阿尔茨海默病的胆碱酯酶抑制剂治疗进展

阿尔茨海默病即老年性痴呆,是一种中枢神经系统退行性疾病,发病原因尚不清楚。目前利用胆碱酯酶抑制剂提高乙酰胆碱的水平,达到治疗改善效果。本文就他克林、多奈哌齐、卡巴拉汀和加兰他敏4种胆碱酯酶抑制剂药物的研究进展进行了综述,以期对临床治疗和进一步研究提供参考。     

阿尔茨海默病的药物治疗研究进展

阿尔茨海默病是一种以进行性认知功能减退为主要临床症状的慢性中枢神经系统退行性疾病,发病机制目前仍未完全阐明。阿尔茨海默病的治疗包括抗氧化剂、抗炎药物、激素替代疗法、神经保护疗法、胆碱酯酶抑制剂、抗淀粉样蛋白的治疗和精神药理学药物等。本文主要阐述阿尔茨海默病药物治疗,尤其是胆碱酯酶抑制剂的研究进展。     

基因治疗与阿尔茨海默病

阿尔茨海默病(Alzheimer’s disease,AD)是一种进行性的神经退行性疾病,临床上表现为记忆和认知功能减 退、行为异常和语言功能障碍。其病理特点表现为神经元外β-淀粉样蛋白聚集形成老年斑、细胞内异常磷酸化的tau 蛋白聚集形成神经纤维缠结、神经元的缺失和脑血管淀粉样变性。目前用于AD临床治疗的药物有乙酰胆碱酯酶抑制 剂、NMDA受体拮抗剂、非甾体抗炎药等,这些药物仅能缓解AD的症状,而基因治疗通过载体介导的转基因技术可 以将DNA或RNA直接导入靶细胞,实现保护性或治疗性蛋白的表达及某些致病基因的沉默,从根本上治疗AD。     

阿尔茨海默病药物治疗的中英指南对比及解析

阿尔茨海默病（AD）的临床症状多样且以认知功能损害为主，给患者和家庭带来了巨大的精神压力和沉重的经济负担。目前尚无根治AD的药物，临床上常采用胆碱酯酶抑制剂和美金刚改善AD症状，但其疗效不一且安全性和成本效果性存在差异。为给患者选择安全、有效、经济的用药方案，中国和英国分别在2018年更新发表了AD药物治疗相关的指南。中国发布《2018中国痴呆与认知障碍诊治指南（二）：阿尔茨海默病诊治指南》在AD的诊断、药物治疗和临床疗效进行了阐述，英国国家卫生与临床优化研究所（NICE）发布的Donepezil，galantamine，rivastigmine and memantine for the treatment of Alzheimer's disease进行AD常用治疗药物的临床效果和药物经济学方面的分析。本文重点比较两个指南在药物方面的异同之处，旨在为临床医生和基层医生开具AD治疗药物时提供更多参考。     

Pharmacological treatment of cognitive deficits in Alzheimer's disease

Clinical trials and independent reviews support the use of cholinesterase inhibitors for treating the symptoms of patients with mild to moderate Alzheimer's disease (AD). Before initiating cholinesterase inhibitor therapy, patients should be thoroughly assessed, and the diagnosis confirmed, preferably by a specialist. Compliance with cholinesterase inhibitor therapy should be monitored and the response (in global, cognitive, functional and behavioural domains) reassessed after 2-3 months of treatment. Vitamin E may be protective against AD, and therapy with 1000 IU twice daily may be considered. There is insufficient evidence to support the use of other antioxidant agents, anti-inflammatory agents, monoamine oxidase B inhibitors, folate/homocysteine or antihypertensive drugs in patients with AD, or hormone replacement therapy in affected women.     

阿尔茨海默病的发病机制和动物模型研究进展

阿尔茨海默病（Alzheimer's disease,AD）是一种慢性中枢神经系统退行性疾病。AD的病因不明、发病机制复杂,因此动物模型的建立对探索其发病机制及寻找防治疾病的药物具有重要作用。在动物模型中,转基因小鼠模型和转基因果蝇模型已成为研究热点。本文就阿尔茨海默病的发病机制和动物模型的研究现状进行综述。     

老年性痴呆动物模型研究进展及其评价

老年性痴呆(Alzheimer's disease,AD)是一种与年龄相关的中枢神经系统退行性病变。由于至今其病因不明、发病机制复杂,制约了该病动物模型的制作研究工作。本文对各类AD动物模型的研究进展及其优劣进行了评价,认为Tg2576转基因小鼠已成为较合适的防治AD新药研究的动物模型。     

Diagnosis and management of Alzheimer's disease--an update

Alzheimer's disease (AD) has become recognised as a major cause of morbidity and mortality in the ageing population worldwide. Over 20 million people worldwide are affected by AD, which ensures that the disease imposes a major economic burden. Alzheimer's disease is a progressive neurodegenerative disorder with characteristic clinical and neuropathological features. Neurofibrillary tangles, neuritic plaques and amyloid angiopathy occur in varying severity in brains of patient's with Alzheimer's disease. Biological markers of AD allowing an early definitive premorbid diagnoses are currently not available. Memory loss for recent events is invariable and often the earliest prominent symptom. Language disorders, difficulties with complex tasks, depression, psychotic symptoms and behavioral changes are other common manifestations of AD. Diagnosis involves the early detection of cognitive decline and ruling out other causes of dementia like vascular dementia, Lewy body dementia, fronto-temporal degeneration or reversible causes like hypothyroidism. Acetylcholinesterase inhibitors have shown to be effective in mild to moderate AD in improving the cognitive function of patients in clinical trials. Caregiver intervention programs have considerable potential to improve both the caregiver and patient quality of life.     

Alzheimer's disease and frontotemporal dementia: prospects of a tailored therapy?

Alzheimer's disease (AD) is the most prevalent dementia (accounting for 50%-75% of cases of dementia in people aged over 65 years), followed by frontotemporal dementia (FTD) (10%-20% of cases). AD is characterised histopathologically by Abeta-containing amyloid plaques and tau-containing neurofibrillary tangles, whereas FTD exhibits neurofibrillary tangles alone. Current symptomatic treatments of AD are of limited benefit, as they are not directed at the underlying biological basis of the disease. The development of transgenic animal models has provided insight into disease mechanisms and helped define novel drug targets. More than 50 drugs are currently in clinical trials, and novel and more effective drugs targeting both AD and FTD are expected to become available within 5-10 years.     

中枢肾素-血管紧张素系统与阿尔茨海默病

阿尔茨海默病（Alzheimer's disease,AD）是全球共同关注的重大公共卫生课题和日益严重的社会问题,发掘防治AD的新靶标和新药物是当今医药领域亟待破解的难题。越来越多的研究显示,中枢肾素-血管紧张素系统（central rennin-angiotensin system,CRAS）与AD密切相关。本文根据相关文献报道,综述CRAS中血管紧张素II（angiotensin II,Ang II）及其受体（angiotensin II type 1 receptor,AT₁R;angiotensin II type 2 receptor,AT₂R）,血管紧张素IV（angiotensin IV,Ang IV）及其受体（angiotensin II type 4 receptor,AT₄R）以及血管紧张素转化酶（angiotensin converting enzyme,ACE）在AD发生发展中的作用,揭示可能成为防治AD的新靶标,提出开发新型抗AD药物的新思路。     

阿尔茨海默病的药物治疗研究进展

阿尔茨海默病（Alzheimer’s disease，AD）引起了严重的公共健康问题，目前只有两类药物被食品药品监督管理局（Food and Drug Administration，FDA）批准用于AD 的治疗，但这些药物只可以控制症状，甚至不能延缓，更不能阻断疾病的发展进程。该文阐述了AD 可能的发病机制，并介绍了目前被FDA 批准的用于AD 治疗的两类药物：胆碱酯酶抑制剂和N- 甲基-D- 天门冬氨酸（N-methyl-D-aspartate，NMDA）受体阻滞剂，最后再以神经退行性病变的可能机制为基础来探讨未来可能用于治疗AD 的潜在药物，为以后研制AD 新药提供思路。     

Genetics and epigenetics of Alzheimer's disease

Alzheimer's disease (AD) is a highly prevalent condition that predominantly affects older adults. AD is a complex multifactorial disorder with a number of genetic, epigenetic and environmental factors which ultimately lead to premature neuronal death. Predictive and susceptibility genes play a role in AD. Early-onset familial AD is a rare autosomal dominant disorder. Genome-wide association studies have identified many potential susceptibility genes for late-onset AD, but the clinical relevance of many of these susceptibility genes is unclear. The genetic variation by susceptibility genes plays a crucial role in determining the risk of late-onset AD, as well as the onset of the disease, the course of the AD and the therapeutic response of patients to conventional drugs for AD. The newer understanding of the epigenetics in AD has also been highlighted. Recent advances in genetics, epigenetics and pharmacogenetics of AD pose new challenges to the future management of AD.     

Protective Effect of Hydroxysafflor Yellow A against Chronic Mild Stress-induced Memory Impairments by Suppressing Tau Phosphorylation in Mice

Chronic stress plays a critical role in the etiology of sporadic Alzheimer's disease(AD).However,there are currently no effective drugs that can target chronic ...     

核苷酸结合寡聚化结构域样受体3炎症小体与阿尔茨海默病

阿尔茨海默病(AD)是一种慢性神经退行性疾病,发病原因至今未明。聚集在大脑内部的β淀粉样蛋白斑块是AD的主要病理特征之一,然而靶向细胞外β淀粉样蛋白斑块的药物均未能治愈疾病。固有免疫应答与神经炎症在AD的发病及进展中发挥重要作用。小胶质细胞作为中枢神经系统中的巨噬细胞,参与细胞外β淀粉样蛋白沉积、细胞内tau蛋白形成神经原纤维缠结和神经元损伤过程。越来越多的研究显示,小胶质细胞中核苷酸结合寡聚化结构域样受体3(NLRP3)炎症小体的激活与AD的发生和发展相关,提示该信号通路可能是治疗AD的新靶点。本文总结了NLRP3炎症小体激活与调节在AD中的作用机制及以该通路为靶标治疗AD的研究现状,以期为未来该领域的研究提供参考。     

抑制肾素-血管紧张肽系统药物研究

肾素-血管紧张肽系统(RAS)是药物治疗心血管系统疾病的关键作用靶点。目前的主要药物是血管紧张肽转化酶抑制剂(ACEI)和血管紧张肽Ⅰ受体拮抗剂(ARBs),因此被认为是作用于RAS治疗心血管疾病的经典药物,但是还有许多能够通过其他途径而产生对RAS的抑制作用。本文综述了目前发现的一些其他途径以及和经典途径的联系以及阻断它们产生的可能效应,包括ACEI抑制剂、ARBs、肾素抑制剂、糜蛋白酶抑制剂、血管紧张肽转化酶2、中性肽链内切酶抑制剂、醛固酮抑制剂以及针对RAS的基因治疗和免疫治疗。     

阿尔茨海默病的A2G plus管理模式

With the aging of society and the development of medically diagnostic techniques,the incidence and diagnosis rate of Alzheimer's disease (AD) have been increasing.However,there is no breakthrough in the treatment of AD at present.Thus,it is necessary to explore the optimal management for AD patients under the current condition.AD is characterized by multi-target mechanisms of pathogenesis and complexity of clinical symptoms,which requires more comprehensive treatment and management.Here,we elaborate of A2G plus (one or more of A to G and other plus measures) comprehensive management model for AD patients.This model is built upon 4 international authoritative guidelines,multi-target mechanisms of disease,existing therapeutic drugs and methods,and long-term clinical experiences and patient' s individual condition,and provides a new model of comprehensive treatment and management for AD patients.     

细胞自噬作用在阿尔茨海默病治疗过程中的作用

阿尔茨海默病(Alzheimer’s disease,AD),是一种以进行性认知障碍和记忆力损害为主的脑部神经退行性疾病。在该疾病中,其发病机制尚未明确,因此目前仍无有效的治疗方法。自噬在清除异常积聚的蛋白以及受损细胞器、维持细胞内稳态和细胞代谢中扮演重要角色。本文对细胞自噬作用在阿尔兹海默病治疗过程中的作用进行了综述,以期为发现阿尔兹海默病的新的治疗靶点提供参考。     

肾素-血管紧张素系统与阿尔茨海默病

阿尔茨海默病(AD)是常见的进行性认知障碍和记忆力损害为主的中枢神经系统退行性疾病,已经成为继心血管疾病、肿瘤和脑卒中之后的第四位死亡原因。这一世界性的健康难题,其治疗和护理成本逐年上升。中老年人高血压与其日后认知功能障碍风险升高有关。降压药物中的血管紧张素转化酶(ACE)抑制剂能够减缓AD的发病进程、降低发病率。然而,ACE抑制剂的使用可伴有β淀粉样蛋白1-42(Aβ1-42)聚集的增多。该文对脑中肾素-血管紧张素系统,特别是ACE抑制剂作为AD药物的作用及血管紧张素4受体(AT4)进行综述,预测AT4是治疗AD所致的记忆障碍的新的治疗靶点。     

Atorvastatin attenuates oxidative stress in Alzheimer＇s disease

Objective： To investigate serum level of SOD, MDA, ox-LDL, AchE and Ach in AD, to study atorvastatin influence on serum level of SOD, MDA, ox-LDL, Ache and Ach in AD and its neuroprotection mechanisms. Methods Subjects were divided into： normal blood lipid level group with Alzheimer＇s disease （A）, higher blood lipid level group with Alzheimer＇s disease （AH）, normal blood lipid level Alzheimer＇s disease group with atorvastatin treeatment （AT）, higher blood lipid level Alzheimer＇s disease group with atorvastatin treeatment（AHT）. Ox-LDL was measured by enzyme linked immunosorbent assay; SOD, MDA, ox-LDL, AchE, Ach and blood lipid level in AD was measured by biochemistry. Results： The serum level of MDA, Ache in AH group after atorvastatin treatment is lower ;The serum level of SOD, Ach in AH group is more increased than that of in A group; The serum level of ox-LDL in AH, A groups is lower than that of in A group; The dementia degree is lower after atorvastatin treatment. Conclusion： Atorvastatin can decrease serum level of MDA, AchE and ox-LDL, and increase that of SOD, Ach, and attenuate dementia symptom in AD, especially, with hyperlipemia. The hypothesis of atorvastatin neuroprotection is concluded that atorvastatin may restrain free radical reaction and retard oxidation in AD.     

多奈哌齐治疗轻中度阿尔茨海默病患者的临床研究

目的研究多奈哌齐治疗我国轻中度阿尔茨海默病(AD)患者的疗效和安全性.方法将48例轻中度AD患者随机均分为两组,用多奈吸哌齐和卡巴拉汀治疗16周.采用简易精神状态量表(MMSE)、Blessed-Roth量表和总体衰退量表(GDS)评定疗效.安全性检查包括生命体征,实验室及心电图检查,每4周1次.结果两组治疗前后MMSE,GDS和Blessed-Roth评分均有显著改善(P＜0.05).但两组治疗前后相关量表总分差值的t检验均无显著意义(P＞0.05).两组治疗前后Blessed-Roth各亚项分数差值比较无显著性(P＞0.05).不良反应为胃肠道反应,发生率在15.0%～29.5%之间,以卡巴拉汀组多见.结论多奈吸哌齐和卡巴拉汀可显著改善AD患者的认知功能、痴呆程度和日常生活能力,疗效相当,较为安全,耐受性较好.