Viswanath Devanarayan, Michael C. Donohue, Reisa A. Sperling, Keith A. Johnson, Yuanqing Ye, Arnaud Charil, Thomas Doherty, Lu Tian, Rema Raman, Paul S. Aisen, Lynn D. Kramer, Michael C. Irizarry, Shobha Dhadda
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引用次数: 0
Abstract
INTRODUCTION
Cognitive decline in asymptomatic preclinical Alzheimer's disease (AD) is slow and variable, limiting detection of treatment effects. This study developed models to forecast trajectories and improve trial efficiency.
METHODS
Models were trained on longitudinal Preclinical Alzheimer's Cognitive Composite (PACC) data up to 240 weeks from the Phase III A4 study of solanezumab. Baseline inputs included demographics, apolipoprotein E (APOE) ε4, clinical scores, amyloid positron emission tomography (PET), plasma pTau217, magnetic resonance imaging (MRI), and tau PET (sub-study). Stochastic gradient boosting was used, with evaluation via cross-validation and trial simulations.
RESULTS
The best model without tau PET used pTau217, clinical, and MRI data (R2 = 0.32; area under the receiver operating characteristic curve (AUROC) for classifying a 0.5-point PACC decline = 78.6%). Replacing MRI with tau PET improved performance (R2 = 0.42; AUROC = 83.1%). Predicted trajectories as a prognostic covariate reduced sample sizes by 35% and increased power from 80% to 94.7%.
DISCUSSION
Prognostic models can predict decline in preclinical AD and improve trial efficiency.
CLINICALTRIALS.GOV IDENTIFIERS
NCT02008357 (Clinical Trial of Solanezumab for Older Individuals Who May be at Risk for Memory Loss (A4))
期刊介绍:
Alzheimer's & Dementia is a peer-reviewed journal that aims to bridge knowledge gaps in dementia research by covering the entire spectrum, from basic science to clinical trials to social and behavioral investigations. It provides a platform for rapid communication of new findings and ideas, optimal translation of research into practical applications, increasing knowledge across diverse disciplines for early detection, diagnosis, and intervention, and identifying promising new research directions. In July 2008, Alzheimer's & Dementia was accepted for indexing by MEDLINE, recognizing its scientific merit and contribution to Alzheimer's research.