比 观察组治疗总有效率较对照组高,差异有统计学意义(P<0.05)。见表2。
表1 2组用药前后MoCA评分对比 (x±s,分)
Table 1 Comparison of MoCA scores before and after treatment (x±s,score)
组别 |
n |
用药前 |
用药3个月后 |
观察组 |
46 |
18.10±1.69 |
27.40±1.16 |
对照组 |
45 |
18.05±1.27 |
22.21±2.02 |
t值 |
|
0.159 |
15.071 |
P值 |
|
0.874 |
0.000 |
表2 2组临床疗效对比 [n(%)]
Table 2 Comparison of clinical efficacy between the two groups [n(%)]
组别 |
n |
无效 |
好转 |
显著好转 |
总有效 |
观察组 |
46 |
5(10.87) |
19(41.30) |
22(47.83) |
41(89.13) |
对照组 |
45 |
14(31.11) |
11(24.44) |
20(44.44) |
31(68.89) |
χ2值 |
|
|
|
|
5.642 |
P值 |
|
|
|
|
0.018 |
2.3 2组不良反应对比 观察组不良反应发生率(15.22%)相较于对照组(6.67%),差异无统计学意义(P>0.05)。见表3。
2.4 2组QOL评分比较 用药3个月后相比于对照组,观察组QOL评分较高,差异有统计学意义(P<0.05)。见表4。
3 讨论
CSVD为临床常见隐袭性脑血管病变,多发于中老年人群,随着人口老龄化进程加速,近年来其患病率逐年激增,其诱发的认知功能障碍患病人数亦逐年递增,已成为危害中老年人群生命健康的主要疾患之一[17-21]。CSVD致认知功能障碍危害大,需及早给予治疗,其主要发病机制为小动脉低灌注及小动脉狭窄致使动脉边缘带缺血,损害侧脑深部及室旁白质,破坏患者额叶-皮层下环路,进而损害其认知功能;此外小动脉阻滞引发的腔隙性梗死亦可损害患者皮层下白质,诱发认知功能障碍[22-25]。有学者研究指出乙酰胆碱水平的降低与CSVD发生、发展关系密切,其水平降低可促使患者记忆力减退,降低其认知、学习能力[26]。故如何选取合理、有效药物,改善患者中枢神经系统乙酰胆碱水平,促进其认知功能恢复,已成为临床研究重点。
盐酸多奈哌齐为六氢吡啶衍生物的一种,可选择性抑制患者中枢神经系统胆碱酯酶,提高脑组织神经突触间乙酰胆碱浓度,进而改善患者认知及记忆能力;且其可改善脑血流,将N受体激活,降低谷氨酸及自由基对脑神经的毒性作用,促进脑组织功能恢复,保护脑细胞。尼莫地平片为钙离子通道阻滞剂,具有较高脂溶性,口服后可迅速穿透血脑屏障,将L2型钙离子通道阻断,阻断异常的钙离子内流,抑制血管平滑肌细胞钙内流,改善脑细胞钙超载现象,增加脑血流,调节脑血管,预防脑血管痉挛,减轻患者脑组织损伤程度,促进其脑功能恢复,且不产生盗血作用,安全性高;同时该药物可抑制脑血管周围组织常见的脂质沉积及纤维变性发生,有助于患者认知功能的改善;此外其可抑制神经元凋亡、坏死,稳定神经细胞功能,提升患者记忆力及学习能力[27-28]。与盐酸多奈哌齐联合使用,可发挥药物间协同效应,互增药效,恢复其认知功能,疗效显著。本研究发现,用药3个月后观察组治疗总有效率及MoCA评分均高于对照组,表明对CSVD致认知功能障碍患者给予尼莫地平片与盐酸多奈哌齐联合治疗,可改善患者认知功能障碍,提高疗效;同时本研究发现观察组用药3个月后QOL评分高于对照组,且2组不良反应发生率均较低,旨在说明在使用盐酸多奈哌齐治疗的同时加用尼莫地平片可提高CSVD致认知功能障碍患者生活质量,用药安全性高。
尼莫地平片与盐酸多奈哌齐联合应用于脑小血管病致认知功能障碍患者,效果较佳,有助于其认知功能恢复,改善其生活质量,安全性高。
表3 2组不良反应发生率对比 [n(%)]
Table 3 Comparison of the incidence of adverse reactions between the two groups [n(%)]
组别 |
n |
面部潮红 |
头晕 |
血压下降 |
嗜睡 |
心动过缓 |
不良反应发生率 |
观察组 |
46 |
2(4.35) |
1(2.17) |
1(2.17) |
2(4.35) |
1(2.17) |
7(15.22) |
对照组 |
45 |
0 |
2(4.44) |
|
0 |
1(2.22) |
3(6.67) |
χ2值 |
|
|
|
|
|
|
0.939 |
P值 |
|
|
|
|
|
|
0.333 |
表4 2组用药前后QOL评分对比 (x±s,分)
Table 4 Comparison of QOL scores before and after treatment (x±s,score)
组别 |
n |
用药前 |
用药3个月后 |
观察组 |
46 |
47.10±7.01 |
80.01±7.12 |
对照组 |
45 |
48.32±8.12 |
60.06±6.23 |
t值 |
|
0.768 |
14.213 |
P值 |
|
0.445 |
0.000 |
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(收稿2018-10-11 修回2018-11-08)
本文责编:关慧
本文引用信息:尹刘杰,李世泽.多奈哌齐联合尼莫地平片对脑小血管病患者认知功能的影响[J].中国实用神经疾病杂志,2018,21(24):2703-2707.DOI:10.12083/SYSJ.2018.24.564
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