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Presymptomatic atrophy in autosomal dominant Alzheimer's disease: A serial magnetic resonance imaging study
Author(s) -
Kinnunen Kirsi M.,
Cash David M.,
Poole Teresa,
Frost Chris,
Benzinger Tammie L.S.,
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 P.,
Correia Stephen,
Sperling Reisa A.,
Chhatwal Jasmeer P.,
Mayeux Richard P.,
Brickman Adam M.,
Martins Ralph N.,
Farlow Martin R.,
Ghetti Bernardino,
Saykin Andrew J.,
Jack Clifford R.,
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.
Publication year - 2018
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2017.06.2268
Subject(s) - magnetic resonance imaging , atrophy , disease , medicine , pathology , neuroscience , psychology , radiology
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.