Please use this identifier to cite or link to this item: 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
metadata.dc.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: http://ahro.austin.org.au/austinjspui/handle/1/16728
DOI: 10.1016/j.jalz.2017.06.2268
ORCID: 0000-0003-3910-2453
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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