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     

葛根素注射液联合多奈哌齐治疗帕金森病的疗效观察

目的探讨葛根素注射液联合盐酸多奈哌齐片治疗帕金森病的临床疗效。方法选取2016年2月—2017年12月南阳市中心医院收治的帕金森病患者98例为研究对象,所有患者随机分为对照组和治疗组,每组各49例。对照组患者睡前口服盐酸多奈哌齐片,1片/次,1次/d,维持1个月,然后根据治疗效果增加剂量至2片/次,1片/d。治疗组在对照组基础上静脉滴注葛根素注射液,400 mg加入到5%葡萄糖溶液500 m L中,1次/d。15 d为1个疗程,两组患者连续治疗3个疗程。观察两组的临床疗效,比较两组的改良Webster症状评分。结果治疗后,对照组和治疗组的总有效率分别为79.59%、91.83%,两组比较差异有统计学意义(P0.05)。治疗后,两组患者改良Webster症状评分均显著下降,同组治疗前后比较差异具有统计学意义(P0.05);且治疗组患者改良Webster症状评分显著低于对照组,两组比较差异具有统计学意义(P0.05)。结论葛根素注射液联合盐酸多奈哌齐片治疗帕金森病具有较好的临床疗效,可改善临床症状,安全性较好,具有一定的临床推广应用价值。     

丹红注射液联合多奈哌齐治疗阿尔茨海默病的临床研究

目的探讨应用丹红注射液联合多奈哌齐治疗阿尔茨海默病的临床效果。方法选取2015年6月—2017年6月中国人民解放军白求恩国际和平医院收治的阿尔茨海默病患者106例,随机分成对照组(53例)与治疗组(53例)。对照组睡前口服盐酸多奈哌齐片,5 mg/次,1次/d。治疗组在对照组基础上静脉滴注丹红注射液,40 m L加入250 m L生理盐水,1次/d。两组均连续治疗4周。评价两组患者临床疗效,同时比较治疗前后两组患者简易精神状态量表(MMSE)评分、脑血流动力学和血清学指标。结果治疗后,对照组临床有效率为77.4%,显著低于治疗组的92.5%,两组比较差异具有统计学意义(P0.05)。治疗后,两组MMSE评分较治疗前均显著增加(P0.05);且治疗组比对照组升高更显著(P0.05)。治疗后,治疗组基底动脉(BA)和双侧大脑中动脉(MCA)的平均血流速度(MFV)值均显著升高(P0.05),搏动指数(PI)值显著下降(P0.05);且治疗后治疗组BA和双侧MCA的MFV值和PI值比对照组改善更显著(P0.05)。治疗后,两组血清血清磷酸化tau蛋白(P-tau)、丙二醛(MDA)、白细胞介素(IL)-8和超敏C反应蛋白(hs-CRP)水平较治疗前均显著降低(P0.05),超氧化物歧化酶(SOD)水平均显著增加(P0.05);且治疗组上述血清学指标比对照组改善更显著(P0.05)。结论应用丹红注射液联合多奈哌齐治疗阿尔茨海默病可有效改善患者脑血流状态,减轻机体氧化应激与炎症损伤,提高认知功能,延缓病情进展。     

重复经颅磁刺激联合多奈哌齐治疗阿尔茨海默病的临床对照研究

目的:探讨重复经颅磁刺激(rTMS)联合多奈哌齐对轻、中度阿尔茨海默病(AD)患者的疗效及安全性。方法:52例轻、中度AD患者随机分为研究组和对照组各26例,研究组采用rTMS联合多奈哌齐治疗,对照组单用多奈哌齐治疗。2组患者分别在治疗前及治疗4周、8周、12周后进行阿尔茨海默病评定量表认知分量表(ADASCog)、简易精神状态检查量表(MMSE)、日常生活能力量表(ADL)评定,于治疗前及治疗12周后进行事件相关电位P300检测。通过实验室检查和临床观察评定不良反应。结果:治疗4周后,研究组ADAS-Cog、MMSE、ADL评分与治疗前比较差异无统计学意义,治疗8及12周后,研究组ADAS-Cog及ADL评分较治疗前呈持续下降(P0.05),MMSE评分较治疗前持续增高(P0.05);对照组治疗4及8周后ADAS-Cog、MMSE、ADL评分与治疗前比较均差异无统计学意义,治疗12周后ADAS-Cog评分、ADL评分较治疗前明显下降(P0.05)、MMSE评分较治疗前明显增高(P0.05)。组间比较,治疗4周、8周后2组各量表评分差异均无统计学意义,治疗12周后研究组ADAS-Cog评分、ADL评分明显低于对照组(P0.05)、MMSE评分明显高于对照组(P0.05)。治疗12周后,2组P300潜伏期均较治疗前明显缩短(P0.05)、波幅明显升高(P0.05);组间比较,研究组P300潜伏期明显低于对照组(P0.05)、波幅明显高于对照组(P0.05)。结论:rTMS辅助多奈哌齐治疗AD,能有效改善患者的认知功能和日常生活能力,延缓大脑功能衰退,安全性高,且疗效优于单用多奈哌齐。     

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.     

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.     

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.     

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.