Lancet Neurology最新文献

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Targeting C9orf72 in people with ALS. 针对 ALS 患者的 C9orf72。
IF 46.5 1区 医学
Lancet Neurology Pub Date : 2024-09-01 Epub Date: 2024-07-23 DOI: 10.1016/S1474-4422(24)00284-9
Susanne Petri
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引用次数: 0
Durable benefit of thrombectomy 6-24 h after stroke onset. 中风发作 6-24 小时后血栓切除术的持久疗效。
IF 46.5 1区 医学
Lancet Neurology Pub Date : 2024-09-01 Epub Date: 2024-06-20 DOI: 10.1016/S1474-4422(24)00261-8
Bruce C V Campbell
{"title":"Durable benefit of thrombectomy 6-24 h after stroke onset.","authors":"Bruce C V Campbell","doi":"10.1016/S1474-4422(24)00261-8","DOIUrl":"10.1016/S1474-4422(24)00261-8","url":null,"abstract":"","PeriodicalId":17989,"journal":{"name":"Lancet Neurology","volume":null,"pages":null},"PeriodicalIF":46.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141442985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Amyloid β, γ-secretase, and familial Alzheimer's disease. 淀粉样蛋白β、γ-分泌酶和家族性阿尔茨海默病。
IF 46.5 1区 医学
Lancet Neurology Pub Date : 2024-09-01 Epub Date: 2024-07-26 DOI: 10.1016/S1474-4422(24)00292-8
Marie-Claude Potier, Harald Steiner, Lucía Chávez-Gutiérrez
{"title":"Amyloid β, γ-secretase, and familial Alzheimer's disease.","authors":"Marie-Claude Potier, Harald Steiner, Lucía Chávez-Gutiérrez","doi":"10.1016/S1474-4422(24)00292-8","DOIUrl":"10.1016/S1474-4422(24)00292-8","url":null,"abstract":"","PeriodicalId":17989,"journal":{"name":"Lancet Neurology","volume":null,"pages":null},"PeriodicalIF":46.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141792803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Endovascular thrombectomy for acute ischaemic stroke with established large infarct (TENSION): 12-month outcomes of a multicentre, open-label, randomised trial. 大面积梗死急性缺血性中风的血管内血栓切除术(TENSION):一项多中心、开放标签、随机试验的 12 个月结果。
IF 46.5 1区 医学
Lancet Neurology Pub Date : 2024-09-01 Epub Date: 2024-07-26 DOI: 10.1016/S1474-4422(24)00278-3
Götz Thomalla, Jens Fiehler, Fabien Subtil, Susanne Bonekamp, Anne Hege Aamodt, Blanca Fuentes, Elke R Gizewski, Michael D Hill, Antonin Krajina, Laurent Pierot, Claus Z Simonsen, Kamil Zeleňák, Rolf A Blauenfeldt, Bastian Cheng, Angélique Denis, Hannes Deutschmann, Franziska Dorn, Fabian Flottmann, Susanne Gellißen, Johannes C Gerber, Mayank Goyal, Jozef Haring, Christian Herweh, Silke Hopf-Jensen, Vi Tuan Hua, Märit Jensen, Andreas Kastrup, Christiane Fee Keil, Andrej Klepanec, Egon Kurča, Ronni Mikkelsen, Markus Möhlenbruch, Stefan Müller-Hülsbeck, Nico Münnich, Paolo Pagano, Panagiotis Papanagiotou, Gabor C Petzold, Mirko Pham, Volker Puetz, Jan Raupach, Gernot Reimann, Peter Arthur Ringleb, Maximilian Schell, Eckhard Schlemm, Silvia Schönenberger, Bjørn Tennøe, Christian Ulfert, Kateřina Vališ, Eva Vítková, Dominik F Vollherbst, Wolfgang Wick, Martin Bendszus
{"title":"Endovascular thrombectomy for acute ischaemic stroke with established large infarct (TENSION): 12-month outcomes of a multicentre, open-label, randomised trial.","authors":"Götz Thomalla, Jens Fiehler, Fabien Subtil, Susanne Bonekamp, Anne Hege Aamodt, Blanca Fuentes, Elke R Gizewski, Michael D Hill, Antonin Krajina, Laurent Pierot, Claus Z Simonsen, Kamil Zeleňák, Rolf A Blauenfeldt, Bastian Cheng, Angélique Denis, Hannes Deutschmann, Franziska Dorn, Fabian Flottmann, Susanne Gellißen, Johannes C Gerber, Mayank Goyal, Jozef Haring, Christian Herweh, Silke Hopf-Jensen, Vi Tuan Hua, Märit Jensen, Andreas Kastrup, Christiane Fee Keil, Andrej Klepanec, Egon Kurča, Ronni Mikkelsen, Markus Möhlenbruch, Stefan Müller-Hülsbeck, Nico Münnich, Paolo Pagano, Panagiotis Papanagiotou, Gabor C Petzold, Mirko Pham, Volker Puetz, Jan Raupach, Gernot Reimann, Peter Arthur Ringleb, Maximilian Schell, Eckhard Schlemm, Silvia Schönenberger, Bjørn Tennøe, Christian Ulfert, Kateřina Vališ, Eva Vítková, Dominik F Vollherbst, Wolfgang Wick, Martin Bendszus","doi":"10.1016/S1474-4422(24)00278-3","DOIUrl":"10.1016/S1474-4422(24)00278-3","url":null,"abstract":"<p><strong>Background: </strong>Long-term data showing the benefits of endovascular thrombectomy for stroke with large infarct are scarce. The TENSION trial showed the safety and efficacy of endovascular thrombectomy in patients with ischaemic stroke and large infarct at 90 days. We aimed to investigate the safety and efficacy at 12 months of endovascular thrombectomy in patients who were enrolled in the TENSION trial.</p><p><strong>Methods: </strong>TENSION was an open-label, blinded endpoint, randomised trial done at 40 hospitals across Europe and one hospital in Canada. We included patients (aged ≥18 years) with acute ischaemic stroke due to large vessel occlusion in the anterior circulation and who had a large infarct, as indicated by an Alberta Stroke Program Early Computed Tomographic Score (ASPECTS) of 3-5 on standard-of-care stroke imaging. We randomly assigned patients (1:1) to receive either endovascular thrombectomy with medical treatment or medical treatment only up to 12 h from stroke onset. The primary outcome was functional outcome across the entire range of the modified Rankin Scale at 90 days. Here, we report the prespecified 12-month follow-up analyses for functional outcome (using the simplified modified Rankin Scale questionnaire), quality of life (using the Patient-Reported Outcomes Measurement Information System 10-item [PROMIS-10] and EQ-5D questionnaires), post-stroke anxiety and depression (using the Patient Health Questionnaire-4 [PHQ-4]), and overall survival. Outcomes (except survival) were assessed in the intention-to-treat population; the survival analysis was based on treatment received. This trial is registered with ClinicalTrials.gov, NCT03094715, and is completed.</p><p><strong>Findings: </strong>We enrolled patients between July 17, 2018, and Feb 21, 2023, when the trial was stopped early for efficacy. 253 patients were randomly assigned, 125 (49%) to endovascular thrombectomy and 128 (51%) to medical treatment only. Median follow-up was 8·36 months (IQR 0·02-12·00). Endovascular thrombectomy was associated with a shift in the distribution of scores on the modified Rankin Scale towards better functional outcome at 12 months (adjusted common odds ratio 2·39 [95% CI 1·47-3·90]). Endovascular thrombectomy was also associated with a better quality of life compared with medical treatment only, as reflected by median scores on the EQ-5D questionnaire index (0·7 [IQR 0·4-0·9] vs 0·4 [0·2-0·7]), median scores for health status on the EQ-5D questionnaire visual analogue scale (50 [IQR 35-70] vs 30 [5-60]), and median global physical health scores on the PROMIS-10 questionnaire (T-score 39·8 [IQR 37·4-50·8] vs 37·4 [32·4-44·9]); although there was not enough evidence to suggest a difference between groups in global mental health scores on PROMIS-10 (41·1 [IQR 36·3-48·3] vs 38·8 [31·3-44·7]) or the numbers of patients reporting anxiety (13 [22%] of 58 vs 15 [42%] of 36) and depression (18 [31%] vs 18 [50%]) on PHQ-4. Overa","PeriodicalId":17989,"journal":{"name":"Lancet Neurology","volume":null,"pages":null},"PeriodicalIF":46.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141792804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Endovascular thrombectomy for large ischaemic stroke: outcomes beyond 90 days. 大面积缺血性脑卒中的血管内血栓切除术:90 天后的疗效。
IF 46.5 1区 医学
Lancet Neurology Pub Date : 2024-09-01 Epub Date: 2024-07-26 DOI: 10.1016/S1474-4422(24)00290-4
Takeshi Morimoto, Fumihiro Sakakibara
{"title":"Endovascular thrombectomy for large ischaemic stroke: outcomes beyond 90 days.","authors":"Takeshi Morimoto, Fumihiro Sakakibara","doi":"10.1016/S1474-4422(24)00290-4","DOIUrl":"10.1016/S1474-4422(24)00290-4","url":null,"abstract":"","PeriodicalId":17989,"journal":{"name":"Lancet Neurology","volume":null,"pages":null},"PeriodicalIF":46.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141792850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
World Brain Day 2024: a focus on brain health and prevention. 2024 年世界脑日:关注大脑健康和预防。
IF 46.5 1区 医学
Lancet Neurology Pub Date : 2024-09-01 Epub Date: 2024-07-18 DOI: 10.1016/S1474-4422(24)00270-9
Wolfgang Grisold, David W Dodick, Alla Guekht, Steven L Lewis, Tissa Wijeratne
{"title":"World Brain Day 2024: a focus on brain health and prevention.","authors":"Wolfgang Grisold, David W Dodick, Alla Guekht, Steven L Lewis, Tissa Wijeratne","doi":"10.1016/S1474-4422(24)00270-9","DOIUrl":"10.1016/S1474-4422(24)00270-9","url":null,"abstract":"","PeriodicalId":17989,"journal":{"name":"Lancet Neurology","volume":null,"pages":null},"PeriodicalIF":46.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141734515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Safety, tolerability, and pharmacokinetics of antisense oligonucleotide BIIB078 in adults with C9orf72-associated amyotrophic lateral sclerosis: a phase 1, randomised, double blinded, placebo-controlled, multiple ascending dose study. 反义寡核苷酸 BIIB078 在 C9orf72 相关肌萎缩性脊髓侧索硬化症成人患者中的安全性、耐受性和药代动力学:1 期随机、双盲、安慰剂对照、多剂量递增研究。
IF 46.5 1区 医学
Lancet Neurology Pub Date : 2024-09-01 Epub Date: 2024-07-23 DOI: 10.1016/S1474-4422(24)00216-3
Leonard H van den Berg, Jeffrey D Rothstein, Pamela J Shaw, Suma Babu, Michael Benatar, Robert C Bucelli, Angela Genge, Jonathan D Glass, Orla Hardiman, Vincenzo Libri, Theodore Mobach, Björn Oskarsson, Gary L Pattee, John Ravits, Christopher E Shaw, Markus Weber, Lorne Zinman, Paymaan Jafar-Nejad, Frank Rigo, Luan Lin, Toby A Ferguson, Anthony L Gotter, Danielle Graham, Michael Monine, Jennifer Inra, Susie Sinks, Satish Eraly, Steve Garafalo, Stephanie Fradette
{"title":"Safety, tolerability, and pharmacokinetics of antisense oligonucleotide BIIB078 in adults with C9orf72-associated amyotrophic lateral sclerosis: a phase 1, randomised, double blinded, placebo-controlled, multiple ascending dose study.","authors":"Leonard H van den Berg, Jeffrey D Rothstein, Pamela J Shaw, Suma Babu, Michael Benatar, Robert C Bucelli, Angela Genge, Jonathan D Glass, Orla Hardiman, Vincenzo Libri, Theodore Mobach, Björn Oskarsson, Gary L Pattee, John Ravits, Christopher E Shaw, Markus Weber, Lorne Zinman, Paymaan Jafar-Nejad, Frank Rigo, Luan Lin, Toby A Ferguson, Anthony L Gotter, Danielle Graham, Michael Monine, Jennifer Inra, Susie Sinks, Satish Eraly, Steve Garafalo, Stephanie Fradette","doi":"10.1016/S1474-4422(24)00216-3","DOIUrl":"10.1016/S1474-4422(24)00216-3","url":null,"abstract":"<p><strong>Background: </strong>Hexanucleotide repeat expansion of C9orf72 is a common genetic cause of amyotrophic lateral sclerosis (ALS). No C9orf72-targeted treatments are available. BIIB078 is an investigational antisense oligonucleotide targeting C9orf72 sense RNA. We aimed to assess the safety, tolerability, and pharmacokinetics of BIIB078 in participants with C9orf72-associated ALS.</p><p><strong>Methods: </strong>This phase 1, randomised controlled trial was done at 22 sites in six countries (Canada, Ireland, Netherlands, Switzerland, UK, and USA). Adults with ALS and a pathogenic repeat expansion in C9orf72 were randomly assigned within six cohorts, via Interactive Response Technology in a 3:1 ratio per cohort, to receive BIIB078 (5 mg, 10 mg, 20 mg, 35 mg, 60 mg, or 90 mg in cohorts 1-6, respectively) or placebo, via an intrathecal bolus injection. The treatment period consisted of three loading doses of study treatment, administered approximately once every 2 weeks, followed by monthly maintenance doses during a treatment period of about 3 months for cohorts 1-3 and about 6 months for cohorts 4-6. Patients and investigators were masked to treatment assignment. The primary endpoint was the incidence of adverse events and serious adverse events. This trial was registered with ClinicalTrials.gov (NCT03626012) and is completed.</p><p><strong>Findings: </strong>Between Sept 10, 2018, and Nov 17, 2021, 124 patients were screened for inclusion in the study. 18 patients were excluded and 106 participants were enrolled and randomly assigned to receive 5 mg (n=6), 10 mg (n=9), 20 mg (n=9), 35 mg (n=19), 60 mg (n=18), or 90 mg (n=18) of BIIB078, or placebo (n=27). 58 (55%) of 106 patients were female. All patients received at least one dose of study treatment and were included in all analyses. All participants had at least one adverse event; most adverse events were mild or moderate in severity and did not lead to treatment discontinuation. The most common adverse events in BIIB078-treated participants were falls, procedural pain, headache, and post lumbar puncture syndrome. 14 (18%) of 79 patients who received any dose of BIIB078 reported serious adverse events, compared with nine (33%) of 27 patients who received placebo. Five participants who received BIIB078 and three participants who received placebo had fatal adverse events: respiratory failure in a participant who received 10 mg BIIB078, ALS worsening in two participants who received 35 mg BIIB078, traumatic intracerebral haemorrhage in one participant who received 35 mg BIIB078, pulmonary embolism in one participant who received 60 mg BIIB078, and respiratory failure in three participants who received placebo. All deaths were assessed as not related to the study treatment by the reporting investigator.</p><p><strong>Interpretation: </strong>On the basis of these phase 1 study results, including secondary and exploratory findings showing no reduction in neurofilament levels and no benefit","PeriodicalId":17989,"journal":{"name":"Lancet Neurology","volume":null,"pages":null},"PeriodicalIF":46.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141766471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Sleep and sleep disorders in people with Parkinson's disease. 帕金森病患者的睡眠和睡眠障碍。
IF 46.5 1区 医学
Lancet Neurology Pub Date : 2024-09-01 Epub Date: 2024-06-25 DOI: 10.1016/S1474-4422(24)00170-4
Alex Iranzo, Valerie Cochen De Cock, María Livia Fantini, Laura Pérez-Carbonell, Lynn Marie Trotti
{"title":"Sleep and sleep disorders in people with Parkinson's disease.","authors":"Alex Iranzo, Valerie Cochen De Cock, María Livia Fantini, Laura Pérez-Carbonell, Lynn Marie Trotti","doi":"10.1016/S1474-4422(24)00170-4","DOIUrl":"10.1016/S1474-4422(24)00170-4","url":null,"abstract":"<p><p>Sleep disorders are common in people with Parkinson's disease. These disorders, which increase in frequency throughout the course of the neurodegenerative disease and impair quality of life, include insomnia, excessive daytime sleepiness, circadian disorders, obstructive sleep apnoea, restless legs syndrome, and rapid eye movement (REM) sleep behaviour disorder. The causes of these sleep disorders are complex and multifactorial, including the degeneration of the neural structures that modulate sleep, the detrimental effect of some medications on sleep, the parkinsonian symptoms that interfere with mobility and comfort in bed, and comorbidities that disrupt sleep quality and quantity. The clinical evaluation of sleep disorders include both subjective (eg, questionnaires or diaries) and objective (eg, actigraphy or video polysomnography) assessments. The management of patients with Parkinson's disease and a sleep disorder is challenging and should be individualised. Treatment can include education aiming at changes in behaviour (ie, sleep hygiene), cognitive behavioural therapy, continuous dopaminergic stimulation at night, and specific medications. REM sleep behaviour disorder can occur several years before the onset of parkinsonism, suggesting that the implementation of trials of neuroprotective therapies should focus on people with this sleep disorder.</p>","PeriodicalId":17989,"journal":{"name":"Lancet Neurology","volume":null,"pages":null},"PeriodicalIF":46.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141469170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Collateral-based selection for endovascular treatment of acute ischaemic stroke in the late window (MR CLEAN-LATE): 2-year follow-up of a phase 3, multicentre, open-label, randomised controlled trial in the Netherlands. 基于侧支选择的急性缺血性脑卒中晚期血管内治疗(MR CLEAN-LATE):荷兰一项多中心、开放标签、随机对照试验的 3 期 2 年随访。
IF 46.5 1区 医学
Lancet Neurology Pub Date : 2024-09-01 Epub Date: 2024-06-20 DOI: 10.1016/S1474-4422(24)00228-X
Ilse Huijberts, Florentina M E Pinckaers, Susanne G H Olthuis, Sander M J van Kuijk, Alida A Postma, Hieronymus D Boogaarts, Yvo B W E M Roos, Charles B L M Majoie, Aad van der Lugt, Diederik W J Dippel, Wim H van Zwam, Robert J van Oostenbrugge
{"title":"Collateral-based selection for endovascular treatment of acute ischaemic stroke in the late window (MR CLEAN-LATE): 2-year follow-up of a phase 3, multicentre, open-label, randomised controlled trial in the Netherlands.","authors":"Ilse Huijberts, Florentina M E Pinckaers, Susanne G H Olthuis, Sander M J van Kuijk, Alida A Postma, Hieronymus D Boogaarts, Yvo B W E M Roos, Charles B L M Majoie, Aad van der Lugt, Diederik W J Dippel, Wim H van Zwam, Robert J van Oostenbrugge","doi":"10.1016/S1474-4422(24)00228-X","DOIUrl":"10.1016/S1474-4422(24)00228-X","url":null,"abstract":"<p><strong>Background: </strong>The MR CLEAN-LATE trial provided evidence for the safety and efficacy of endovascular treatment for acute ischaemic stroke within the late window (after 6-24 h) in patients who were preselected based on the presence of collateral flow on CT angiography. We aimed to evaluate clinical outcomes 2 years after randomisation.</p><p><strong>Methods: </strong>MR CLEAN-LATE was a phase 3, multicentre, open-label, blinded-endpoint, randomised controlled trial conducted at 18 stroke intervention centres in the Netherlands. If endovascular treatment could be initiated within 6-24 h of symptom onset or last seen well, patients (aged 18 years or older) with an acute ischaemic stroke due to a large vessel occlusion in the anterior circulation and at least some collateral flow in the affected middle cerebral artery territory on CT angiography were randomly assigned (1:1) to either endovascular treatment with best medical treatment (endovascular treatment group) or best medical treatment alone (control group). Web-based randomisation, stratified by centre, was performed with the use of permuted blocks (block size eight to 20). The researchers who collected clinical outcomes and analysed the results were masked to treatment allocation; treating physicians, local investigators, and patients were aware of the received treatment. The primary outcome of MR CLEAN-LATE was the modified Rankin Scale (mRS) score at 90 days after randomisation. For this 2-year prespecified analysis, the primary outcome was mRS score at 2 years (minus 3 months to plus 6 months). Primary and safety analyses were performed based on the modified intention-to-treat principle, and included patients who provided (deferred) consent or died before consent could be obtained. Missing data were handled with multiple imputation by chained equations. The trial is completed and is registered at ISRCTN, ISRCTN19922220.</p><p><strong>Findings: </strong>Between Feb 2, 2018, and Jan 27, 2022, 535 patients were randomly assigned in the MR CLEAN-LATE trial, of whom 502 (94%) gave deferred consent and comprised the modified intention-to-treat population (255 in the endovascular treatment group and 247 in the control group). 261 (52%) patients were female and 241 (48%) were male. Data for mRS score at 2 years were available for 226 (89%) patients in the endovascular treatment group and for 202 (82%) patients in the control group. The median mRS score at 2 years was 4 (IQR 2-6) in the endovascular treatment group and 6 (2-6) in the control group. The endovascular treatment group demonstrated a shift towards better functional outcomes on the mRS (adjusted common odds ratio 1·41 [95% CI 1·00-1·99]; p=0·049). All-cause mortality at 2 years was 34% (87 of 255) in the endovascular treatment group and 41% (101 of 247) in the control group (adjusted hazard ratio 0·81 [95% CI 0·60-1·08]; p=0·15). Major vascular events (ie, transient ischaemic attack, ischaemic stroke, haemorrhagic stroke, ","PeriodicalId":17989,"journal":{"name":"Lancet Neurology","volume":null,"pages":null},"PeriodicalIF":46.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141442984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
γ-Secretase activity, clinical features, and biomarkers of autosomal dominant Alzheimer's disease: cross-sectional and longitudinal analysis of the Dominantly Inherited Alzheimer Network observational study (DIAN-OBS). 常染色体显性阿尔茨海默病的γ-分泌酶活性、临床特征和生物标志物:显性遗传性阿尔茨海默病网络观察研究(DIAN-OBS)的横断面和纵向分析。
IF 46.5 1区 医学
Lancet Neurology Pub Date : 2024-09-01 Epub Date: 2024-07-26 DOI: 10.1016/S1474-4422(24)00236-9
Stephanie A Schultz, Lei Liu, Aaron P Schultz, Colleen D Fitzpatrick, Raina Levin, Jean-Pierre Bellier, Zahra Shirzadi, Nelly Joseph-Mathurin, Charles D Chen, Tammie L S Benzinger, Gregory S Day, Martin R Farlow, Brian A Gordon, Jason J Hassenstab, Clifford R Jack, Mathias Jucker, Celeste M Karch, Jae-Hong Lee, Johannes Levin, Richard J Perrin, Peter R Schofield, Chengjie Xiong, Keith A Johnson, Eric McDade, Randall J Bateman, Reisa A Sperling, Dennis J Selkoe, Jasmeer P Chhatwal
{"title":"γ-Secretase activity, clinical features, and biomarkers of autosomal dominant Alzheimer's disease: cross-sectional and longitudinal analysis of the Dominantly Inherited Alzheimer Network observational study (DIAN-OBS).","authors":"Stephanie A Schultz, Lei Liu, Aaron P Schultz, Colleen D Fitzpatrick, Raina Levin, Jean-Pierre Bellier, Zahra Shirzadi, Nelly Joseph-Mathurin, Charles D Chen, Tammie L S Benzinger, Gregory S Day, Martin R Farlow, Brian A Gordon, Jason J Hassenstab, Clifford R Jack, Mathias Jucker, Celeste M Karch, Jae-Hong Lee, Johannes Levin, Richard J Perrin, Peter R Schofield, Chengjie Xiong, Keith A Johnson, Eric McDade, Randall J Bateman, Reisa A Sperling, Dennis J Selkoe, Jasmeer P Chhatwal","doi":"10.1016/S1474-4422(24)00236-9","DOIUrl":"10.1016/S1474-4422(24)00236-9","url":null,"abstract":"<p><strong>Background: </strong>Genetic variants that cause autosomal dominant Alzheimer's disease are highly penetrant but vary substantially regarding age at symptom onset (AAO), rates of cognitive decline, and biomarker changes. Most pathogenic variants that cause autosomal dominant Alzheimer's disease are in presenilin 1 (PSEN1), which encodes the catalytic core of γ-secretase, an enzyme complex that is crucial in production of amyloid β. We aimed to investigate whether the heterogeneity in AAO and biomarker trajectories in carriers of PSEN1 pathogenic variants could be predicted on the basis of the effects of individual PSEN1 variants on γ-secretase activity and amyloid β production.</p><p><strong>Methods: </strong>For this cross-sectional and longitudinal analysis, we used data from participants enrolled in the Dominantly Inherited Alzheimer Network observational study (DIAN-OBS) via the DIAN-OBS data freeze version 15 (data collected between Feb 29, 2008, and June 30, 2020). The data freeze included data from 20 study sites in research institutions, universities, hospitals, and clinics across Europe, North and South America, Asia, and Oceania. We included individuals with PSEN1 pathogenic variants for whom relevant genetic, clinical, imaging, and CSF data were available. PSEN1 pathogenic variants were characterised via genetically modified PSEN1 and PSEN2 double-knockout human embryonic kidney 293T cells and immunoassays for Aβ37, Aβ38, Aβ40, Aβ42, and Aβ43. A summary measure of γ-secretase activity (γ-secretase composite [GSC]) was calculated for each variant and compared with clinical history-derived AAO using correlation analyses. We used linear mixed-effect models to assess associations between GSC scores and multimodal-biomarker and clinical data from DIAN-OBS. We used separate models to assess associations with Clinical Dementia Rating Sum of Boxes (CDR-SB), Mini-Mental State Examination (MMSE), and Wechsler Memory Scale-Revised (WMS-R) Logical Memory Delayed Recall, [<sup>11</sup>C]Pittsburgh compound B (PiB)-PET and brain glucose metabolism using [<sup>18</sup>F] fluorodeoxyglucose (FDG)-PET, CSF Aβ42-to-Aβ40 ratio (Aβ42/40), CSF log<sub>10</sub> (phosphorylated tau 181), CSF log<sub>10</sub> (phosphorylated tau 217), and MRI-based hippocampal volume.</p><p><strong>Findings: </strong>Data were included from 190 people carrying PSEN1 pathogenic variants, among whom median age was 39·0 years (IQR 32·0 to 48·0) and AAO was 44·5 years (40·6 to 51·4). 109 (57%) of 190 carriers were female and 81 (43%) were male. Lower GSC values (ie, lower γ-secretase activity than wild-type PSEN1) were associated with earlier AAO (r=0·58; p<0·0001). GSC was associated with MMSE (β=0·08, SE 0·03; p=0·0043), CDR-SB (-0·05, 0·02; p=0·0027), and WMS-R Logical Memory Delayed Recall scores (0·09, 0·02; p=0·0006). Lower GSC values were associated with faster increase in PiB-PET signal (p=0·0054), more rapid decreases in hippocampal volume (4·19, 0·77; p<0·000","PeriodicalId":17989,"journal":{"name":"Lancet Neurology","volume":null,"pages":null},"PeriodicalIF":46.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141792851","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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