The Lancet Neurology最新文献

{"title":"Global, regional, and national burden of headache disorders, 1990–2023: a systematic analysis for the Global Burden of Disease Study 2023","authors":"Andreas Kattem Hus⊘y, Yvonne Yiru Xu, Jaimie D Steinmetz, Mohammad Amin Aalipour, Hasan Aalruz, Deldar Morad Abdulah, Richard Gyan Aboagye, Dariush Abtahi, Samir Abu Rumeileh, Salahdein Aburuz, Qorinah Estiningtyas Sakilah Adnani, Obed Adonteng-Kissi, Giuseppina Affinito, Danish Ahmad, Negar Sadat Ahmadi, Ali Ahmed, Asma Ahmed, Shahzaib Ahmed, Mohammad Ahmmad Mahmoud Al Zoubi, Sawsan Alabbad, Yazan Al-Ajlouni, Mohammed Albashtawy, Fadwa Naji Alhalaiqa, Ashraf Alhumaidi, Mohammed Usman Ali, Syed Shujait Ali, Montaha Al-Iede, Joseph Uy Almazan, Najim Z Alshahrani, Awais Altaf, Mohammad Al-Wardat, Yaser Mohammed Al-Worafi, Karem H Alzoubi, Sohrab Amiri, Ganiyu Adeniyi Amusa, David B Anderson, Abhishek Anil, Jalal Arabloo, Aleksandr Y Aravkin, Demelash Areda, Mahsa Asadi Anar, Mohammad Asghari-Jafarabadi, Sait Ashina, Khursheed Aurangzeb, Arian Azadnia, Ahmed Y Azzam, Youngoh Bae, Razieh Bahreini, Soham Bandyopadhyay, Hiba Jawdat Barqawi, Azadeh Bashiri, Rehana Basri, Mohammad-Mahdi Bastan, Jina Behjati, Maryam Bemanalizadeh, Jeetendra Bhandari, Sonu Bhaskar, Gurjit Kaur Bhatti, Jasvinder Singh Bhatti, Rajbir Bhatti, Bijit Biswas, Bruno Bizzozero-Peroni, Archith Boloor, Meriem Boukhiam, Yasser Bustanji, Sanjay C J, Luis Alberto Cámera, Edoardo Caronna, Ana Paula Carvalho-e-Silva, Sandip Chakraborty, Vijay Kumar Chattu, Anis Ahmad Chaudhary, Patrick R Ching, Hongyuan Chu, Josielli Comachio, Daniela Contreras, Natalia Cruz-Martins, Omid Dadras, Xiaochen Dai, Emanuele D'Amico, Anh Kim Dang, Lucio D'Anna, Sindhura Deekonda, Pouria Delbari, Andreas K Demetriades, Emina Derviševic, Vinoth Gnana Chellaiyan Devanbu, Amol S Dhane, Bibha Dhungel, Xueting Ding, Huyen Phuc Do, Ojas Prakashbhai Doshi, Siddhartha Dutta, Lamiaa Labieb Mahmoud Ebraheim, Ebrahim Eini, Michael Ekholuenetale, Sharareh Eskandarieh, Andre Faro, Valery L Feigin, Gelana Fekadu, Ginenus Fekadu, Seyed-Mohammad Fereshtehnejad, Abdullah H Feroze, Pietro Ferrara, Nuno Ferreira, Claudio Fiorilla, Florian Fischer, Arianna Fornari, Celia Fortuna Rodrigues, Matteo Foschi, Abdelrahman Gamil Gad, Márió Gajdács, David Garcia-Azorin, Zisis Gatzioufas, Rupesh K Gautam, Miglas Welay Gebregergis, Elena V Gnedovskaya, Massimiliano Gobbo, Mahaveer Golechha, Pouya Goleij, Alessandra C Goulart, Ishita Gupta, Sapna Gupta, Roberth Steven Gutiérrez-Murillo, Najah R Hadi, Faraidoon Haghdoost, Hailey Hagins, Mohamed Hamed, Victoria Funmilayo Hanson, Amr Hassan, Simon I Hay, Khezar Hayat, Jeffrey J Hebert, Golnaz Heidari, Bartosz Helfer, Mehdi Hoseinzadeh, Md Jubayer Hossain, Yongsong Huang, Luigi Francesco Iannone, Segun Emmanuel Ibitoye, Olayinka Stephen Ilesanmi, Irena M Ilic, Muhana Fawwazy Ilyas, Salim Ilyasu, Md Rabiul Islam, Md Sahidul Islam, Nahlah Elkudssiah Ismail, Louis Jacob, Haitham Jahrami, Ammar Abdulrahman Jairoun, Navid Jamali, Manthan Dilipkumar Janodia, Ruwan Duminda Jayasinghe, Shuai Jin, Jost B Jonas, Nitin Joseph, Charity Ehimwenma Joshua, Saltanat Kamenova, Arun Kamireddy, Rami S Kantar, Sujita Kumar Kar, Mohmed Isaqali Karobari, Himanshu Khajuria, Sameer Uttamaro Khasbage, Jagdish Khubchandani, Yun Jin Kim, Omid Kohandel Gargari, Farzad Kompani, Aida Kondybayeva, Kewal Krishan, Barthelemy Kuate Defo, Mukhtar Kulimbet, Chandan Kumar, Rakesh Kumar, Vijay Kumar, Ville Kytö, Caterina Ledda, Seung Won Lee, Jacopo Lenzi, Jianan Li, Linyan Li, Yanxue Lian, Giancarlo Lucchetti, Jay B Lusk, Ricardo Lutzky Saute, Sasikumar Mahalingam, Rituparna Maiti, Ahmad Azam Malik, Birhanemaskal Malkamu, Vahid Mansouri, Konstantinos Margetis, Roy Rillera Marzo, Yasith Mathangasinghe, Georgios Mavrovounis, Hadush Negash Meles, Atte Meretoja, Tomislav Mestrovic, Sachith Mettananda, Bartosz Miazgowski, Giuseppe Minervini, Archana Mishra, Arup Kumar Misra, Khabab Abbasher Hussien Mohamed Ahmed, Omer Mohammed, Shafiu Mohammed, Ali H Mokdad, Shaher Momani, Maziar Moradi-Lakeh, Mahdis Morovvati, Reza Mosaddeghi Heris, Kavita Munjal, Yanjinlkham Munkhsaikhan, Efren Murillo-Zamora, Christopher J L Murray, Ghulam Mustafa, Fatemehzahra Naddafi, Zuhair S Natto, Gaurav Nepal, Charles Richard James Newton, Cao Duy Nguyen, Cuong Tat Nguyen, Hien Thu Nguyen, Long Nguyen, Robina Khan Niazi, Luciano Nieddu, Fred Nugen, Chijindu N Nwakama, Ogochukwu Janet Nzoputam, Bogdan Oancea, Michael Safo Oduro, Hassan Okati-Aliabad, Andrew T Olagunju, Arão Belitardo Oliveira, Jia Ouyang, Mark Overton, Mayowa O Owolabi, Mahesh P A, Giuseppina Palena, Leonidas D Panos, Ioannis Pantazopoulos, Shahina Pardhan, Romil R Parikh, Arpit Parmar, Maja Pasovic, Shankargouda Patil, Apurba Patra, Paolo Pedersini, Mario F P Peres, Simone Perna, Wajida Perveen, Hai Quang Pham, Sanjay Prakash, Akila Prashant, Jagadeesh Puvvula, Maja R Radojcic, Alberto Raggi, Mohammad Meshbahur Rahman, Amir Masoud Rahmani, Mahmoud Mohammed Ramadan, Devarajan Rathish, Salman Rawaf, Mohsen Rezaeian, Taeho Gregory Rhee, Debby Syahru Romadlon, Michele Romoli, Marina Romozzi, Umar Saeed, Amene Saghazadeh, Amirhossein Sahebkar, Mohamed A Saleh, Sohrab Salimi, Abdallah M Samy, Lucas H C C Santos, Aswini Saravanan, Hemen Sarma, Yigit Can Senol, Yashendra Sethi, Yara Khaled Fouad Sayed Shaalan, Wajeehah Shahid, Anas Shamsi, Dan Shan, Amin Sharifan, Rekha Raghuveer Shenoy, Premalatha K Shetty, Zahra Shokati Eshkiki, Sunil Shrestha, Harmanjit Singh, Jasvinder A Singh, Satwinder Singh, Valentin Yurievich Skryabin, Farrukh Sobia, Reed J D Sorensen, Sebastian Straube, Chandan Kumar Swain, Sree Sudha T Y, Payam Tabaee Damavandi, Celine Tabche, Mohsan Tanveer, Minale Tareke, Claudia Baptista Tavares, Mohamad-Hani Temsah, Masayuki Teramoto, Arun James Thirunavukarasu, Ashutosh Tiwari, Thang Huu Tran, Nguyen Tran Minh Duc, Vasilis-Spyridon Tseriotis, Santhosh Kumar Tumkur Narayanappa, Aniefiok John Udoakang, Himayat Ullah, Jibrin Sammani Usman, Abdulkadir Usman Sambo, Jef Van den Eynde, Tommi Juhani Vasankari, Narayanaswamy Venketasubramanian, Jorge Hugo Villafañe, Arvinder Wander, Wei Wang, Xingxin Wang, Yuan-Pang Wang, Taweewat Wiangkham, Mieszko Wieckiewicz, Wanqing Xu, Saba Yahoo (Syed), Yazachew Engida Yismaw, Dong Keon Yon, Naohiro Yonemoto, Abdilahi Yousuf, Aurora Zanghì, Michael Zastrozhin, Anthony Lin Zhang, Zhongyi Zhao, Magdalena Zielinska, Kanyin Liane Ong, Timothy J Steiner, Theo Vos","doi":"10.1016/s1474-4422(25)00402-8","DOIUrl":"https://doi.org/10.1016/s1474-4422(25)00402-8","url":null,"abstract":"<h3>Background</h3>The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023 estimates health loss from migraine, tension-type headache, and medication-overuse headache. This study presents updated results on headache-attributed burden from 1990 to 2023, along with clinical and public health implications.<h3>Methods</h3>Data on the prevalence, incidence, or remission of migraine, tension-type headache, and medication-overuse headache were extracted from published population-based studies. We used hierarchical Bayesian meta-regression modelling to estimate global, regional, and country-level prevalence of headache disorders. For the first time in GBD 2023, age-specific and sex-specific estimates of time in symptomatic state were applied by meta-analysing individual participant data from 41 653 individuals from the general populations of 18 countries from all parts of the world. Disability weights were applied to calculate years lived with disability (YLDs). Since medication-overuse headache is a sequela of a mistreated primary headache (due to medication overuse), its burden was reattributed to migraine or tension-type headache, informed by a meta-analysis of three longitudinal studies.<h3>Findings</h3>In 2023, 2·9 billion individuals (95% uncertainty interval 2·6–3·1) were affected by headache disorders, with a global age-standardised prevalence of 34·6% (31·6–37·5) and a YLD rate of 541·9 (373·4–739·9) per 100 000 population, with 487·5 (323·0–678·8) per 100 000 population attributed to migraine. The prevalence rates of these headache disorders have remained stable over the past three decades. YLD rates due to headache disorders were more than twice as high in females (739·9 [511·2–1011·5] per 100 000) as in males (346·1 [240·4–481·8] per 100 000). Medication-overuse headache contributed 58·9% of the YLD estimates for tension-type headache in males and 56·1% in females, as well as 22·6% of the YLD estimates for migraines in males and 14·1% in females.<h3>Interpretation</h3>Headache disorders, in particular migraine, continue to be a major global health challenge, emphasising the need for effective management and prevention strategies. Much headache-attributed burden could be averted or eliminated by avoiding overuse of medication (including over-the-counter medication), underscoring the importance of public education.<h3>Funding</h3>Gates Foundation.","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"85 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145498747","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":"Celebrating decades of progress in Lewy bodies research","authors":"","doi":"10.1016/s1474-4422(25)00389-8","DOIUrl":"https://doi.org/10.1016/s1474-4422(25)00389-8","url":null,"abstract":"No Abstract","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145498701","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":"Neuropathological changes and amyloid-related imaging abnormalities in Alzheimer's disease treated with aducanumab versus untreated: a retrospective case–control study","authors":"Baayla D C Boon, Yoav D Piura, Christina M Moloney, Jessica L Chalk, Sarah J Lincoln, Matthew H Rutledge, Darren M Rothberg, Naomi Kouri, Kelly M Hinkle, Shanu F Roemer, Derek R Johnson, Brian J Burkett, Val J Lowe, Ronald C Petersen, Dennis W Dickson, R Ross Reichard, Aivi T Nguyen, Jonathan Graff-Radford, David S Knopman, Neill R Graff-Radford, Melissa E Murray","doi":"10.1016/s1474-4422(25)00313-8","DOIUrl":"https://doi.org/10.1016/s1474-4422(25)00313-8","url":null,"abstract":"<h3>Background</h3>Understanding the neuropathological effects of amyloid β (Aβ)-targeting therapies and amyloid-related imaging abnormalities (ARIA) in Alzheimer's disease is critical for optimising treatment efficacy and patient outcomes. Comparing Aβ PET imaging with neuropathological assessments provides context for evaluating the extent of Aβ clearance and interpreting in-vivo biomarkers. We aimed to assess clinicopathological changes and ARIA-related effects in aducanumab-treated versus untreated Alzheimer's disease.<h3>Methods</h3>This retrospective case–control study included five aducanumab-treated participants from clinical trials conducted at the Mayo Clinic (2016–21) who underwent autopsy (2020–23). Treated participants were matched by autosomal dominant Alzheimer's disease mutation or <em>APOE</em> genotype, age at cognitive symptom onset, and sex to 12 untreated participants from the Mayo Clinic Alzheimer's Disease Research Center and Mayo Clinic Study of Aging cohorts in the Mayo Clinic brain bank (Jacksonville, FL, USA). Cognitive, imaging, and neuropathological outcomes were compared using descriptive analyses and Mann–Whitney <em>U</em> tests.<h3>Findings</h3>Aducanumab-treated participants comprised four males and one female, all carrying at least one <em>APOE</em> ∊4 allele, with two harbouring a <em>PSEN1</em> mutation. Cumulative dosages of aducanumab ranged from 5 mg/kg to 241 mg/kg; all participants cognitively declined during treatment, and two exhibited ARIA. Reductions in [¹⁸F]florbetapir PET Centiloid values ranged from –6% to –81% compared with baseline. Treatment-to-death intervals ranged from 5 months to 41 months. Neuropathological analyses revealed clearance of Aβaa1–8 and Aβ42 localised to cortical layer I in treated participants, with no significant clearance in deeper cortical layers. Regions corresponding to ARIA on MRI showed microinfarcts with haemosiderin, complement activation, and CD68-positive vessel walls originating from Aβ-laden leptomeningeal and penetrating vessels.<h3>Interpretation</h3>Disproportionate Aβ clearance and ARIA-associated neuropathology localised to superficial cortical layers suggest a distinctive pattern of target engagement by aducanumab. These findings inform understanding and monitoring of similar Aβ-targeting therapies.<h3>Funding</h3>Alzheimer Nederland, National Institute on Aging, and Alzheimer's Association.","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"30 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145295444","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":"Multidomain lifestyle interventions for cognitive function","authors":"Sandrine Andrieu, Nicola Coley, Bruno Vellas","doi":"10.1016/s1474-4422(25)00353-9","DOIUrl":"https://doi.org/10.1016/s1474-4422(25)00353-9","url":null,"abstract":"No Abstract","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"93 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145295439","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":"Environmental toxicants and Parkinson's disease: recent evidence, risks, and prevention opportunities","authors":"E Ray Dorsey, Briana R De Miranda, Sarrah Hussain, Bastiaan R Bloem, Alexis Elbaz, Jorge Llibre-Guerra, Raymond Y Lo, Samuel M Goldman, Caroline M Tanner","doi":"10.1016/s1474-4422(25)00287-x","DOIUrl":"https://doi.org/10.1016/s1474-4422(25)00287-x","url":null,"abstract":"The global burden of Parkinson's disease is rising. Large-scale genetic studies have confirmed that extrinsic or environmental factors, rather than genetic predisposition, play a dominant role in its cause. Increasing evidence implicates three classes of toxicants—certain pesticides, the dry-cleaning chemicals trichloroethylene and perchloroethylene, and air pollution—in the development of Parkinson's disease. These toxicants are widely prevalent, impair mitochondrial or lysosomal function, or both, and contribute to, if not cause, the disease. Parkinson's disease could be thus largely preventable. Uncertainties remain regarding the relevant doses, timing, and routes of exposure, the nature of genetic and environmental interactions, the effects of combined exposures, the role of the microbiome, and the identity of other environmental risks. Methodological limitations and structural challenges hinder our understanding. However, improved measurement of toxicant exposure in individuals and the environment, long-term prospective studies, increased funding for prevention, and policy changes can precipitate the fall of the burden of Parkinson's disease.","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"150 1","pages":"976-986"},"PeriodicalIF":0.0,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145295447","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":"Neuropathology of Alzheimer's disease after anti-amyloid β antibody treatment","authors":"Takeshi Iwatsubo","doi":"10.1016/s1474-4422(25)00348-5","DOIUrl":"https://doi.org/10.1016/s1474-4422(25)00348-5","url":null,"abstract":"No Abstract","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"65 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145295378","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":"William Harvey, neurologist?","authors":"Mark Weatherall","doi":"10.1016/s1474-4422(25)00360-6","DOIUrl":"https://doi.org/10.1016/s1474-4422(25)00360-6","url":null,"abstract":"No Abstract","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145295437","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":"Advances in screening and management of unruptured intracranial aneurysms","authors":"Gabriel J E Rinkel, Ynte M Ruigrok, Timo Krings, Nima Etminan, Mervyn D I Vergouwen","doi":"10.1016/s1474-4422(25)00265-0","DOIUrl":"https://doi.org/10.1016/s1474-4422(25)00265-0","url":null,"abstract":"The clinical evaluation and decision making associated with the management of unruptured intracranial aneurysms are complex. In the past 5 years, studies have evaluated the benefits of screening in people at high-risk, such as those with a family history of aneurysmal subarachnoid haemorrhage or unruptured intracranial aneurysms, people with genetic or other disorders associated with intracranial aneurysms, and people who smoke and have hypertension. If an aneurysm is detected during screening or incidentally, prediction models now allow for estimating the risk of complications from preventive aneurysm occlusion. Other prediction models can estimate the risk of aneurysm growth and the risk of rupture after growth. Thus, screening and management strategies are shifting towards a personalised approach. Uncertainties remain regarding the value of screening in some individuals, the long-term benefits of preventive occlusion, and the effectiveness of medical treatment strategies to prevent aneurysm growth and rupture.","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"65 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145295446","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":"High-sensitivity C-reactive protein, LDL cholesterol, lipoprotein(a) and 30-year risk of stroke in healthy women: a prospective, longitudinal cohort study","authors":"Ask T Nordestgaard, M Vinayaga Moorthy, Nancy R Cook, Nader Rifai, I-Min Lee, Julie E Buring, Paul M Ridker","doi":"10.1016/s1474-4422(25)00306-0","DOIUrl":"https://doi.org/10.1016/s1474-4422(25)00306-0","url":null,"abstract":"&lt;h3&gt;Background&lt;/h3&gt;Primary stroke prevention guidelines recommend routine screening of individuals for elevated LDL cholesterol from the age of 40 years, but recommendations are ambiguous for high-sensitivity C-reactive protein (hsCRP) and lipoprotein(a). We aimed to examine correlations between hsCRP, LDL cholesterol, and lipoprotein(a) and 30-year risk of stroke in healthy women.&lt;h3&gt;Methods&lt;/h3&gt;In this prospective, longitudinal cohort study, participants who were enrolled in the Women's Health Study (a randomised controlled trial of aspirin and vitamin E for the prevention of cardiovascular disease and cancer in women in the USA that completed in 2004) were prospectively followed for up to 30 years via annual questionnaires. Healthy women (ie, without cardiovascular disease and cancer) aged 45 years and older were eligible for the original trial. Individuals with available baseline measurements for hsCRP, LDL cholesterol, or lipoprotein(a) were included in our analyses. We constructed cumulative incidence curves and calculated hazard ratios (HRs) for total, ischaemic, and haemorrhagic stroke across biomarker quintiles and for combined elevation of all biomarkers from age-adjusted and multivariable-adjusted cause-specific Cox models.&lt;h3&gt;Findings&lt;/h3&gt;Between September, 1992 and May, 1995, 39 876 women were enrolled in the Women's Health Study, of whom 28 345 consented to participate in further follow-up and provided a baseline blood sample. Baseline concentrations of hsCRP and LDL cholesterol were available for 27 939 participants, with lipoprotein(a) measurements also reported for most participants. At enrolment, median age was 53 years (IQR 49–59), median BMI was 25 kg/m&lt;sup&gt;2&lt;/sup&gt; (22–28), 3252 (12%) were current smokers, 7026 (25%) had hypertension, and 685 (2%) had a history of diabetes. 1345 stroke events accrued during a median of 27·7 years (IQR 23·1–29·0) of follow-up. Baseline hsCRP concentrations increasing from the lowest quintile (&lt;0·7 mg/L) to the highest quintile (≥5·2 mg/L) were associated with an increasing cumulative incidence of total stroke. Only individuals in the highest LDL cholesterol (≥3·4 mmol/L) and lipoprotein(a) quintiles (≥44·1 mg/dL) had higher cumulative incidences of total stroke than those in the lowest quintiles (&lt;2·5 mmol/L and &lt;3·6 mg/dL, respectively). Multivariable-adjusted hazard ratios (HRs) for total and ischaemic stroke for quintile five versus quintile one were 1·32 (95% CI 1·07–1·61) and 1·56 (1·22–1·99), respectively, for hsCRP; 1·05 (0·88–1·25) and 1·17 (0·95–1·45), respectively, for LDL cholesterol; and 1·23 (1·04–1·45) and 1·27 (1·05–1·55), respectively, for lipoprotein(a). Women with three versus no biomarkers in the fifth quintile had HRs of 1·60 (1·10–2·34) for total stroke and 1·79 (1·23–2·61) for ischaemic stroke. None of the biomarkers correlated with risk of haemorrhagic stroke.&lt;h3&gt;Interpretation&lt;/h3&gt;Elevated plasma concentrations of hsCRP, LDL cholesterol, and lipoprotein(a), indi","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"27 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145295443","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":"Intravenous alteplase versus oral aspirin for acute central retinal artery occlusion within 4·5 h of severe vision loss (THEIA): a multicentre, double-dummy, patient-blinded and assessor-blinded, randomised, controlled, phase 3 trial","authors":"Cécile Préterre, Aurélie Gaultier, Michael Obadia, Catherine Vignal, Isabelle Mourand, Julien Plat, Denis Sablot, Marie Gaudron, Gilles Rodier, Gaëlle Godeneche, Cédric Urbanczyk, Guillaume Marc, Evelyne Massardier, Sarah Adam, Marion Boulanger, Sébastien Marcel, Laura Mechtouff, Thomas Ronzière, Lionel Calvière, Sophie Godard-Ducceschi, Catherine Cochard","doi":"10.1016/s1474-4422(25)00308-4","DOIUrl":"https://doi.org/10.1016/s1474-4422(25)00308-4","url":null,"abstract":"<h3>Background</h3>Central retinal artery occlusion (CRAO) is a subtype of ischaemic stroke that results in acute monocular vision loss. Although open-label studies and meta-analyses have suggested that early intravenous thrombolysis might improve visual acuity, no randomised controlled trials have yet confirmed this benefit. We aimed to compare the safety and efficacy of intravenous alteplase with oral aspirin in patients with CRAO treated within 4·5 h of onset of severe vision loss.<h3>Methods</h3>THEIA was a multicentre, double-dummy, patient-blinded, assessor-blinded, randomised, controlled, phase 3 trial conducted across 16 hospitals with stroke units in France. Adults (aged ≥18 years) presenting with sudden, severe, and persistent monocular vision loss (Snellen &lt;20/400) due to suspected non-arteritic acute CRAO were eligible for inclusion. Participants were randomly assigned (1:1), stratified by centre, to receive either 0·9 mg/kg of bodyweight intravenous alteplase and oral placebo (alteplase group) or 300 mg oral aspirin and intravenous saline placebo (aspirin group) within 4·5 h of symptom onset. Patients, outcome assessors, and the study sponsor were masked to treatment allocation; treating nurses and neurologists were unmasked. The primary efficacy outcome was improvement in visual acuity of at least 0·3 logarithm of the minimum angle of resolution (LogMAR) from baseline to 1 month, analysed in the full analysis set, which included all patients who received the complete intervention and a visual acuity assessment at baseline. Safety outcomes included serious adverse events, particularly intracranial and extracranial bleeding, analysed in all randomly assigned participants. This study is registered at <span><span>ClinicalTrials.gov</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span> (<span><span>NCT03197194</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span>) and is completed.<h3>Findings</h3>Between June 8, 2018, and Oct 2, 2023, 70 patients (mean age 70 years [SD 9]; 25 [36%] women and 45 [64%] men) were enrolled and randomly assigned to either the alteplase group (35 [50%]) or the aspirin group (35 [50%]). In total, 65 (93%) patients received the allocated treatment: 34 (97%) in the alteplase group and 31 (89%) in the aspirin group. Mean time from symptom onset to treatment initiation was 232·4 min (SD 43·6). Among 56 patients with available data on the primary endpoint, 19 (66%) of 29 patients in the alteplase group and 13 (48%) of 27 patients in the aspirin group showed an improvement in visual acuity of at least 0·3 LogMAR at 1 month (unadjusted risk difference 17·4 [95% CI –11·8 to 46·5]; adjusted odds ratio 1·1 ","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"25 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145295442","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}