更新于：2024-11-01

Intracranial Arteriosclerosis

颅内动脉粥样硬化

更新于：2024-11-01

基本信息

别名

Arterioscleroses, Intracranial、Arteriosclerosis, Intracranial、Intracranial Arterioscleroses

+ [15]

简介

Vascular diseases characterized by thickening and hardening of the walls of ARTERIES inside the SKULL. There are three subtypes: (1) atherosclerosis with fatty deposits in the ARTERIAL INTIMA; (2) Monckeberg's sclerosis with calcium deposits in the media and (3) arteriolosclerosis involving the small caliber arteries. Clinical signs include HEADACHE; CONFUSION; transient blindness (AMAUROSIS FUGAX); speech impairment; and HEMIPARESIS.

关联

项与颅内动脉粥样硬化相关的药物

Udenafil

乌地那非

靶点

PDE5A

作用机制

PDE5A抑制剂

在研机构

Mezzion Pharma Co., Ltd. [+2]

原研机构

Dong-A Pharmaceutical Co., Ltd.

在研适应症

勃起功能障碍 [+1]

非在研适应症

阿尔茨海默症 [+14]

最高研发阶段批准上市

首次获批国家/地区

韩国

首次获批日期2005-11-29

YinDanXinNaoTong

银丹心脑通

靶点-

作用机制-

在研机构

贵州百灵企业集团制药股份有限公司

原研机构

贵州百灵企业集团制药股份有限公司

在研适应症

心绞痛 [+3]

非在研适应症-

最高研发阶段批准上市

首次获批国家/地区

中国

首次获批日期2002-11-30

Butylphthalide

丁苯酞

靶点

KCNK

作用机制

KCNK 抑制剂 [+1]

在研机构

原研机构

在研适应症

非在研适应症

最高研发阶段批准上市

首次获批国家/地区

中国

首次获批日期2002-09-30

475

项与颅内动脉粥样硬化相关的临床试验

NCT06298474 / Not yet recruitingN/A

The BRAIN App (Phase 2 SBIR): Building Relationships Using Artificial Intelligence and Nostalgia

There are currently 6.7 million Americans living with dementia and, without significant breakthroughs, this figure will double to 12.7 million by 2050. There are about 46,000 long-term care (LTC) facilities in the U.S. More than half of LTC residents have some form of dementia (Alzheimer's Association, 2018). Responsive behaviors and dysfunction of the dementia care triad-i.e., the PLWD, professional Care Partner (CP), and Family Member (FM)-are inexorably linked. The emergence of responsive behaviors can lead to disruption of the triad's function. Thus, it is imperative to maintain positive relationships and a high quality of life (QoL) within the triad to reduce BPSD. Cognitive Stimulation Therapy (CST) has demonstrated improvements in QoL and relationships for PLWD. CST is a psychosocial intervention that promotes communication and engagement in PLWD via a structured program of meaningful and enjoyable theme. While clinical trials have shown improvement in cognition and QoL, the potential large-scale impact of CST has been hampered by low adherence, with less than 40% completing trials. One likely reason for the low adherence to CST is the reliance on generic and non-digital tools (e.g., paper-based agendas, tools, DVDs, and board games) in facilitating the intervention. That is, even though CST aims to be personalized, the specific interventions used in the field tend to be generic and not tailored to each PLWD's specific interests. The use of digital technology to implement CST would offer considerable advantages to expand and personalize the range of stimulation content and provide a means for monitoring responses, optimizing protocols, and promoting adherence.
The proposed Phase II study will involve the continued development and evaluation of a multi-faceted software platform called "Building Relationships using Artificial Intelligence and Nostalgia" or BRAIN. The BRAIN Platform will be the first-ever Artificial Intelligence (AI) powered CST digital therapy platform for PLWD. The platform, which has been shown to be effective in an initial Phase I clinical trial, has three main goals: to improve the quality of life of PLWD, to reduce BPSD in PLWD, and to foster positive relationships between members of the care triad. The proposed Phase II project has the following Specific Aims: 1. Create an improved Beta version of the BRAIN Platform's eight components: (1) the Admin Management Dashboard, (2) the Annotation Dashboard, (3) the Log Viewer, (4) the Content Management System (CMS), (5) the Private CMS, (6) the Control App, (7) the Home App, and (8) the Training Dashboard. 2. Fine-tune the different classes of AI algorithms-i.e., behavioral analytics, personalized content recommendation, and personalized program generation-in the BRAIN app such that they can (a) recognize and track 12 distinct behaviors and indicators of PLWD, (b) use these behavioral traits as a basis for automatically rating the relative success of each activity, and (c) automatically recommend personalized activities that are likely to be successful for individual PLWD. 3. Conduct a Cluster Randomized Trial (CRT) of the BRAIN App to examine the app's impact on engagement/affect, quality of life, and responsive behaviors. 4. Examine satisfaction and ease of use of the app for PLWD, LTC staff, and FMs.

开始日期2025-02-15

申办/合作机构-

NCT06079216 / Not yet recruitingN/A

Making Connections Thru Music: A Group Music Therapy-Based Intervention for Persons With Dementia

Healthcare systems around the world, including within the United States, have long-established shortages of trained caregivers. The American Health Care Association states that "the health care system has experienced a shortage of trained caregivers for critical roles for some time." This scarcity directly impacts the 45,800 Long-Term Care (LTC) communities throughout the U.S.
Concurrent with this staff shortage, more than half of LTC residents have some form of dementia. These two issues create a serious public health concern, since dementia is associated with a variety of behavioral expressions, such as aggression, anxiety, and agitation. Behavioral expressions of dementia can be successfully managed with the use of tailored, psychosocial interventions and communication support. Unfortunately, existing staff shortages make the facilitation of such interventions challenging.
One powerful and often-overlooked approach to ameliorating staffing shortages involves the utilization of retired volunteers to facilitate interventions for persons with dementia (PWD). Based on the nearly universal love of music and a promising pilot study, the product to be developed and tested in this STTR will build upon the combined prior work of the Principal Investigators. Making Connections Thru Music (MCTM), an urgently needed product, will enable retired volunteers to facilitate an evidence-based music and discussion intervention with PWD. MCTM aims to improve engagement, enhance quality of life, and reduce behavioral expressions in PWD. The intervention will consist of two main components: (1) a comprehensive online training course for volunteers, which will provide a general overview of dementia, demonstrate effective communication strategies to use with PWD, and instruct volunteers to effectively facilitate MCTM sessions, and (2) an app containing a structured MCTM intervention protocol and toolkit, which will be the means by which volunteers facilitate MCTM. MCTM will be marketed to LTC communities.

开始日期2024-12-01

申办/合作机构

Hopeful Beginnings

ITMCTR2024000461 / SuspendedIIT

Evidence based evaluation of the Tongdu Tiaoshen Yizhi rehabilitation program for mild cognitive impairment after stroke

开始日期2024-12-01

申办/合作机构

中国中医科学院

100 项与颅内动脉粥样硬化相关的临床结果

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100 项与颅内动脉粥样硬化相关的转化医学

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0 项与颅内动脉粥样硬化相关的专利（医药）

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13,364

项与颅内动脉粥样硬化相关的文献（医药）

2025-02-01·Neural Regeneration Research

The emerging role of nitric oxide in the synaptic dysfunction of vascular dementia

Article

作者: Xiong, Yinyi ; Zhang, Xiaorong ; Zhu, Ling-Qiang ; Chen, Zhiying ; Liu, Dan ; Zhou, Qin

With an increase in global aging, the number of people affected by cerebrovascular diseases is also increasing, and the incidence of vascular dementia—closely related to cerebrovascular risk—is increasing at an epidemic rate. However, few therapeutic options exist that can markedly improve the cognitive impairment and prognosis of vascular dementia patients. Similarly in Alzheimer’s disease and other neurological disorders, synaptic dysfunction is recognized as the main reason for cognitive decline. Nitric oxide is one of the ubiquitous gaseous cellular messengers involved in multiple physiological and pathological processes of the central nervous system. Recently, nitric oxide has been implicated in regulating synaptic plasticity and plays an important role in the pathogenesis of vascular dementia. This review introduces in detail the emerging role of nitric oxide in physiological and pathological states of vascular dementia and summarizes the diverse effects of nitric oxide on different aspects of synaptic dysfunction, neuroinflammation, oxidative stress, and blood–brain barrier dysfunction that underlie the progress of vascular dementia. Additionally, we propose that targeting the nitric oxide-sGC-cGMP pathway using certain specific approaches may provide a novel therapeutic strategy for vascular dementia.

2025-02-01·Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy

Identification of Alzheimer’s disease and vascular dementia based on a Deep Forest and near-infrared spectroscopy analysis method

Article

作者: Li, Yuanpeng ; Xue, Mengjiao ; Huang, Furong ; Hua, Yisheng ; Tu, Shan ; Huang, Wenchang ; Liu, Lingli ; Chen, Meiyuan ; Hu, Junhui ; Zeng, Rui

Alzheimer's disease (AD) and vascular dementia (VaD) typically do not exhibit distinct differences in clinical manifestations and auxiliary examination results, which leads to a high misdiagnosis rate. However, significant differences in treatment approaches and prognosis between these two diseases underscore the critical need for an accurate diagnosis of AD and VaD. In this study, serum samples from 33 patients with AD patients, 37 patients with VaD, and 130 healthy individuals were collected, employing near-infrared aquaphotomics technology in combination with deep learning for differential diagnoses. Through an analysis of water absorption patterns among different diseases via aquaphotomics, the efficacies of traditional machine learning methods (Support Vector Machine and Decision Trees) and deep learning approaches (Deep Forest) in modeling were compared. Ultimately, by leveraging feature extraction techniques in conjunction with deep learning, a differential diagnostic model for AD and VaD was successfully developed. The results revealed that aquaphotomics could identify a certain correlation between the number of hydrogen bonds in water molecules and the development of AD and VaD; the deep learning model was found to be superior to traditional machine learning models, achieving an accuracy of 98.67 %, sensitivity of 97.33 %, and specificity of 100.00 %. The bands identified using the Competitive Adaptive Reweighting Algorithm method, primarily located at approximately 1300-1500 nm, showed a significant correlation with water molecules containing four hydrogen bonds. These results highlighted the potential role of the water molecule hydrogen-bond network in disease development and were consistent with the aquaphotomics analysis results. Therefore, the differential diagnostic model developed by integrating near-infrared spectroscopy and deep learning was proven to be effective and feasible, providing accurate and rapid diagnostic methods for AD and VaD diagnoses.

2025-01-01·Brain Research

Molecular profiling of a rat model of vascular dementia: Evidences from proteomics, metabolomics and experimental validations

Article

作者: Ban, Wenming ; Zhen, Yilan ; Zhu, Guoqi ; Wang, Xueqing ; Wang, Jingji ; Yang, Jun

Decrease of cerebral blood flow is the primary cause of vascular dementia (VD), but its pathophysiological mechanisms are still not known. This study aims to profile the molecular changes of a rat model of VD induced by bilateral common carotid artery ligation. The Morris water maze and new object recognition tasks were used to test the cognitive function of rats. Hematoxylin and Eosin (HE) staining was used to detect pathological changes in the hippocampus. After confirming the model, proteomics was used to detect differentially expressed proteins in the hippocampus, and metabolomics was used to detect differential metabolites in rat serum. Thereafter, bioinformatics were used to integrate and analyze the potential molecular profile. The results showed that compared with the sham control group, the spatial and recognition memory of the rats were significantly reduced, and pathological changes were observed in the hippocampal CA1 region of the model group. Proteomic analysis suggested 206 differentially expressed proteins in the hippocampus of VD rats, with 117 proteins upregulated and 89 downregulated. Protein-protein interaction network analysis suggested that those differentially expressed proteins might play crucial roles in lipid metabolism, cell adhesion, intracellular transport, and signal transduction. Metabolomics analysis identified 103 differential metabolites, and comparison with the human metabolome database revealed 22 common metabolites, which predicted 265 potential targets. Afterwards, by intersecting the predicted results from metabolomics with the differentially expressed proteins from proteomics, we identified five potential targets, namely ACE, GABBR1, Rock1, Abcc1 and Mapk10. Furthermore, western blotting confirmed that compared with control group, hippocampal GABBR1 and Rock1 were enhanced in the model group. Together, this study showed the molecular profile of VD rats through a combination of proteomics, metabolomics, and experimental confirmation methods, offering crucial molecular targets for the diagnosis and treatment of VD.

182

项与颅内动脉粥样硬化相关的新闻（医药）

2024-10-30

·喜鹊医药公司

新药创始人秋季论坛在京举办，喜鹊医药创始人王玉强教授领衔策划“中枢神经系统领域创新实践”主题研讨 | 喜鹊动态

点击蓝字关注我们 10月24日，新药创始人北京秋季论坛在北京新生巢创新中心圆满落幕。本次论坛以“和伙”为核心理念，寓意生物医药领域的同仁们并肩同行，围绕政策监管与产业发展、临床与科研资源助推产业发展、中枢神经系统(CNS)领域创新实践等议题展开讨论。喜鹊医药创始人、董事长兼总经理、CNS创业社社长王玉强教授领衔策划CNS领域创新实践主题研讨活动，以《阿尔茨海默病药物研发的创新路径与实践》为题发表主题演讲，并参与圆桌讨论。论坛吸引了众多来自北京乃至全国生物医药产业的领军人物、投资界精英及科研先锋，通过深度对话与智慧交融，为生物医药产业注入蓬勃生机与创新灵感。在《阿尔茨海默病药物研发的创新路径与实践》的主题演讲中，王玉强教授点明了阿尔茨海默病 (AD) 诊疗当前面临的临床药物疗效受限且研发进程滞后的现状，同时也强调了AD研发管线方向上呈现出抗体、小分子药物及中药等多种技术路径并行发展、百花齐放的局面。接着，他分享了喜鹊医药在AD药物研发方面的实践与成果，重点介绍了喜鹊医药团队独家设计开发的创新化学药物MN-08，其具有独特新颖的作用机理，既可变构抑制NMDA受体抑制钙离子超载又能靶向NMDA受体释放NO扩张脑血管、改善脑血流，从而有效恢复脑部营养供给，起到治疗AD与血管性痴呆 (VD) 等神经退行性疾病的作用。临床1期研究证明MN-08具有良好的安全性与耐受性。目前，MN-08治疗中重度AD的2期临床试验正在进行，现有数据已初步显示出增加脑血流的积极效果，有望成为标本兼治的AD与VD新一代治疗药物。最后，王玉强教授总结了AD药物研发的挑战与机遇，并期待未来能有更多创新药物问世，为患者带来福音。嘉宾从左至右依次为：凯斯艾生物董事长/CEO庄永杰、科恩里斯生物CEO吴庭鹤、睿健医药CEO魏君、喜鹊医药董事长/CEO王玉强随后王玉强教授加入主题论坛，与凯斯艾生物董事长/CEO庄永杰、科恩里斯生物CEO吴庭鹤、睿健医药CEO魏君等行业资深专家，就中枢神经系统领域创新实践进行深入讨论。讨论概要如下： 1）帕金森及相关领域细胞移植治疗帕金森探索出现早，但直到2021年Blue Rock公司的一款药物疗法获批进入临床才标志正式进入临床体系。坚持颠覆性创新，通过临床验证效果。Blue Rock公司的经验可供学习，其产品进入2期会引起更多关注。 2）外泌体相关外泌体作为药物递送载体迎来前所未有的机会。核酸类药物靶向递送方面，后疫情时代，mRNA疫苗向mRNA治疗性药物转型，由于LNP 技术靶向递送能力上的局限，外泌体作为核酸药物递送载体迎来机会。相比 LNP 在工程化修饰、免疫原性、给药方式等方面有优势，尤其在递送核酸类药物透脑靶向递送上机会最大。科恩里斯公司在核酸类药物装载的CMC工艺方向有突破，实现了细胞内装载，突破了领域的CMC工艺放大瓶颈，并显著提高了装载能力。天然外泌体药物方向，由于海外已有管线提交BLA申报，因此外泌体药物元年即将到来。科恩里斯公司在天然外泌体管线方面，细分亚群的天然外泌体早期适应症有肺纤维化、薄型子宫内膜修复、炎症性肠炎等，部分已开展 IIT临床研究，且首批病人效果显著。在CNS适应症上，药效学数据较积极。天然外泌体在医美方面有前景，今年年初FDA已经将间充质干细胞来源外泌体列入化妆品添加成分列表，外泌体具有医美活性已经得到广泛认同。 3）血脑屏障相关动物模型显示血脑屏障破坏和血流减少可能是AD的突破点。有Science文章显示AD病人脑血流下降，但脑血流下降是原因还是结果不明确。从药物递送角度，急性期可借助血脑屏障打开，干细胞有修复血脑屏障的可能性，但需考虑剂量效应等问题。在紧凑而充实的一天时间里，与会者围绕关键议题，展开了热烈而深入的探讨。思想的火花在交流中碰撞，智慧的涟漪在互动中荡漾，不仅加深了彼此的了解与合作，更激发了新的创意与合作契机。相信在“和伙”精神的引领下，生物医药产业的同仁们将继续携手共进，以更加坚定的步伐迎接新的挑战与机遇，共同书写生物医药产业更加辉煌灿烂的篇章。

疫苗临床2期信使RNA临床1期核酸药物

2024-10-28

·绿谷医药科技

绿谷医药科技深度参与2024国际阿尔茨海默病协会第27届亚太区会议

2024年10月25日-26日，国际阿尔茨海默病协会第27届亚太区域会议暨中国老年保健协会阿尔茨海默病分会年会在西安成功召开。绿谷医药科技深度参与，与阿尔茨海默病基础研究与临床领域的国内外著名专家学者齐聚一堂，共话研究前沿，并就当前认知障碍相关疾病治疗难点及未来发展趋势进行了深入研讨。在世界卫生组织的支持下，本次大会围绕“参与、合作、进步”的主题，研讨内容涵盖全球视野与国际合作、跨文化研究、政策倡导、社会化行动与教育、护理与机构服务、友好化环境、心理卫生、精神行为异常、中西医结合防治、肠道微生态机制与多靶点治疗、临床与基础进展、创新性服务与研究、非药物治疗等各领域。其中，靶向脑肠轴系统治疗AD成为本次大会的研讨热点。国际老年痴呆协会(ADI) 首席执行官Paola Barbarino，中国工程院田金洲院士、芝加哥大学神经生物学系Sangram Sisodia教授等海内外专家及学者进行了主旨演讲。哈佛医学院莱夫勒学者、绿谷医药科技首席执行官李金河博士应邀于 “阿尔茨海默病（AD）治疗领域的进展”分论坛上发表题为“阿尔茨海默病药物研究进展”的主旨发言，并参与圆桌讨论。李金河博士表示，阿尔茨海默病是一种系统性的病理性衰老，并不应被视为仅限于大脑的疾病。高达90%的阿尔茨海默病患者存在非阿尔茨海默病相关的共病病理。这些共病因素同样影响着疾病进展。这也可以进一步解释为什么临床试验中患者脑内的Aβ和tau蛋白明明已经显著减少，但疾病仍在进展，单一靶点干预具有局限性。“肠道菌群在阿尔茨海默病临床症状前就已发生变化。肠道菌群失衡(包括菌群丰度和代谢产物失衡），破坏外周免疫系统，进而引发中枢神经系统炎症反应，最后导致神经细胞损伤，认知功能下降。这也是当前全球注册临床研究管线分布格局从原先靶向Aβ转向系统抑制神经炎症的一大原因。”李金河博士总结道。甘露特钠胶囊（商品名：九期一®）是全球首个靶向脑肠轴、抑制神经炎症，系统治疗阿尔茨海默病的寡糖药物，获国家重大新药创制科技重大专项支持，2021年被纳入国家医保目录。最新公布的甘露特钠上市后临床研究中期分析数据显示，甘露特钠单药治疗明显优于使用甘露特钠联合常规治疗，患者认知功能（ADAS-cog、MMSE）和日常生活能力（ADAS-ADL）均可获得基线以上持续改善，在早期患者中显示出逆转病程的趋势，且安全性良好，在老年人常见伴发疾病下及老年人常用药物合并使用下，不存在潜在安全性风险。深度参与此次盛会，是绿谷医药科技大力推动全球脑肠轴科研发展和AD基础科研及临床的具体举措。面对全球健康挑战，绿谷医药科技将始终坚持把脑肠轴科研与人工智能双轮驱动作为第一发展战略，聚焦阿尔茨海默病、血管性痴呆、帕金森、自闭症等神经系统疾病的治疗领域，致力于通过基础科研和新药研发，探索认知健康产业发展的新路径，实现中国认知生命科学产业的原创突围，为全球病患贡献个体化的认知健康方案。关于绿谷医药科技绿谷医药科技秉承“提升人类认知健康”的使命，聚焦神经退行性疾病的诊断和治疗产品创新。与多方合作研发的甘露特钠胶囊（九期一®）是中国原研、全球首个靶向脑肠轴的系统治疗阿尔茨海默病的寡糖药物，打破了该领域17年无新药上市的困局，2021年被纳入国家医保目录。以“九期一”为基础，绿谷医药科技不断推动脑肠轴理论创新，以人工智能和脑肠轴理论为核心，整合全球资源，建设集专家、临床医生、患者协同的认知产业生态系统，开创数据驱动的认知健康产业模式，贡献集药物创新和疾病诊断于一体的个体化认知健康方案，引领提升人类认知健康。更多信息，请访问www.greenvalleypharma.com。

微生物疗法临床结果

2024-10-26

·药明康德

颠覆认知！这种潜伏在老年人体内的病毒，竟可引发阿尔茨海默病？

▎药明康德内容团队编辑当我们谈论起痴呆症时，往往首先联想到的是记忆、认知减退等典型症状，鲜少有人会将这种疾病与水痘相联系。然而，最新的研究结果开始颠覆我们对阿尔茨海默病（AD）和其他类型痴呆症起源的传统认知。一些研究表明，阿尔茨海默病及其它类型的痴呆症的起因或许比我们想象中更为复杂。特别是，有证据显示某些病毒感染，如水痘-带状疱疹病毒（VZV），可能在痴呆症的发展过程中发挥着重要作用。这一发现正在逐步改变我们对于这类疾病成因的传统认识。图片来源：123RF 痴呆症通常被归类为一种神经退行性疾病，它在全球范围内影响着数以百万计的个体，且患病风险随着年龄的增长而增加。痴呆症涉及一系列认知功能的丧失，包括思维、记忆和推理能力的减退，这些认知功能的损害严重干扰了患者的日常生活和各种活动。此外，某些痴呆症患者还可能会遭遇情绪控制障碍和性格上的显著变化。痴呆症的发生是由于大脑中的神经细胞及其连接的损伤或丧失引起的。当大脑中负责学习、记忆、决策或语言等功能区域受到感染或疾病的侵袭时，可能会触发痴呆症的发生。症状的具体表现取决于大脑中受损区域的特定位置。AD是引起痴呆症的最常见原因，但也有其他多种已知的病因，包括血管性痴呆症、路易体痴呆症、额颞叶痴呆症，以及由药物副作用或甲状腺问题等可逆因素引起的痴呆症。图片来源：123RF 带状疱疹是由VZV引起的，据估计，几乎所有老年人的神经系统内都有这种病毒潜伏。随着年龄的增长，免疫细胞的抗感染能力逐渐减弱，为病毒的重新激活提供了可乘之机。带状疱疹病毒的再度活化会导致患者胸部、腹部或面部出现水泡，并伴有剧烈疼痛。令人惊讶的是，一些研究已经发现了带状疱疹病毒重新激活与痴呆症风险增加之间的显著关联。这些新证据不仅改变了我们对这种疾病的理解，还突出了疫苗在提供保护性益处方面的潜力，这些益处不仅限于预防感染，还有望预防痴呆症的发生。随着科学家们对病毒与痴呆症之间相互作用的研究不断深入，这些发现对于痴呆症的治疗和预防策略可能带来深远影响。去年发布在medRxiv平台的一项预印本论文（尚未经同行审查）研究对比分析了接种/未接种带状疱疹疫苗Zostavax人群的痴呆症发生状况。科学家们发现，在为期七年的随访期内，接种Zostavax的人群中痴呆症确诊率减少了约五分之一。为了证实这一发现不是由于其他混杂因素所造成的，研究人员进行了进一步分析，结果显示接种带状疱疹疫苗仅仅与痴呆症的减少相关，而没有与任何其他常见的死亡或疾病成因有关联；接种带状疱疹疫苗也没有导致其他疫苗接种或预防性健康措施的增加。此外，探索性分析结果还表明，对于全因性痴呆和阿尔茨海默病，该疫苗的保护效果在女性当中尤为显著。病毒感染至少在某些痴呆症病例中起作用的观点可以追溯到几十年前。但在阿尔茨海默病领域，这一观点仍然存在争议。在过去的十年中，病原体与痴呆症之间的联系逐渐得到加强，越来越多的研究人员开始更加认真地考虑这一可能性。随着研究的深入，越来越多的科学家投身于探索病毒感染与痴呆症发生之间的关系。目前，Zostavax疫苗已在包括美国在内的许多国家和地区停用，大多数民众所接受的是带状疱疹重组蛋白疫苗Shingrix。为了验证带状疱疹疫苗在预防痴呆症方面的潜在作用，以及不同类型疫苗（Zostavax和Shingrix）之间是否存在效果差异，英国牛津大学的科学家们对美国的电子健康记录（EHR）进行了分析。这项分析涵盖了过去十年中在美国接种了Zostavax或Shingrix疫苗的20多万人的数据。具体来说，约一半的参与者在2014年10月至2017年9月期间接种了Zostavax，而其余人则在2017年11月至2020年10月期间接种了Shingrix疫苗。这项研究旨在比较这两种疫苗在预防痴呆症方面的有效性，并探讨它们在保护效果上是否存在差异。分析结果表明，接种Shingrix的人群在随后的6年内，与接种Zostavax的人群相比，患痴呆症的风险显著降低。具体而言，接种过Shingrix的个体在无痴呆确诊时间上延长了17%，相当于延长了无痴呆状态164天。与其他两种常用于老年人的疫苗（流感疫苗和破伤风-白喉-百日咳疫苗）相比，也显示出Shingrix在降低罹患痴呆症风险方面的优越性。值得一提的是，在这项研究中，Shingrix在男性与女性个体当中均观察到痴呆预防的作用，但在女性中表现更为显著。结果发表在今年7月的《自然医学》（Nature Medicine）杂志上。这些研究结果为带状疱疹病毒可能导致痴呆症的假设提供了更多证据。论文的通讯作者Paul Harrison博士指出：“这些结果不仅增强了带状疱疹病毒可能导致痴呆症的证据，而且也警醒人们，疫苗的作用可能不仅仅是预防感染。” 一些学者将研究重点转向了带状疱疹病毒。哈佛大学和布莱根妇女医院（Brigham and Women's Hospital）的研究人员从几项针对医疗工作者的大型、长期队列研究中提取并分析了数据。这些分析结果表明，一次带状疱疹的发作与多种远期并发症风险的增加有关，例如心脏病（包括严重的心脏事件）和中风。在针对同一队列数据的进一步研究中，研究人员还发现带状疱疹与主观认知能力下降的风险增加有关——这是阿尔茨海默病和相关痴呆症的早期症状之一。科学家们开始在细胞和分子生物学层面探索带状疱疹病毒再激活与痴呆症风险增加之间的联系。最近，一项发表在IBRO Neuroscience Reports杂志的研究提供了新的见解。研究人员发现，当使用单纯疱疹病毒1型（HSV-1）感染未分化的人类嗅觉上皮细胞培养物时，会引起β淀粉样蛋白和环核苷酸门控通道亚基alpha 2（CNGA2，成熟嗅觉感觉神经元的标记）的表达显著增加。β淀粉样蛋白的积累可能形成神经毒性斑块，这正是阿尔茨海默病的一个标志性特征。这些发现暗示病毒感染可能会破坏嗅觉功能和海马体的下游功能，从而加速阿尔茨海默病的进展。尽管VZV再激活与痴呆症风险增加之间的确切机制尚不明确，仍需要进一步的研究来阐明，但这一领域的研究已经激发了新的科学兴趣，并催生了多项研究。目前，一项临床2期试验（试验注册号：NCT03282916）正在进行中，旨在研究针对包括VZV在内的抗病毒药物伐昔洛韦（valacyclovir）是否能够延缓阿尔茨海默病早期患者的病情发展。该试验纳入了130名HSV-1或HSV-2检测呈阳性的轻度阿尔茨海默病患者，其中65名接受伐昔洛韦治疗，65名接受安慰剂治疗。研究人员将使用正电子发射断层成像（PET）技术来监测淀粉样蛋白积累和tau蛋白等阿尔茨海默病病理特征的变化。随着研究人员继续探索病毒可能影响神经变性的复杂机制，我们期待他们能开发创新方法应对这一日益严峻的公共卫生挑战，最终改善数百万受认知能力下降影响的人的生活质量。 ▲欲了解更多前沿技术在生物医药产业中的应用，请长按扫描上方二维码，即可访问“药明直播间”，观看相关话题的直播讨论与精彩回放参考资料 [1] Chickenpox, shingles, Alzheimer’s? Evidence mounts for a viral cause of dementia，Retrieved Oct 25, 2024 from https://www.statnews.com/2024/10/18/dementia-alzheimers-evidence-for-viral-cause-grows/ [2] What Is Dementia? Symptoms, Types, and Diagnosis，Retrieved Oct 25, 2024 from https://www.nia.nih.gov/health/alzheimers-and-dementia/what-dementia-symptoms-types-and-diagnosis [3] Dementia，Retrieved Oct 25, 2024 from https://my.clevelandclinic.org/health/diseases/9170-dementia [4] Eyting M, Xie M, Heß S, Geldsetzer P. Causal evidence that herpes zoster vaccination prevents a proportion of dementia cases. medRxiv [Preprint]. 2023 May 25:2023.05.23.23290253. doi: 10.1101/2023.05.23.23290253. PMID: 37292746; PMCID: PMC10246135. [5] Taquet M, Dercon Q, Todd JA, Harrison PJ. The recombinant shingles vaccine is associated with lower risk of dementia. Nat Med. 2024 Jul 25. doi: 10.1038/s41591-024-03201-5. Epub ahead of print. PMID: 39053634. [6] Curhan, Sharon G et al. “Herpes Zoster and Long-Term Risk of Cardiovascular Disease.” Journal of the American Heart Association vol. 11,23 (2022): e027451. doi:10.1161/JAHA.122.027451 [7] Yeh, TS., Curhan, G.C., Yawn, B.P. et al. Herpes zoster and long-term risk of subjective cognitive decline. Alz Res Therapy 16, 180 (2024). https://doi.org/10.1186/s13195-024-01511-x [8] Restrepo, Diego et al. INFECTION OF HUMAN OLFACTORY EPITHELIUM WITH ALPHAHERPESVIRUS ELICITS EXPRESSION OF BETA AMYLOID. IBRO Neuroscience Reports, Volume 15, S484 免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。版权说明：本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。分享，点赞，在看，聚焦全球生物医药健康创新

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