多奈哌齐联合鼠神经生长因子治疗阿尔茨海默病48例临床观察

目的：探讨多奈哌齐联合鼠神经生长因子联合治疗阿尔茨海默病的临床疗效。方法48例患者随机分为2组，分别接受多奈哌齐或多奈哌齐联合鼠神经生长因子治疗，总疗程12周，根据MMSE、ADL、ADAS‐cog量表评价2组治疗前后认知功能及生活能力变化。结果2组在日常生活能力及缓解认知功能的减退方面，显示有效；且联合治疗组较单纯使用多奈哌齐组在MMSE和ADL评分上改善更为显著。结论多奈哌齐联合鼠神经生长因子治疗能有效改善AD患者的认知、行为能力，并且具有良好安全性。     

盐酸美金刚治疗阿尔茨海默病的多中心随机对照研究

目的 与盐酸多奈哌齐对照评价盐酸荚金刚片治疗阿尔茨海默病(AD)的有效性和安全性.方法 241例AD患者(MMSE评分3-24分)随机分为2组,采用双盲双模拟的方法,埘照组给予盐酸多奈哌齐10 mg/d,试验组给予盐酸美金刚20 mg/d,疗程24周,分别在基线、第4、12和24周进行随访.主要疗效指标为印象变化(CIBIC-Plus)、AD评估量表-认知部分(ADAS-cog)和日常生活能力(ADL)量表,次要疗效指标为神经精神症状问卷(NPI)和MMSE.结果 207例患者完成试验,盐酸美金刚组和盐酸多奈哌齐组治疗24周后各量表评分均较基线有显著改善.盐酸美金刚组与盐酸多奈哌齐组相比较,各量表的评分变化分别为:CIBIC-Plus评分:3.4±0.8、3.5±0.8;ADAS-cog评分:-4.7±5.8、-4.6±6.5;ADL评分:-2.4±6.7、-2.2±5.3;NPI评分:-5.8±9.0、-3.1±8.5;MMSE评分:1.7±3.1、1.8±2.8;差异均无统计学意义.不良事件发生率盐酸多奈哌齐组41.88%,盐酸美金刚组30.58%.结论 盐酸美金刚作为治疗AD的新药,町以改善AD患者的总体功能、认知障碍、日常生活能力和精神行为症状,疗效与盐酸多奈哌齐相当,且具有良好的安全性和耐受性.     

多奈哌齐与他克林治疗阿尔茨海默病的对照研究

目的：验证多奈哌齐治疗阿尔茨海默病（AD）的安全性及有效性。方法：对61例AD患者进行多奈哌齐和他克林的多中心开放，对照治疗，其中多奈哌齐组33例（5mg/d)，他克林组28例（平均100mg/d）；共治疗12 ，应用简易精神状态检查（MMSE），日常生活能力量表（ADL）评定临床疗效。用副反应量表（TESS）评定副反应，结果：多奈哌齐组治疗总有效率为70％，显效率为51％，他克林组分别为68％和46％，起效时间均在治疗第4周末，两组间差异无显著性（X^2值分别为0．023和0．011，P＞0．05）。组间比较，多奈哌齐组和他克林组治疗前后MMSET评分及加分离，ADL评分及减分率的羞匀无显著性（P＞0．05），多奈哌齐组的不良反应较他克林组显著少而轻（X^2＝7．79，P＜0．01），仅有6例患者存在轻度的恶心或食欲减退，结论：多奈哌齐能有效治疗AD，且不良反应少而轻微。     

盐酸美金刚与盐酸多奈哌齐治疗阿尔茨海默病疗效对比

目的比较盐酸美金刚与盐酸多奈哌齐治疗阿尔茨海默病(AD)的有效性和安全性。方法将72例AD患者随机分为2组:美金刚组36例给予盐酸美金刚片20mg/d,多奈哌齐组36例给予盐酸多奈哌齐10mg/d,2组疗程均为6个月。2组患者治疗前和治疗3个月、6个月后均采用简易智能精神状态检查量表(MMSE)和AD评定量表的认知次级量表(ADAS-cog)评价患者认知功能、精神行为及痴呆严重程度。结果经治疗3个月、6个月后,2组患者MMSE、ADAS-cog评分均较治疗前明显好转(P<0.05或P<0.01);治疗3个月、6个月后,2组患者MMSE、ADAS-cog评分比较差异无统计学意义(均P>0.05);美金刚组的不良反应发生率低于多奈哌齐组(χ2=4.5714,P>0.05)。结论盐酸美金刚与盐酸多奈哌齐均能显著改善AD患者的认知功能、日常生活能力和人格情感障碍,两药疗效无明显差异,且盐酸美金刚具有良好的安全性。     

多奈哌齐联合养血清脑颗粒改善轻度认知功能障碍的效应

目的评价多奈哌齐联合养血清脑颗粒对轻度认知功能障碍患者的疗效。方法30例轻度认知功能障碍患者随机分为多奈哌齐组14例;多奈哌齐联合养血清脑颗粒16例,共服用16周。分别测定两组治疗前后简易智力状态量表(MMSE)总分及成人韦氏记忆测验记忆商(MQ);经颅多普勒(TCD)检查评估两组治疗前后的脑血流参数改变。结果(1)治疗前多奈哌齐组及多奈哌齐联合养血清脑颗粒治疗组在MMSE的亚项记忆力和回忆力无显著差别(P>0.05);治疗16周后多奈哌齐组及多奈哌齐联合养血清脑颗粒治疗组在MMSE的亚项记忆力和回忆力上较治疗前有显著差别(P<0.05);(2)治疗前多奈哌齐组及多奈哌齐联合养血清脑颗粒治疗组在MQ的亚项图片回忆、再认及背数方面上无显著差别,治疗后多奈哌齐组及多奈哌齐联合养血清脑颗粒治疗组在亚项图片回忆、再认及背数方面较治疗前均有提高;联合治疗组更为显著。(3)治疗前TCD检测两组患者均可显示双侧脑血流不对称、血管阻力指数增高,治疗后自身对照脑血流趋于对称,血管阻力指数降低,多奈哌齐联合养血清脑颗粒组改变明显(P<0.05),多奈哌齐组无显著改善(P>0.05)。结论多奈哌齐联合养血清脑颗粒对改善轻度认知功能障碍患者的记忆力及脑血流改善有明显疗效。     

复方海蛇胶囊和多奈哌齐治疗阿尔茨海默病的临床观察

目的　探讨复方海蛇胶囊和多奈哌齐治疗阿尔茨海默病 (AD)的临床疗效。方法　将 86例AD患者随机分为复方海蛇胶囊组和多奈哌齐组 ,在治疗前、治疗后 3周、6周、12周和 2 4周末分别进行简易智能状态检查 (MMSE)评分和临床疗效评定。结果　在治疗后第 3周末MMSE评分和临床疗效 ,复方海蛇胶囊组要优于多奈哌齐组 ,第 6周末两组相仿 ,在第 12周和 2 4周末多奈哌齐组明显优于复方海蛇胶囊组。结论　复方海蛇胶囊起效快 ,短期疗效好 ,而多奈哌齐虽然起效相对较慢 ,但是有较好的远期疗效     

盐酸美金刚治疗阿尔茨海默病的临床研究

目的 与盐酸多奈哌齐对照比较盐酸美金刚治疗阿尔茨海默病(Alzheimer disease, AD)的有效性和安全性.方法 将36例AD患者随机分为两组,采用双盲双模拟的方法,对照组给予盐酸多奈哌齐10 mg/d,试验组给予盐酸美金刚20 mg/d,疗程16周,每4周随访1次,评估简易精神状态量表(MMSE)、阿尔茨海默病评价量表-认知分量表(ADAS-cog)、日常生活能力量表(ADL)、临床疗效总评量表(CGI)、快速词汇测验(RVR)和数字广度测验(Ds).结果 32例患者完成了本试验,盐酸多奈哌齐组MMSE、ADAS-cog、ADL、RVR和DS评分治疗前后比较均有统计学意义(P<0.05),盐酸美金刚组ADL、ADAS-cog和MMSE评分治疗前后比较有统计学意义(P<0.05).治疗前两组各量表评分比较(P>0.05)与治疗16周后两组评分比较(P>0.05),均无统计学差异.结论 盐酸美金刚作为治疗AD的新药,可以改善AD患者的症状,疗效与盐酸多奈哌齐相当,且具有良好的安全性和耐受性.     

盐酸美金刚与盐酸多奈呱齐片治疗阿尔茨海默病疗效对比

目的 探讨盐酸美金刚治疗阿尔茨海默病（AD）的有效性及安全性.方法 回顾性分析86例AD患者的临床资料,随机分为多奈呱齐片组（n=43,予以盐酸多奈呱齐片治疗）和美金刚组（n=43,予以盐酸美金刚治疗）,疗程16周,于治疗前及治疗16周后采用AD评定认知次级量表（ADAS-cog）、精神检查量表（MMSE）以及Barthel量表对2组患者的认知、精神以及日常生活能力进行评价.结果 治疗16周后,2组患者Barthel、MMSE以及ADAS-cog评分均较治疗前明显好转（P＜0.05）;且美金刚组Barthel、MMSE以及ADAS-cog等评分改善指数优于多奈呱齐片组,差异无统计学意义（P＞0.05）;美金刚组发生不良反应事件的概率16.3%明显低于多奈呱齐片组37.2%（P＜0.05）.结论 盐酸美金刚能显著改善AD患者的认知功能、人格情感障碍以及日常生活能力,与盐酸多奈呱齐片相比,疗效无明显差异,但盐酸美金刚不良反应少,具有良好的安全性.     

卡巴拉汀与多奈哌齐治疗轻中度阿尔茨海默病患者的比较研究

目的　比较卡巴拉汀和多奈哌齐治疗轻中度阿尔茨海默病 (AD)患者的疗效和安全性。方法　将 40例轻中度 AD患者随机均分为两组 ,用卡巴拉汀和多奈哌齐治疗 16周。采用简易精神状态量表 (MMSE)、Blessed-Roth量表和总体衰退量表 (GDS)评定疗效。安全性检查包括生命体征、实验室及心电图检查 ,每 4周 1次。结果　两组治疗前后 MMSE、GDS和 Blessed-Roth评分均有显著改善 (P<0 .0 5)。但两组治疗前后相关量表总分差值的 t检验均无显著意义 (P>0 .0 5)。两组治疗前后 Blessed-Roth各亚项分数差值比较无显著性 (P>0 .0 5) ,仅在社会活动能力方面卡巴拉组汀稍优于多奈哌齐组 (P>0 .0 5)。不良反应为胃肠道反应 ,发生率在 15.0 %～ 2 9.5%之间 ,以卡巴拉汀组多见。结论　卡巴拉汀和多奈哌齐可显著改善 AD患者的认知功能、痴呆程度和日常生活能力 ,疗效相当 ,较为安全 ,耐受性好     

盐酸多奈哌齐与奥氮平治疗痴呆行为和精神症状疗效观察

目的观察盐酸多奈哌齐与奥氮平治疗痴呆行为和精神症状(BPSD)的疗效及安全性。方法将86例BPSD患者随机分为盐酸多奈哌齐组与奥氮平组,每组43例,观察8周,于治疗前后采用痴呆病理行为评定量表(BEHAVE-AD)评定疗效,简易精神状况检查量表(MMSE)评定认知功能,日常生活能力量表(ADL)评定生活质量,治疗中需处理的不良反应症状量表(TESS)评定不良反应。结果盐酸多奈哌齐组BEHAVE-AD评分、MMSE评分、ADL评分、不良反应以锥体外系反应及头晕、嗜睡、视物模糊、体质量增加等方面均优于奥氮平组,差异有统计学意义(P0.05)。结论盐酸多奈哌齐与奥氮平相比,治疗BPSD疗效肯定,能有效改善患者认知功能及提高日常生活能力,安全性好。     

Donepezil in Alzheimer's disease: eighteen month results from Southampton Memory Clinic

The objective of this study was to assess the efficacy of donepezil in patients with mild to moderate Alzheimer's disease (AD) in clinical practice. This was an open-label study in which patients were referred to an elderly mental health clinic in Southampton, UK. Eighty patients with mild to moderate AD received 5 mg/day donepezil for the first 4 weeks, after which, if tolerated, the dose was increased to 10 mg/day. Efficacy and safety assessments were carried out every 3 months. Efficacy was assessed by the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog), Mini-Mental State Examination (MMSE), Neuropsychiatric Inventory (NPI), Neuropsychiatric Inventory-carer Distress Scale (NPI-D). Mean improvements from baseline were observed at the 3-month assessment on all four efficacy measures. At 3 months, 39% of patients showed an improvement of at least 4 points on the ADAS-cog, and 37% of patients had improved by 4 points or more on the NPI. In those patients who showed improvement and were maintained on donepezil, improvements were sustained for 18 months on the MMSE and NPI, 15 months on the NPI-D, and for 6 months on the ADAS-cog. Six per cent of patients discontinued medication due to adverse events. In a typical clinical practice setting, patients with mild to moderate AD tolerated donepezil well. Clinically meaningful improvements in cognitive function and a reduction in neuropsychiatric symptoms were demonstrated in nearly 40% of patients with associated reduction in carer distress. Continued benefit was seen for up to 18 months in the selected group of patients who initially responded in treatment.     

Cognitive stimulation therapy for Alzheimer's disease: the effect of cognitive stimulation therapy on the progression of mild Alzheimer's disease in patients treated with donepezil

BACKGROUND: There is general consensus regarding the benefit of acetylcholinesterase inhibitors (e.g. donepezil) in Alzheimer's disease (AD). However, the combined effect of acetylcholinesterase and cognitive stimulation therapy (CST) is still controversial. OBJECTIVE: This study examines their combined effect on the progression of cognitive decline in AD by comparing the cognitive performance of 17 AD patients treated with CST and donepezil (combined treatment group) and 13 AD patients treated with donepezil alone (control group). METHODS: Patients in the combined treatment group received 5 mg of donepezil per day and about 20 one-hour CST sessions for one year, whereas the control group received only 5 mg of donepezil per day. The first eight sessions were carried out once a week, and subsequent sessions were generally once every two weeks. The patients were evaluated for changes in cognitive ability by administering the Mini-mental State Examination (MMSE) before the start of CST (baseline) and about one year later (follow-up). RESULTS: A repeated-measure analysis of variance revealed a significant group x time interaction. The MMSE score decreased significantly in the control group, but did not change significantly in the combined treatment group. Three patients in the control group declined by four points on the MMSE, compared to none in the combined treatment group. Effect size (ES) in the control group was relatively large and negative, while the ES in the combined treatment group was close to zero. CONCLUSIONS: The results suggest the possibility that donepezil plus CST slowed the rate of cognitive decline more than the administration of donepezil alone.     

An observational clinical study of the efficacy and tolerability of donepezil in the treatment of Alzheimer's disease

An open-label, observational Post-Marketing Surveillance (PMS) study was undertaken in Germany to examine the efficacy and tolerability of donepezil in routine clinical practice. Alzheimer's disease (AD) patients were treated with donepezil (5 or 10 mg once daily) and observed for a period of approximately 3 months. Study assessments included the Mini-Mental State Examination (MMSE), the Nurses' Observation Scale for Geriatric Patients (NOSGER), and adverse events (AEs). A total of 2,092 patients (mean age 73.0 years; mean +/- SD MMSE score 17.8 +/- 5.8) were included in the efficacy assessments. MMSE and NOSGER scores showed statistically significant improvements in the total patient population and in the subpopulations with severe AD or AD with concomitant Parkinsonian symptoms (ADPS cohort). AEs were reported in a total of 12% of patients and were mostly due to peripheral cholinergic effects. In this observational PMS study, donepezil was shown to be an effective and well-tolerated therapy in the overall patient population, in patients with severe AD, and in the ADPS cohort.     

多奈哌齐治疗阿尔茨海默病临床疗效分析

目的 探讨多奈哌齐对阿尔茨海默病治疗的有效性及安全性。方法 采用分组对照，治疗组给予多奈哌齐及脑复康治疗16周，对照组只给予脑复康治疗。治疗前后采用AD评定量表的认知次级量表(ADAS-cog)和简易智能精神状态检查量表(MMSE)评价患者认知功能、精神行为及痴呆严重程度结果多奈哌齐治疗组患者较对照组患者ADAS-cog及MMSE评分改善明显，而对照组患者评分无明显改变。治疗患者无明显药物副作用。结论 多奈哌齐可以安全地用于治疗阿尔茨海默病。     

Efficacy and safety of donepezil in patients with more severe Alzheimer's disease: a subgroup analysis from a randomized, placebo-controlled trial

BACKGROUND: There have been very limited investigations of cholinesterase inhibitor therapy in more advanced stages of Alzheimer's disease (AD). The efficacy and safety of donepezil were evaluated in post hoc analyses of a subgroup of patients with more severe AD (standardized Mini-Mental State Examination [sMMSE] score 5-12) within a randomized, placebo-controlled trial in moderate to severe AD (MSAD study). Additional analyses examined whether donepezil's treatment effects were consistent across the full range of baseline AD severity studied (sMMSE score 5-17). METHODS: Patients with moderate to severe AD (n = 290) who were living in the community or in assisted living facilities received donepezil or placebo for 24 weeks; n = 145 in the more severe AD subgroup. The primary outcome measure was the Clinician's Interview-Based Impression of Change (CIBIC-plus) with secondary outcomes including the sMMSE, Severe Impairment Battery, Neuropsychiatric Inventory, and Disability Assessment for Dementia. Analysis of Variance and Analysis of Covariance models tested for treatment x disease severity interaction in the full MSAD study sample. RESULTS: CIBIC-plus scores for donepezil patients were significantly improved compared with placebo for each time-point, with a 0.70 mean treatment difference at Week 24 last observation carried forward (LOCF; p = 0.0002). Significant differences favoring donepezil were noted at Week 24 LOCF for all secondary measures. There were no treatment x severity interactions for any of the efficacy measures. CONCLUSIONS: In this analysis, donepezil had significant benefits over placebo on global, cognitive, functional, and behavioral measures in a subgroup of patients with more severe AD. Furthermore, the treatment effects of donepezil were not driven by a particular stratum within the moderate to severe dementia range.     

Donepezil for Alzheimer's disease in clinical practice--The DONALD Study. A multicenter 24-week clinical trial in Germany

This multicenter open-label clinical trial was designed to investigate the safety and efficacy of donepezil, a selective acetylcholinesterase inhibitor, in the treatment of Alzheimer's disease (AD) in routine clinical practice in Germany. A total of 237 patients with mild-to-moderate AD were treated with donepezil for 24 weeks, 186 completed the study according to the protocol. In the completer group, mean MMSE score for efficacy showed an improvement from baseline of +1.6 points at week 12 (95% CI +1.1 to +2.1) and of +1.1 points at week 24 (95% CI +0.5 to +1.7). In more than 80% of the patients, global tolerability was rated to be very good or good. There were only insignificant effects on ECG parameters. This study confirms the results obtained in previous double-blind trials, which showed that donepezil is effective and well tolerated in patients with mild-to-moderately severe AD.     

Donepezil in the treatment of Alzheimer's disease: long-term efficacy and safety

OBJECTIVES: The aim of this study was to evaluate the long-term efficacy, safety and tolerability of donepezil in the treatment of Alzheimer's disease (AD). METHODS: Twenty-five patients (15 females and 10 males) with mild to moderate AD, according to DSM IV criteria, were recruited in the study. The principal efficacy measures were Alzheimer Disease Assessment Scale-cognitive subscale score (ADAS-cog), Mini Mental State Examination (MMSE) and Physical Self-Maintenance Scale (PSMS). Patients were treated with donepezil 5 mg/day for 1 month, after which an increase to 10 mg/day was encouraged. Evaluations were carried out prior to the start of the treatment and every 3 months for a period of 1 year. RESULTS: A significant improvement from baseline score of cognitive performances was seen through Week 24. Beginning with Week 36, performances declined relative to baseline, indicating continued disease progression. CONCLUSIONS: Donepezil improved cognition and global functioning and was well tolerated especially considered the long duration of the observation period.     

Clinical efficacy and safety of donepezil on cognitive and global function in patients with Alzheimer's disease. A 24-week, multicenter, double-blind, placebo-controlled study in Japan. E2020 Study Group

This study evaluated efficacy and safety of donepezil hydrochloride (donepezil) at 5 mg/day in patients with mild to moderately severe Alzheimer's disease for 24 weeks in a double-blind, placebo-controlled comparative trial. In this study, 268 patients were enrolled and 39 of these (15%) were withdrawn. In the evaluable population of efficacy, Protocol-Compatible (PC) analyzed patients (n = 228), better effects than that of placebo were confirmed using two primary efficacy measures: a cognitive performance test, the Japanese version of the Alzheimer's Disease Assessment Scale - cognitive subscale (ADAS-J cog, p = 0.003) and a clinical global assessment, the Japanese version of the Clinical Global Impression of Change (J-CGIC, p = 0.000). The superiority of donepezil was also shown by secondary measures: the Sum of the Boxes of the Clinical Dementia Rating (CDR-SB), the Mental Function Impairment Scale (MENFIS) and the caregiver-rated modified Crichton scale (CMCS). The same results were obtained in the intention-to-treat (ITT) analysis (n = 263). The incidence of drug-related adverse events was 10% (14/136) in the donepezil and 8% (10/131) in the placebo group; no significant difference was seen between the two groups. The main adverse events were gastrointestinal symptoms, and these were almost all mild, and they all disappeared with continued administration or temporary discontinuation of donepezil. These results indicate that the donepezil appears to be effective and well tolerated in patients with mild to moderately severe Alzheimer's disease.     

A 24-week, double-blind, placebo-controlled trial of donepezil in patients with Down syndrome and Alzheimer's disease--pilot study

BACKGROUND: Donepezil Hydrochloride (Aricept) is a selective anticholinesterase inhibitor developed for the treatment of Alzheimer's disease (AD). This study investigated the safety and efficacy of the drug to treat Down syndrome (DS) adults with mild to moderate AD. METHOD: This was a 24-week, double blind, placebo controlled, parallel-group trial. Patients were randomized to receive placebo or donepezil (5 mg per day during the first four weeks, and then 10 mg per day thereafter). Primary efficacy was measured using the Dementia Scale for Mentally Retarded Persons (DMR), and secondary efficacy was measured using the Severe Impairment Battery (SIB), Neuropsychiatric Inventory (NPI) and by the Adaptive Behavior Scale (ABS). RESULTS: A total of 30 DS patients with AD entered the study of which 27 were included in the subsequent data analysis. The donepezil group had non-statistically significant reduction in deterioration in DMR, SIB, and ABS mean scores relative to the placebo group. However NPI scores showed less improvement in the donepezil group when compared to the placebo group. Fifty percent of subjects in the donepezil group showed improvement in mean DMR scores at the end point compared to baseline, when compared to 31% on placebo. There were no life threatening adverse effects associated with treating adults with DS with donepezil. A number of side-effects did occur including diarrhoea, insomnia, fatigue, and nausea. CONCLUSION: Donepezil Hydrochloride administered once a day appears to be generally well tolerated and safe in DS adults who have AD. There is some possible efficacy in the treatment of symptoms of mild to moderate Alzheimer's disease in this population, although the sample size of this study was too small for statistical significance. It is recommended that donepezil, with the appropriate precautions, should be considered for the treatment of AD in adults with DS as deemed by a specialist.