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Activity Number: 384 - Recent Statistical Advances in Diagnostic Medicine
Type: Invited
Date/Time: Wednesday, August 5, 2020 : 1:00 PM to 2:50 PM
Sponsor: Section on Medical Devices and Diagnostics
Abstract #309189
Title: Early Diagnosis of Neurological Disease Using Peak Degeneration Ages of Multiple Biomarkers
Author(s): Fei Gao* and Yuanjia Wang and Donglin Zeng
Companies: Fred Hutchinson Cancer Research Center and Columbia University and University of North Carolina at Chapel Hill
Keywords: Alzheimer’s disease; Huntington’s disease; inflection point; measurement error; nonlinear mixed effects model; sigmoid function

Neurological diseases are due to the loss of structure or function of neurons that eventually leads to cognitive deficit, neuropsychiatric symptoms, and impaired activities of daily living. Identifying sensitive and specific biological and clinical markers for early diagnosis allows recruiting patients into a clinical trial to test therapeutic intervention. We use longitudinally collected measurements from multiple biomarkers and measurement error-corrected clinical diagnosis ages to identify which biomarkers and what features of biomarker trajectories are useful for early diagnosis. Specifically, we assume that the subject-specific biomarker trajectories depend on unobserved states of underlying latent variables with the conditional mean follows a nonlinear sigmoid shape. We show that peak degeneration age of the biomarker trajectory is useful for early diagnosis. We propose an Expectation-Maximization (EM) algorithm to obtain the maximum likelihood estimates of all parameters. We apply our methods to studies of Alzheimer’s disease and Huntington’s disease and identify a few important biomarkers that can be used for early diagnosis.

Authors who are presenting talks have a * after their name.

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