Keret, OphirStaffaroni, Adam M.Ringman, John M.Cobigo, YannGoh, Sheng-Yang M.Wolf, AmyAllen, Isabel ElaineSalloway, StephenChhatwal, JasmeerBrickman, Adam M.Reyes-Dumeyer, DollyBateman, Randal J.Benzinger, Tammie L.S.Morris, John C.Ances, Beau M.Joseph-Mathurin, NellyPerrin, Richard J.Gordon, Brian A.Levin, JohannesVöglein, JonathanJucker, Mathiasla Fougère, ChristianMartins, Ralph N.Sohrabi, Hamid R.Taddei, KevinVillemagne, Victor L.Schofield, Peter R.Brooks, William S.Fulham, MichaelMasters, Colin L.Ghetti, BernardinoSaykin, Andrew J.Jack, Clifford R.Graff-Radford, Neill R.Weiner, MichaelCash, David M.Allegri, Ricardo F.Chrem, PatricioYi, SuMiller, Bruce L.Rabinovici, Gil D.Rosen, Howard J.2023-02-102023-02-102021-07-05Keret O, Staffaroni AM, Ringman JM, et al. Pattern and degree of individual brain atrophy predicts dementia onset in dominantly inherited Alzheimer's disease. Alzheimers Dement (Amst). 2021;13(1):e12197. Published 2021 Jul 5. doi:10.1002/dad2.12197https://hdl.handle.net/1805/31205Introduction: 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.en-USAttribution-NonCommercial-NoDerivatives 4.0 InternationalDominantly Inherited Alzheimer NetworkAutosomal dominant Alzheimer's diseaseBrain atrophyPreclinical Alzheimer's diseaseArticle