多奈哌齐治疗阿尔茨海默病的系统评价

目的 Meta分析评价多奈哌齐治疗阿尔茨海默病(AD)的临床疗效和安全性。方法计算机检索Medline、EMBASE、Ovid、CNKI及万方数据库。以AD患者服用多奈哌齐5mg和10mg口服干预12~30周为标准,以安慰剂为对照,选取自各数据库建库至2013年9月,筛选符合纳入标准的所有文献,并进行Meta分析。结果共检索到198篇相关文献,9篇随机对照试验文献符合纳入标准,AD患者共3064例。多奈哌齐对AD患者总体功能评价的改善效果均优于安慰剂(OR=1.86,95%CI:1.56~2.21,P<0.01)。与5mg治疗比较,多奈哌齐10mg治疗对AD患者总体功能评价的改善效果差异无统计学意义(OR=0.91,95%CI:0.72~1.15,P=0.43)。多奈哌齐的严重不良事件发生率与安慰剂比较,差异无统计学意义(OR=1.04,95%CI:0.88~1.24,P=0.65)。多奈哌齐5mg、10mg治疗AD的严重不良事件发生率比较,差异无统计学意义(OR=0.70,95%CI:0.47~1.04,P=0.08)。结论多奈哌齐可显著改善AD患者的总体功能评价,安全性好,但疗效并不存在剂量依赖性。但限于纳入的研究文献较少及疗法学质量上的局限,本系统评价结果尚需更多高质量的随机对照试验进一步验证。     

国产与进口盐酸多奈哌齐片治疗阿尔茨海默病的疗效比较

目的 比较等剂量国产与进口盐酸多奈哌齐片对轻中度阿尔茨海默病患者的疗效及安全性. 方法 选择250例就诊于天津市环湖医院的轻中度阿尔茨海默病患者作为观察对象,随机分为试验组125例和对照组125例,分别给予等剂量国产和进口盐酸多奈哌齐片治疗,并于治疗前、治疗1个月、3个月和6个月时从认知能力、总体印象、日常功能和精神行为症状4个方面对两组患者治疗效果及药物不良反应进行评价. 结果 除进口盐酸多奈哌齐片在治疗患者6个月时和国产盐酸多奈哌齐片在治疗患者1个月时与治疗前比较,阿尔茨海默病协作研究日常生活能力量表(ADCS-ADL)评分差异无统计学意义,且临床痴呆评定表(CDR)评分治疗各时段与治疗前比较差异均无统计学意义,简易智力状态检查量表(MMSE)、蒙特利尔认知评估量表(MOCA)、阿尔茨海默病评估量表认知部分(ADAS-cog)、神经精神量表(NPI)、临床印象变化量表(CIBIC-PLUS)和汉密尔顿抑郁量表(HAMD)评分均较治疗前有所改善(均P＜0.05);而两种药物治疗AD患者1个月、3个月和6个月时各项评分指标差异均无统计学意义(均P＞0.05).不良反应发生率差异无统计学意义(P＞0.05). 结论 等剂量国产和进口盐酸多奈哌齐片对轻中度阿尔茨海默病患者的疗效及安全性相似.     

卡巴拉汀治疗阿尔茨海默病的远期疗效观察

目的观察卡巴拉汀治疗阿尔茨海默病(AD)的远期疗效和安全性。方法选择阿尔茨海默病患者56例,随机分为治疗组28例和对照组28例。对照组服用脑复康、银杏叶片进行常规治疗,治疗组在常规治疗的基础上每日加服卡巴拉汀3～9mg。以简易智能状态检查量表(mini mental state examination,MMSE)、AD评估量表认知分量表(ADAS-cog)、日常生活活动能力量表(ADL)、总体衰退量表(GDS)等评分作为主要评价指标,比较2组患者在治疗前与治疗3、6、12、18、24、30和36个月后的认知能力、精神状况、日常生活能力的改善情况。结果治疗组患者MMSE、ADAS-cog、GDS评分6个月以后明显优于对照组,ADL评分12个月以后明显优于对照组,差异有统计学意义(P<0.05)。卡巴拉汀在连续用药12个月内疗效递增,12个月时疗效最佳,之后开始下降,36个月时仍明显优于基线水平。MMSE、ADAS-cog、GDS评分改善程度优于ADL。结论卡巴拉汀治疗AD远期疗效满意,安全可靠。     

多奈哌齐治疗早期卒中后失语:随机对照研究

目的 探讨多奈哌齐治疗早期卒中后失语(post-stroke aphasia,PSA)的有效性.方法 纳入发病1个月内的PSA患者,并随机分为多奈哌齐组和对照组.多奈哌齐组在常规用药基础上给予盐酸多奈哌齐5mg/d.4周后随访.治疗前及治疗后均采用汉语失语症成套测验(Aphasia Battery of Chinese,ABC)、美国国立卫生研究院卒中量表(National Institute of Health Stroke Scale,NIHSS)、中文版卒中后失语患者抑郁问卷(Stroke Aphasic Depression Questionnaire Version,SADQ)和治疗相关意外症状量表(Treatment Emergent Symptom Scale,TESS)进行评估.结果 共纳入48例PSA患者,多奈哌齐组和对照组各24例,且均完成研究.多奈哌齐组年龄、受教育年限、NIHSS评分、SADQ评分、卒中病程以及性别、高血压、糖尿病、高脂血症、心脏病、既往卒中或短暂性脑缺血发作史、吸烟、饮酒、卒中类型、病灶部位的构成比均无显著性差异(P均＞0.05).多奈哌齐组和对照组治疗前后各语言分项评分均存在显著性差异(P均＜0.01).多奈哌齐组听理解[(47.8 ±24.7)分对(22.0±15.4)分;=4.342,P=0.000]和阅读理解[(20.5±14.0)分对(8.1±10.5)分;t=3.483,P＜0.01]评分治疗前后差值均显著性高于对照组,而言语信息量、流利性、系列语言、复述、命名和朗读评分则无显著性差异(P均＞0.05).多奈哌齐组治疗前后SADQ评分差值与对照组比较存在显著性差异[(6.2±6.0)分对(2.5±3.0)分;=2.717,P=0.009].两组均未出现严重不良反应.结论 早期PSA患者在常规卒中治疗基础上加用盐酸多奈哌齐,对语言功能的听理解和阅读理解改善有促进作用,且安全性良好.     

盐酸多奈哌齐治疗阿尔茨海默病的疗效观察

45例阿尔茨海默病(AD)患者随机分为治疗组24例(采用盐酸多奈哌齐与脑复康口服)和对照组21例(采用脑复康口服),治疗12周,以简易智能量表(MMSE)、AD评定量表认知部分次级量表(ADAS-Cog)、日常生活活动量表(ADL)分数评定疗效.结果与治疗前比较,治疗12周两组MMsE评分升高,ADAA-Cog、ADL评分降低.治疗后治疗组MMSE、ADAS-Cog、ADL评分变化更明显,与对照组组比较差异有统计学意义(P<0.05).认为盐酸多奈哌齐治疗AD安全、有效,无明显不良反应.     

盐酸多奈哌齐治疗阿尔茨海默病的临床疗效观察

目的探讨盐酸多奈哌齐对阿尔茨海默病患者认知功能和行为能力的治疗作用。方法收集徐汇区中心医院阿尔茨海默病患者120例,随机分为治疗组与对照组各60例,治疗组采用盐酸多奈哌齐,对照组不使用盐酸多奈哌齐等防治阿尔茨海默病药物。两组患者分别在治疗前和治疗12w、24w后进行MMSE评分及ADL评分的检查。结果治疗组盐酸多奈哌齐治疗后认知、行为能力均较治疗前有明显改善,治疗12w、24w后,MMSE评分分别提高13．8％和23％,ADL评分分别降低9．6％和18．7％（P〈0．01）。结论盐酸多奈哌齐对阿尔茨海默病患者认知、行为能力有显著改善作用。     

盐酸多奈哌齐治疗阿尔茨海默病的临床疗效

<正>1资料与方法收集我院2002年6月～2003年9月期间住院的阿尔茨海默病(AD)患者37例,随机分为2组。治疗组19例,其中男10例,女9例,年龄58～79岁,文化程度为文盲2例,小学5例,中学11例,大学1例。对照组18例,男9例,女9例,年龄60～82岁。均符合美国神经病学,语言障碍卒中老年性     

盐酸多奈哌齐治疗血管性痴呆的有效性和安全性

目的　评价盐酸多奈哌齐治疗血管性痴呆的有效性及安全性。方法　选择 4 0例血管性痴呆患者 ,用盐酸多奈哌齐进行 12周的治疗 (5mg/d) ,按简易精神状态量表 (MMSE)、临床痴呆量表 (CDR)及日常生活自理量表 (ADL)进行治疗前后的疗效评定。结果　盐酸多奈哌齐治疗 12周后较治疗前MMSE、CDR及ADL分数分别改善 4 .1、0 .7、8.2分 ,差异有显著性意义。 4 0例患者中 ,2例出现头晕、恶心 ,1例出现运动减少、肌肉强直等帕金森综合征的表现 ,1例出现轻度的躁动、情绪易激惹等阳性精神症状。结论　盐酸多奈哌齐能有效治疗血管性痴呆患者 ,对患者的认知功能、痴呆程度和日常生活自理能力均有改善。     

多奈哌齐治疗类阿尔茨海默病模型大鼠的实验研究

阿尔茨海默病（Alzheimer’s disease AD）主要临床表现为进行性记忆力减退，智能障碍以及人格改变。中枢胆碱能神经系统与学习和记忆有关，乙酰胆碱酯酶（AchE）在AD大脑中活性的增高致使乙酰胆碱（Ach）缺失，而且已证实Ach缺失的严重程度与痴呆程度密切相关，因此安理申（盐酸多奈哌齐）作为乙酰胆碱酯酶抑制剂（CHEIs）治疗AD已广泛应用于临床。在临床上，多奈哌齐作为治疗AD是主要强调了其抑制AchE的作用，而对其是否有抗氧化作用、抑制Aβ聚集及减少细胞调亡等其他的作用尚不清楚。我们将通过多奈哌齐治疗Aβ25-35。所致类AD模型大鼠，进一步探讨多奈哌齐治疗AD大鼠的其它作用机制，从而为临床治疗提供科学依据。     

多奈哌齐和石杉碱甲治疗老年人轻度认知功能障碍的疗效对比研究

目的 研究多奈哌齐和石杉碱甲治疗老年轻度认知功能障碍(MCI)患者的疗效.方法 122例老年MCI患者分为两组:多奈哌齐组71例患者和石杉碱甲51例患者,多奈哌齐组予口服多奈哌齐5.0 mg,1次/d;石杉碱甲组口服石杉碱甲0.1 mg,2次/d.所有患者随访24周,用药前、用药12周及24周后分别进行认知功能的评定,包括简易智能状态量表检查(MMSE)、蒙特利尔认知评估(北京版)量表(MOCA)、阿尔茨海默病评定量表-记忆分量表(ADAS-cog)、临床痴呆量表(CDR)、总体衰退量表(GDS)、日常生活能力量表(ADL)、Hachinski缺血指数评分(HIS)和汉密尔顿抑郁量表(HAMD).结果 两组患者年龄、性别、受教育年限、用药前神经心理学量表评分差异均无统计学意义.与用药前比较,多奈哌齐组患者用药12周、24周后,MMSE评分均明显升高(t=4.47、6.16,均P＜0.01),ADAS-cog明显降低(t=2.33、3.68,均P＜0.05);与用药前比较,多奈哌齐组患者用药24周后MOCA评分明显升高(t=2.56,P＜0.05).石杉碱甲组用药24周后,MMSE评分较用药前明显升高(t=2.80,P＜0.05),石杉碱甲组用药后12周、24周MOCA、ADAS-cog评分与用药前比较差异均无统计学意义.用药24周后两组比较,多奈哌齐组患者MMSE评分较石杉碱甲组明显升高(t=2.01,P＜0.05),ADAS-cog较石杉碱甲组降低(t=2.09,P＜0.05).多奈哌齐组治疗有效30例,总有效率42.3％,石杉碱甲组治疗有效9例,总有效率17.6％,两组有效率比较差异有统计学意义(x2 =8.26,P＜0.01).多奈哌齐组5例、石杉碱甲组3例患者出现轻微不良反应,继续用药或调整用药时间后消失.结论 在老年MCI患者的治疗中,乙酰胆碱酯酶抑制剂多奈哌齐和石杉碱甲均安全有效,且多奈哌齐起效较石杉碱甲更快,作用更明显.     

Cognitive profiles and response to donepezil treatment in Alzheimer's disease patients

Background:   The aim of this study was to determine whether there are certain characteristic neuropsychological profiles, assessed by the Mini-Mental State Examination (MMSE) at baseline, which predict donepezil treatment response.
Methods:   A total of 112 consecutive outpatients with Alzheimer's disease (AD) were treated with donepezil for 3–4 months. Multiple regression analysis was performed to estimate the relative contributions of individual subscales at baseline to the MMSE change (study point – baseline). To identify the characteristic patterns in cognitive deficits of patients with AD who responded to donepezil therapy, the subscales of the MMSE at baseline of responders and non-responders were compared.
Results:   Multiple regression analysis revealed that lower scores on attention and calculation, and language function, and a higher scale on orientation (date) are related to an improvement of the MMSE. When an improvement of 4 or more points on the MMSE score was defined as a significant response, responders scored significantly lower than non-responders on attention and calculation, whereas non-responders scored significantly lower than responders on memory.
Conclusion:   Our results suggest that individual differences in patterns of neuropsychological impairments may partly contribute to the diversity of the response to donepezil treatment. Although further studies with more detailed neuropsychological tests are needed to confirm our results, the MMSE may add to the prediction of response to donepezil treatment in patients with AD.     

美金刚胺治疗中重度阿尔茨海默病的Meta分析

目的 系统评价美金刚胺治疗中重度阿尔茨海默病(AD)的疗效与安全性. 方法检索中国期刊全文数据库(CJFD)、美国国立医学生物信息中心PubMed数据库(PubMed)、美国国立.卫生院临床试验数据库(Clinicaltrials.gov)、美金刚胺生产商麦氏(Merz)、灵北(Lundbeck)和森林实验室(Forest laboratories)的出版物以及森林实验室临床试验中心(Forest clinical trials registry)关于美金刚胺治疗中莺度AD的随机、双肓、安慰剂对照研究.对符合条件的研究结果用Revman 5.0软件进行Meta分析.以美金刚胺组相对于安慰剂组在总体功能、认知功能、日常生活能力和精神行为4个方面的加权均数差(WMD)为指标进行疗效评价,以两组在不良事件和严重不良事件两方面的相对危险度(RR)为指标进行安全性评价. 结果共纳入4项研究,1683名患者被随机分配,其中美金刚胺组849名,安慰剂组834名.Meta分析结果显示,美金刚胺组相对于安慰剂组在总体功能(CIBIC-PIus)、认知功能(SIB)、日常生活能力(ADCS-ADL19)和精神行为(NPI)4个方面的WMD分别为-0.29(P<0.00001)、2.79(P<0.00001)、1.03(P=0.002)、-2.85(P=0.002);美金刚胺组相对于安慰剂组在不良事件和严重不良事件的RR值分别为1.01(P=0.66)和0.98(P=0.90).除认知功能(P=0.05)外,4项研究在其他方面均未见明显统计异质性. 结论美金刚胺同安慰剂相比可以改善患者总体功能、认知功能、日常生活能力及精神行为症状,美金刚胺的安伞性和耐受性同安慰剂相比差异无统计学意义.     

A randomized, double-blind, placebo-controlled study of the efficacy and safety of donepezil in patients with Alzheimer's disease in the nursing home setting

OBJECTIVES: To evaluate the safety and efficacy of donepezil in the management of patients with Alzheimer's disease (AD) residing in nursing home facilities. DESIGN: Twenty-four-week, randomized, multicenter, parallel-group, double-blind, placebo-controlled trial. SETTING: Twenty-seven nursing homes across the United States. PARTICIPANTS: Two hundred eight nursing home patients with a diagnosis of probable or possible AD, or AD with cerebrovascular disease; mean Mini-Mental State Examination (MMSE) score 14.4; mean age 85.7. MEASUREMENTS: The primary outcome measure was the Neuropsychiatric Inventory-Nursing Home Version (NPI-NH). Secondary efficacy measures were the Clinical Dementia Rating (Nursing Home Version)-Sum of the Boxes (CDR-SB), MMSE, and the Physical Self-Maintenance Scale (PSMS). Safety was monitored by physical examinations, vital signs, clinical laboratory tests, electrocardiograms (ECGs), and treatment-emergent adverse events (AEs). RESULTS: Eighty-two percent of donepezil- and 74% of placebo-treated patients completed the trial. Eleven percent of donepezil- and 18% of placebo-treated patients withdrew because of AEs. Mean NPI-NH 12-item total scores improved relative to baseline for both groups, with no significant differences observed between the groups at any assessment. Mean change from baseline CDR-SB total score improved significantly with donepezil compared with placebo at Week 24 (P < .05). The change in CDR-SB total score was not influenced by age. Differences in mean change from baseline on the MMSE favored donepezil over placebo at Weeks 8, 16, and 20 (P < .05). No significant differences were observed between the groups on the PSMS. Overall rates of occurrence and severity of AEs were similar between the two groups (97% placebo, 96% donepezil). Gastrointestinal AEs occurred more frequently in donepezil-treated patients. In general, AEs were similar in older and younger donepezil-treated patients, with the majority of patients experiencing only AEs that were transient and mild or moderate in severity. Weight loss was reported as an AE more frequently in older patients, although a loss at last visit of >or=7% of screening weight occurred at the same rate in older and younger patients (9% of donepezil- and 6% of placebo-treated patients). No significant differences between groups in vital sign changes, bradycardia, or rates of clinically significant laboratory or ECG abnormalities were observed. CONCLUSION: Patients treated with donepezil maintained or improved in cognition and overall dementia severity in contrast to placebo-treated patients who declined during the 6-month treatment period. The safety and tolerability profile was comparable with that reported in outpatient studies of donepezil. These findings also suggest that advanced age, comorbid illnesses, and high concomitant medication usage should not be barriers to donepezil treatment. Given the apparent improvement in behavior in the placebo group, and the high use of concomitant medications in both groups, the impact of donepezil on behavior in the nursing home setting is unresolved and merits further investigation. In summary, effects on cognition, overall dementia severity, and safety and tolerability findings are consistent with previous findings in outpatients and support the use of donepezil in patients with AD who reside in nursing homes.     

Alteration of a clinically meaningful outcome in the natural history of Alzheimer's disease by cholinesterase inhibition

OBJECTIVES: To describe the effect of cholinesterase inhibitors (CEIs) on the natural course of Alzheimer's disease (AD) using clinically meaningful outcomes. DESIGN: Cross-sectional and longitudinal study. SETTING: Referral dementia clinic. PARTICIPANTS: One hundred thirty-five matched pairs of patients with probable AD. MEASUREMENTS: The risk of AD patients being classified as slow progressors (Mini-Mental State Examination (MMSE) score change 相似文献   

Significance of syncope in patients with Alzheimer's disease treated with cholinesterase inhibitors.

We describe three cases of patients with Alzheimer's disease who presented with cardiac syncope soon after initiation of a cholinesterase inhibitor therapy (donepezil). Bradyarrhythmia was documented in two patients, considered probable in one, and was presumed related to the cholinergic therapy. Pacemaker implantation seemed justified rather than donepezil cessation. More over, it permitted an increase in donepezil dosage.     

Long-term cognitive benefits of donepezil in Alzheimer's disease: A retrospective comparison between 1994–1999 and 2000–2004

Objective:   In order to address an issue of how long Alzheimer's disease (AD) patients should receive donepezil, we estimated long-term effect of donepezil on cognition as well as its influential factors. We also evaluated the additional effect of cerebrospinal fluid (CSF)-tau protein levels on diagnosis.
Methods:   We compared cognitive changes between current (2000–2004) AD patients (donepezil users) and previous AD patients, seen by us 1994–1999, without receiving donepezil (non-donepezil users) by a mixed effect model. Cognition was assessed by Mini-Mental State Examination (MMSE) at 6-month intervals up to 24 months. Sensitivity analysis was performed exclusively on patients with high CSF-tau protein levels (CSF-tau >330 pg/mL) to minimize inaccuracies of the diagnosis
Results:   From 495 AD patients reviewed, 192 patients (120 donepezil users and 72 controls) were eligible. Estimated annual decline of MMSE was 1.2 points (95% confidence interval (95%CI), 0.9–1.5) in the donepezil users, whereas it was 2.8 points (95%CI, 2.1–3.6) in the control group. The difference was statistically significant ( P  < 0.001). The sensitivity analysis demonstrated that these declines were 1.2 (95%CI, 0.8–1.6) and 3.1 (95%CI, 2.3–3.9) points in the donepezil users and control groups, respectively.
Conclusions:   Long-term donepezil use for at least 2 years appeared to be beneficial in maintaining cognition in AD patients. As the cholinergic central nervous system consistently degenerates over time, long-term use of donepezil may be an appropriate therapy. Discontinuation of donepezil may not be recommended as far as patients are in a stable condition.     

Combination of intensive cognitive rehabilitation and donepezil therapy in Alzheimer's disease (AD)

Acetylcholinesterase inhibitors (AchEIs) are extensively used in Alzheimer's disease (AD) while reality orientation therapy (ROT) is a cognitive rehabilitation indicated for mentally deteriorated patients. We aimed to evaluate the efficacy of the combination of donepezil with an intensive ROT with active participation of the caregiver. Patients with AD (n = 100, mean age 78.4 ± 4.3 years) initiated treatment with donepezil, 5 mg/day; 62 of them underwent a 3-week, daily ROT and physical reactivation training with the caregiver (Group A); 38 participants received only donepezil therapy (Group B). All subjects were tested for cognitive and functional abilities at baseline, at the end of the training program, and after 2 months of follow-up. There was a significant improvement in mini-mental state examination (MMSE) score (p < 0.001) and the AD assessment scale-cognitive (ADAS-Cog) subscale (p < 0.001), without changes in impaired activity of daily living (ADL) and instrumental ADL (IADL) after intensive ROT training in Group A. MMSE was maintained after 2 months in-home ROT continuation. There were no significant changes in MMSE in drug-only treated patients (Group B) after 3 weeks, with a non-significant tendency to improvement in ADAS-Cog. Our results suggest benefit of an intensive ROT program in dementia patients receiving donepezil that seems to be maintained as far as ROT is continued by the caregiver.