Elucidation of the mechanism of cognitive decline in mild cognitive impairment (MCI) using causal discovery

Abstract

Mild cognitive impairment (MCI) is the stage between the expected cognitive decline of normal aging and the more serious decline of dementia. Since MCI may increase risk of later developing dementia caused by Alzheimer's disease (AD) or other neurological conditions, it is important to detect and treat MCI early in order to prevent dementia. Causal discovery, which can visualize causal relationships (cause and effect) among data, has recently been attracting attention. One of its algorithms, the Linear Non-Gaussian Acyclic Model (LiNGAM), can extract causal relationships among variables from statistical data only, using probability distributions of variables that are generally non-Gaussian. In this study, we used LiNGAM to analyze gene expression data in the hippocampus of healthy subjects and of MCI patients, and also the Mini-Mental State Examination (MMSE) scores, which are used to assess cognitive decline. We found that cell adhesion molecule 4 (CADM4) gene regulates cognitive processes that are measured in terms of MMSE scores. Our results revealed a causal relationship between gene expression changes and MMSE scores, and allowed us to identify the genes responsible for cognitive decline..