Prediction of Mild Cognitive Impairment Using Blood Multi-Omics Data

Daniel Zhang^1,2Cigdem Sevim Bayrak²Qi Zeng²Minghui Wang²Bin Zhang^2*

• ¹Rice University, Houston, Texas, United States
• ²Icahn School of Medicine at Mount Sinai, New York, New York, United States

Mild cognitive impairment (MCI) represents an initial phase of memory or other cognitive function decline and is viewed as an intermediary stage between normal aging and Alzheimer's disease (AD), the most prevalent type of dementia. Individuals with MCI face a heightened risk of progressing to AD, and early detection of MCI can facilitate the prevention of such progression through timely interventions. Nonetheless, diagnosing MCI is challenging because its symptoms can be subtle and are easily missed. Using genomic data from blood samples has been proposed as a non-invasive and cost-efficient approach to build machine learning predictive models for assisting MCI diagnosis. However, these models often exhibit poor performance. In this study, we developed an XGBoost-based machine learning model with AUC (the Area Under the receiver operating characteristic Curve) of 0.9398 utilizing gene expression and copy number variation (CNV) data from patient blood samples. We demonstrated, for the first time, that data at a genome structure level such as CNVs could be as informative as gene expression data to classify MCI patients from normal controls. We identified 149 genomic features that are important for MCI prediction. Notably, these features are enriched in the pathways associated with neurodegenerative diseases, such as neuron development and G protein-coupled receptor activity. Overall, our study not only demonstrates the effectiveness of utilizing blood sample-based multi-omics for predicting MCI, but also provides insights into crucial molecular characteristics of MCI.