多奈哌齐治疗AD源性轻度认知功能障碍患者的临床研究

Clinical trial of donepezil in the treatment of patients with AD induced mild cognitive impairment

目的探索多奈哌齐治疗阿兹海默病(AD)源性轻度认知功能障碍(MCI)患者的有效性。方法将AD源性MCI患者分为试验组和对照组。对照组接受多认知域的认知功能训练,每周5次,每次1h;试验组在对照组治疗的基础上给予盐酸多奈哌齐片治疗,初始剂量为5mg·d^(-1),qd,连续服用6周;6周后增至10mg·d^(-1),qd,服用至第12个月。比较2组患者的临床疗效,评估患者认知功能[简易智能状态量表(MMSE)、阿尔茨海默病疾病评估量表-认知子量表(ADAS-Cog)、California词语学习测验(CVLT)],测量海马体积,计算海马萎缩率,统计治疗期间进展为AD的例数,并进行安全性评价。结果试验组和对照组分别纳入53例和47例。治疗后,试验组和对照组的总有效率分别为62.26%(33例/53例)和55.32%(26例/47例),在统计学上差异无统计学意义(P>0.05)。治疗12个月后,试验组和对照组的MMSE评分分别为(25.84±2.21)和(26.07±2.18)分,ADAS-Cog评分分别为(11.69±2.36)和(11.75±2.24)分,CVLT短时自由记忆数分别为(13.01±2.04)和(12.78±1.98)个,在统计学上差异均无统计学意义(均P>0.05)。治疗12个月后,试验组和对照组的海马萎缩率分别为(1.86±0.38)%和(3.34±0.34)%,进展为AD的发生率分别为0(0例/53例)和8.51%(4例/47例),在统计学上差异均有统计学意义(均P<0.05)。试验组的药物不良反应主要有恶心、头痛,对照组未发生药物不良反应。试验组和对照组的总药物不良反应发生率分别为5.66%(3例/53例)和0(0例/47例),在统计学上差异无统计学意义(P>0.05)。结论多奈哌齐对AD源性MCI患者的认知功能无明显改善作用,但可降低患者海马萎缩率,延缓AD进展。

Objective To explore the effectiveness of donepezil in the treatment of patients with Alzheimer's disease(AD)induced mild cognitive impairment(MCI).Methods Patients with AD-derived MCI were divided into treatment group and control group.The control group received multi-domain cognitive function training,5 times a week for 1 h each time;the treatment group was treated with donepezil hydrochloride tablets at the initial dose of 5 mg·d^(-1),qd,for 6 weeks.After 6 weeks,it was increased to 10 mg·d^(-1),qd,and taken until the 12^(th)month.The clinical efficacy of the two groups was compared;and the cognitive function of the patients was evaluated[mini mental state examination(MMSE),Alzheimer's Disease Assessment scale-Cognitive Subscale(ADAS-Cog),California verbal-learning test(CVLT)].Hippocampal volume was calculated;and the rate of hippocampal atrophy was calculated;the number of cases progressing to AD during treatment was counted;and the safety was evaluated.Results Finally,53 cases and 47 cases were included in the treatment group and the control group,respectively.After treatment,the total effective rates of the treatment group and the control group were 62.26%(33 cases/53 cases)and 55.32%(26 cases/47 cases),without statistically significant difference(P>0.05).After 12 months of treatment,the MMSE scores of the treatment group and the control group were 25.84±2.21 and 26.07±2.18;the ADAS-Cog scores were(11.69±2.36)and(11.75±2.24)point;the quantity of short-term free memories in the CVLT were 13.01±2.04 and 12.78±1.98.The differences between two groups were not statistically significant(all P>0.05).After 12 months of treatment,hippocampal atrophy rates in the treatment group and the control grouwp ere(1.86±0.38)%and(3.34±0.34)%;the incidence rates of progression to AD were 0(0 cases/53 cases)and 8.51%(4 cases/47 cases).The differences were statistically significant(all P<0.05).Adverse drug reactions of the treatment group mainly included nausea and headache but no adverse drug reaction was observed in the control group.The total incidence rates of adverse drug reactions in the treatment group and the control group were 5.66%(3 cases/53 cases)and 0(0 cases/47 cases),without statistically significant difference(P>0.05).Conclusion Donepezil has no significant improvement effect on cognitive function in patients with AD induced MCI,but it can reduce the rate of hippocampal atrophy and delay the progression of AD.