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

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

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

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.

Original languageEnglish
Article numbere12197
Number of pages11
JournalAlzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring
Volume13
Issue number1
DOIs
Publication statusPublished - 2021

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