首页 > 最新文献

medRxiv - Neurology最新文献

英文 中文
A DOUBLE-BLIND, PLACEBO-CONTROLLED, RANDOMIZED, MULTI-CENTRE, PHASE III STUDY OF MLC901 (NEUROAID II™) FOR THE TREATMENT OF COGNITIVE IMPAIRMENT AFTER MILD TRAUMATIC BRAIN INJURY MLC901(neuroaid II™)治疗轻度脑外伤后认知障碍的双盲、安慰剂对照、随机、多中心、III 期研究
Pub Date : 2024-08-29 DOI: 10.1101/2024.08.28.24312757
Pavel I. Pilipenko, Anna A. Ivanova, Yulia V. Kotsiubinskaya, Vera N. Grigoryeva, Alexey Y. Khrulev, Anatoly V. Skorokhodov, Maxim M. Gavrik, Nona N. Mkrtchan, Marek Majdan, Peter Valkovic, Daria Babarova, Suzanne Barker-Collo, Kelly Jones, Valery L. Feigin
Introduction About half of the world population will suffer from a traumatic brain injury (TBI) during their lifetime, of which about 90% of cases are mild TBI. About 15-40% of adults with TBI experience persistent cognitive deficits, and there is a lack of proven-effective treatment to facilitate cognitive recovery after mild TBI.
导言 世界上大约有一半的人在一生中会遭受创伤性脑损伤(TBI),其中约 90% 的病例属于轻度 TBI。约 15-40% 的成人创伤性脑损伤患者会出现持续的认知障碍,而目前尚缺乏行之有效的治疗方法来促进轻度创伤性脑损伤后的认知恢复。
{"title":"A DOUBLE-BLIND, PLACEBO-CONTROLLED, RANDOMIZED, MULTI-CENTRE, PHASE III STUDY OF MLC901 (NEUROAID II™) FOR THE TREATMENT OF COGNITIVE IMPAIRMENT AFTER MILD TRAUMATIC BRAIN INJURY","authors":"Pavel I. Pilipenko, Anna A. Ivanova, Yulia V. Kotsiubinskaya, Vera N. Grigoryeva, Alexey Y. Khrulev, Anatoly V. Skorokhodov, Maxim M. Gavrik, Nona N. Mkrtchan, Marek Majdan, Peter Valkovic, Daria Babarova, Suzanne Barker-Collo, Kelly Jones, Valery L. Feigin","doi":"10.1101/2024.08.28.24312757","DOIUrl":"https://doi.org/10.1101/2024.08.28.24312757","url":null,"abstract":"<strong>Introduction</strong> About half of the world population will suffer from a traumatic brain injury (TBI) during their lifetime, of which about 90% of cases are mild TBI. About 15-40% of adults with TBI experience persistent cognitive deficits, and there is a lack of proven-effective treatment to facilitate cognitive recovery after mild TBI.","PeriodicalId":501367,"journal":{"name":"medRxiv - Neurology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142197407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Antihypertensive medications and dementia in older adults with hypertension 抗高血压药物与高血压老年人痴呆症
Pub Date : 2024-08-29 DOI: 10.1101/2024.08.28.24312754
Suzanne G. Orchard, Zhen Zhou, Michelle Fravel, Joanne Ryan, Robyn L. Woods, Rory Wolfe, Raj C. Shah, Anne Murray, Ajay Sood, Christopher M. Reid, Mark R. Nelson, Lawrie Bellin, Kevan R Polkinghorne, Nigel Stocks, Michael E. Ernst
Background Studies on middle-aged or individuals with cognitive or cardiovascular impairments, have established that intensive blood pressure (BP) control reduces cognitive decline risk. However, uncertainty exists on differential effects between antihypertensive medications (AHM) classes on this risk, independent of BP-lowering efficacy, particularly in community-dwelling hypertensive older adults.
背景 对中年人或有认知障碍或心血管障碍的人进行的研究证实,加强血压(BP)控制可降低认知能力下降的风险。然而,降压药(AHM)类别对这一风险的不同影响还存在不确定性,这与降压疗效无关,尤其是在社区居住的高血压老年人中。
{"title":"Antihypertensive medications and dementia in older adults with hypertension","authors":"Suzanne G. Orchard, Zhen Zhou, Michelle Fravel, Joanne Ryan, Robyn L. Woods, Rory Wolfe, Raj C. Shah, Anne Murray, Ajay Sood, Christopher M. Reid, Mark R. Nelson, Lawrie Bellin, Kevan R Polkinghorne, Nigel Stocks, Michael E. Ernst","doi":"10.1101/2024.08.28.24312754","DOIUrl":"https://doi.org/10.1101/2024.08.28.24312754","url":null,"abstract":"<strong>Background</strong> Studies on middle-aged or individuals with cognitive or cardiovascular impairments, have established that intensive blood pressure (BP) control reduces cognitive decline risk. However, uncertainty exists on differential effects between antihypertensive medications (AHM) classes on this risk, independent of BP-lowering efficacy, particularly in community-dwelling hypertensive older adults.","PeriodicalId":501367,"journal":{"name":"medRxiv - Neurology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142197406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Validation of dementia care-related scales among informal caregivers of Latinos with dementia or mild cognitive impairment 在患有痴呆症或轻度认知障碍的拉美裔非正式照护者中验证痴呆症照护相关量表
Pub Date : 2024-08-29 DOI: 10.1101/2024.08.28.24312743
Jaime Perales-Puchalt, Irene Checa, Begoña Espejo, Marta de la C. Martín Carbonell, Mónica Fracachán-Cabrera, Christina Baker, Mariana Ramírez-Mantilla, Prisca Mendez-Asaro, Malissia Zimmer, Kristine Williams, K. Allen Greiner, Jana Zaudke, Hector Arreaza, Idaly Velez-Uribe, Henry Moore, Vanessa Sepulveda-Rivera, Kylie Meyer, Donna Benton, Krystal Kittle, Lindsey Gillen, Jeffrey M Burns
Objectives To test the psychometric properties of several dementia care-related scales among Latinos in the US.
目的 在美国拉美裔人群中测试几种痴呆症护理相关量表的心理测量特性。
{"title":"Validation of dementia care-related scales among informal caregivers of Latinos with dementia or mild cognitive impairment","authors":"Jaime Perales-Puchalt, Irene Checa, Begoña Espejo, Marta de la C. Martín Carbonell, Mónica Fracachán-Cabrera, Christina Baker, Mariana Ramírez-Mantilla, Prisca Mendez-Asaro, Malissia Zimmer, Kristine Williams, K. Allen Greiner, Jana Zaudke, Hector Arreaza, Idaly Velez-Uribe, Henry Moore, Vanessa Sepulveda-Rivera, Kylie Meyer, Donna Benton, Krystal Kittle, Lindsey Gillen, Jeffrey M Burns","doi":"10.1101/2024.08.28.24312743","DOIUrl":"https://doi.org/10.1101/2024.08.28.24312743","url":null,"abstract":"<strong>Objectives</strong> To test the psychometric properties of several dementia care-related scales among Latinos in the US.","PeriodicalId":501367,"journal":{"name":"medRxiv - Neurology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142197405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A systematic review of etiopathogenesis and treatment modalities for Moyamoya disease. 对 Moyamoya 病的发病机制和治疗方法进行系统回顾。
Pub Date : 2024-08-10 DOI: 10.1101/2024.08.10.24311757
Ganesh Chilikuri, Amy Job, Amba Vishwanathan, Vivek Joshi
Introduction: Moyamoya disease (MMD) is a rare and chronic cerebrovascular disease characterized by progressive stenosis or occlusion of the blood vessels within the terminal intracranial aspect of the internal carotid artery and the circle of Willis, leading to the compensatory development of a fragile collateral vessel network at the base of the brain. These vascular features are responsible for the recurrent ischemic and/or hemorrhagic strokes seen in affected patients. Numerous studies have attempted to clarify the clinical features of Moyamoya, including its etiopathology and interventions. In recent years, the development of neuroimaging and surgical techniques has enhanced the understanding of MMD in patients. The purpose of this review is to discuss the hypothesized etiopathogenesis, clinical manifestations, and the current possible treatment options available for Moyamoya disease. Methods: The PRISMA protocol was utilized to perform an extensive literature search on Google Scholar, Scopus, Web of Science, and PubMed for articles about etiopathogenesis and clinical presentation of Moyamoya disease and the treatment protocols followed in different parts of the world. A comprehensive analysis was also conducted for original articles to better understand the possible clinical presentation and diagnostic criteria used. Results: Based on the literature review, the RNF213 mutation, mitochondrial dysfunction, and misregulation of growth factors in endothelial cells are the most acceptable etiopathogenesis of MMD via their involvement in neurovascular inflammation. Conclusion: The diagnostic test of choice is magnetic resonance angiography while direct & indirect revascularization surgeries are both effective and established treatments for managing symptoms of Moyamoya disease.
导言:莫亚莫亚病(MMD)是一种罕见的慢性脑血管疾病,其特点是颈内动脉颅内末端和威利斯圈内的血管进行性狭窄或闭塞,导致脑底部脆弱的侧支血管网络代偿性发育。这些血管特征是导致患者反复发生缺血性和/或出血性中风的原因。许多研究都试图阐明 Moyamoya 的临床特征,包括病因学和干预措施。近年来,神经影像学和外科技术的发展加深了人们对 MMD 的了解。本综述旨在讨论假设的发病机制、临床表现以及目前可用于治疗 Moyamoya 病的方案。方法:利用 PRISMA 协议在 Google Scholar、Scopus、Web of Science 和 PubMed 上对有关 Moyamoya 病的发病机制、临床表现以及世界各地采用的治疗方案的文章进行了广泛的文献检索。此外,还对原创文章进行了综合分析,以更好地了解可能的临床表现和所用的诊断标准。结果:根据文献综述,RNF213 基因突变、线粒体功能障碍和内皮细胞生长因子调节失常是最易被接受的MMD发病机制,因为它们参与了神经血管炎症。结论磁共振血管造影术是首选的诊断检查方法,而直接血管重建手术和间接血管重建手术都是治疗莫亚莫亚病症状的有效且成熟的治疗方法。
{"title":"A systematic review of etiopathogenesis and treatment modalities for Moyamoya disease.","authors":"Ganesh Chilikuri, Amy Job, Amba Vishwanathan, Vivek Joshi","doi":"10.1101/2024.08.10.24311757","DOIUrl":"https://doi.org/10.1101/2024.08.10.24311757","url":null,"abstract":"Introduction: Moyamoya disease (MMD) is a rare and chronic cerebrovascular disease characterized by progressive stenosis or occlusion of the blood vessels within the terminal intracranial aspect of the internal carotid artery and the circle of Willis, leading to the compensatory development of a fragile collateral vessel network at the base of the brain. These vascular features are responsible for the recurrent ischemic and/or hemorrhagic strokes seen in affected patients. Numerous studies have attempted to clarify the clinical features of Moyamoya, including its etiopathology and interventions. In recent years, the development of neuroimaging and surgical techniques has enhanced the understanding of MMD in patients. The purpose of this review is to discuss the hypothesized etiopathogenesis, clinical manifestations, and the current possible treatment options available for Moyamoya disease. Methods: The PRISMA protocol was utilized to perform an extensive literature search on Google Scholar, Scopus, Web of Science, and PubMed for articles about etiopathogenesis and clinical presentation of Moyamoya disease and the treatment protocols followed in different parts of the world. A comprehensive analysis was also conducted for original articles to better understand the possible clinical presentation and diagnostic criteria used. Results: Based on the literature review, the RNF213 mutation, mitochondrial dysfunction, and misregulation of growth factors in endothelial cells are the most acceptable etiopathogenesis of MMD via their involvement in neurovascular inflammation. Conclusion: The diagnostic test of choice is magnetic resonance angiography while direct &amp; indirect revascularization surgeries are both effective and established treatments for managing symptoms of Moyamoya disease.","PeriodicalId":501367,"journal":{"name":"medRxiv - Neurology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141934451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Large scale serum proteomics identifies proteins associated with performance decline and clinical milestones in Duchenne muscular dystrophy 大规模血清蛋白质组学鉴定与杜兴氏肌肉萎缩症患者表现下降和临床里程碑相关的蛋白质
Pub Date : 2024-08-07 DOI: 10.1101/2024.08.05.24311516
Nadine Ikelaar, Alison Barnard, Simon Eng, Sharzad Hosseini Vajargah, Kevin Ha, Hermien Kan, Krista Vandenborne, Erik Niks, Glenn Walter, Pietro Spitali
Serum biomarkers are promising minimally invasive outcome measures in clinical studies in Duchenne muscular dystrophy (DMD). However, biomarkers strongly associated with clinical progression and predicting performance decline are lacking. In this study we aimed to identify serum biomarkers associated with clinical performance and able to predict clinical milestones in DMD. Towards this aim we present a retrospective multi-center cohort study including serum samples and clinical data collected in research participants with DMD as part of a natural history study at the University of Florida (UF) and real-world observations at Leiden University Medical Center (LUMC) between 2009-2022. The 7K SomaScan assay was used to analyse protein levels in in individual serum samples. Serum biomarkers predicted age at loss of ambulation (LoA), age at loss of overhead reach (OHR) and age at loss of hand to mouth function (HTM). Secondary outcomes were the association of biomarkers with age, corticosteroid (CS) usage, and clinical performance based on the North Star Ambulatory Assessment (NSAA), 10 meter run velocity (10mrv), 6 minute walk (6MWT) and Performance of the Upper Limb (PUL2.0). A total of 716 serum samples were collected in 79 participants at UF and 74 at LUMC (mean[SD] age; 10.9[3.2] vs 8.4[3.4]). 244 serum proteins showed an association with CS usage in both cohorts independent of CS type and regimen, including MMP3 and IGLL1. 318 probes (corresponding to 294 proteins) showed significant associations with NSAA, 10mrv, 6MWT and/or PUL2.0 across both cohorts. The expression of 38 probes corresponding to 36 proteins such as RGMA, EHMT2, ART3, ANTXR2 and DLK1 was associated with risk of both lower and upper limb clinical milestones in both the LUMC and UF cohort. In conclusion, multiple biomarkers were associated with CS use, motor function and upper lower and upper limb disease milestones in DMD. These biomarkers were validated across two independent cohorts, increasing their likelihood of translation for use within the broader DMD population.
在杜氏肌营养不良症(DMD)的临床研究中,血清生物标志物是很有前途的微创结果测量指标。然而,目前还缺乏与临床进展密切相关并能预测机能下降的生物标志物。在本研究中,我们旨在确定与临床表现相关并能预测 DMD 临床里程碑的血清生物标志物。为此,我们开展了一项回顾性多中心队列研究,其中包括作为佛罗里达大学(UF)自然史研究一部分的 DMD 研究参与者的血清样本和临床数据,以及 2009-2022 年间莱顿大学医学中心(LUMC)的实际观察结果。7K SomaScan 分析法用于分析个体血清样本中的蛋白质水平。血清生物标志物可预测丧失行动能力(LoA)的年龄、丧失高空伸展能力(OHR)的年龄和丧失手到口功能(HTM)的年龄。次要结果是生物标志物与年龄、皮质类固醇(CS)使用情况和临床表现(基于北极星非卧床评估(NSAA)、10 米跑速度(10mrv)、6 分钟步行(6MWT)和上肢表现(PUL2.0))的关系。研究人员共采集了 716 份血清样本,其中和睦家医院 79 人,路睦家医院 74 人(平均[标码]年龄;10.9[3.2] 对 8.4[3.4])。244个血清蛋白显示,在两个组群中,CS的使用与CS类型和治疗方案无关,其中包括MMP3和IGLL1。在两个队列中,318个探针(对应294个蛋白质)与NSAA、10mrv、6MWT和/或PUL2.0有显著相关性。在 LUMC 和 UF 队列中,38 个探针(对应 36 种蛋白质,如 RGMA、EHMT2、ART3、ANTXR2 和 DLK1)的表达与下肢和上肢临床里程碑的风险相关。总之,多种生物标志物与 DMD 患者使用 CS、运动功能和上下肢疾病里程碑相关。这些生物标志物在两个独立的队列中得到了验证,从而提高了它们在更广泛的 DMD 群体中应用的可能性。
{"title":"Large scale serum proteomics identifies proteins associated with performance decline and clinical milestones in Duchenne muscular dystrophy","authors":"Nadine Ikelaar, Alison Barnard, Simon Eng, Sharzad Hosseini Vajargah, Kevin Ha, Hermien Kan, Krista Vandenborne, Erik Niks, Glenn Walter, Pietro Spitali","doi":"10.1101/2024.08.05.24311516","DOIUrl":"https://doi.org/10.1101/2024.08.05.24311516","url":null,"abstract":"Serum biomarkers are promising minimally invasive outcome measures in clinical studies in Duchenne muscular dystrophy (DMD). However, biomarkers strongly associated with clinical progression and predicting performance decline are lacking. In this study we aimed to identify serum biomarkers associated with clinical performance and able to predict clinical milestones in DMD. Towards this aim we present a retrospective multi-center cohort study including serum samples and clinical data collected in research participants with DMD as part of a natural history study at the University of Florida (UF) and real-world observations at Leiden University Medical Center (LUMC) between 2009-2022. The 7K SomaScan assay was used to analyse protein levels in in individual serum samples. Serum biomarkers predicted age at loss of ambulation (LoA), age at loss of overhead reach (OHR) and age at loss of hand to mouth function (HTM). Secondary outcomes were the association of biomarkers with age, corticosteroid (CS) usage, and clinical performance based on the North Star Ambulatory Assessment (NSAA), 10 meter run velocity (10mrv), 6 minute walk (6MWT) and Performance of the Upper Limb (PUL2.0). A total of 716 serum samples were collected in 79 participants at UF and 74 at LUMC (mean[SD] age; 10.9[3.2] vs 8.4[3.4]). 244 serum proteins showed an association with CS usage in both cohorts independent of CS type and regimen, including MMP3 and IGLL1. 318 probes (corresponding to 294 proteins) showed significant associations with NSAA, 10mrv, 6MWT and/or PUL2.0 across both cohorts. The expression of 38 probes corresponding to 36 proteins such as RGMA, EHMT2, ART3, ANTXR2 and DLK1 was associated with risk of both lower and upper limb clinical milestones in both the LUMC and UF cohort. In conclusion, multiple biomarkers were associated with CS use, motor function and upper lower and upper limb disease milestones in DMD. These biomarkers were validated across two independent cohorts, increasing their likelihood of translation for use within the broader DMD population.","PeriodicalId":501367,"journal":{"name":"medRxiv - Neurology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141934572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Blood p-tau association with cognitive status and future memory decline in early Alzheimers disease 血液 p-tau 与早期阿尔茨海默氏症患者认知状况和未来记忆力衰退的关系
Pub Date : 2024-08-07 DOI: 10.1101/2024.08.06.24311532
Fernando Gonzalez-Ortiz, Bjorn-Eivind Kirsebom, Yara Yakoub, Julia K. Gundersen, Lene Palhauge, Knut K Waterloo, Per Selnes, Jonas Alexander Jarholm, Berglind Gisladottir, Arvid Rongve, Ragnhild Eide Skogseth, Geir Brathen, Dag Aarsland, Michael Turton, Peter Harrison, Henrik Zetterberg, Sylvia Villeneuve, Tormod Fladby, Kaj Blennow
Importance: Detecting early Alzheimers disease (AD) biological and clinical changes is crucial for early diagnostic and therapeutic interventions.Objective: To explore the associations between plasma p-tau biomarkers, cognitive- and biological profiles in predementia AD.Design, Setting, and Participants: In this study (n=619), we examined two independent cohorts consisting of preclinical and prodromal AD. Cohort-1 included 431 participants classified as either cognitively normal (CN) or mild cognitive impaired (MCI) with normal or abnormal cerebrospinal fluid (CSF) AB42/40 ratio (A) and p-tau181 (T) [CN A-/T-, n=169; A+/T-, CN=26; MCI=24; A+/T+, CN=40; MCI=105; CN=34; MCI=33]. A total of n=418 of the participants had longitudinal assessments of verbal memory up to 9.67 years from baseline. Cohort-2 included 190 participants in whom amyloid status was determined using AB positron emission tomography (PET) [AB- CN= 118; AB+ CN= 49; AB+ MCI= 21]. Exposure: CSF and plasma p-tau181, p-tau217 and p-tau231. Main Outcomes and Results: In cohort-1, plasma p-tau217 showed a moderate correlation with its corresponding CSF biomarker (rho=0.65, p<.001) and high accuracy identifying AB+ participants (AUC: 0.85). Diagnostic accuracy of plasma p-tau217 was significantly greater for MCI AB+ (AUC: 0.89) versus CN AB+ (AUC: 0.79, p<.05) and for A+/T+ (AUC: 0.88) versus A+/T- (AUC: 0.78, p<.05). P-tau181 and p-tau231 showed significantly weaker CSF-plasma correlations (rho= 0.47, and rho=0.32, p<.001, respectively) and levels were not as tightly associated with cognitive status in the AB+ group. Moreover, p-tau217 was the only plasma marker that associated with future memory decline (B=0.05, p<0.05). Additionally, plasma p-tau217 had the weakest correlation with glomerular filtration rate (rho=-14, p<.05), followed by p-tau181 (rho=-17, p<.01) and p-tau231 (rho=-22, p<.001). In cohort 1 and 2, plasma p-tau217 showed significantly higher concentrations in MCI AB+ as compared to CN AB+. Furthermore, plasma p-tau217 demonstrates similar biomarker elevations when compared to CN AB- controls in both cohorts.Conclusions: Our findings show that, unlike p-tau181 and p-tau231, plasma p-tau217 aligns consistently with cognitive status in AB+ individuals, potentially reducing disagreements between clinical and biochemical findings. Plasma p-tau217 associations with baseline and future cognitive decline make it a valuable complement to clinical evaluation in preclinical and prodromal AD.
重要性:检测阿尔茨海默病(AD)早期的生物学和临床变化对于早期诊断和治疗干预至关重要:探讨痴呆前期AD血浆p-tau生物标志物、认知和生物学特征之间的关联:在这项研究中(n=619),我们对两个独立的队列进行了研究,这两个队列分别由临床前AD和前驱AD组成。队列-1包括431名认知正常(CN)或轻度认知障碍(MCI)、脑脊液(CSF)AB42/40比值(A)和p-tau181(T)正常或异常的参与者[CN A-/T-,n=169;A+/T-,CN=26;MCI=24;A+/T+,CN=40;MCI=105;CN=34;MCI=33]。共有418名参与者进行了纵向言语记忆评估,评估时间从基线开始长达9.67年。队列-2包括190名参与者,他们的淀粉样蛋白状态是通过AB正电子发射断层扫描(PET)确定的[AB- CN= 118;AB+ CN= 49;AB+ MCI= 21]。暴露:CSF 和血浆 p-tau181、p-tau217 和 p-tau231。主要结果和结果:在队列-1中,血浆p-tau217与其相应的CSF生物标记物呈中度相关性(rho=0.65,p<.001),识别AB+参与者的准确性较高(AUC:0.85)。血浆p-tau217对MCI AB+(AUC:0.89)与CN AB+(AUC:0.79,p<.05)和A+/T+(AUC:0.88)与A+/T-(AUC:0.78,p<.05)的诊断准确性明显更高。P-tau181和p-tau231的CSF-血浆相关性明显较弱(分别为rho=0.47和rho=0.32,p<.001),在AB+组中,其水平与认知状态的相关性也不强。此外,p-tau217 是唯一与未来记忆力衰退相关的血浆标记物(B=0.05,p<0.05)。此外,血浆p-tau217与肾小球滤过率的相关性最弱(rho=-14,p<.05),其次是p-tau181(rho=-17,p<.01)和p-tau231(rho=-22,p<.001)。在队列1和队列2中,与CN AB+相比,MCI AB+的血浆p-tau217浓度明显更高。此外,在两个队列中,血浆p-tau217与CN AB-对照组相比,显示出相似的生物标志物升高:我们的研究结果表明,与p-tau181和p-tau231不同,血浆p-tau217与AB+患者的认知状况一致,这可能会减少临床和生化研究结果之间的差异。血浆p-tau217与基线和未来认知能力下降的关系使其成为临床评估AD前期和前驱期的重要补充。
{"title":"Blood p-tau association with cognitive status and future memory decline in early Alzheimers disease","authors":"Fernando Gonzalez-Ortiz, Bjorn-Eivind Kirsebom, Yara Yakoub, Julia K. Gundersen, Lene Palhauge, Knut K Waterloo, Per Selnes, Jonas Alexander Jarholm, Berglind Gisladottir, Arvid Rongve, Ragnhild Eide Skogseth, Geir Brathen, Dag Aarsland, Michael Turton, Peter Harrison, Henrik Zetterberg, Sylvia Villeneuve, Tormod Fladby, Kaj Blennow","doi":"10.1101/2024.08.06.24311532","DOIUrl":"https://doi.org/10.1101/2024.08.06.24311532","url":null,"abstract":"Importance: Detecting early Alzheimers disease (AD) biological and clinical changes is crucial for early diagnostic and therapeutic interventions.\u0000Objective: To explore the associations between plasma p-tau biomarkers, cognitive- and biological profiles in predementia AD.\u0000Design, Setting, and Participants: In this study (n=619), we examined two independent cohorts consisting of preclinical and prodromal AD. Cohort-1 included 431 participants classified as either cognitively normal (CN) or mild cognitive impaired (MCI) with normal or abnormal cerebrospinal fluid (CSF) AB42/40 ratio (A) and p-tau181 (T) [CN A-/T-, n=169; A+/T-, CN=26; MCI=24; A+/T+, CN=40; MCI=105; CN=34; MCI=33]. A total of n=418 of the participants had longitudinal assessments of verbal memory up to 9.67 years from baseline. Cohort-2 included 190 participants in whom amyloid status was determined using AB positron emission tomography (PET) [AB- CN= 118; AB+ CN= 49; AB+ MCI= 21]. Exposure: CSF and plasma p-tau181, p-tau217 and p-tau231. Main Outcomes and Results: In cohort-1, plasma p-tau217 showed a moderate correlation with its corresponding CSF biomarker (rho=0.65, p&lt;.001) and high accuracy identifying AB+ participants (AUC: 0.85). Diagnostic accuracy of plasma p-tau217 was significantly greater for MCI AB+ (AUC: 0.89) versus CN AB+ (AUC: 0.79, p&lt;.05) and for A+/T+ (AUC: 0.88) versus A+/T- (AUC: 0.78, p&lt;.05). P-tau181 and p-tau231 showed significantly weaker CSF-plasma correlations (rho= 0.47, and rho=0.32, p&lt;.001, respectively) and levels were not as tightly associated with cognitive status in the AB+ group. Moreover, p-tau217 was the only plasma marker that associated with future memory decline (B=0.05, p&lt;0.05). Additionally, plasma p-tau217 had the weakest correlation with glomerular filtration rate (rho=-14, p&lt;.05), followed by p-tau181 (rho=-17, p&lt;.01) and p-tau231 (rho=-22, p&lt;.001). In cohort 1 and 2, plasma p-tau217 showed significantly higher concentrations in MCI AB+ as compared to CN AB+. Furthermore, plasma p-tau217 demonstrates similar biomarker elevations when compared to CN AB- controls in both cohorts.\u0000Conclusions: Our findings show that, unlike p-tau181 and p-tau231, plasma p-tau217 aligns consistently with cognitive status in AB+ individuals, potentially reducing disagreements between clinical and biochemical findings. Plasma p-tau217 associations with baseline and future cognitive decline make it a valuable complement to clinical evaluation in preclinical and prodromal AD.","PeriodicalId":501367,"journal":{"name":"medRxiv - Neurology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141968904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Implementation of a Goals-of-Care Communication Priming Intervention Tailored to Outpatient Stroke Survivors 针对门诊脑卒中幸存者实施护理目标沟通引导干预措施
Pub Date : 2024-08-07 DOI: 10.1101/2024.08.04.24311479
Nauzley C. Abedini, Erin K. Kross, Ruth A Engelberg, Gigi Garzio, Claire J. Creutzfeldt
Background: Goals-of-care conversations (GOCC) are important but infrequent after stroke. Serious illness communication priming guides like the Jumpstart Guide can increase GOCC, but have not been evaluated in the stroke population. Methods: We conducted a randomized pilot study to evaluate feasibility and acceptability of the Jumpstart Guide adapted for outpatient stroke survivors, their surrogates, and clinicians. We recruited stroke survivors ?60 years presenting for care at a single academically-affiliated stroke clinic. We enrolled surrogates if the patient had communication or cognitive impairment. Patients/surrogates were randomized to intervention (patient/surrogate and clinician received pre-visit Jumpstart Guide) or control arms. We assessed feasibility of participant enrollment, survey completion and extraction of GOCC documentation from the electronic medical record. We assessed acceptability using patient/surrogate and clinician surveys. Results: We enrolled 15/24 (63%) eligible patients or surrogates. We randomized 5 patients alone and 3 patients with surrogates to the intervention arm, and 5 patients alone and 2 patients with surrogates to the control arm. Six clinicians were enrolled for the 8 intervention encounters. Patient characteristics in both groups were similar with mean age 74.7 years, 10/15 male, 12/15 white, and 10/15 with acute ischemic stroke. Most patients/surrogates (7/8 intervention vs 7/7 control) and all intervention clinicians completed post-visit surveys. Most intervention participants reported successful pre-visit receipt of the Jumpstart Guide (6/7 patient/surrogates; 6/8 clinicians). Of these, all intervention patients/surrogates and 5/6 clinicians stated they would ?definitely? or ?probably? recommend it to others. Two intervention vs no control patients had newly documented GOCC post-visit. Intervention patients/surrogates more frequently reported discussing GOCC during their clinic visit (6/7 intervention vs 4/7 control). Conclusions: Implementation of a stroke-specific GOCC priming guide (Jumpstart Guide) in an outpatient stroke clinic is feasible and acceptable. A large randomized controlled trial is needed to evaluate its efficacy in improving outpatient stroke clinic GOCC.
背景:护理目标对话(GOCC)非常重要,但在中风后并不常见。重症沟通引导指南(如《起步指南》)可增加护理目标对话,但尚未在中风人群中进行评估。方法:我们进行了一项随机试验研究,以评估针对门诊脑卒中幸存者、其代理人和临床医生改编的《起跳指南》的可行性和可接受性。我们招募了在一家学术附属中风诊所就诊的 60 岁以下中风幸存者。如果患者有交流障碍或认知障碍,我们还招募了代治者。患者/代治者被随机分配到干预组(患者/代治者和临床医生接受就诊前《起步指南》)或对照组。我们评估了参与者注册、调查完成以及从电子病历中提取 GOCC 文件的可行性。我们通过患者/代治者和临床医生调查来评估可接受性。结果:我们招募了 15/24 名(63%)符合条件的患者或代理人。我们将 5 名单独患者和 3 名有代理的患者随机分配到干预组,将 5 名单独患者和 2 名有代理的患者随机分配到对照组。6 名临床医生参与了 8 次干预治疗。两组患者的特征相似,平均年龄 74.7 岁,10/15 为男性,12/15 为白人,10/15 为急性缺血性中风患者。大多数患者/代治者(干预组 7/8 对对照组 7/7)和所有干预组临床医生都完成了就诊后调查。大多数干预参与者报告在就诊前成功收到了《起步指南》(6/7 名患者/代治者;6/8 名临床医生)。其中,所有干预患者/代治者和 5/6 名临床医生均表示 "肯定 "或 "可能 "向他人推荐该指南。两名干预患者(无对照组患者)在就诊后新记录了 GOCC。干预患者/代治者更频繁地报告在就诊期间讨论过GOCC(干预6/7例,对照4/7例)。结论在卒中门诊实施卒中专用 GOCC 引导指南(Jumpstart Guide)是可行且可接受的。需要进行大规模随机对照试验,以评估其在改善卒中门诊 GOCC 方面的效果。
{"title":"Implementation of a Goals-of-Care Communication Priming Intervention Tailored to Outpatient Stroke Survivors","authors":"Nauzley C. Abedini, Erin K. Kross, Ruth A Engelberg, Gigi Garzio, Claire J. Creutzfeldt","doi":"10.1101/2024.08.04.24311479","DOIUrl":"https://doi.org/10.1101/2024.08.04.24311479","url":null,"abstract":"Background: Goals-of-care conversations (GOCC) are important but infrequent after stroke. Serious illness communication priming guides like the Jumpstart Guide can increase GOCC, but have not been evaluated in the stroke population. Methods: We conducted a randomized pilot study to evaluate feasibility and acceptability of the Jumpstart Guide adapted for outpatient stroke survivors, their surrogates, and clinicians. We recruited stroke survivors ?60 years presenting for care at a single academically-affiliated stroke clinic. We enrolled surrogates if the patient had communication or cognitive impairment. Patients/surrogates were randomized to intervention (patient/surrogate and clinician received pre-visit Jumpstart Guide) or control arms. We assessed feasibility of participant enrollment, survey completion and extraction of GOCC documentation from the electronic medical record. We assessed acceptability using patient/surrogate and clinician surveys. Results: We enrolled 15/24 (63%) eligible patients or surrogates. We randomized 5 patients alone and 3 patients with surrogates to the intervention arm, and 5 patients alone and 2 patients with surrogates to the control arm. Six clinicians were enrolled for the 8 intervention encounters. Patient characteristics in both groups were similar with mean age 74.7 years, 10/15 male, 12/15 white, and 10/15 with acute ischemic stroke. Most patients/surrogates (7/8 intervention vs 7/7 control) and all intervention clinicians completed post-visit surveys. Most intervention participants reported successful pre-visit receipt of the Jumpstart Guide (6/7 patient/surrogates; 6/8 clinicians). Of these, all intervention patients/surrogates and 5/6 clinicians stated they would ?definitely? or ?probably? recommend it to others. Two intervention vs no control patients had newly documented GOCC post-visit. Intervention patients/surrogates more frequently reported discussing GOCC during their clinic visit (6/7 intervention vs 4/7 control). Conclusions: Implementation of a stroke-specific GOCC priming guide (Jumpstart Guide) in an outpatient stroke clinic is feasible and acceptable. A large randomized controlled trial is needed to evaluate its efficacy in improving outpatient stroke clinic GOCC.","PeriodicalId":501367,"journal":{"name":"medRxiv - Neurology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141934527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Preliminary reference values for Alzheimers disease plasma biomarkers in Congolese individuals with and without Alzheimers disease 刚果阿尔茨海默氏症患者和非阿尔茨海默氏症患者血浆生物标志物的初步参考值
Pub Date : 2024-08-07 DOI: 10.1101/2024.08.06.24311577
Jean Ikanga, Kharine Jean, Priscilla Medina, Saranya Sundaram Patel, Megan Claire Schwinne, Emmanuel Epenge, Guy Gikelekele, Nathan Tshengele, Immaculee Kavugho, Samuel Mampunza, Lelo Mananga, Charlotte Teunissen, Anthony Stringer, Julio Rojas, Brandon Chan, Argentina Lario Lago, Joel Kramer, Adam Boxer, Andreas Jeromin, Alden Gross, Alvaro Alonso
Background: Western countries have provided reference values (RV) for Alzheimers disease (AD) plasma biomarkers, but there are not available in Sub-Saharan African populations. Objective: We provide preliminary RV for AD and other plasma biomarkers including amyloid-β (AB;42/40), phosphorylated tau-181 and 217 (p-tau181, p-tau217), neurofilament light (Nfl), glial fibrillary acidic protein (GFAP), interleukin 1b and 10 (IL-1b and IL-10) and tumor necrosis factor a; (TNFa) in Congolese adults with and without dementia. Methods: 85 adults (40 healthy and 45 dementia) over 50 years old were included. Blood samples were provided for plasma AD biomarkers AB;42/40 and p-tau181, p-tau217; Nfl and GFAP; IL-1b and IL-10 and TNFa; analyzed using SIMOA. Linear and logistic regressions were conducted to evaluate differences in biomarkers by age and gender and neurological status, and for the prediction of dementia status by each individual biomarker. RV were those that optimized sensitivity and specificity based on Youdens index. Results: In this sample of 85 adults, 40 (47%) had dementia, 38 (45.0%) were male, overall mean age was 73.2 (SD 7.6) years with 8.3 (5.4) years of education. There were no significant differences in age, gender, and education based on neurological status. Biomarker concentrations did not significantly differ by age except for p-tau181 and GFAP and did not differ by sex. Preliminary cutoffs of various plasma in pg/ml were 0.061 for AB;42/40, 4.50 for p-tau 181, 0.008 for p-tau 217, 36.5 for Nfl, 176 for GFAP, 1.16 for TNFa, 0.011 for IL-1b, and 0.38 for IL-10. All AUCs ranged between 0.64-0.74. P-tau 217 [0.74 (0.61, 0.86)] followed by GFAP [0.72 (0.61, 0.83), and Nfl [0.71 (0.60, 0.82)] had the highest AUC compared to other plasma biomarkers. Conclusions: This study provides RV which could be of preliminary utility to facilitate the screening, clinical diagnostic adjudication, classification, and prognosis of AD in Congolese adults.
背景:西方国家提供了阿尔茨海默病(AD)血浆生物标志物的参考值(RV),但撒哈拉以南非洲地区的人群却没有。我们的目标是我们提供了患有和未患有痴呆症的刚果成年人的AD和其他血浆生物标记物的初步参考值,包括淀粉样蛋白-β(AB;42/40)、磷酸化tau-181和217(p-tau181和p-tau217)、神经丝光(Nfl)、胶质纤维酸性蛋白(GFAP)、白细胞介素1b和10(IL-1b和IL-10)以及肿瘤坏死因子a(TNFa)。方法:纳入 85 名 50 岁以上的成年人(40 名健康人和 45 名痴呆症患者)。提供血样,使用 SIMOA 分析血浆 AD 生物标记物 AB;42/40 和 p-tau181, p-tau217;Nfl 和 GFAP;IL-1b 和 IL-10 以及 TNFa。进行了线性回归和逻辑回归,以评估不同年龄、性别和神经系统状态下生物标志物的差异,并通过每个生物标志物预测痴呆状态。根据尤登斯指数优化灵敏度和特异性的生物标志物为 RV。结果在85名成人样本中,40人(47%)患有痴呆症,38人(45.0%)为男性,总平均年龄为73.2岁(标准差为7.6岁),受教育年限为8.3年(5.4年)。神经系统状况在年龄、性别和教育程度上没有明显差异。除 p-tau181 和 GFAP 外,生物标志物浓度在不同年龄段没有明显差异,在不同性别也没有差异。以 pg/ml 为单位的各种血浆初步临界值为:AB;42/40 为 0.061、p-tau 181 为 4.50、p-tau 217 为 0.008、Nfl 为 36.5、GFAP 为 176、TNFa 为 1.16、IL-1b 为 0.011、IL-10 为 0.38。所有 AUC 在 0.64-0.74 之间。与其他血浆生物标记物相比,P-tau 217 [0.74 (0.61, 0.86)]的AUC最高,其次是GFAP [0.72 (0.61, 0.83)]和Nfl [0.71 (0.60, 0.82)]。结论:本研究提供的 RV 可初步用于刚果成人注意力缺失症的筛查、临床诊断、分类和预后判断。
{"title":"Preliminary reference values for Alzheimers disease plasma biomarkers in Congolese individuals with and without Alzheimers disease","authors":"Jean Ikanga, Kharine Jean, Priscilla Medina, Saranya Sundaram Patel, Megan Claire Schwinne, Emmanuel Epenge, Guy Gikelekele, Nathan Tshengele, Immaculee Kavugho, Samuel Mampunza, Lelo Mananga, Charlotte Teunissen, Anthony Stringer, Julio Rojas, Brandon Chan, Argentina Lario Lago, Joel Kramer, Adam Boxer, Andreas Jeromin, Alden Gross, Alvaro Alonso","doi":"10.1101/2024.08.06.24311577","DOIUrl":"https://doi.org/10.1101/2024.08.06.24311577","url":null,"abstract":"Background: Western countries have provided reference values (RV) for Alzheimers disease (AD) plasma biomarkers, but there are not available in Sub-Saharan African populations. Objective: We provide preliminary RV for AD and other plasma biomarkers including amyloid-β (AB;42/40), phosphorylated tau-181 and 217 (p-tau181, p-tau217), neurofilament light (Nfl), glial fibrillary acidic protein (GFAP), interleukin 1b and 10 (IL-1b and IL-10) and tumor necrosis factor a; (TNFa) in Congolese adults with and without dementia. Methods: 85 adults (40 healthy and 45 dementia) over 50 years old were included. Blood samples were provided for plasma AD biomarkers AB;42/40 and p-tau181, p-tau217; Nfl and GFAP; IL-1b and IL-10 and TNFa; analyzed using SIMOA. Linear and logistic regressions were conducted to evaluate differences in biomarkers by age and gender and neurological status, and for the prediction of dementia status by each individual biomarker. RV were those that optimized sensitivity and specificity based on Youdens index. Results: In this sample of 85 adults, 40 (47%) had dementia, 38 (45.0%) were male, overall mean age was 73.2 (SD 7.6) years with 8.3 (5.4) years of education. There were no significant differences in age, gender, and education based on neurological status. Biomarker concentrations did not significantly differ by age except for p-tau181 and GFAP and did not differ by sex. Preliminary cutoffs of various plasma in pg/ml were 0.061 for AB;42/40, 4.50 for p-tau 181, 0.008 for p-tau 217, 36.5 for Nfl, 176 for GFAP, 1.16 for TNFa, 0.011 for IL-1b, and 0.38 for IL-10. All AUCs ranged between 0.64-0.74. P-tau 217 [0.74 (0.61, 0.86)] followed by GFAP [0.72 (0.61, 0.83), and Nfl [0.71 (0.60, 0.82)] had the highest AUC compared to other plasma biomarkers. Conclusions: This study provides RV which could be of preliminary utility to facilitate the screening, clinical diagnostic adjudication, classification, and prognosis of AD in Congolese adults.","PeriodicalId":501367,"journal":{"name":"medRxiv - Neurology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141934571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Adjunctive Intra-arterial Urokinase after Successful Endovascular Thrombectomy in Patients with Large Vessel Occlusion Stroke (POST-UK): Study protocol of a multicenter, prospective, randomized, open-label, blinded-endpoint trial 大血管闭塞性卒中患者血管内血栓切除术成功后的辅助性动脉内尿激酶(POST-UK):一项多中心、前瞻性、随机、开放标签、盲端点试验的研究方案
Pub Date : 2024-08-06 DOI: 10.1101/2024.08.05.24311528
Chang Liu, Fengli Li, Jiaxing Song, Xu Xu, Jiacheng Huang, Changwei Guo, Weilin Kong, Jie Yang, Xiaolei Shi, Jinfu Ma, Shihai Yang, Zhixi Wang, Shitao Fan, Xiang Liu, Wenzhe Sun, Nizhen Yu, Chengsong Yue, Zhouzhou Peng, Linyu Li, Cheng Huang, Dahong Yang, Duolao Wang, Jeffrey L Saver, Thanh N. Nguyen, Raul G. Nogueira, YangMei Chen, Wenjie Zi
Background: Intra-arterial infusion of an adjunctive thrombolytic agent after macrovascular recanalization by endovascular thrombectomy (EVT) was regarded as a promising strategy to promote outcomes of stroke patients. Given the characteristics of urokinase (UK) as an affordable, available, and widely applied medication, especially in eastern countries, this trial aims to assess the safety and efficacy of intra-arterial UK as adjunct to EVT in improving outcomes among patients with anterior large vessel occlusion stroke after excellent to complete reperfusion. Methods: The Adjunctive Intra-arterial Urokinase after Successful Endovascular Thrombectomy in Patients with Large Vessel Occlusion Stroke (POST-UK) trial is a multicenter, prospective, randomized, open-label, blinded-endpoint trial conducted in China. The planned sample size is 498. Those eligible patients with anterior circulation large vessel occlusion stroke and achieving excellent to complete reperfusion by EVT are planned to be consecutively randomized in a 1:1 ratio to the experimental group (a single dose of intra-arterial urokinase) or to standard of care.Results: The primary outcome is a freedom from disability (modified Rankin Scale, mRS, of 0-1) at 90±7 days. The safety outcomes are mortality within 90±7 days and symptomatic intracranial hemorrhage within 48 hours. Conclusions: The POST-UK trial will provide valuable insight of efficacy and safety of intra-arterial UK in patients with large vessel occlusion stroke after achieving excellent to complete reperfusion by EVT.
背景:通过血管内血栓切除术(EVT)进行大血管再通之后,动脉内输注辅助溶栓药物被认为是促进卒中患者预后的一种有前途的策略。鉴于尿激酶(UK)价格低廉、易于获得且应用广泛的特点,尤其是在东方国家,本试验旨在评估动脉内输注尿激酶(UK)作为 EVT 的辅助药物在改善前大血管闭塞性卒中患者极佳至完全再灌注后的预后方面的安全性和有效性。研究方法大血管闭塞性卒中患者成功血管内血栓切除术后辅助动脉内注射尿激酶(POST-UK)试验是一项在中国进行的多中心、前瞻性、随机、开放标签、盲法终点试验。计划样本量为 498 例。计划将符合条件的前循环大血管闭塞性卒中患者以1:1的比例连续随机分配到实验组(单剂量动脉内尿激酶)或标准治疗组:主要结果是在90±7天内无残疾(改良Rankin量表,mRS为0-1)。安全性结果是 90±7 天内的死亡率和 48 小时内的无症状颅内出血。结论:POST-UK试验将为大血管闭塞性卒中患者在通过EVT获得良好或完全再灌注后进行动脉内UK治疗的疗效和安全性提供有价值的见解。
{"title":"Adjunctive Intra-arterial Urokinase after Successful Endovascular Thrombectomy in Patients with Large Vessel Occlusion Stroke (POST-UK): Study protocol of a multicenter, prospective, randomized, open-label, blinded-endpoint trial","authors":"Chang Liu, Fengli Li, Jiaxing Song, Xu Xu, Jiacheng Huang, Changwei Guo, Weilin Kong, Jie Yang, Xiaolei Shi, Jinfu Ma, Shihai Yang, Zhixi Wang, Shitao Fan, Xiang Liu, Wenzhe Sun, Nizhen Yu, Chengsong Yue, Zhouzhou Peng, Linyu Li, Cheng Huang, Dahong Yang, Duolao Wang, Jeffrey L Saver, Thanh N. Nguyen, Raul G. Nogueira, YangMei Chen, Wenjie Zi","doi":"10.1101/2024.08.05.24311528","DOIUrl":"https://doi.org/10.1101/2024.08.05.24311528","url":null,"abstract":"Background: Intra-arterial infusion of an adjunctive thrombolytic agent after macrovascular recanalization by endovascular thrombectomy (EVT) was regarded as a promising strategy to promote outcomes of stroke patients. Given the characteristics of urokinase (UK) as an affordable, available, and widely applied medication, especially in eastern countries, this trial aims to assess the safety and efficacy of intra-arterial UK as adjunct to EVT in improving outcomes among patients with anterior large vessel occlusion stroke after excellent to complete reperfusion. Methods: The Adjunctive Intra-arterial Urokinase after Successful Endovascular Thrombectomy in Patients with Large Vessel Occlusion Stroke (POST-UK) trial is a multicenter, prospective, randomized, open-label, blinded-endpoint trial conducted in China. The planned sample size is 498. Those eligible patients with anterior circulation large vessel occlusion stroke and achieving excellent to complete reperfusion by EVT are planned to be consecutively randomized in a 1:1 ratio to the experimental group (a single dose of intra-arterial urokinase) or to standard of care.\u0000Results: The primary outcome is a freedom from disability (modified Rankin Scale, mRS, of 0-1) at 90±7 days. The safety outcomes are mortality within 90±7 days and symptomatic intracranial hemorrhage within 48 hours. Conclusions: The POST-UK trial will provide valuable insight of efficacy and safety of intra-arterial UK in patients with large vessel occlusion stroke after achieving excellent to complete reperfusion by EVT.","PeriodicalId":501367,"journal":{"name":"medRxiv - Neurology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141934525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
AROMHA Brain Health Test: A Remote Olfactory Assessment as a Screen for Cognitive Impairment AROMHA 脑健康测试:作为认知障碍筛查手段的远程嗅觉评估
Pub Date : 2024-08-06 DOI: 10.1101/2024.08.03.24311283
Benoit Jobin, Colin Magdamo, Daniela Delphus, Andreas Runde, Sean Reineke, Alysa Alejandro Soto, Beyzanur Ergun, Alefiya Dhilla Albers, Mark W Albers
Cost-effective, noninvasive screening methods for preclinical Alzheimer's disease (AD) and other neurocognitive disorders remain an unmet need. The olfactory neural circuits develop AD pathological changes prior to symptom onset. To probe these vulnerable circuits, we developed the digital remote AROMHA Brain Health Test (ABHT), an at-home odor identification, discrimination, memory, and intensity assessment.The ABHT was self-administered among cognitively normal (CN) English and Spanish speakers (n=127), participants with subjective cognitive complaints (SCC; n=34), and mild cognitive impairment (MCI; n=19). Self-administered tests took place remotely at home under unobserved (among interested CN participants) and observed modalities (CN, SCC, and MCI), as well as in-person with a research assistant present (CN, SCC, and MCI).Olfactory performance was similar across observed and unobserved remote self-administration and between English and Spanish speakers. Odor memory, identification, and discrimination scores decreased with age, and olfactory identification and discrimination were lower in the MCI group compared to CN and SCC groups, independent of age, sex, and education.The ABHT revealed age-related olfactory decline, and discriminated CN older adults from those with cognitive impairment. Replication of our results in other populations would support the use of the ABHT to identify and monitor individuals at risk for developing dementia. Keywords: Remote assessment, screening, Alzheimer's disease, Mild cognitive impairment, olfaction.
临床前阿尔茨海默病(AD)和其他神经认知障碍的成本效益型无创筛查方法仍是一项尚未满足的需求。嗅觉神经回路在症状出现之前就已经发生了阿尔茨海默病的病理变化。为了探究这些脆弱的回路,我们开发了数字远程阿罗姆哈脑健康测试(ABHT),这是一种在家进行的气味识别、辨别、记忆和强度评估。ABHT由认知能力正常(CN)的英语和西班牙语使用者(人数=127)、有主观认知抱怨(SCC;人数=34)的参与者和轻度认知障碍(MCI;人数=19)进行自我管理。自我管理测试在家中进行,测试方式包括无观察(感兴趣的 CN 参与者)和观察(CN、SCC 和 MCI),以及有研究助理在场的面对面测试(CN、SCC 和 MCI)。ABHT揭示了与年龄相关的嗅觉衰退,并能区分CN老年人和认知障碍老年人。在其他人群中复制我们的结果将支持使用 ABHT 来识别和监测有痴呆风险的人群。关键词远程评估 筛查 阿尔茨海默病 轻度认知障碍 嗅觉
{"title":"AROMHA Brain Health Test: A Remote Olfactory Assessment as a Screen for Cognitive Impairment","authors":"Benoit Jobin, Colin Magdamo, Daniela Delphus, Andreas Runde, Sean Reineke, Alysa Alejandro Soto, Beyzanur Ergun, Alefiya Dhilla Albers, Mark W Albers","doi":"10.1101/2024.08.03.24311283","DOIUrl":"https://doi.org/10.1101/2024.08.03.24311283","url":null,"abstract":"Cost-effective, noninvasive screening methods for preclinical Alzheimer's disease (AD) and other neurocognitive disorders remain an unmet need. The olfactory neural circuits develop AD pathological changes prior to symptom onset. To probe these vulnerable circuits, we developed the digital remote AROMHA Brain Health Test (ABHT), an at-home odor identification, discrimination, memory, and intensity assessment.\u0000The ABHT was self-administered among cognitively normal (CN) English and Spanish speakers (n=127), participants with subjective cognitive complaints (SCC; n=34), and mild cognitive impairment (MCI; n=19). Self-administered tests took place remotely at home under unobserved (among interested CN participants) and observed modalities (CN, SCC, and MCI), as well as in-person with a research assistant present (CN, SCC, and MCI).\u0000Olfactory performance was similar across observed and unobserved remote self-administration and between English and Spanish speakers. Odor memory, identification, and discrimination scores decreased with age, and olfactory identification and discrimination were lower in the MCI group compared to CN and SCC groups, independent of age, sex, and education.\u0000The ABHT revealed age-related olfactory decline, and discriminated CN older adults from those with cognitive impairment. Replication of our results in other populations would support the use of the ABHT to identify and monitor individuals at risk for developing dementia. Keywords: Remote assessment, screening, Alzheimer's disease, Mild cognitive impairment, olfaction.","PeriodicalId":501367,"journal":{"name":"medRxiv - Neurology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141934506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
期刊
medRxiv - Neurology
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1