安理申治疗轻中度阿尔茨海默病有效性及安全性的临床研究

目的　评价安理申 (aricept)治疗轻、中度阿尔茨海默病 (Alzheimerdisease ,AD)的有效性及安全性。方法　对 188例轻、中度AD[简易智能状态量表 (MMSE) 10～ 2 4分 ]患者进行了多中心、随机 12周临床试验 ,其中 89例为单盲、安慰剂对照研究 ,99例为自身对照研究。结果　随机、单盲、安慰剂对照组研究结果表明 ,5mg/d安理申治疗 12周时 ,安理申组较安慰剂组MMSE、临床痴呆程度量表 (CDR)及日常生活自理量表 (ADL)分数显著改善 (P依次 <0 0 1、0 0 5、0 0 1)。自身对照组研究结果显示 ,5mg/d安理申治疗 12周时 ,治疗后较治疗前MMSE、CDR及ADL分数分别改善 3 5、0 6、7 1分(P依次 <0 0 1、0 0 5、0 0 1)。安理申治疗 4周时 ,MMSE分数已有提高 (P <0 0 5 )。 145例服用安理申的患者中 ,7例 (4 8%)出现轻度胆碱能兴奋性不良反应 ,43例安慰剂组中 ,2例 (4 7%)出现头晕、恶心 ,两组差异无显著意义 (P >0 0 5 )。结论　安理申能有效治疗轻、中度AD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 ,耐受性好 ,安全性高。     

多奈哌齐治疗轻中度阿尔茨海默病作用机制研究进展

多奈哌齐是第2代胆碱酯酶抑制剂,对轻中度阿尔茨海默病有较好疗效。近年关于多奈哌齐作用机制的相关研究较为丰富,本文拟就我国阿尔茨海默病诊断与治疗现状和多奈哌齐治疗轻中度阿尔茨海默病作用机制研究进展进行概述。     

盐酸美金刚治疗阿尔茨海默病的疗效观察

目的 评估盐酸美金刚片(美金刚)治疗中、重度(MMSE<20)阿尔茨海默病(Alzheimer's disease,AD)的临床疗效和安全性.方法 30例经GDS评分3~6分的可能或很可能中、重度AD 患者接受美金刚治疗20周,每周随访1次,评估采用简易智能状态检查量表(MMSE)、Blessed-Roth 量表和全面衰退量表(GDS).结果 自身前后比较差别有统计学意义,不良反应率为6.7%.结论 美金刚能显著改善轻、中度AD 患者的认知功能、日常生活能力和人格情感障碍,且具有较好的安全性.     

盐酸美金刚治疗阿尔茨海默病疗效观察

NMDA受体阻滞剂盐酸美金刚(memantine hydrochloride)是FDA批准的第1个用于治疗中、重度AD的药物[1].为了进一步研究美金刚对AD的疗效及安全性,对在我院进行治疗的100例中、重度AD患者进行观察,报告如下.     

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。     

轻度认知损害向老年性痴呆转化的临床研究

目的 研究轻度认知损害(mild cognitive impairment,MCI)向痴呆自然转化过程及多奈哌齐对转化的干预影响.方法 总结98例MCI患者情况,将服用多奈哌齐和未服用任何胆碱酯酶抑制剂的遗忘型MCI(aMCI)及非aMCI患者按年龄、性别、认知减退程度及ApoEε4携带情况分层配对研究,分析各组向痴呆转化率以及MMSE、阿尔茨海默病(AD)评定量表(ADAS-Cog)和aMCI组修订韦氏记忆量表(WMS-R)变化.结果 由aMCI向AD转化率,服用和未服用多奈哌齐组于1年时分别为15.1%和8.3%(P＜0.05),2年时分别为24.2%和12.5%(P＜0.01).由非aMCI向AD转化率,服用和未服用多奈哌齐组,于1年时分别为13.0%和5.5%(P＜0.05),2年时分别为21.7%和16.6%(P＜0.05).服用多奈哌齐6个月时,aMCI组MMSE提高(0.1±1.3)分,对照组下降(0.3±2.4)分;ADAS-Cog下降(1.4±4.7)分,对照组升高(0.03±4.55)分;WMS-R改善(4.8±4.1)分,对照组下降(3.7±5.2)分,治疗组与自然病程对照组比较差异有统计学意义(P＜0.01),并可维持1～2年.多奈哌齐还能延缓携带ApoEε4的MCI患者向AD转化,但与自然病程组比较无统计学意义(P＞0.05),尚有待扩大样本量继续研究观察.多奈哌齐对认知相关区脑萎缩有减缓趋势.结论 本组资料提示,多奈哌齐能推迟MCI向AD转化.     

美金刚在阿尔茨海默病患者中的疗效与耐受性多中心研究

目的 评价美金刚对阿尔茨海默病（Alzheimer disease，AD）患者的疗效与安全性。方法多中心、随机、双盲、安慰剂对照研究。共纳入AD患者258例（MMSE检查5～18分），随机分入安慰剂组（PBO，n=130）或美金刚组（MEM，n=128），分别仅给予安慰剂或安慰剂及美金刚（10～20mg／d）治疗，共16周。主要疗效评估以坚持服用研究药物并在第16周接受严重障碍量表（SIB）评估的患者（完成16周研究集，CS16集）为对象，以SIB评分相对于基线的变化为指标；次要疗效评估分别以CS16集和全分析集（FAS）为对象，以MMSE、神经精神科问卷（NPI）和AD合作研究-日常生活能力量表（ADCS-ADL19）为指标。安全性评估包括体格检查、实验室检查、心电图和不良事件。结果 共236例患者（MEM 117例；PBO 119例）进入疗效分析，尽管两组的SIB评分均较基线时有所提高，两组的主要和次要疗效分析差异均无统计学意义（均P〉0．05）。Post—hoc数据评估发现有两个因素造成疗效分析结果的偏倚，舍弃受这些因素影响的患者数据后再次进行分析：美金刚组（n=94）的16周末SIB（MEM：PBO=2．2：0．3，P=0．04）、MMSE（MEM：PBO=1．0：0．1，P=0．03）和ADL评分变化（MEM：PBO=0．1：-1．6，P=0．02）与安慰剂组（n=95）差异均有统计学意义，提示美金刚的疗效优于安慰剂，显著改善AD患者的认知功能，并使日常生活能力维持稳定。美金刚的耐受性良好，其不良事件特征与安慰剂相似。结论 本研究为已有资料提供了更多支持，表明美金刚对中重度AD患者有效、安全且耐受性良好。     

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.     

阿托伐他汀联合美金刚治疗中重度阿尔茨海默病的疗效和安全性

目的 探讨阿托伐他汀联合美金刚治疗中重度老年性痴呆患者的疗效及安全性.方法 将52例中重度老年性痴呆患者随机分为联合用药组(阿托伐他汀联合美金刚)和美金刚组.在治疗前和治疗24周后分别进行血脂水平、简易精神状态量表(MMSE)、日常生活能力量表(ADL)及全面衰退量表(GDS)的检测和评分,并进行比较.结果 联合用药组治疗前、后的血脂水平差异有统计学意义(P<0.05),而美金刚组差异无统计学意义(P>0.05).每组治疗前、后的MMSE、ADL及GDS评分比较,差异均有统计学意义(P<0.05),而2组治疗后的各项评分比较,差异有统计学意义(P<0.05).结论 阿托伐他汀联合美金刚能有效改善中重度老年性痴呆患者的认知功能和日常生活能力,效果优于单独使用美金刚,且安全性高.     

小剂量多奈哌齐联合美金刚治疗老年性痴呆的疗效及安全性

目的观察多奈哌齐联合美金刚治疗老年性痴呆患者认知功能和行为能力的改善作用及安全性。方法将30例老年性痴呆患者随机分为多奈哌齐对照组和多奈哌齐联合美金刚试验组。疗程16周,每4周随访1次,评估简易精神状态量表(MMSE);治疗16周后进行有效性评估:采用阿尔茨海默病评定量表的认知分量表(ADAS-Cog)评定患者认知功能;采用临床医生访谈时对病情变化的印象补充量表(CIBIC-Plus)评价患者总体功能变化情况;采用神经精神科问卷(NPI)了解患者精神行为症状的变化;采用日常生活能力量表(ADL)了解患者日常功能情况。结果 29例患者完成最后随访,对照组MMSE,ADAS-Cog,CIBIC-Plus,NPI,ADL评分治疗前后比较有统计学意义(P<0.05);试验组MMSE,ADAS-Cog,CIBIC-Plus,NPI,ADL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无统计学意义;治疗16周后,两组比较,试验组较对照组患者NPI评分明显下降(P<0.05),表现在脱抑制和激越等情绪方面;CIBIC-Plus总体功能变化实验组较对照组好转明显(P<0.05),余各项评分两组间无显著性差异(P>0.05)。结论多奈哌齐及多奈哌齐联合美金刚治疗老年性痴呆均有效,后者更优于前者,尤其对情绪方面的阳性症状控制较好,且具有良好的安全性和耐受性。     

Home based training for dexterity in Parkinson's disease: A randomized controlled trial

BackgroundPatients with Parkinson's disease exhibit disturbed manual dexterity. This impairment leads to difficulties in activities of daily living, such as buttoning a shirt or hand-writing. The aim of the present study was to investigate the effectiveness of a home-based dexterity program on fine motor skills in a single-blinded, randomized controlled trial, in patients with Parkinson's disease.MethodsOne hundred and three patients with Parkinson's disease (aged between 48 and 80 years, Hoehn & Yahr stage I-IV) were randomized to either a home-based dexterity program (HOMEDEXT) or Thera-band program. All patients trained over a period of 4 weeks, 5 times/week, 30 min for each session. A baseline, post-intervention, and follow-up assessment (12 weeks later, time period without intervention) were done. The primary outcome measure was dexterity as measured with the Nine Hole peg test (9-HPT). Secondary outcome measures included strength, motor parkinsonian symptoms, dexterity-related activities of daily living (ADL) and Health-related Quality of Life (HrQoL).ResultsThere was a significant difference in favor of the HOMEDEXT group as compared to the Thera-band group on the primary outcome 9-HPT (p = 0.006) and dexterity-related ADL (p = 0.02) at post intervention. No significant differences were found for the other outcomes, nor at follow-up.ConclusionThis is the first randomized controlled trial showing that an intensive, task specific home-based dexterity program significantly improved fine motor skills in Parkinson's disease. The effect generalized to dexterity-related ADL functions. As these improvements did not sustain, the finding suggest that continuous training is required to maintain the benefit.     

Randomized, controlled clinical trial of zonisamide as adjunctive treatment for refractory partial seizures

PURPOSE: This study was designed to evaluate efficacy and safety of zonisamide (ZNS) as adjunctive treatment for patients with refractory partial seizures. METHODS: This randomized, double-blind, placebo-controlled study was conducted at four epilepsy treatment centers. It included a baseline phase (8 to 12 weeks) and a double-blind treatment phase (12 weeks). Initially, patients randomized to ZNS treatment were given a 7-mg/kg/d dosage. When investigators found that adverse effects could be reduced by gradually introducing ZNS, patients were allowed to begin treatment at lower doses (100 mg or approximately 1.5 mg/kg/d) titrated over several weeks to a maximum of 400 to 600 mg/d. Primary and secondary efficacy measures were the median percentage reduction from baseline in seizure frequency and the proportion of patients achieving a > or =50% reduction from baseline (responder rate). Patient and physician global assessments also served as indicators of efficacy. Safety was assessed primarily by treatment-emergent adverse events. RESULTS: ZNS-treated patients had a 28.9% reduction in seizure frequency, which differed significantly from the 4.7% increase in placebo-treated patients. The responder rate for ZNS-treated patients was 26.9%, compared with 16.2% for placebo-treated patients. At study's end, 66.2% of ZNS-treated patients and 12.3% of placebo-treated patients considered their condition improved; similarly, physicians assessed 63.6% of ZNS-treated patients and 10.8% of placebo-treated patients as improved. The most frequently reported adverse events with ZNS treatment included somnolence, irritability, dizziness, nausea, and fatigue. CONCLUSIONS: As adjunctive treatment, ZNS was generally well tolerated and significantly improved seizure control among patients with refractory partial seizures.     

艾司西酞普兰治疗抑郁症的随机双盲对照试验

目的比较艾司西酞普兰和西酞普兰治疗抑郁症的疗效和安全性。方法本研究为6周的多中心、随机、双盲双模拟、平行阳性对照试验。共入组240例符合中国精神障碍分类与诊断标准第3版的抑郁症诊断标准的患者,其中试验组（艾司西酞普兰）120例和对照组（西酞普兰）120例。试验组剂量为10～20mg/d,对照组剂量为20～40mg/d,评估量表为17项汉密尔顿抑郁量表（HAMD-17）,汉密尔顿焦虑量表（HAMA）以及临床总体印象量表（CGI）。安全性评估包括评估不良事件、体检、实验室检查和心电图检查等。结果 212例患者完成了研究,试验组108例,对照组104例。全分析集（FAS）结果显示：治疗6周后,试验组的HAMD减分为（15.4±7.1）分,对照组为（14.5±7.1）分;试验组的有效率为78.3%,临床痊愈率为57.5%,对照组分别为73.3%、52.5%;两组差异无统计学意义。两组治疗后HAMA评分均下降,组间差异无统计学意义。两组在各访视点CGI严重程度评分差异皆无统计学意义。治疗第2周时,试验组的有效率高于对照组（分别为22.5%,10.8%,χ^2=5.88,P=0.02）,临床痊愈率也高于对照组（分别为11.7%,2.5%,χ^2=7.66,P〈0.01）。试验组中有39例（32.5%）发生不良反应,对照组中有37例（30.8%）发生不良反应,两组差异无统计学意义。试验组常见的不良反应为恶心（12.5%）、口干（10.0%）、头晕（9.2%）,对照组为恶心（14.2%）、口干（7.5%）。结论艾司西酞普兰治疗抑郁与西酞普兰的疗效相当,耐受性好,起效可能更快。     

Effects of working memory training in patients with Parkinson's disease without cognitive impairment: A randomized controlled trial

ObjectiveTo determine the feasibility and evaluate effects of a computerized working memory (WM) training (WMT) in patients with Parkinson's Disease (PD) on cognitive and clinical outcomes.Methods76 patients with PD without cognitive impairment were randomized to either the WMT group (n = 37), who participated in a 5-week adaptive WMT, or a passive waiting-list control group (CG, n = 39). Patients underwent clinical and neuropsychological examination at baseline, after training, and at 3-months follow-up, with verbal WM and non-verbal WM as primary outcomes. Outcome assessors were blinded for group allocation.ResultsAll WMT participants completed the training successfully and reported high levels of motivation for and satisfaction with the training. Repeated-measures, linear mixed-effects models revealed positive training effects for the WMT group compared to the CG in verbal working memory with a small relative effect size 0.39 [95%CI 0.05; 0.76] for the 3-months follow-up only. No other reliable training effects in cognitive and clinical variables were found for either point of time.ConclusionsIn this randomized controlled trial, WMT was feasible and yielded some evidence for 3-months follow-up training gains in patients with PD. WMT might be an effective intervention to prevent cognitive decline in this patient group, however, more longitudinal studies with longer follow-up periods and more sensitive assessment tools will have to proof this concept.Trial registrationGerman Clinical Trials Register (DRKS00009379).     

Design considerations for a multicenter randomized controlled trial of early surgery for mesial temporal lobe epilepsy

Purpose: To describe the trial design for the multicenter Early Randomized Surgical Epilepsy Trial (ERSET). Patients with pharmacoresistant epilepsy are generally referred for surgical treatment an average of two decades after onset of seizures, often too late to avoid irreversible disability. ERSET was designed to assess the safety and efficacy of early surgical intervention compared to continued pharmacotherapy. Methods: ERSET is a randomized controlled, parallel group clinical trial with blinded outcome adjudication. Participants are patients with mesial temporal lobe epilepsy (MTLE) older than the age of 12 who have had pharmacoresistant seizures for not >2 years and are determined by detailed evaluation to be surgical candidates prior to randomization. The primary outcome measure is seizure freedom in the second year of a 2‐year follow‐up period. Health‐related quality of life (HRQOL), neurocognitive function, ancillary outcomes, and adverse events were also measured. Results: Significant methodologic problems addressed by the study design included the following: recruitment of participants early in the course of epilepsy; establishment of operational definitions for “pharmacoresistant” and “early”; and standardization of diagnostic testing, medical treatment, and surgical interventions across multiple centers. Discussion: Rigorous trial designs to assess surgical interventions in epilepsy are necessary to provide evidence to guide treatment. This article is the first of a series; trial results will be reported in subsequent publications.