不同剂量多奈哌齐联合美金刚治疗阿尔茨海默病的疗效比较

Efficacy of different doses donepezil combined with memantine in the treatment of Alzheimer′s disease:a comparative study

目的比较不同剂量多奈哌齐联合美金刚对阿尔茨海默病(AD)患者认知功能、精神行为症状、血清学指标及日常生活能力的影响。方法将149例AD患者随机分为高剂量组(n=57)、低剂量组(n=49)和对照组(n=43)。3组患者均接受美金刚治疗,在此基础上,高剂量组给予高剂量多奈哌齐(5 mg/次、1次/d,4周后增至10 mg/次、1次/d)治疗,低剂量组给予常规剂量多奈哌齐(5 mg/次、1次/d)治疗,对照组给予等量安慰剂治疗。比较3组患者治疗前、治疗3个月后的认知功能[简易智能精神状态检查(MMSE)量表评分、阿尔茨海默病评价量表-认知分量表(ADAS-Cog)评分]、精神行为症状[Cohen-Mansfield激越问卷(CMAI)评分、阿尔茨海默病病理行为评价量表(BEHAVE-AD)评分和痴呆行为评定量表(BRSD)评分]、血清学指标[β淀粉样蛋白1-42(Aβ1-42)、β淀粉样蛋白前体蛋白(APP)、胰岛素样生长因子1(IGF-1)]和日常生活能力[日常生活能力(ADL)量表评分]的变化。结果治疗后,高剂量组、低剂量组、对照组的MMSE量表评分、ADL量表评分和血清IGF-1水平依次降低;ADAS-Cog评分、CMAI评分、BEHAVE-AD评分、BRSD评分和血清APP、Aβ1-42水平依次升高(均P<0.05)。结论与美金刚单独治疗相比,多奈哌齐联合美金刚可以更好地降低AD患者的血清APP水平、促进Aβ1-42清除、上调IGF-1的表达,从而改善患者的认知功能、精神行为症状及日常生活能力,且高剂量多奈哌齐与美金刚联合应用的效果更佳。

Objective To compare the effect of different doses donepezil combined with memantine on cognitive function,psychological and behavioral symptoms,serological indicators and activities of daily living in patients with Alzheimer′s disease(AD).Methods A total of 149 patients with AD were randomly divided into high dose group(n=57),low dose group(n=49),or control group(n=43).All patients were treated with memantine in the three groups,based on which patients in the high dose group were treated with high-dose donepezil(5 mg per time,1 time per day,and then increased to 10 mg per time,1 time per day after 4 weeks),patients in the low dose group were treated with routine-dose donepezil(5 mg per time,1 time per day),and patients in the control group were treated with placebo with equivalent volume.The changes of pre-and 3-month post-treatment cognitive function(Mini Mental State Examination[MMSE]scale score,Alzheimer′s Disease Assessment Scale-Cognitive Subscale[ADAS-Cog]score),psychological and behavioral symptoms(Cohen-Mansfield Agitation Inventory[CMAI]score,Behavior Pathology in Alzheimer′s Disease Rating Scale[BEHAVE-AD]score,and Behavior Rating Scale of Dementia[BRSD]score),serological indicators(amyloid-β1-42 protein[Aβ1-42],β-amyloid protein precursor protein[APP],and insulin-like growth factor 1[IGF-1]),and activities of daily living(activities of daily living[ADL]scale score)were compared between the three groups.Results After treatment,the MMSE scale score,ADL scale score and serum IGF-1 level were decreased in a descending order following the high dose group,the low dose group,and the control group,whereas the scores of ADAS-Cog,CMAI,BEHAVE-AD,BRSD,and levels of serum APP,Aβ1-42 were elevated successively(all P<0.05).Conclusion Compared with the therapy of memantine alone,donepezil combined with memantine can preferably decrease serum APP level in patients with AD,promote elimination of Aβ1-42,up-regulat e IGF-1 expression,so as to ameliorate cognitive function,psychological and behavioral symptoms,and activities of daily living in patients,and the combined application of high-dose donepezil and memantine exerts a superior effect.