多奈哌齐治疗阿尔茨海默病的临床观察

目的探讨多奈哌齐单用与合用其他药物治疗阿尔茨海默病(AD)的临床疗效。方法将60例AD患者随机分为单用多奈哌齐(单用组)和综合治疗(合用组)，在治疗前、治疗后6周、12周和24周末分别进行简易智能状态检查(MMSE)评分和临床疗效评定。结果两组在治疗后6周和12周末MMSE评分和临床疗效无明显差异，在24周末合用组显著优于单用组。结论多奈哌齐单独使用和药物综合治疗AD短期疗效相仿，而远期疗效以综合治疗较好。     

多奈哌齐合并复方海蛇胶囊治疗阿尔茨海默病性痴呆患者对照研究

目的:探讨多奈哌齐合并复方海蛇胶囊对阿尔茨海默病(AD)患者认知功能和行为能力的改善作用。方法:90例AD患者随机分为3组:联合治疗组(给予多奈哌齐合并复方海蛇胶囊治疗)30例、多奈哌齐治疗组(单用多奈哌齐治疗)30例、对照组(仅予常规治疗,不予痴呆药物)30例。观察3个月。分别在治疗前和治疗3个月后采用简易精神状态检查量表(MMSE)及日常生活能力量表(ADL)测评3组患者的认知功能和生活能力。结果:治疗3个月,联合治疗组MMSE减分值明显高于多奈哌齐治疗组(t=5.09,P0.01)和对照组(t=7.71,P0.01);多奈哌齐治疗组减分值明显高于对照组(t=3.10,P0.01)。联合治疗组ADL评分减分值明显高于多奈哌齐治疗组(t=-2.33,P=0.02)和对照组(t=-6.88,P0.01);多奈哌齐治疗组减分值明显高于对照组(t=-5.50,P0.01)。结论:多奈哌齐和复方海蛇胶囊联合治疗对AD患者的认知功能及行为能力有显著的改善作用。     

多奈哌齐联合尼莫地平治疗中重度阿尔茨海默病的疗效及安全性

目的：观察多奈哌齐联合尼莫地平治疗中、重度阿尔茨海默病（AD）的疗效及安全性。方法：32例中、重度AD患者随机分为多奈哌齐组及多奈哌齐＋尼莫地平（联用尼莫地平）组。采用简易精神状态量表（MMSE）、临床痴呆评定量表（CDR）歧全面衰退量表（GDS）评定疗效。结果：多奈哌齐组MMSE和CDR评分较治疗前明显改善；联用尼莫地平组3种量表评分较治疗前均显著改善。两组均无严重不良反应。结论：多奈哌齐联用尼莫地平较单用多奈哌齐可能更显著改善中、重度AD的认知功能，两种药物安全性俱佳。     

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.     

加兰他敏与多奈哌齐治疗阿尔茨海默病型痴呆的疗效比较

目的 比较加兰他敏与多奈哌齐治疗阿尔茨海默病(AD)的临床疗效,为临床用药提供依据.方法 采用随机平行分组法将80例AD患者分为A组与B组各40例,分别给予加兰他敏与多奈哌齐治疗,连续治疗12周后比较2组临床疗效.结果 2组MMSE评分比较无明显差异(P＞0.05),B组ADL评分明显优于A组(P＜0.05);2组治疗后MMSE及MBI量表评分均较治疗前明显改善(P＜0.05),但组间比较并无明显差异(P＞0.05);B组不良反应发生率明显低于A组,差异有统计学意义(P＜0.05).结论 加兰他敏与多奈哌齐治疗AD疗效类似,但后者安全性更高,更有利于提高老年患者生活质量水平.     

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。     

阿尔茨海默病与脑血管性痴呆的诱发电位比较

目的 :探讨阿尔茨海默痴呆 (AD)和脑血管性痴呆 (VD)的诱发电位特点。方法 :收集 2 5例AD组、2 4例VD组及 2 2名正常老年人 (NC) ,完成听觉诱发电位 (AEP)和视觉诱发电位 (VEP)检查。结果 :AD组和VD组及NC组在潜伏期AEP/N1、P2 ,VEP/P1,波幅AEP/P2、P3,VEP/P2、P3上有显著性差异 (P <0 0 5～ 0 0 1)。与NC组相比 ,AD组潜伏期AEP/N1、P2 ,VEP/P1延迟 ,波幅AEP/P2、P3,VEP/P2、P3降低。与NC组相比 ,VD组在潜伏期VEP/P1延迟 ,波幅P2、P3降低。AD组与VD组相比 ,在潜伏期AEP/N1、N2上有显著差异 ,AD组延迟于VD组。AD组VEP的P1潜伏期 ,VD组AEP的P3波幅及VEP的N1潜伏期改变上与其MMSE评分有关联。结论 :AD组与VD组的诱发电位变化有类似的异常 ,但AD组病损范围广 ,经不同感觉系统诱发的脑诱发电位均有异常。两组痴呆中的三个指标与MMSE关联的特点 ,值得进一步随访     

天智颗粒治疗轻、中度阿尔茨海默病临床研究

目的评价天智颗粒治疗轻、中度阿尔茨海默病(alzheimer disease,AD)的有效性及安全性。方法选择简易智能状态量表(MMSE)轻、中度AD患者60例,随机分成治疗组和对照组各30例,治疗组给予天智颗粒联合吡拉西坦治疗,对照组给予吡拉西坦治疗,观察12周。治疗前后应用简易智能状态量表MMSE,日常生活能力量表(ADL)评价临床疗效;用不良反应量表(TESS)评定不良反应。结果观察12周,天智颗粒治疗组较对照组MMES、ADL评分明显改善(P<0.01)。治疗组天智颗粒治疗12周后较治疗前MMSE与ADL分数分别改善3.8分和8.0分(P<0.05,P<0.01)。天智颗粒治疗组不良反应轻,与吡拉西坦对照组比较2组差异无显著意义(P>0.05)。结论天智颗粒能有效治疗轻、中度AD患者,对患者的认知功能和日常生活自理能力均有改善,耐受性好,安全性高。     

Efficacy and safety of Cerebrolysin in moderate to moderately severe Alzheimer’s disease: results of a randomized,double‐blind,controlled trial investigating three dosages of Cerebrolysin

Background: Cerebrolysin is a neuropeptide preparation mimicking the effects of neurotrophic factors. This subgroup analysis assessed safety and efficacy of Cerebrolysin in patients with moderate to moderately severe Alzheimer’s disease (AD) (ITT data set: N = 133; MMSE: 14–20) included in a dose‐finding study (ITT data set: N = 251; MMSE: 14–25). Results of the mild AD subgroup (ITT data set: N = 118; MMSE: 21–25) are also presented. Methods: Patients with AD received 100 ml IV infusions of Cerebrolysin (10, 30 or 60 ml diluted in saline; N = 32, 34 and 35, respectively) or placebo (saline; N = 32) over twelve weeks (5 days per week for 4 weeks and 2 days per week for another 8 weeks). Primary efficacy criteria ADAS‐cog+ (Alzheimer’s Disease Assessment Scale Cognitive Subpart Modified) and CIBIC+ (Clinical Interview‐based Impression of Change with Caregiver Input) were assessed 24 weeks after baseline. Results: At week 24, Cerebrolysin improved the global clinical function significantly with all three dosages and induced significant improvements in cognition, initiation of activities of daily living (ADL) and neuropsychiatric symptoms at 10‐, 30‐ and 60‐ml doses, respectively. Treatment effects on total ADL and other secondary parameters (MMSE, Trail‐making test) were not significant. Cerebrolysin was safe and well tolerated. Conclusions: These results demonstrate the efficacy of Cerebrolysin in moderate to moderately severe AD, showing dose‐specific effects similar to those reported for patients with mild to moderate AD. The benefits of Cerebrolysin in advanced AD need to be confirmed in larger trials.     

A multicentre, randomized, double-blind, placebo-controlled study to evaluate the efficacy, tolerability and safety of two doses of metrifonate in patients with mild-to-moderate Alzheimer's disease: the MALT study

BACKGROUND: Metrifonate is a long-lasting acetylcholinesterase inhibitor being developed for the symptomatic treatment of Alzheimer's disease (AD).OBJECTIVES: This study compared the efficacy, tolerability and safety of two doses of metrifonate in patients with mild-to-moderate AD, over a 26-week treatment period. METHODS: Six hundred and five patients were randomized to placebo (n=208), a 40/50 mg dose (40 or 50 mg by weight; n=200) or a 60/80 mg dose (60 or 80 mg by weight; n=197) metrifonate. Patients randomized to receive metrifonate were administered a once-daily loading dose of 80 or 120 mg based on weight for 2 weeks, followed by the relevant maintenance dose for 24 weeks. Four main clinical domains of AD were assessed: cognition (ADAS-cog and MMSE), psychiatric and behavioural symptoms (ADAS-noncog and NPI), instrumental and basic activities of daily living (DAD) and global functioning (CIBIC-plus, CIBIS-plus and GDS).RESULTS: ADAS-cog performance was significantly improved in the 60/80 mg and 40/50 mg dose groups, compared with placebo, in the intention-to-treat (ITT) population. In addition, statistically significant treatment differences were demonstrated between the 60/80 mg dose group and placebo on MMSE, ADAS-noncog, the NPI subitems of hallucinations and apathy, DAD, CIBIC-plus, CIBIS-plus and the GDS. The performance of the 40/50 mg dose group was also significantly superior to placebo on the CIBIS-plus and the NPI subitem aberrant motor behaviour. CONCLUSIONS: Metrifonate significantly improved a wide range of symptoms across all four clinical domains of AD in a dose-dependent manner, and was safe and well tolerated at both doses studied.     

Investigation of the short- and long-term effects of donepezil on cognitive function in Alzheimer's disease

Background: Donepezil is effective in maintaining cognitive function in patients with mild to moderate Alzheimer's disease (AD). However, not all patients respond to donepezil. In the present study, we examined the short‐ and long‐term effects of donepezil on cognitive function after 2 years treatment. Methods: The present retrospective study was performed on 122 AD outpatients who had been taking donepezil for ≥1 year. All subjects underwent periodic examination of cognitive function (Mini‐Mental State Examination (MMSE), Rorschach Cognitive Index (RCI)) and clinical evaluation on the Clinical Dementia Rating (CDR); first before starting treatment and then at 4‐month intervals after initiation of donepezil. Patients were divided into three groups: (i) MG, the ‘maintained’ group, in which the global CDR score was maintained during treatment; (ii) DeG, the ‘declined’ group, in which the global CDR score increased; and (iii) DrG, the drop out group, who discontinued the treatment. Changes in scores on the MMSE and RCI were compared before treatment and at 4‐month intervals within each group. In addition, over each 4‐month period, MMSE and RCI scores were compared between the three groups. Furthermore, to investigate the condition of effective treatment, the reasons why donepezil treatment was discontinued in the DrG were examined. Results: The most frequent reason for discontinuation was the appearance of behavioral and psychiatric symptoms of dementia (BPSD), which were more frequently observed in the DrG. Although depression and/or disinclination were more frequent in the MG, hyperactivity was more frequent in the DeG and DrG. Before treatment, patients in the DrG exhibited significantly lower scores on the MMSE than did patients in the MG and DeG. Upon examination 4 months after starting treatment, patients in the MG showed cognitive improvement on the MMSE and RCI, whereas those in the DeG showed cognitive deterioration on the MMSE. Conclusion: The results of the present study suggest that when a short‐term beneficial effect of the donepezil on cognitive functions is seen, long‐term effect may also be expected at 2 years. Periodic clinical evaluation and examination of cognitive function is indispensable for effective donepezil treatment.     

Relationship of cognitive measures and gray and white matter in Alzheimer's disease

OBJECTIVE: To examine the relationship between commonly used screening cognitive measures with gray and white matter integrity in patients with mild to moderate AD. BACKGROUND: New neuroimaging techniques, such as voxel-based morphometry (VBM), make it possible to study the relationship between structural brain integrity and cognitive functioning in AD. METHODS: Gray and white matter integrity was evaluated using VBM in fifteen patients with mild to moderate AD. ADAS-Cog and MMSE scores were also performed as part of the baseline assessment for a larger clinical trial in the AD patients. Correlations between cognitive measures and VBM were performed. RESULTS: Both the ADAS-Cog and the MMSE showed a similar relationship with gray matter degeneration, reflecting greater cognitive impairment with decreased gray matter in the left temporal lobe. However, the MMSE score was much more reflective of underlying white matter changes than ADAS-Cog scores, particularly in frontotemporal region. These findings suggest that the ADAS-Cog and MMSE reflect different aspects of the underlying brain changes observed in AD. The ADAS-Cog was more specific to gray matter integrity whereas the MMSE reflected a more global reduction in both gray and white matter. CONCLUSIONS: These results support using neuroimaging markers of neural integrity as an important consideration when evaluating treatment efficacy. Furthermore, whole-brain analyses such as VBM help to evaluate neural systems that are not necessarily targeted by the treatment.     

临床疗效总评量表在阿尔茨海默病疗效评估中的应用探讨

目的探讨临床疗效总评量表(CGI)在阿尔茨海默病(AD)疗效评估中的应用价值。方法对30例接受盐酸美金刚治疗的阿尔茨海默病患者,在治疗前、治疗4个月末分别进行简易智力状态检查(MMSE)、阿尔茨海默病评定量表-认知分量表(ADAS-cog)、日常生活能力量表(ADL)、CGI评分,通过相关分析考察CGI的效度。结果基线时病情严重程度(SI)与MMSE时间定向、地点定向、注意力及计算力、执行功能、书面表达的分值及总分的相关系数为-0.516～-0.680(P<0.01),与ADAS-cog所有因子分及总分的相关系数为0.507～0.880(P<0.01),与ADL行走、做饭、做家务、吃饭、穿衣、梳洗、洗衣、洗澡、购物、上厕所、打电话、自理经济、躯体生活自理量表、工具性日常生活能力量表的分值及总分的相关系数为0.462～0.745(P<0.05)。4个月末疗效总评(GI)与ADAS-cog单词回忆、命名、口语理解的分值及总分、ADL打电话的分值等治疗前后差值的相关系数为-0.365～-0.444(P<0.05),4个月末疗效指数(EI)与ADAS-cog命名、结构、回忆指令、找词困难的分值及总分治疗前后差值的相关...     

石杉碱甲治疗精神分裂症认知功能障碍的半年随访

目的探讨石杉碱甲治疗精神分裂症认知功能障碍的疗效。方法慢性精神分裂症患者被随机分为两组,一组予石杉碱甲治疗,另一组为对照组,两组患者均维持原来的抗精神病药物治疗,疗程24周。治疗前、8周末和24周末进行韦氏成人智力量表(WAIS)、威斯康星卡片分类测验(WCST)、简明智力状态检查(MMSE)测定。结果共收集意向治疗人群(ITT)107例,治疗组58例,对照组49例。两组患者之间治疗前、8周末和24周末的WAIS、WCST、MMSE评分均无显著性差异。结论石杉碱甲对慢性精神分裂症认知功能障碍的疗效不明显。