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Presymptomatic atrophy in autosomal dominant Alzheimer's disease: A serial MRI study

Kinnunen, KM; Cash, DM; Poole, T; Frost, C; Benzinger, TLS; Ahsan, RL; Leung, KK; ... Dominantly Inherited Alzheimer Network (DIAN), .; + view all (2017) Presymptomatic atrophy in autosomal dominant Alzheimer's disease: A serial MRI study. Alzheimer's & Dementia , 14 (1) pp. 43-53. 10.1016/j.jalz.2017.06.2268. Green open access

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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.

Type: Article
Title: Presymptomatic atrophy in autosomal dominant Alzheimer's disease: A serial MRI study
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.jalz.2017.06.2268
Publisher version: http://doi.org/10.1016/j.jalz.2017.06.2268
Language: English
Additional information: © 2017 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved. This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Alzheimer's disease, Atrophy, Autosomal dominant, Boundary Shift Integral, Change-point, Dementia, Longitudinal, MRI, Neuroimaging, Nonlinear modeling
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Med Phys and Biomedical Eng
URI: https://discovery.ucl.ac.uk/id/eprint/1560260
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