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