Jin-Tai Yu1, Jie-Qiong Li2, John Suckling3, Lei Feng4, An Pan5, Yan-Jiang Wang6, Bo Song7, Shan-Liang Zhu8, De-Hu Li8, Hui-Fu Wang2, Chen-Chen Tan2, Qiang Dong9, Lan Tan2, Vincent Mok10, Paul S Aisen11, Michael M Weiner12. 1. Department of Neurology and Institute of Neurology, WHO Collaborating Center for Research and Training in Neurosciences, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China. Electronic address: jintai_yu@fudan.edu.cn. 2. Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China. 3. Department of Psychiatry, University of Cambridge, Cambridge, UK; Medical Research Council and Wellcome Trust Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK; Cambridgeshire and Peterborough NHS Trust, Cambridge, UK. 4. Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. 5. Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. 6. Department of Neurology, Daping Hospital, Third Military Medical University, Chongqing, China. 7. College of Information Science and Technology, Qingdao University of Science and Technology, Qingdao, China. 8. Research Center for Mathematical Modeling, School of Mathematics and Physics, Qingdao University of Science and Technology, Qingdao, China. 9. Department of Neurology and Institute of Neurology, WHO Collaborating Center for Research and Training in Neurosciences, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China. 10. Gerald Choa Neuroscience Centre, Lui Che Woo Institute of Innovative Medicine, Therese Pei Fong Chow Research Center for Prevention of Dementia, Division of Neurology, Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China. 11. Alzheimer's Therapeutic Research Institute, University of Southern California, San Diego, CA, USA. 12. Department of Veterans Affairs Medical Center, Center for Imaging of Neurodegenerative Diseases, San Francisco, CA, USA; Department of Radiology, University of California, San Francisco, CA, USA; Department of Medicine, University of California, San Francisco, CA, USA; Department of Psychiatry, University of California, San Francisco, CA, USA; Department of Neurology, University of California, San Francisco, CA, USA.
Abstract
INTRODUCTION: We aimed to estimate the frequency of each AT(N) (β-amyloid deposition [A], pathologic tau [T], and neurodegeneration [N]) profile in different clinical diagnosis groups and to describe the longitudinal change in clinical outcomes of individuals in each group. METHODS: Longitudinal change in clinical outcomes and conversion risk of AT(N) profiles are assessed using linear mixed-effects models and multivariate Cox proportional-hazard models, respectively. RESULTS: Participants with A+T+N+ showed faster clinical progression than those with A-T-N- and A+T±N-. Compared with A-T-N-, participants with A+T+N± had an increased risk of conversion from cognitively normal (CN) to incident prodromal stage of Alzheimer's disease (AD), and from MCI to AD dementia. A+T+N+ showed an increased conversion risk when compared with A+T±N-. DISCUSSION: The 2018 research framework may provide prognostic information of clinical change and progression. It may also be useful for targeted recruitment of participants with AD into clinical trials.
INTRODUCTION: We aimed to estimate the frequency of each AT(N) (β-amyloid deposition [A], pathologic tau [T], and neurodegeneration [N]) profile in different clinical diagnosis groups and to describe the longitudinal change in clinical outcomes of individuals in each group. METHODS: Longitudinal change in clinical outcomes and conversion risk of AT(N) profiles are assessed using linear mixed-effects models and multivariate Cox proportional-hazard models, respectively. RESULTS:Participants with A+T+N+ showed faster clinical progression than those with A-T-N- and A+T±N-. Compared with A-T-N-, participants with A+T+N± had an increased risk of conversion from cognitively normal (CN) to incident prodromal stage of Alzheimer's disease (AD), and from MCI to AD dementia. A+T+N+ showed an increased conversion risk when compared with A+T±N-. DISCUSSION: The 2018 research framework may provide prognostic information of clinical change and progression. It may also be useful for targeted recruitment of participants with AD into clinical trials.
Authors: Bruno Dubois; Nicolas Villain; Giovanni B Frisoni; Gil D Rabinovici; Marwan Sabbagh; Stefano Cappa; Alexandre Bejanin; Stéphanie Bombois; Stéphane Epelbaum; Marc Teichmann; Marie-Odile Habert; Agneta Nordberg; Kaj Blennow; Douglas Galasko; Yaakov Stern; Christopher C Rowe; Stephen Salloway; Lon S Schneider; Jeffrey L Cummings; Howard H Feldman Journal: Lancet Neurol Date: 2021-04-29 Impact factor: 59.935
Authors: Liu Shi; Laura M Winchester; Benjamine Y Liu; Richard Killick; Elena M Ribe; Sarah Westwood; Alison L Baird; Noel J Buckley; Shengjun Hong; Valerija Dobricic; Fabian Kilpert; Andre Franke; Steven Kiddle; Martina Sattlecker; Richard Dobson; Antonio Cuadrado; Abdul Hye; Nicholas J Ashton; Angharad R Morgan; Isabelle Bos; Stephanie J B Vos; Mara Ten Kate; Philip Scheltens; Rik Vandenberghe; Silvy Gabel; Karen Meersmans; Sebastiaan Engelborghs; Ellen E De Roeck; Kristel Sleegers; Giovanni B Frisoni; Olivier Blin; Jill C Richardson; Régis Bordet; José L Molinuevo; Lorena Rami; Anders Wallin; Petronella Kettunen; Magda Tsolaki; Frans Verhey; Alberto Lleó; Daniel Alcolea; Julius Popp; Gwendoline Peyratout; Pablo Martinez-Lage; Mikel Tainta; Peter Johannsen; Charlotte E Teunissen; Yvonne Freund-Levi; Lutz Frölich; Cristina Legido-Quigley; Frederik Barkhof; Kaj Blennow; Katrine Laura Rasmussen; Børge Grønne Nordestgaard; Ruth Frikke-Schmidt; Sune Fallgaard Nielsen; Hilkka Soininen; Bruno Vellas; Iwona Kloszewska; Patrizia Mecocci; Henrik Zetterberg; B Paul Morgan; Johannes Streffer; Pieter Jelle Visser; Lars Bertram; Alejo J Nevado-Holgado; Simon Lovestone Journal: J Alzheimers Dis Date: 2020 Impact factor: 4.472