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Pattern and degree of individual brain atrophy predicts dementia onset in dominantly inherited Alzheimer's disease
- 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;
- Network, Dominantly Inherited Alzheimer
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.Many UC-authored scholarly publications are freely available on this site because of the UC's open access policies. Let us know how this access is important for you.
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