阿尔茨海默病药物治疗的研究进展

阿尔茨海默病（AD）是65岁及以上老年人最常见的慢性神经退行性疾病,发病率随年龄增长而上升。AD患者主要表现为失语、失认等认知功能障碍及行为异常等精神症状,给患者家庭带来极大的心理和经济负担。AD累及多个系统,病因复杂,病理机制尚不完全明确,且目前尚无治疗AD的特效药,只能延缓其病情进展。通过检索国内外文献,可以发现AD的病理生理学基础主要是β淀粉样蛋白（Aβ）异常沉积、tau蛋白的异常磷酸化、乙酰胆碱含量活性降低、谷氨酸毒性反应、自噬作用、炎症反应及一些血管性疾病等。目前美国食品药品监督管理局（FDA）批准用于临床的5种药物为他克林、多奈哌齐、卡巴拉汀、加兰他敏（乙酰胆碱酯酶抑制剂）、美金刚（Ｎ-甲基-Ｄ-天冬氨酸受体拮抗剂）。该文对这5种药物的作用机理、适应证、临床用药方式、不良反应进行了简要的描述。另外,该文重点介绍了一些进入临床试验的新药,这些药物针对的是Aβ沉积过多和tau蛋白异常磷酸化这一病理变化,其主要机制是以减少Aβ的生成、防止其沉积、加速清除及稳定微管、防止tau聚集和加速tau清除。但大多治疗药物研究试验并不理想,因临床不良反应过多或疗效不佳而终止试验,如LY2811376、verubecestat等;还有一些药物尚在二期或三期试验中,如azeliragon、gosuranemab等。该文旨在通过文献综述,梳理AD发生发展中可能的病理生理学机制,目前已有的临床治疗药物,正在研发药物所遇到的瓶颈,以及未来药物研发可能的作用靶点和治疗策略,以期为今后AD的药物治疗提供新思路、新方法。     

阿尔茨海默病发病机制及药物治疗方法研究进展

阿尔茨海默病(AD)是>65岁老年人中最典型的神经退行性疾病,严重影响老年人的生活质量,给亲属和社会带来严重负担.目前AD发病机制尚不明确,分子生物学家提出多种假说,主要有β淀粉样蛋白假说和tau蛋白过度磷酸化假说,并提出与之相关的胆碱能神经元损伤、异常免疫应答引起的炎症和基因突变等机制.根据这些机制,药物研究者研发出...     

阿尔茨海默病认知损害的非药物治疗研究进展

阿尔茨海默病(AD)是一种神经退行性疾病,主要临床症状为认知损害。AD的发病机制目前仍未明确,也没有可以阻止或逆转病程的特效药物,因此探索AD新的治疗手段具有重要临床意义。物理治疗、中医传统康复、心理治疗和认知训练等非药物治疗方法可以通过多途径控制和延缓AD病情发展。文中就AD患者的非药物治疗改善认知损害的相关研究进展进行总结,以期为临床干预提供新思路。     

药物综合治疗阿尔茨海默病的临床观察

目的探讨药物综合治疗阿尔茨海默病的疗效.方法13例轻中度患者,用盐酸多奈哌齐、肠溶性阿斯匹林、氢化麦角碱和银可络综合治疗,持续12周.第6周和12周时进行疗效评估.结果治疗6周后11例有效(11/13)、12周后10例有效(10/13),两者的MMSE评分均比治疗前有显著意义的提高,主要是注意力、计算力评分及语言评分.而6周与12周之间的MMSE评分无显著差异.除个别患者出现胃肠道反应外无其他严重副反应.结论本组药物综合治疗可改善症状,近期效果肯定,且副反应小.远期疗效尚有待观察.     

阿尔茨海默病诊断和药物治疗新进展

正阿尔茨海默病(Alzheimer's disease,AD)俗称老年痴呆,是一种常见的神经退行性疾病,以逐渐加重的认知功能损害和日常生活能力下降为主要特征。据阿尔茨海默病国际协会(Alzheimer’s Disease International,ADI)2015年发布的公告,目前全球痴呆总人数已达4680万,其中中国患     

纳米药物在阿尔茨海默病诊断治疗中的研究进展

AD是一种以认识功能障碍为主的渐进性中枢神经系统退行性疾病.截至2015年为止,中国已经有约1275万人受其影响;而预计到2050年,中国阿尔茨海默病(Alzheimer,s disease,AD)的患者人数将达到约3000万 [1].AD已经成为严重危害社会健康的疾病.近年来,对于AD的治疗药物较少,现有药物以对症治...     

阿尔茨海默病疾病修饰药物研发述评

阿尔茨海默病（AD）是最常见的神经系统变性疾病之一,疾病负担沉重。目前 AD 发病机 制未明,缺乏能够逆转或延缓疾病进展的疾病修饰药物。现阐述基于 AD 主要发病机制学说的疾病修 饰药物研究,包括以Aβ、tau或其他生物标志物为靶点及老药新用的药物试验。其中,绝大部分药物试 验终止于研发或临床试验进程的某一阶段,也有一些正在进行。AD发病机制研究与疾病修饰药物研发 之间是互相促进和验证的关系,基础研究的突破有可能为药物研发带来新的希望,而某个方向药物试验 的成败又是对其理论基础的检验。从探索 AD 致病机制,到研发疾病修饰药物,至广泛临床应用的道路 仍然漫长。     

阿尔茨海默病药物治疗探索

阿尔茨海默病药物治疗探索苏美芳阿尔茨海默病（ＡＤ）病因不明，治疗棘手，但药物探索研究一直在进行［１］。本文介绍ＡＤ认知与记忆障碍药物探索性治疗的现状。一、神经递质类及肽类神经递质的研究范围比较广泛，其中胆碱能疗法是热点，期望通过补充乙酰胆碱前体、抑制...     

阿尔茨海默病的神经再生研究进展

阿尔茨海默病（AD）是一种神经退行性疾病，其病理特征表现为β 淀粉样蛋白（Aβ）的异 常沉积，tau 蛋白异常磷酸化，以及由这些引发的神经元变性、坏死。已有研究表明海马神经再生与AD 息息相关，采用海马神经再生治疗AD已成为具有意义和前景的研究。现对AD 及海马神经再生之间的 关系进行综述。     

阿尔茨海默病行为和精神症状的药物治疗

本文介绍了阿尔茨海默病(AD)行为和精神症状的概念、发生率等，并综述各类有关的药物治疗。     

Etiological factors of Alzheimer disease and recent advances of its treatment

OBJECTIVE: To investigate the etiological factors of Alzheimer disease (AD) and the advance in drug treatment. DATA SOURCES: Using the terms "Alzheimer disease, etiology, drug treatment", we searched Medline database for AD treatment-related English literatures which were published between January 1993 and September 2006. Other literatures were obtained by searching concrete magazines and papers by hand. STUDY SELECTION: The data were selected primarily. Epidemiologic study and randomized controlled clinical trials were selected, and those studies with repetitive or similar contents were excluded. DATA EXTRACTION: Totally 1 537 AD and its treatment-related literatures were collected, and 32 of them were involved. Altogether 1 505 non-randomized controlled clinical trials, repetitive studies and reviews were excluded. DATA SYNTHESIS: The restriction of curative effect is a progressive neural degenerative disease. Although the etiological hypothesis of this disease has been introduced, the etiological factors of this disease are still unclear. The current treatments mainly involve: preventing against Aβ formation and clearing Aβ, application of antioxidant and free radical scavengers, application of anti-inflammatory preparation, application of cholinergic preparation, hormonal therapy, application of metabolic enhancer, application of neurotrophic factor and nerve protectant, gene therapy and so on. CONCLUSION: The etiological factors of AD are still unclear, and symptomatic treatment is much taken in clinical therapy. Therefore, the curative effects of AD are still not very ideal.     

Etiological factors of Alzheimer disease and recen advances of its treatment

OBJECTIVE： To investigate the etiological factors of Alzheimer disease （AD） and the advance in drug treatment. DATA SOURCES： Using the terms ＂Alzheimer disease, etiology, drug treatment＂, we searched Medline database for AD treatment-related English literatures which were published between January 1993 and September 2006. Other literatures were obtained by searching concrete magazines and papers by hand. STUDY SELECTION： The data were selected primarily. Epidemiologic study and randomized controlled clinical trials were selected, and those studies with repetitive or similar contents were excluded. DATA EXTRACTION： Totally 1 537 AD and its treatment-related literatures were collected, and 32 of them were involved. Altogether 1 505 non-randomized controlled clinical trials, repetitive studies and reviews were excluded. DATA SYNTHESIS： The restriction of curative effect is a progressive neural degenerative disease. Although the etiological hypothesis of this disease has been introduced, the etiological factors of this disease are still unclear. The current treatments mainly involve： preventing against A 13 formation and clearing A 13, application of antioxidant and free radical scavengers, application of anti-inflammatory preparation, application of cholinergic preparation, hormonal therapy, application of metabolic enhancer, application of neurotrophic factor and nerve protectant, gene therapy and so on. CONCLUSION： The etiological factors of AD are still unclear, and symptomatic treatment is much taken in clinical therapy. Therefore, the curative effects of AD are still not very ideal.     

成人烟雾病治疗的相关研究进展

烟雾病（moyamoya disease,MMD）是一种慢性进行性脑血管疾病,涉及颈内动脉末端和/或其近端分支狭窄闭塞,导致侧支血管网形成。这些变化引起脑实质慢性缺血,随后发生严重的脑血管意外。成人MMD患者在未经治疗的情况下会逐渐累及认知功能,且病死率是儿童MMD患者的2倍。由于MMD发展病因的复杂性和后果的严重性,该病的治疗尤为棘手且迫切。外科血管重建术作为MMD治疗的基石,主要分为直接血管重建术、间接血管重建术和联合血管重建术三类。考虑到间接血管重建术不能降低围手术期脑卒中的发生率,直接血管重建术通常是缺血型MMD患者治疗的首选术式。若为了预防出血型MMD患者再发出血,选择直接血管重建术或联合血管重建术能够更容易建立侧支循环,促进血运重建,达到治疗的目的。当患者术后出现新发的缺血脑卒中,则优先考虑间接血管重建术。对于血流动力学不稳定的成人MMD患者,直接血管重建术或联合血管重建术则是首要选择。由于目前无逆转MMD病情进展的特效药,内科治疗仅局限于对症治疗和围手术期的管理。临床上通常使用阿司匹林抗血小板聚集,促红细胞生成素和他汀类药物等促进侧支血管发育和地塞米松促进新生血管的形成等。远隔缺血适应训练改善MMD患者的后遗症的疗效已经得到了业界的肯定。发病机制研究的深入为MMD的诊疗手段提供更多的可能性。甲硫氨酸循环异常参与了MMD的发病,提示甲硫氨酸循环相关风险评分对烟雾病风险具有良好的预测能力。此外,内皮祖细胞移植可能成为临床上治疗MMD的新策略。 [国际神经病学神经外科学杂志, 2023, 50(3): 78-83]     

Models and modeling systems in Alzheimer disease drug discovery

The rapid pace of neurobiology research has increased the prospects of developing drugs to prevent neurodegenerative disorders. Although the goal of delaying the onset of brain disorders may be within the grasp of modern medicine, there are several critical barriers to progress. Among these is the lack of appropriate models and modeling systems for specific neurodegenerative diseases. Traditionally, in drug discovery, testing, and development, a combination of models is used. These include in vitro, in vivo, transgenic, and other animal models. However, each of these models has limitations. In this article, the author advocates the use of "in silico" modeling systems, which could complement currently available models and enable investigators to simulate alternative strategies to modulate neural function in a dynamic interactive mode. Advances in computer technology, including increasing speed and memory, and ready access to parallel processing systems have made it easier for investigators to develop databases for computer abstractions of neural function and dysfunction and to begin to develop prototypes for use in complex systems modeling environments. Multimodeling systems have been widely used in other areas of science to study emergent behavior of complex systems, such as the impact of atmospheric changes on weather, flight patterns of birds in a flock, and the behavior of traders in a commodities market. Adoption of such approaches should increase understanding of the complexities of signal transduction pathways in neural networks and accelerate the drug discovery process.