小剂量奥氮平联合多奈哌齐对老年性痴呆精神行为症状及免疫、认知功能的影响

目的探讨小剂量奥氮平联合多奈哌齐治疗老年性痴呆患者精神行为症状的疗效及其对免疫功能、认知功能的影响。 方法随机将88例老年性痴呆患者均分为对照组(多奈哌齐治疗)和联合组(小剂量奥氮平联合多奈哌齐治疗)。比较两组疗效、血清P物质(SP)、神经肽Y(NPY)、同型半胱氨酸(Hcy)、免疫功能、血脂、神经精神科问卷(NPI)评分、阿尔茨海默病评价量表-认知量表(ADAS-cog)评分及不良反应情况。 结果联合组治疗总有效率高于对照组(P＜0.05)。与对照组治疗后比较,联合组治疗后SP、Hcy、ADAS-cog评分、NPI评分均下降(P＜0.05),NPY升高(P＜0.05)；血脂和免疫指标差异无显著性(P＞0.05)。 结论小剂量奥氮平联合多奈哌齐治疗老年性痴呆精神行为症状患者疗效确切,可有效改善其精神行为症状和认知功能。     

Characteristic Effects of Anti-dementia Drugs on Rat Sleep Patterns

The present study was undertaken to clarify the effects of anti-dementia drugs on sleep pattern in rats. Electrodes were chronically implanted into the frontal cortex and the dorsal neck muscle of rats for the electroencephalogram (EEG) and electromyogram (EMG), respectively. EEG and EMG were recorded with an electroencephalograph. SleepSigh ver. 2.0 was used for analysis of the sleep–wake state. Total times of waking, non-rapid eye movement (non-REM) sleep, and rapid eye movement (REM) sleep were measured from 10:30 to 16:30. Galantamine had no significant influence on the sleep pattern. On the other hand, donepezil and memantine showed significant increases in sleep latency and total waking time and a decrease in total non-REM sleep time. Furthermore, memantine decreased total REM sleep time. To investigate the characteristics of non-REM sleep in detail, non-REM sleep was classified as stage 1, 2, or 3 according to the depth of sleep. Different from donepezil and galantamine, memantine significantly decreased stage 1 and increased stage 3 in non-REM sleep. From these findings, it can be concluded that galantamine caused no sleep disturbance, different from donepezil and memantine.     

Donepezil improves obstructive sleep apnea in Alzheimer disease: a double-blind, placebo-controlled study

BACKGROUND: There is an association between Alzheimer disease and sleep-disordered breathing. Donepezil is the drug most frequently used to treat cognitive symptoms in Alzheimer disease. This study evaluates the effects of donepezil on obstructive sleep apnea in patients with Alzheimer disease. METHODS: Randomized, double-blind, placebo-controlled design. Twenty-three patients with mild-to-moderate Alzheimer disease and apnea-hypopnea index (AHI) > 5/h were allocated to two groups: donepezil treated (n = 11) and placebo treated (n = 12). Polysomnography and cognitive evaluation using Alzheimer disease assessment scale-cognitive (ADAS-cog) subscale were performed at baseline and after 3 months. Cognitive and sleep data were analyzed using analysis of variance. RESULTS: AHI and oxygen saturation improved significantly after donepezil treatment compared to baseline and placebo (p < 0.05). Rapid eye movement (REM) sleep duration increased after donepezil treatment (p < 0.05). ADAS-cog scores improved after donepezil treatment, although they did not correlate with REM sleep increase and sleep apnea improvement (p < 0.01). CONCLUSIONS: Donepezil treatment improved AHI and oxygen saturation in patients with Alzheimer disease. Treatment also increased REM sleep duration and reduced ADAS-cog scores. Trial registration: ClinicalTrials.gov Identifier: NCT00480870.     

Cholinesterase inhibitors in dementia with Lewy bodies: a comparative analysis

OBJECTIVE: To compare efficacy of different cholinesterase inhibitors (ChEIs) for treating patients with dementia with Lewy bodies (DLB). DESIGN: Retrospective comparison of three independent clinical studies of ChEI treatment using donepezil, galantamine or rivastigmine in patients with DLB. METHOD: Data was obtained from open label trials of donepezil and galantamine and a placebo controlled randomized trial of rivastigmine in DLB. Changes in Mini Mental State Examination (MMSE), Neuropsychiatric Inventory (NPI) and United Parkinson's Disease Rating Scale (UPDRS-III) scores were compared between the three treatments at 12 and 20 weeks. RESULTS: All ChEIs significantly improved cognitive and neuropsychiatric measures. Reduction in the total NPI score appeared significantly greater after donepezil treatment. There was no significant increase in UPDRS-III scores. CONCLUSIONS: It is unclear to what extent these findings reflect true differences between ChEIs or are due to methodological artefacts of comparing different studies. There is so far no compelling evidence that any one ChEI is better than the other in treating DLB but head to head comparative studies of different ChEIs are warranted to clarify this.     

Donepezil in the treatment of musical hallucinations

Musical hallucinations (MH) typically occur among elderly individuals and are associated with hearing impairment. The authors describe a patient with features of typical MH who was successfully treated with donepezil, a cholinesterase inhibitor, as a combination therapy and who has not shown any subsequent cognitive decline for approximately 5 years. The efficacy of donepezil in this patient indicates that age-dependent dysfunction of cholinergic neurons might be related to the development of MH.     

Effect of Tong Luo Jiu Nao on Aβ-degrading enzymes in AD rat brains

Ethnopharmacological relevance

Tong Luo Jiu Nao (TLJN) is a modern Chinese formula based on Traditional Chinese Medicine theory that has been used to treat ischemic cerebral stroke and vascular dementia. TLJN belongs to the ethnopharmacological family of medicines. In this study, we investigated the mechanism of the TLJN effect on Alzheimer's disease (AD).

Aim of the study

To investigate the effect of TLJN on β-amyloid-degrading enzymes and learning and memory in the AD rat brain.

Materials and methods

AD rats whose disease was induced by Aβ_25-35 injection into the bilateral hippocampus CA1 region were subjected to intragastric administration of various preparations. The experimental animals were healthy male Sprague-Dawley rats which were randomly divided into normal, sham, model, TLJN min, TLJN max and donepezil hydrochloride groups. Spontaneous alternation and passive avoidance behavior, which are regarded as measures of spatial learning and memory, were investigated using Y-maze testing. Western blotting and immunohistochemistry were used to observe the therapeutic effect of TLJN on the deposits of amyloid plaque and on the expression of synaptophysin, insulin-degrading enzyme and neprilysin.

Results

Y-maze results showed that the AD model group presented with spatial learning and memory impairments. Hematoxylin-eosin and Congo red staining indicated neuronal impairment and deposits of amyloid plaque in the model group and these results were consistent with their learning and memory deficits in the Y-maze. The TLJN-treated groups exhibited prolonged a cavity delitescence, decreased arm entries and improvement in learning and memory. Moreover, the structure of the neurons of the treated groups was restored and the expression of synaptophysin increased in both the hippocampus and cortex. In addition, their levels of insulin-degrading enzyme and neprilysin in the cortex and hippocampus were upregulated and the amyloid plaque was decreased.

Conclusion

TLJN can improve learning and memory, up-regulate insulin-degrading enzyme and neprilysin levels, promote the degrading of Aβ and clear amyloid plaque from the AD rat brain. In future, TLJN may have significant therapeutic potential in the treatment of AD patients.     

金钱草颗粒剂质量标准的研究

目的探讨金钱草颗粒剂的质量标准。方法采用TLC对金钱草颗粒剂处方中的柴胡、延胡索及大黄进行定性鉴别;采用HPLC对其主药金钱草中的槲皮素进行定量分析。结果该方法定性鉴别薄层色谱特征明显,专属性强;样品中槲皮素在1.8960～30.3360μg·mL-1内线性关系良好（r=0.9998）,平均回收率为97.73%,RSD=1.34%。结论用该方法作定性、定量分析简便、快速、专属性强,可有效控制制剂的质量。     

Randomized double-blind placebo-controlled donepezil augmentation in antidepressant-treated elderly patients with depression and cognitive impairment: a pilot study

OBJECTIVE: To assess combined antidepressant and cognitive enhancer treatment in elderly patients presenting with depression plus cognitive impairment. METHODS: Twenty-three elderly (>50 years old) depressed, cognitively impaired (DEP-CI) patients participated in a pilot study. We evaluated whether, after 8 weeks of open antidepressant treatment, donepezil HCl (Aricept) would afford added cognitive benefit compared to placebo in a randomized 12-week trial. A subsample continued in an 8-month extension phase of open treatment with donepezil. Neuropsychological testing (NPT) was performed and antidepressant response monitored at baseline and the 8, 20, and 52-week time points. RESULTS: At 8-weeks, the antidepressant response rate was 61% (14/23). Improvement in SRT immediate recall (SRT-IR; e.g. episodic verbal memory) was observed in responders compared to non-responders. During the 12-week, placebo-controlled, donepezil add-on trial, patients on donepezil showed further improvement in SRT-IR versus patients on placebo. In the open extension phase, patients who continued open donepezil treatment (n = 6) maintained improvement in memory and tended to show an advantage over patients who never received donepezil and were evaluated at the 52-week time point (n = 6). There were no observed significant donepezil effects on non-memory cognitive domains. CONCLUSION: These preliminary findings suggest that addition of a cholinesterase inhibitor (AChEI) following antidepressant medication treatment in elderly Dep-CI patients may improve cognition, and support the need for a confirmatory, larger randomized placebo-controlled trial.     

美金刚对比多奈哌齐治疗帕金森病痴呆的Meta分析

目的 系统评价美金刚对比多奈哌齐治疗帕金森病痴呆的疗效与安全性。方法 检索中国学术期刊全文数据库（CNKI）、万方数据库（Wanfang Data）、维普中文期刊全文数据库（VIP）和中国生物医学文献数据库（SinoMed）、Cochrane Library、PubMed、Web of Science等数据库自建库起至2022年7月1日收录的有关美金刚、多奈哌齐分别联合多巴丝肼治疗帕金森病痴呆的临床随机对照试验（RCT）。评估偏倚风险,并收集患者治疗后的简易精神状态量表（MMSE）评分、蒙特利尔认知评估量表（MoCA）评分变化情况,临床总有效率及不良反应发生率,采用RevMan5.3软件进行Meta分析。结果 共纳入14项RCTs,总计1219名患者,其中美金刚联合多巴丝肼组610例、多奈哌齐联合多巴丝肼组609例。Meta分析结果显示,美金刚联合多巴丝肼在改善MMSE评分、改善MoCA评分、提高临床总有效率方面效果均优于多奈哌齐联合多巴丝肼,其差异有统计学意义（P＜0.05）;美金刚对比多奈哌齐治疗帕金森病痴呆的不良反应发生率更低。结论 美金刚对帕金森病痴呆患者的认知功能改善效果优于多奈哌齐,临床总有效率更高,且治疗后不良反应发生率低。     

乙酰胆碱酯酶抑制剂他克林和多奈哌齐抗星形孢菌素致凋亡作用的比较

目的用星形孢菌素(STS)诱导NG108-15和HeLa细胞凋亡,观察他克林和多奈哌齐是否具有抗凋亡作用。方法MTT测定分析细胞损伤状况;相差显微镜和Hoechst 33342染色观察细胞及胞核形态;DNA提取及琼脂糖凝胶电泳观察凋亡特征性梯带;免疫印迹分析Bcl-2和Bax的表达水平。结果经0.1 mmol·L^-1他克林预处理后,由STS诱导的NG108-15细胞凋亡受到明显抑制。多奈哌齐预处理无保护作用。免疫印迹表明他克林可显著抑制Bax的表达,同时还可促进Bcl-2的表达。多奈哌齐和他克林预处理对STS诱导的HeLa细胞损伤无明显的保护作用。结论 他克林的抗凋亡作用与AChE抑制作用似乎没有明显关联。他克林对STS损伤的保护作用有细胞选择性。