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
{"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":"202 1","pages":""},"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}
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
{"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":"11 1","pages":""},"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}
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
{"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":"98 1","pages":""},"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}
{"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 & indirect revascularization surgeries are both effective and established treatments for managing symptoms of Moyamoya disease.","PeriodicalId":501367,"journal":{"name":"medRxiv - Neurology","volume":"40 1","pages":""},"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}
Nadine Ikelaar, Alison Barnard, Simon Eng, Sharzad Hosseini Vajargah, Kevin Ha, Hermien Kan, Krista Vandenborne, Erik Niks, Glenn Walter, Pietro Spitali
{"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":"21 1","pages":""},"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}
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
{"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<.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.\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":"141 1","pages":""},"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}
Nauzley C. Abedini, Erin K. Kross, Ruth A Engelberg, Gigi Garzio, Claire J. Creutzfeldt
{"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":"47 1","pages":""},"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}
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
{"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":"86 1","pages":""},"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}
{"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":"119 1","pages":""},"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}
Benoit Jobin, Colin Magdamo, Daniela Delphus, Andreas Runde, Sean Reineke, Alysa Alejandro Soto, Beyzanur Ergun, Alefiya Dhilla Albers, Mark W Albers
{"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":"41 1","pages":""},"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}