A PHASE II CLINICAL TRIAL FOR THE EVALUATION OF THE EFFICACY OF DISULFIRAM/COPPER COMBINATION AS AN ADJUVANT AND CONCURRENT CHEMOTHERAPY IN THE TREATMENT OF NEWLY DIAGNOSED GLIOBLASTOMA MULTIFORM

Glioblastoma multiform (GBM) is the most common malignant primary brain tumor in adults. Despite maximal treatment tumor relapse occurs regularly accompanied by unfavourable prognosis. Among other reasons, it is believed that this could be in part due to the existence of the so-called tumor stem cells (TSCs), a cellular subfraction within GBM which escape therapy by being highly resistant to irradiation and chemotherapy and thus constituting the source of tumor recurrence.
GBM, like many other cancers, show a sub-population of aldehyde dehydrogenase (ALDH) overexpressing TSCs. More specifically, ALDH1A1, a cytoplasmatic isoform of ALDH, proved to be a novel stem cell marker in human GBM. In addition, ALDH1A1 has been shown to be a mediator for resistance of GBM to temozolomide (TMZ) and a reliable predictor of clinical outcome; prognosis of patients with a high level of ALDH1A1 expression was poor compared with that of patients with low levels. Consequently, ALDH1A1 may serve as a potential target to improve treatment of human GBM through inhibition of the enzyme.
Disulfiram (DSF) has been used for more than sixty years in the treatment of chronic alcoholism because of the unpleasant symptoms it provokes after ethanol intake. The underlying mechanism is believed to be the accumulation of acetaldehyde in the blood, due to inhibition of the liver ALDHs. Actually, DSF is a strong inhibitor of ALDH1A1 and relatively non-toxic at therapeutic (for chronic alcoholism) doses that can penetrate the blood-brain barrier. In addition, DSF has been shown to be cytotoxic on GBM stem-like cells, inhibiting the growth of TMZ resistant GBM cells and blocking self-renewal by
100% , while it has been identified as an inhibitor of human GBM stem cells in high-throughput chemical screens. Interestingly, a number of these actions were copper-dependent.
In the current Phase II clinical trial, DSF/copper combination will be tested as an adjunctive and concurrent chemotherapy in the treatment of newly diagnosed GBM. According to our hypothesis, initiation of DSF chemotherapy after the resection of the tumor and before the introduction of the standard radio-chemotherapy will inhibit ALDH1A1 of GBM TSCs making them more susceptible to radio-chemotherapy and possibly reducing the recurrence rate of GBM. On the other hand, the addition of copper will probably enhance the cytotoxic effects of DSF possibly through augmentation of its pro-apoptotic and proteasomal inhibitory actions.

开始日期2027-01-01

申办/合作机构

Universität Ulm

[+2]

NCT06934187

/ Not yet recruitingN/AIIT

eFficacy Of Carpal tUnnel releaSe (FOCUS) - Protocol for Randomised Controlled Multicentre Triple-Blinded Placebo Surgery Carpal Tunnel Release Trial With Observational Group

Background Carpal tunnel syndrome (CTS) is a prevalent condition that affects 2.7% of the population, especially women. It arises due to compression of the median nerve in the wrist and is linked to factors like diabetes, obesity, and physical workload. Non-surgical treatments such as splinting and corticosteroid injections are often the first approach for mild to moderate CTS but show mixed long-term results. Surgical intervention, carpal tunnel release (CTR), is frequently necessary and has a success rate of 75-88%. CTR is a safe procedure, but like any surgery, it carries risks, including scarring and nerve injury.
Rationale Despite its widespread use, the effectiveness of CTR surgery has not been rigorously tested through randomised controlled trials (RCT) against placebo. This leaves a critical gap in understanding whether observed improvements result from surgery or the natural course of CTS, which can sometimes resolve on its own. Previous RCT in hand surgery have faced methodological issues, emphasising the need for high-quality research to validate the benefits of CTR surgery.
Objectives
FOCUS (eFficacy Of Carpal tUnnel release) trial, aims to provide robust evidence of CTR's effectiveness compared to placebo. The null and alternative hypotheses of the trial are as follows:
* Null Hypothesis: The treatment effect of CTR is not superior to placebo surgery.
* Alternative Hypothesis: The treatment effect of CTR is superior to placebo surgery
Trial Design This multinational, triple-blinded RCT includes two groups: one receiving CTR and the other undergoing placebo surgery. An additional observational cohort will enhance the trial's generalisability. Recruitment begins in Finland, with plans to expand to Denmark, China and Australia. Experienced hand surgeons will perform all procedures, and the study adheres to rigorous international guidelines (SPIRIT).
Methods Eligible participants are screened and randomised 1:1 to receive either CTR or placebo surgery. In CTR, surgeons relieve pressure on the median nerve through a small incision. Placebo surgery involves a similar incision without addressing the nerve compression. Both procedures use the same pre- and post-operative care protocols to maintain participant blinding.
Data collection involves comprehensive patient assessments at six months, one, two, and five years. A validated tool, the 6-CTS scale, is the primary outcome measure, while secondary measures include nerve conduction tests, hand strength, and patient-reported satisfaction.
The study includes 96 participants, allowing for statistical analysis with 80% power to detect meaningful differences in outcomes.Trial is triple-blinded ensuring that participants, outcome assessors, and investigators remain unaware of treatment assignments, minimising bias. Patients will be randomly assigned to 1:1 parallel groups using an internet-based randomisation program.
Ethical considerations The trial complies with the Declaration of Helsinki and national regulations. Participants provide informed consent and can withdraw at any time.
Data Management and Safety Data is securely stored in compliance with GDPR, and interim analyses are conducted to monitor safety. An independent Data Safety and Monitoring Committee (DSMC) oversees the trial, reviewing any serious adverse events.
Expected Outcomes and Significance
Discussion The trial seeks to determine whether CTR surgery provides superior outcomes compared to placebo, addressing a critical gap in evidence for this common procedure. By including patient-reported outcomes and rigorous blinding, the study emphasises improvements that matter most to individuals with CTS.
This research has far-reaching implications for patients, surgeons, and policymakers, offering insights into the value of CTR surgery. The results could refine treatment guidelines, ensuring that surgical interventions are evidence-based and benefit those most in need.
Conclusion The FOCUS-trial represents a significant step forward in validating the effectiveness of CTR surgery. By setting a high standard for surgical research, it aims to provide clarity on a widely performed procedure, contributing to improved care and outcomes for individuals with CTS worldwide.

开始日期2026-01-01

申办/合作机构

University of Eastern Finland

NCT07239843

/ Enrolling by invitationN/AIIT

Synapsing's Multinational Sociodemographic Study

This is a prospective observational study to identify sociodemographic factors that predict mental health outcomes in the European population and provide evidence linking common, modifiable sociodemographic risk factors for psychiatric symptoms with biological changes in patients suffering from a mental disorder (MD) or a neurodegenerative disease (ND).

开始日期2026-01-01

申办/合作机构

Fundacio Institut De Recerca De L'Hospital De La Santa Creu I Sant Pau

[+4]

100 项与 University of Eastern Finland 相关的临床结果

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项与 University of Eastern Finland 相关的文献（医药）

2026-04-01·TOXICOLOGY IN VITRO

Optimisation of ultrafine particle exposure in an alveolar tri-culture model at the air-liquid interface

Article

作者: Huang, Jingwen ; Yang, Mo ; Kanninen, Katja ; Hensel, Anna-Katharina ; Hakkarainen, Henri ; Mussalo, Laura ; Jalava, Pasi ; Fayad, Claire

Air-liquid interface (ALI) systems have emerged as a physiologically relevant in vitro platform for evaluating the toxicological impact and potential health effects of airborne pollutants. When utilizing collected ultrafine particles (UFPs), application volume and liquid type are critical parameters. Using a smaller volume of liquid for the cell exposure results in a heterogeneous distribution of UFPs across the cell monolayer, whereas application of a sufficient volume optimises even UFP distribution. A buffered solution for UFP administration minimises potential side effects and unravels dose-dependent effects in toxicological endpoints. However, standardised exposure methodologies limit reproducibility and comparability across studies. Therefore, we propose a refined manual exposure technique of suspended airborne pollutants in an adequate exposure volume that bridges the gap between conventional submerged cultures and ALI systems. Our model uses cell culture inserts with A549 epithelial cells, THP-1 macrophages, and EA.hy926 endothelial cells to mimic the in vivo alveolar barrier within the lungs. This approach offers a balance of experimental reproducibility whilst addressing the current challenges of standardisation and feasibility in exposure studies with manual UFP exposure. In conjunction with existing aerosol ALI continuous flow exposure systems, our studies are advancing translational in vitro evaluations, aligning with the 3R principle.

2026-03-01·EUROPEAN NEUROPSYCHOPHARMACOLOGY

Mental health, coping and related risk factors during the first 2 years of the COVID-19 pandemic in children: Nationally representative, multi-wave, cross-sectional results from 12 countries from the global COH-FIT study

Article

Few multinational studies have assessed risk factors and coping strategies associated with the impact of the COVID-19 pandemic on children's mental health over time. The Collaborative Outcomes study on Health and Functioning during Infection Times (COH-FIT) is the largest transcontinental, multi-wave, cross-sectional survey collecting multi-nation data on well-being and psychopathology during the pandemic. We analyzed country-specific, general-population-based, representative COH-FIT data of 6067 children aged 6-13 years from 12 countries across repeated cross-sectional waves over a period of >2 years (Apr/2020-May/2022), addressing through current and retrospective assessment pre- to intra-pandemic changes in well-being (WHO-5) and general psychopathology scores (P_c) (0-100) in relation to COVID-related deaths, stringency index, eight a priori risk factors, and 16 coping strategies in different responders at each wave. From pre- to intra-pandemic, WHO-5 scores decreased (-4.59, 95 %CI=-6.18 to -2.99, p < 0.001), while PC-scores increased (+6.68, 95 %CI=4.48-8.88, p < 0.001) significantly, following distinct time patterns but both returning to near pre-pandemic levels. Changes in both scores varied by country. WHO-5 scores correlated strongly with P_C and subdomain scores. Both score changes were significantly but minimally associated to COVID-19 deaths/stringency index. The proportion of children screening positive for depression increased from 3.9 % to 8.3 % (χ²=145.70, p < 0.001) and for major depression from 0.6 % to 2.2 % (χ²=68.64, p < 0.001) intrapandemic. WHO-5 and P_C-score changes were significantly associated with female gender, school closure, and pre-existing physical and mental conditions, with cumulative effects. The five most frequently endorsed coping strategies were family contact (85.2 %), friends (67.3 %), outdoor play (54.0 %), pet interaction (51.5 %), and internet use (50.9 %). Identified risk groups and coping strategies can inform targeted interventions and global public health policy. Trial Registration: ClinicalTrials.gov; Identifier: NCT04383470.

2026-03-01·MARINE POLLUTION BULLETIN

Perfluorooctanesulfonate (PFOS) exposure in ringed seals (Pusa saimensis) in Lake Saimaa, Finland

Article

作者: Kunnasranta, Mervi ; Simola, Jesse ; Auriola, Seppo ; Akkanen, Jarkko

Perfluorooctanesulfonate (PFOS) is common in the environment, highly accumulative, toxic, and thus a good indicator for per- and polyfluorinated alkyl acid (PFAS) contamination. In this study, PFOS was analysed from the tissues of Saimaa ringed seal (Pusa saimensis) pups and adults to investigate the exposure to PFAS in Lake Saimaa. Additionally, a toxicity evaluation was performed for the seals based on the thresholds from the literature, PFOS concentration data from the national exposure database, and the current study. For all studied specimens, the highest PFOS concentrations were found in the liver, but interestingly, high concentrations were also observed in the kidneys of lanugo pups. The toxicity evaluation indicated that the PFOS concentrations in the prey fish are so high that the tolerable daily and weekly intake values from literature as well as the environmental quality standards calculated in this study were exceeded. Furthermore, a mixture of PFAS has been observed in the fish of Lake Saimaa, which means that these seals are exposed to multitudes of PFAS. This mixture of PFAS may be more harmful than PFOS alone and together with PFOS toxicity evaluation results, despite the confounding factors of the assessment, this raises concern that PFAS contamination in Lake Saimaa may cause detrimental effects in Saimaa ringed seals.

项与 University of Eastern Finland 相关的新闻（医药）

2025-12-28

·生物谷

两项研究表明巨噬细胞“燃料”短缺导致动脉粥样硬化

两项互补性研究揭示了巨噬细胞（动脉壁中的关键免疫细胞）能量供应不足如何驱动动脉粥样硬化的进展，以及这些认识如何能带来更好的诊断和未来的疗法。东芬兰大学深入参与了这两项研究。动脉粥样硬化——动脉内脂肪斑块的积聚——是导致全球心脏病发作和中风的主要原因。虽然胆固醇在斑块形成中的作用长期以来是关注焦点，但科学家们日益认识到免疫系统在决定斑块是保持稳定还是变得不稳定（从而容易破裂并可能导致心脏病发作或中风）方面起着决定性作用。在这两项新发表的研究中，一个国际研究团队表明，巨噬细胞中氨基酸谷氨酰胺的供应不足可以决定动脉斑块的恶化。研究人员还发现了检测危险斑块的新方法。免疫细胞需要能量来修复受损动脉巨噬细胞是身体的清洁工。在动脉斑块内，它们吞噬脂肪、清除垂死细胞并帮助修复受损组织。但要执行这些保护性任务，巨噬细胞需要能量。在第一项发表于《Nature Metabolism》的研究中，研究人员发现巨噬细胞严重依赖于从环境中摄取谷氨酰胺来为其修复功能提供能量。一种特定的转运蛋白SLC7A7扮演着让谷氨酰胺进入细胞的"通道"角色。当这个通道受阻时，巨噬细胞会失去能量且功能失常，导致斑块更大、更不稳定，而这是已知导致人类心脏病发作和中风的风险因素。在人类动脉样本中，该通路的活性降低也与更危险的斑块特征相关。 "这些发现表明，恢复或支持巨噬细胞代谢可能有朝一日帮助稳定斑块并预防心脏病发作或中风，"东芬兰大学的Minna Kaikkonen-Määttä教授表示。识别高风险斑块的新工具第二项发表于《Cardiovascular Research》的研究基于这一生物学发现，并向临床应用迈进。通过使用先进的单细胞技术研究巨噬细胞，研究人员识别出了诸如TREM2、FOLR2和SLC7A7等蛋白质标志物，这些标志物能突出高风险斑块。基于这些标志物，PET成像可用于检测炎症性斑块的活跃度，而不仅仅是斑块的大小。研究人员还发现，血液中的可溶性TREM2可能有助于区分稳定斑块和有症状的斑块，这为未来通过血液检测识别最高风险患者提供了可能性。这项研究体现了密切的国际合作，巴塞罗那大学等机构参与了这两项研究。第一项研究由蔚蓝海岸大学领导，第二项研究由图尔库大学共同领导。（生物谷Bioon.com）参考文献： Saloua Benhmammouch et al, Slc7a7 licenses macrophage glutaminolysis for restorative functions in atherosclerosis, Nature Metabolism (2025). DOI: 10.1038/s42255-025-01354-2. Tiit Örd et al, Single-cell to pre-clinical evaluation of Trem2, Folr2, and Slc7a7 as macrophage-associated biomarkers for atherosclerosis, Cardiovascular Research (2025). DOI: 10.1093/cvr/cvaf210.

临床研究

2025-12-25

·天浚脑科学

The Lancet：Alzheimer’s Disease系列综述3：争议与未来

编者：这篇综述非常难于像之前的两篇文献那样归纳梳理重构。因为涉及医学人文，以及多重视角下对创新技术的审视。单纯的字面翻译完成很快，但重构成稿有很大的难度；难点在于无法删减和文字自洽。作为《柳叶刀》AD系列终结篇，本文的价值不在于提供问题的答案，而在于构建了一个多学科对话框架，让生物学、临床医学、公共卫生、经济学和伦理学能在同一平台上诚实交锋。争议会一直持续，未来或许就藏在争议激发的临床探索之中。本文由瑞士日内瓦大学医院康复和老年科Giovanni B Frisoni教授领衔，来自瑞典卡洛琳斯卡大学、隆德大学、哥德堡大学，英国剑桥大学、伦敦大学、伦敦国王学院，法国索邦大学、丹麦哥本哈根大学、东芬兰大学，美国梅奥诊所、威斯康辛大学，澳大利亚墨尔本大学共18位顶尖科学家共同撰写。一、背景与核心命题 1.历史性突破抗β-淀粉样蛋白单克隆抗体（抗Aβ单抗）在3期临床随机对照试验中首次同时实现： - 脑β-淀粉样蛋白病理负荷的减少 - 认知和功能下降速度的减缓 2.引发的核心争议 - 支持方：认可"临床意义的疾病修饰效应" - 反对方：认为"获益-风险比不足"，反对上市授权 3.撰文目的 - 对比AD单抗与肿瘤、多发性硬化（MS）、类风湿关节炎（RA）生物制剂的疗效、社会成本与可推广性； 4.将争议置于现代精准医学大框架下审视 4.1.探讨当前实践意义与未来发展方向 4.1.1.抗Aβ单抗并非AD领域唯一重大创新； 4.1.2.在研的非Aβ通路的药物； 4.1.3.数字技术实现的生理或病理标志物（数字标志物）。 4.2.平衡个体治疗与人群预防策略 - 逐步建立的AD二级预防试点项目，主要针对无认知障碍但AD高风险人群。二、AD历史沿革 1.疾病命名：描述→统一概念→致死性单一疾病 2.治疗探索：对症药物（胆碱酯酶抑制剂→NMDA受体拮抗剂） - 关键拐点：2016年法国取消胆碱酯酶抑制剂医保报销（年省€9000万），标志对AD药物价值的系统性质疑达到政策层面。 3.创新技术：血液标志物和单抗药物交相呼应 3.1.单克隆抗体的出现正值阿尔茨海默病的另一个重大机遇逐渐成熟之际。 3.2.专科医疗环境中，用于测量阿尔茨海默病病理学的血液生物标志物（Aβ42 /40和p-tau217）已在美国、日本、英国和中国等多国进入临床； 3.3.其预测效果与脑脊液检测相当或更优。三、不同维度下的争议 1.原因 1.1.目前的AD检测+治疗创新技术都是基于“淀粉样蛋白级联假说”，未能同步惠及更庞大的老年阿尔茨海默病患者群体（>80岁）； 1.2.这些患者的认知障碍由多因素引起，包括阿尔茨海默病、躯体疾病及心理社会因素在内的神经病理学组合。 1.3.年轻患者群体管理方式的快速变革前景引发了对老年患者群体可能被忽视和边缘化的担忧。 2.三种范式的理论对决（Debate in the field） 2.1.分歧根源：对"AD本质"的根本性认知差异，映射到疾病定义、诊断、治疗全链条。 2.2.三种范式的不同（原文表1） - 编者总结如下表： 2.3.不同范式的共同点：共病和脑储备 2.3.1.AD共病其他病理状态较常见，且其病理特征与认知功能损害程度的相关性较弱，尤其在85岁及以上老年人群中。 2.3.2.观察到环境因素（如高教育水平）和社会因素（如活跃社交网络及较高社会经济地位）能够降低阿尔茨海默病病理表型的表达（即大脑韧性）。 2.3.3.最新修订的阿尔茨海默病诊断与分期标准承认了脑储备和共病的调节作用。 2.3.4.基于AD血液标志物研究进展，通过代表普通人群的多样化队列及长期随访，可以间接评估共病病理学与脑储备的权重；该结果如能在更大规模、更多样化的队列中得到验证，或许能为争议提供实证证据，达成科学共识。四、跨疾病比较分析单抗制剂 1.残疾改善幅度（疗效） 2.安全性 3.结论：AD单抗的疗效不劣于甚至优于其他病种生物制剂，但AD领域似乎风险容忍度更低。 4.争议点：可推广性的巨大挑战是共性问题 4.1.普遍现象：临床试验纳入的人群比真实世界更健康、社会经济地位更高、种族更单一。 4.2.单抗药物普适性有限。 4.3.AD的特殊困境 4.3.1.对许多AD患者家庭和社会而言，首要任务是减少患者处于严重残疾状态的时间。 4.3.2.高龄共病：>80岁患者常伴混合神经病理学改变、合并症及衰弱状态；单抗效果未知。 4.3.3.识别不足：社区中MCI阶段患者识别率<50%，但一旦被识别，潜在候选者可能远超预期（欧洲590万，美国220万）。 5.AD的社会负担 5.1.痴呆症在全球范围内具有最高的残疾生活年数负担，是癌症的1.5倍，是类风湿性关节炎的5倍； 5.2.2000年至2019年间导致伤残调整生命年（DALYs）增幅最大的疾病是痴呆症，且预计这一趋势将持续上升。 5.3.全球痴呆症病例的预估总成本约为1.3万亿美元，欧洲的痴呆症总治疗费用比所有肿瘤高出近40%。 5.4.在高收入国家，约90%的痴呆症治疗费用来自直接非正式照护和非医疗支出，其中医疗费用仅占总支出的约六分之一，药品费用可忽略不计。 5.5.痴呆症治疗费用随病情严重程度急剧上升，轻度与重度阶段每年费用差异约达25,000欧元 5.6.抗Aβ单抗的成本效益 5.6.1.若药物价格和配送成本大幅降低，该（单抗）疗法可能具有成本效益； 5.6.2.单抗疗法的成本效益还需考虑医疗保险和长护险的模式，以及 5.6.3.医疗系统对疾病早期诊断的能力面临巨大挑战。五、未来展望 1.生物标志物（体液和影像）创新技术矩阵 1.1.液体活检技术 1.1.1.血NF-L：作为跨病种神经退行监测标志物具有巨大应用潜力； 1.1.2.血p-tau217：在初级和次级医疗机构中的检测准确率超过90%；双阈值法可使脑脊液和PET影像标志物的使用减少80-85%；已具备颠覆诊断技术的潜力，实施将依赖于地区医疗模式。 1.1.3.脑脊液MTBR-243：用于“精准”排除对单抗无反应的晚期tau病理患者； 1.1.4.血内源性片段MTBR-243：单独或与其他p-tau联用，可能同时检测疾病状态和阶段；WHO正在制定全球标准。 1.2.多病理鉴别诊断 1.2.1.α-突触核蛋白：采用种子扩增检测（CSF准确率90%）；帕金森病和路易体痴呆的关键鉴别。 1.2.2.TDP-43：额颞叶变性的主要病理，与AD共病率达30-50%，导致疾病更快进展和对单抗治疗反应差。 1.2.3.突触PET：[18F]UCB-H等示踪剂直接可视化突触丢失，可能超越传统萎缩影像。 1.3.神经炎症可视化检查 1.3.1.MAO-B示踪剂（[18F]SMBT-1）：早期星形胶质细胞激活信号，与GFAP/YKL-40血浓度相关。 1.3.2.TSPO示踪剂：因信号弱和特异性争议，临床价值存疑。 2.数字生物标志物 2.1.优势 2.1.1.能够在现实场景中实现持续、可扩展的数据收集，并为大规模风险评估开辟新途径。 2.1.2.语音特征、移动设备使用模式（如键盘打字速度）、运动活动、瞳孔反应及个人生理数据的检测率可达85%。 2.2.劣势 2.2.1.需要通过机器学习和人工智能对海量收集的数据进行分析。 2.2.2.还需进行临床有效性（诊断准确性及对早期阶段的敏感性）和临床实用性（改善健康结局）的验证。 2.2.3.法律、伦理、数据安全性存疑。 3.药物研发新格局：从淀粉样蛋白级联假说的确定性观点，向更复杂且能解释共病现象与病理耐受性的病理生理学模型的转变。 3.1.2024年RCT164/182项（30%）测试疾病修饰生物制剂，43%测试疾病修饰小分子药物，14%测试认知增强剂，11%测试神经精神类药物。 3.2.仅33%的试验性药物靶向β -淀粉样蛋白和tau蛋白； 3.3.其余药物均针对不同机制，如肠-脑轴、血管系统、表观遗传学、昼夜节律、生长因子与激素、APOE 状态、脂质代谢、神经发生、氧化应激、蛋白质代谢、生物能量学、突触可塑性、神经递质受体、炎症及免疫系统。 3.4.164项试验联合使用抗β -淀粉样蛋白与抗tau单克隆抗体（NCT05269394）。 4.二元结构的预防策略 4.1.二级预防针对认知未受损高危个体：dBHS模型 4.1.1.认知诊疗流程（原文图2） 4.1.2.排除功能性认知障碍如焦虑、抑郁导致的注意力问题 4.1.3.多维度风险评估 - 不可改变风险：APOE ε4基因型，是散发性晚发型阿尔茨海默病的强风险因素，且与脑β 淀粉样变性密切相关。 - 可改变的脑储备降低风险因素：教育、社交、认知训练。 - 可改变的血管或代谢健康风险因素包括脑微血管疾病风险因素。 - 神经退行性疾病风险因素：血p-tau217浓度。 4.1.4.个性化风险沟通：5年/10年/终身绝对风险信息图； 4.1.5.针对血管和代谢风险因素的多领域老年干预研究：预防认知障碍与残疾（finger）方案； 4.1.6.通过认知训练和无创脑刺激增强认知功能。 4.2.一级预防（全人群）——应对"预防悖论" 4.2.1.70-80%痴呆病例来自"正常风险"人群，而非高危人群； 4.2.2.DIAN-TU一级预防试验（NCT06647498）是首个针对阿尔茨海默病的一级预防药物试验。 4.2.3.其他策略 - 药物：γ分泌酶调节剂以及靶向 APOE ε4 等潜在遗传驱动因素的基因疗法。 - 社会学因素干预：财政政策（如对烟草、酒精和含糖饮料征税）、城市与交通规划（如步行友好型社区、自行车友好型社区，以及更清洁的烹饪炉具和燃料）、营销限制（如对烟草、酒精和高度加工食品的限制）以及立法措施（如职业噪声防护和头盔强制令）。 - 无需大规模资源动员或个体行为改变即可惠及广大人群，意味着具有良好的成本效益并能提升健康公平性。六、结论 1.科学叙事（淀粉样蛋白瀑布）与临床叙述（生物标志物诊断）从脱节走向融合：整合了病理生理学、诊断、治疗和预防（原文图3） 2.需要对AD的定义达成共识：直接影响流行病学、试验设计和公共卫生政策 3.争论还将持续； 4.生物标志物、药物与非药物方法的进步将支持改善个体和社区认知健康与生活质量的共同目标。本文仅代表编辑个人对原文献的翻译理解，不能作为直接引用证据。原文献可通过PubMed或杂志官网获取。

临床3期临床结果

2025-11-07

·drugs

Increased Mortality Seen Among Patients With Early-Onset Dementia

THURSDAY, Nov. 6, 2025 -- Early-onset dementia (EOD) is associated with increased mortality, which varies with EOD subtype, according to a study published online Nov. 4 in the Journal of Neurology, Neurosurgery & Psychiatry . Kasper Katisko, M.D., Ph.D., from the University of Eastern Finland in Kuopio, and colleagues conducted a population-based cohort study involving all incident EOD cases from two defined regions in Finland. The survival and all-cause mortality rates in EOD were examined from January 2010 to December 2021. A total of 794 validated EOD cases of Alzheimer disease, frontotemporal dementia (FTD), alpha-synucleinopathy, and other EOD spectra were identified and matched with 7,930 controls without neurodegenerative diseases. The researchers found that mortality was significantly higher in the total EOD group compared with controls (hazard ratio, 6.56). FTD spectrum patients had the highest all-cause mortality risk among the dementia subtypes compared with controls (hazard ratio, 13.75). Increased mortality was seen in association with male sex, older age, several comorbidities, and lower level of education, but these were not specific to EOD. "Our study provides up-to-date survival rates in EOD, and highlights the substantial effect caused by EOD diagnosis to patients' mortality," the authors write. Several authors disclosed ties to the biopharmaceutical industry. Abstract/Full Text

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