Presymptomatic atrophy in autosomal dominant Alzheimer's disease: A serial magnetic resonance imaging study
Open Access
- 21 July 2017
- journal article
- research article
- Published by Wiley in Alzheimer's & Dementia
- Vol. 14 (1), 43-53
- https://doi.org/10.1016/j.jalz.2017.06.2268
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‐weighted 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.Funding Information
- National Institute on Aging
- National Institute for Health Research
- Alzheimer's Society (AS‐PG‐205)
- Brain Research Trust
- Wolfson Foundation
- Alzheimer's Research Trust (ARUK‐PCRF2014B‐1)
- Alzheimer's Society (AS‐PG‐15‐025)
- National Institute on Handicapped Research
- Economic and Social Research Council
- University of Oxford
- National Institutes of Health (U19AG032438, UL1TR000448, 5P30NS04805)
- Avid Radiopharmaceuticals
- Roche
- National Institutes of Health (P50AG005681, P01AG003991, P01AG026276, U19AG032438)
- National Institutes of Health (U19 AG032438)
- American Academy of Neurology
- AstraZeneca
- BrightFocus Foundation
- Biogen Idec
- Eisai
- National Institutes of Health (2R01NS065667‐05)
- National Institutes of Health (5K23AG030946, P50AG05681)
- Eli Lilly and Company
- Biogen
- Genentech
- Merck
- National Institute on Aging
- American Health Assistance Foundation
- National Institutes of Health (AG034189, AG043337, AG016495, AG036469, AG037212)
- National Institutes of Health (P30 AG010133)
- National Institutes of Health (R01 AG019771, R01 LM011360, R44 AG049540, R01 CA129769, U01 AG032984)
- Avid Radiopharmaceuticals
- National Institute on Aging
- U.S. Department of Defense
- GE Healthcare
- Engineering and Physical Sciences Research Council (EP/H046410/1, EP/J020990/1, EP/K005278)
- Medical Research Council (MR/J01107X/1)
This publication has 42 references indexed in Scilit:
- The DIAN‐TU Next Generation Alzheimer's prevention trial: Adaptive design and disease progression modelAlzheimer's & Dementia, 2016
- Longitudinal assessment of neuroimaging and clinical markers in autosomal dominant Alzheimer's disease: a prospective cohort studyThe Lancet Neurology, 2015
- Imaging endpoints for clinical trials in Alzheimer’s diseaseAlzheimer's Research & Therapy, 2014
- Symptom onset in autosomal dominant Alzheimer diseaseNeurology, 2014
- Regional variability of imaging biomarkers in autosomal dominant Alzheimer’s diseaseProceedings of the National Academy of Sciences of the United States of America, 2013
- Tracking pathophysiological processes in Alzheimer's disease: an updated hypothetical model of dynamic biomarkersThe Lancet Neurology, 2013
- Clinical and Biomarker Changes in Dominantly Inherited Alzheimer's DiseaseThe New England Journal of Medicine, 2012
- Brain MAPS: An automated, accurate and robust brain extraction technique using a template libraryNeuroImage, 2011
- Anti-Aβ Therapeutics in Alzheimer's Disease: The Need for a Paradigm ShiftNeuron, 2011
- Correlating familial Alzheimer’s disease gene mutations with clinical phenotypeBiomarkers in Medicine, 2010