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Pattern and degree of individual brain atrophy predicts dementia onset in dominantly inherited Alzheimer's disease.

  • Author(s): Keret, Ophir
  • Staffaroni, Adam M
  • Ringman, John M
  • Cobigo, Yann
  • Goh, Sheng-Yang M
  • Wolf, Amy
  • Allen, Isabel Elaine
  • Salloway, Stephen
  • Chhatwal, Jasmeer
  • Brickman, Adam M
  • Reyes-Dumeyer, Dolly
  • Bateman, Randal J
  • Benzinger, Tammie LS
  • Morris, John C
  • Ances, Beau M
  • Joseph-Mathurin, Nelly
  • Perrin, Richard J
  • Gordon, Brian A
  • Levin, Johannes
  • Vöglein, Jonathan
  • Jucker, Mathias
  • la Fougère, Christian
  • Martins, Ralph N
  • Sohrabi, Hamid R
  • Taddei, Kevin
  • Villemagne, Victor L
  • Schofield, Peter R
  • Brooks, William S
  • Fulham, Michael
  • Masters, Colin L
  • Ghetti, Bernardino
  • Saykin, Andrew J
  • Jack, Clifford R
  • Graff-Radford, Neill R
  • Weiner, Michael
  • Cash, David M
  • Allegri, Ricardo F
  • Chrem, Patricio
  • Yi, Su
  • Miller, Bruce L
  • Rabinovici, Gil D
  • Rosen, Howard J
  • Dominantly Inherited Alzheimer Network
  • et al.
Abstract

Introduction

Asymptomatic and mildly symptomatic dominantly inherited Alzheimer's disease mutation carriers (DIAD-MC) are ideal candidates for preventative treatment trials aimed at delaying or preventing dementia onset. Brain atrophy is an early feature of DIAD-MC and could help predict risk for dementia during trial enrollment.

Methods

We created a dementia risk score by entering standardized gray-matter volumes from 231 DIAD-MC into a logistic regression to classify participants with and without dementia. The score's predictive utility was assessed using Cox models and receiver operating curves on a separate group of 65 DIAD-MC followed longitudinally.

Results

Our risk score separated asymptomatic versus demented DIAD-MC with 96.4% (standard error = 0.02) and predicted conversion to dementia at next visit (hazard ratio = 1.32, 95% confidence interval [CI: 1.15, 1.49]) and within 2 years (area under the curve = 90.3%, 95% CI [82.3%-98.2%]) and improved prediction beyond established methods based on familial age of onset.

Discussion

Individualized risk scores based on brain atrophy could be useful for establishing enrollment criteria and stratifying DIAD-MC participants for prevention trials.

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