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https://ahro.austin.org.au/austinjspui/handle/1/16728| Title: | Presymptomatic atrophy in autosomal dominant Alzheimer's disease: a serial MRI study | Austin Authors: | Kinnunen, Kirsi M;Cash, David M;Poole, Teresa;Frost, Chris;Benzinger, Tammie LS;Ahsan, R Laila;Leung, Kelvin K;Cardoso, M Jorge;Modat, Marc;Malone, Ian B;Morris, John C;Bateman, Randall J;Marcus, Daniel S;Goate, Alison;Salloway, Stephen;Correia, Stephen;Sperling, Reisa A;Chhatwal, Jasmeer P;Mayeux, Richard;Brickman, Adam M;Martins, Ralph N;Farlow, Martin R;Ghetti, Bernardino;Saykin, Andrew J;Jack, Clifford R Jr;Schofield, Peter R;McDade, Eric;Weiner, Michael W;Ringman, John M;Thompson, Paul M;Masters, Colin L ;Rowe, Christopher C ;Rossor, Martin N;Ourselin, Sebastien;Fox, Nick C;Dominantly Inherited Alzheimer Network (DIAN) | Affiliation: | Dementia Research Centre, UCL Institute of Neurology, London, UK Translational Imaging Group, UCL Centre for Medical Image Computing, London, UK London School of Hygiene & Tropical Medicine, London, UK Department of Radiology, Washington University School of Medicine, St. Louis, MO, USA Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA Department of Neurological Surgery & Psychiatry, Washington University School of Medicine, St. Louis, MO, USA Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA Brown University-Butler Hospital, Providence, RI, USA Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA Department of Neurology, Columbia University Medical Center, New York, NY, USA School of Medical Sciences, Edith Cowan University, Joondalup, WA, Australia Department of Neurology, Indiana University School of Medicine, Indianapolis, IN, USA Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, USA Department of Radiology, Mayo Clinic, Rochester, MN, USA Neuroscience Research Australia, Randwick, NSW, Australia School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia Department of Radiology, School of Medicine, University of California, San Francisco, San Francisco, CA, USA Department of Neurology, Keck USC School of Medicine, Los Angeles, CA, USA Imaging Genetics Center, Keck School of Medicine, University of Southern California, Marina del Rey, CA, USA The Florey Institute, The University of Melbourne, Heidelberg, Victoria, Australia Department of Nuclear Medicine and Centre for PET, Austin Health, Heidelberg, Victoria, Australia Department of Medicine, University of Melbourne, Austin Health, Heidelberg, Victoria, Australia |
Issue Date: | 22-Jul-2017 | Date: | 201-07-22 | Publication information: | Alzheimer's & Dementia 2017; online first: 22 July | Abstract: | INTRODUCTION: Identifying at what point atrophy rates first change in Alzheimer's disease is important for informing design of presymptomatic trials. METHODS: Serial T1-weighed magnetic resonance imaging scans of 94 participants (28 noncarriers, 66 carriers) from the Dominantly Inherited Alzheimer Network were used to measure brain, ventricular, and hippocampal atrophy rates. For each structure, nonlinear mixed-effects models estimated the change-points when atrophy rates deviate from normal and the rates of change before and after this point. RESULTS: Atrophy increased after the change-point, which occurred 1-1.5 years (assuming a single step change in atrophy rate) or 3-8 years (assuming gradual acceleration of atrophy) before expected symptom onset. At expected symptom onset, estimated atrophy rates were at least 3.6 times than those before the change-point. DISCUSSION: Atrophy rates are pathologically increased up to seven years before "expected onset". During this period, atrophy rates may be useful for inclusion and tracking of disease progression. | URI: | https://ahro.austin.org.au/austinjspui/handle/1/16728 | DOI: | 10.1016/j.jalz.2017.06.2268 | ORCID: | 0000-0003-3910-2453 | Journal: | Alzheimer's & Dementia | PubMed URL: | https://pubmed.ncbi.nlm.nih.gov/28738187 | Type: | Journal Article | Subjects: | Alzheimer's disease Atrophy Autosomal dominant Boundary Shift Integral Change-point Dementia Longitudinal MRI Neuroimaging Nonlinear modeling |
| Appears in Collections: | Journal articles |
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