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Item Response Theory in the Neurodegenerative Disease Data Analysis

  • Wang, Wenjia
Publication Date
Jun 21, 2017
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Neurodegenerative diseases, such as Alzheimer’s disease (AD) and Charcot Marie Tooth (CMT), are complex diseases. Their pathological mechanisms are still not well understood, and the progress in the research and development of new potential disease-modifying therapies is slow. Categorical data like rating scales and Genome-Wide Association Studies (GWAS) data are widely utilized in the neurodegenerative diseases in the diagnosis, prediction and progression monitor. It is important to understand and interpret these data correctly if we want to improve the disease research. The purpose of this thesis is to use the modern psychometric Item Response Theory to analyze these categorical data for better understanding the neurodegenerative diseases and facilitating the corresponding drug research. First, we applied the Rasch analysis in order to assess the validity of the Charcot-Marie-Tooth Neuropathy Score (CMTNS), a main endpoint for the CMT disease clinical trials. We then adapted the Rasch model to the analysis of genetic associations and used to identify genes associated with Alzheimer’s disease by summarizing the categorical genotypes of several genetic markers such as Single Nucleotide Polymorphisms (SNPs) into one genetic score. Finally, to select sensitive items in the most used psychometrical tests for Alzheimer’s disease, we calculated the mutual information based on the item response model to evaluate the sensitivity of each item on the ADAS-cog scale.

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