Alzheimer's & dementia : the journal of the Alzheimer's Association · 2020
Predicting sporadic Alzheimer's disease progression via inherited Alzheimer's disease-informed machine-learning.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАПоддержка правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Franzmeier Nicolai, Koutsouleris Nikolaos, Benzinger Tammie, Goate Alison, Karch Celeste M, Fagan Anne M, McDade Eric, Duering Marco, Dichgans Martin, Levin Johannes, Gordon Brian A, Lim Yen Ying, Masters Colin L, Rossor Martin, Fox Nick C, O'Connor Antoinette, Chhatwal Jasmeer, Salloway Stephen, Danek Adrian, Hassenstab Jason, Schofield Peter R, Morris John C, Bateman Randall J, Alzheimer's disease neuroimaging initiative (ADNI), Dominantly Inherited Alzheimer Network (DIAN), Ewers Michael
Аннотация
INTRODUCTION: Developing cross-validated multi-biomarker models for the prediction of the rate of cognitive decline in Alzheimer's disease (AD) is a critical yet unmet clinical challenge.
METHODS: We applied support vector regression to AD biomarkers derived from cerebrospinal fluid, structural magnetic resonance imaging (MRI), amyloid-PET and fluorodeoxyglucose positron-emission tomography (FDG-PET) to predict rates of cognitive decline. Prediction models were trained in autosomal-dominant Alzheimer's disease (ADAD, n = 121) and subsequently cross-validated in sporadic prodromal AD (n = 216). The sample size needed to detect treatment effects when using model-based risk enrichment was estimated.
RESULTS: A model combining all biomarker modalities and established in ADAD predicted the 4-year rate of decline in global cognition (R2 = 24%) and memory (R2 = 25%) in sporadic AD. Model-based risk-enrichment reduced the sample size required for detecting simulated intervention effects by 50%-75%.
DISCUSSION: Our independently validated machine-learning model predicted cognitive decline in sporadic prodromal AD and may substantially reduce sample size needed in clinical trials in AD.
METHODS: We applied support vector regression to AD biomarkers derived from cerebrospinal fluid, structural magnetic resonance imaging (MRI), amyloid-PET and fluorodeoxyglucose positron-emission tomography (FDG-PET) to predict rates of cognitive decline. Prediction models were trained in autosomal-dominant Alzheimer's disease (ADAD, n = 121) and subsequently cross-validated in sporadic prodromal AD (n = 216). The sample size needed to detect treatment effects when using model-based risk enrichment was estimated.
RESULTS: A model combining all biomarker modalities and established in ADAD predicted the 4-year rate of decline in global cognition (R2 = 24%) and memory (R2 = 25%) in sporadic AD. Model-based risk-enrichment reduced the sample size required for detecting simulated intervention effects by 50%-75%.
DISCUSSION: Our independently validated machine-learning model predicted cognitive decline in sporadic prodromal AD and may substantially reduce sample size needed in clinical trials in AD.