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

Kirsi M. Kinnunen, David M. Cash, Teresa Poole, Chris Frost, Tammie L.S. Benzinger, R. Laila Ahsan, Kelvin K. Leung, M. Jorge Cardoso, Marc Modat, Ian B. Malone, John C. Morris, Randall J. Bateman, Daniel S. Marcus, Alison Goate, Stephen P. Salloway, Stephen Correia, Reisa A. Sperling, Jasmeer P. Chhatwal, Richard P. Mayeux, Adam M. BrickmanRalph N. Martins, Martin R. Farlow, Bernardino Ghetti, Andrew J. Saykin, Clifford R Jr. Jack, Peter R. Schofield, Eric McDade, Michael W. Weiner, John M. Ringman, Paul M. Thompson, Colin L. Masters, Christopher C. Rowe, Martin N. Rossor, Sebastien Ourselin, Nick C. Fox

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-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.

Original languageEnglish (US)
JournalAlzheimer's and Dementia
DOIs
StateAccepted/In press - Jan 1 2017

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Atrophy
Alzheimer Disease
Cytomegalovirus Infections
Disease Progression
Magnetic Resonance Imaging
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

Kinnunen, K. M., Cash, D. M., Poole, T., Frost, C., Benzinger, T. L. S., Ahsan, R. L., ... Fox, N. C. (Accepted/In press). Presymptomatic atrophy in autosomal dominant Alzheimer's disease: A serial MRI study. Alzheimer's and Dementia. https://doi.org/10.1016/j.jalz.2017.06.2268

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

In: Alzheimer's and Dementia, 01.01.2017.

Research output: Contribution to journalArticle

Kinnunen, KM, Cash, DM, Poole, T, Frost, C, Benzinger, TLS, Ahsan, RL, Leung, KK, Cardoso, MJ, Modat, M, Malone, IB, Morris, JC, Bateman, RJ, Marcus, DS, Goate, A, Salloway, SP, Correia, S, Sperling, RA, Chhatwal, JP, Mayeux, RP, Brickman, AM, Martins, RN, Farlow, MR, Ghetti, B, Saykin, AJ, Jack, CRJ, Schofield, PR, McDade, E, Weiner, MW, Ringman, JM, Thompson, PM, Masters, CL, Rowe, CC, Rossor, MN, Ourselin, S & Fox, NC 2017, 'Presymptomatic atrophy in autosomal dominant Alzheimer's disease: A serial MRI study', Alzheimer's and Dementia. https://doi.org/10.1016/j.jalz.2017.06.2268
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 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. / Presymptomatic atrophy in autosomal dominant Alzheimer's disease : A serial MRI study. In: Alzheimer's and Dementia. 2017.
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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.",
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T1 - Presymptomatic atrophy in autosomal dominant Alzheimer's disease

T2 - A serial MRI study

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.

AU - Mayeux, Richard P.

AU - Brickman, Adam M.

AU - Martins, Ralph N.

AU - Farlow, Martin R.

AU - Ghetti, Bernardino

AU - Saykin, Andrew J.

AU - Jack, Clifford R Jr.

AU - Schofield, Peter R.

AU - McDade, Eric

AU - Weiner, Michael W.

AU - Ringman, John M.

AU - Thompson, Paul M.

AU - Masters, Colin L.

AU - Rowe, Christopher C.

AU - Rossor, Martin N.

AU - Ourselin, Sebastien

AU - Fox, Nick C.

PY - 2017/1/1

Y1 - 2017/1/1

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-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.

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KW - Autosomal dominant

KW - Boundary Shift Integral

KW - Change-point

KW - Dementia

KW - Longitudinal

KW - MRI

KW - Neuroimaging

KW - Nonlinear modeling

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