灯盏生脉胶囊联合盐酸多奈哌齐治疗阿尔茨海默病的临床研究

目的 观察灯盏生脉胶囊联合盐酸多奈哌齐对阿尔茨海默病患者认知功能、日常生活能力及安全性的影响。方法 将98例阿尔茨海默病患者随机分为治疗组与对照组各49例; 对照组给予每日口服盐酸多奈哌齐5 mg/次,1次/d,治疗组在对照组的基础上口服灯盏生脉胶囊0.36 g/次,3次/d; 比较2组患者治疗前与治疗3、6月后认知功能评分(MMSE、ADAS-cog)、日常生活能力评分(ADAS-ADL)、血清一氧化氮(NO)、内皮素(ET)水平及不良反应发生率。结果 治疗6月后治疗组MMSE评分为(21.85±2.58)分,对照组为(20.48±2.23)分(P<0.05); 治疗3、6月后治疗组ADAS-cog评分为(45.48±5.94)、(41.57±5.10)分,对照组为(48.69±6.23)、(414.24±5.53)分(P<0.05); 治疗3、6月后治疗组ADAS-ADL评分为(43.91±4.25)、(47.57±3.86),对照组为(41.77±4.44)分、(44.46±5.18)分(P<0.05); 治疗3、6月后治疗组NO水平为(41.95±7.62)、(37.89±5.93)μmol/L,对照组为(45.28±6.68)、(41.55±7.92)μmol/L(P<0.05); 治疗3、6月后治疗组ET水平为(140.48±22.94)、(132.04±10.08)ng/L,对照组为(152.08±17.39)、(143.91±17.60)ng/L(P<0.05); 2组药物不良反应主要有恶心、失眠、头痛、乏力、头晕、腹泻、皮疹,治疗组和对照组药物不良反应发生率分别为20.41%和14.28%(P>0.05)。结论 灯盏生脉胶囊联合盐酸多奈哌齐可提高阿尔茨海默病患者认知功能及日常生活能力,减少神经毒性物质NO、ET的生成,且安全性较好     

多奈哌齐对颅脑外伤后患者认知功能障碍的疗效观察

摘 要 目的:观察多奈哌齐对颅脑外伤后患者认知功能障碍的改善作用。方法：颅脑外伤后认知功能障碍住院患者76例随机分为观察组和对照组各38例。两组患者均予控制颅内压、神经营养及防治并发症等基础治疗。观察组患者加用多奈哌齐片5 mg,po qd;对照组患者加用脑复康片1.2 g,po tid。两组均连用2周。观察两组患者治疗前后认知功能指标的变化,比较两组疗效及药品不良反应。结果：治疗2周后,两组患者WMS评分和MOCA评分均较前明显上升(P＜0.05或P＜0.01),且观察组较对照组上升更明显(P＜0.05);观察组患者认知功能总改善率为94.74%,明显高于对照组的76.32%(P＜0.05)。两组药品不良反应发生率比较,差异无统计学意义(P＞0.05)。结论：多奈哌齐对颅脑外伤后患者认知功能障碍具有良好的改善作用,能促进患者认知功能的恢复,且安全性较好。     

A 15-day course of donepezil modulates spectral EEG dynamics related to target auditory stimuli in young,healthy adult volunteers

ObjectiveTo identify possible electroencephalographic (EEG) markers of donepezil’s effect on cortical activity in young, healthy adult volunteers at the group level.MethodsThirty subjects were administered a daily dose of either 5 mg donepezil or placebo for 15 days in a double-blind, randomized, cross-over trial. The electroencephalogram during an auditory oddball paradigm was recorded from 58 scalp electrodes. Current source density (CSD) transformations were applied to EEG epochs. The event-related potential (ERP), inter-trial coherence (ITC: the phase consistency of the EEG spectrum) and event-related spectral perturbation (ERSP: the EEG power spectrum relative to the baseline) were calculated for the target (oddball) stimuli.ResultsThe donepezil and placebo conditions differed in terms of the changes in delta/theta/alpha/beta ITC and ERSP in various regions of the scalp (especially the frontal electrodes) but not in terms of latency and amplitude of the P300-ERP component.ConclusionOur results suggest that ITC and ERSP analyses can provide EEG markers of donepezil’s effects in young, healthy, adult volunteers at a group level.SignificanceNovel EEG markers could be useful to assess the therapeutic potential of drug candidates in Alzheimer’s disease in healthy volunteers prior to the initiation of Phase II/III clinical studies in patients.     

Impact of donepezil treatment for Alzheimer's disease on caregiver time

SUMMARY

Objective: To assess the impact of donepezil treatment compared with placebo on caregiver time spent assisting patients with Alzheimer's disease (AD).

Research design and methods: Patient and caregiver data were collected as part of a 1-year, prospective, double-blind, randomized, placebo-controlled trial. The Resource Utilization in Dementia (RUD) questionnaire was used to record caregiver time at study baseline and at Weeks 12, 24, 36, and 52. This analysis focuses solely on those caregivers who were actively (> 0?h/day reported on the RUD) providing care at study baseline.

Main outcome measures: The change in time relative to baseline that caregivers spent assisting patients over the course of the study.

Results: The active caregiver population was composed of 96 caregivers of donepezil-treated patients and 94 caregivers of patients receiving placebo. Over the course of the 1-year study, and as the condition of the AD patients deteriorated, it was expected that caregiver time would increase. As expected, after 52?weeks, caregivers of placebo patients were providing almost 2?h each day (106.8?min) more care than they had done at study baseline. For those caregivers of donepezil-treated patients, although they were spending more time caring than they had done at study baseline, their time burden had only increased by 42.6?min more each day. This difference in caring time between the 2 groups, relative to baseline at Week 52, was 1.1?h (64.2?min) each day, and was significant (?p = 0.03).

Conclusion: Caregiver time devoted to helping an AD patient typically increases with the severity of the disease. By helping the patient maintain his/her ability to perform activities of daily living for longer, treatment with donepezil is not only beneficial to the patient, but also has positive time-burden implications for the caregiver.     

Ventricular measurements in computed tomography of responders and non-responders to donepezil in the treatment of Alzheimer's disease

INTRODUCTION: We attempt to see whether the ventricular measurements in routine CT scans performed prior to commencing donepezil differed in patients who duly responded well and those who did not, and to explore the potential application of the findings in clinical practice. METHOD: The study included all patients who were prescribed donepezil during a 2-year period in Warrington ( n =59). Two groups of patients were compared in respect of their baseline CT scan ventricular measurements: those who improved or remained stable cognitively on donepezil ( n =43) and those who declined while on donepezil (MMSE < 10) during the study period ( n =16). RESULTS: Significant differences in means between the two groups were found in relation to the bicaudate span and bicaudate ratio. Of ventricular measurements, only the bicaudate parameters were significantly correlated with the baseline Mini Mental State Examination (MMSE) score as well as the rate of decline in cognitive function during the study period ( P < 0.05). CONCLUSION: Baseline bicaudate diameter and ratio may be of some value if included in the initial assessment of patients on donepezil. These measurements, in conjunction with other cognitive and functional assessments, may prove helpful in deciding whether to commence treatment, and give a rough guide to the outcome. Future studies, with sufficient statistical power, are necessary to explore the use of ventricular parameters in predicting and monitoring patients' response to current and future pharmacological treatment in Alzheimer's disease.     

盐酸美金刚与多奈哌齐治疗阿尔茨海默病的对照研究

目的探讨盐酸美金刚与多奈哌齐治疗阿尔茨海默病（AD）的临床疗效及安全性。方法将96例AD患者随机分为盐酸美金刚组和多奈哌齐组,在治疗前、治疗后2周、4周、8周、16周、24周末分别进行简易智能状态检查（MMSE）评分和临床疗效评估。结果在治疗2、4、8周末评估两组相仿,第16、24用末多奈哌齐组优于盐酸美金刚组。结论盐酸美金刚与多奈哌齐短期疗效相仿,多奈哌齐组远期疗效优干盐酸美金刚组,两组均有良好的安全性。     

盐酸多奈哌齐配合综合康复治疗对颅脑外伤后记忆障碍的疗效观察

目的 探讨盐酸多奈哌齐配合综合康复训练治疗颅脑外伤(TBI)后记忆障碍的疗效和安全性.方法 广东省工伤康复医院神经康复科自2008年5月至2010年10月收住院行康复治疗的TBI康复期患者76例,其中给予综合康复治疗38例(对照组),综合康复治疗的基础上加用盐酸多奈哌齐治疗38例(治疗组),疗程3个月,治疗前后采用韦氏记忆量表(WMS)评价疗效并观察不良反应的发生.结果 与治疗前相比,对照组治疗后长时记忆中顺数、短时记忆中图片回忆和再认、瞬时记忆(背数)、WMS量表总分升高,差异均有统计学意义(P＜0.05);与治疗前比较,治疗组治疗后长时记忆(顺数、倒数、积累)、短时记忆中图片回忆、再认、逻辑记忆、瞬时记忆(背数)、WMS量表总分均升高,差异均有统计学意义(P＜0.05);与对照组治疗后比较,治疗组治疗后长时记忆中积累、短时记忆中逻辑记忆、WMS量表总分升高,差异有统计学意义(P＜0.05).盐酸多奈哌齐治疗过程中未见明显不良反应.结论 盐酸多奈哌齐配合综合康复治疗对TBI后记忆障碍较单纯采用综合康复治疗疗效更好.     

Working memory deficits and related disinhibition of the cAMP/PKA/CREB are alleviated by prefrontal α4β2*-nAChRs stimulation in aged mice

The present study investigates in aged mice the working memory (WM) enhancing potential of the selective α4β2* nicotinic receptor agonist S 38232 as compared with the cholinesterase inhibitor donepezil, and their effect on cAMP response element binding protein (CREB) phosphorylation (pCREB) as a marker of neuronal activity. We first showed that aged mice exhibit a WM deficit and an increase of pCREB in the prelimbic cortex (PL) as compared with young mice, whereas no modification appears in the CA1. Further, we showed that systemic administration of S 38232 restored WM in aged mice and alleviated PL CREB overphosphorylation. Donepezil alleviated age-related memory deficits, however, by increasing pCREB in the CA1, while pCREB in PL remained unaffected. Finally, whereas neuronal inhibition by lidocaine infusion in the PL appeared deleterious in young mice, the infusion of Rp-cAMPS (a compound known to inhibit CREB phosphorylation) or S 38232 rescued WM in aged animals. Thus, by targeting the α4β2*-nicotinic receptor of the PL, S 38232 alleviates PL CREB overphosphorylation and restores WM in aged mice, which opens new pharmacologic perspectives of therapeutic strategy.     

Scopolamine-induced deficits in social memory in mice: Reversal by donepezil

Deficits in social behaviour is a characteristic of numerous mental disorders including autism, schizophrenia, depression and Alzheimer's disease. For the assessment of pharmacological and genetic experimental disease models, conventional social interaction tasks bear the uncertainty that any drug-induced abnormality of the investigator may feed back to the drug-free companion modifying its reactions. A considerable technical improvement was recently reported by Moy et al. [Moy SS, Nadler JJ, Perez A, Barbaro RP, Johns JM, Magnuson T, et al. Sociability and preference for social novelty in five inbred strains: an approach to assess autistic-like behaviours in mice. Genes Brain Behav 2004;3:287–302] in which the drug free partner is confined to a small cage and social contacts of the investigator are recorded uncontaminated of any social reactions of the stranger. Using this novel behavioural paradigm, we here show in C57Bl/6 female mice that sociability (social interaction with a stranger mouse) is not impaired after administration of the anxiolytic diazepam (0.1–1 mg/kg) or the muscarinic antagonist scopolamine hydrobromide (0.1–1 mg/kg). However, social memory tested after a short time interval was impaired by both drugs in a dose-dependent manner (diazepam: ≥0.5 mg/kg; scopolamine: ≥0.3 mg/kg). The scopolamine-induced short-term memory deficit was reversed to normal by the choline esterase inhibitor donepezil (1 mg/kg).Given this dependence of social recognition on the cholinergic system, combined with the clinical observation of reduced social contacts in dementia patients, sociability may offer a novel endpoint biomarker with translational value in experimental models of cognitive dysfunction.