Presymptomatic atrophy in autosomal dominant Alzheimer's disease: A serial magnetic resonance imaging study

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Research output: Contribution to journalArticle

10 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)43-53
Number of pages11
JournalAlzheimer's and Dementia
Volume14
Issue number1
DOIs
StatePublished - Jan 1 2018

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Atrophy
Alzheimer Disease
Magnetic Resonance Imaging
Cytomegalovirus Infections
Disease Progression
Brain

Keywords

  • Alzheimer's disease
  • Atrophy
  • Autosomal dominant
  • Boundary Shift Integral
  • Change-point
  • Dementia
  • Longitudinal
  • MRI
  • Neuroimaging
  • Nonlinear modeling

ASJC Scopus subject areas

  • Epidemiology
  • Health Policy
  • Developmental Neuroscience
  • Clinical Neurology
  • Geriatrics and Gerontology
  • Cellular and Molecular Neuroscience
  • Psychiatry and Mental health

Cite this

Presymptomatic atrophy in autosomal dominant Alzheimer's disease : A serial magnetic resonance imaging study. / for the.

In: Alzheimer's and Dementia, Vol. 14, No. 1, 01.01.2018, p. 43-53.

Research output: Contribution to journalArticle

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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-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.",
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T2 - A serial magnetic resonance imaging study

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AU - Kinnunen, Kirsi M.

AU - Cash, David M.

AU - Poole, Teresa

AU - Frost, Chris

AU - Benzinger, Tammie L.S.

AU - Ahsan, R. Laila

AU - Leung, Kelvin K.

AU - Cardoso, M. Jorge

AU - Modat, Marc

AU - Malone, Ian B.

AU - Morris, John C.

AU - Bateman, Randall J.

AU - Marcus, Daniel S.

AU - Goate, Alison

AU - Salloway, Stephen P.

AU - Correia, Stephen

AU - Sperling, Reisa A.

AU - Chhatwal, Jasmeer P.

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AU - Brickman, Adam M.

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AU - Farlow, Martin

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AU - Saykin, Andrew

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AU - Schofield, Peter R.

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AU - Ringman, John M.

AU - Thompson, Paul M.

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AU - Ourselin, Sebastien

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N2 - 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.

AB - 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.

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KW - Autosomal dominant

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KW - Longitudinal

KW - MRI

KW - Neuroimaging

KW - Nonlinear modeling

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