Identification of Alzheimer’s Disease Progression Stages Using Topological Measures of Resting-State Functional Connectivity Networks: A Comparative Study

Abstract

Resting-state functional magnetic resonance imaging (rs-fMRI) has been widely employed to examine brain functional connectivity (FC) alterations in various neurological disorders. At present, various computational methods have been proposed to estimate connectivity strength between different brain regions, as the edge weight of FC networks. However, little is known about which model is more sensitive to Alzheimer’s disease (AD) progression. This study comparatively characterized topological properties of rs-FC networks constructed with Pearson correlation (PC), dynamic time warping (DTW), and group information guided independent component analysis (GIG-ICA), aimed at investigating the sensitivity and effectivity of these methods in differentiating AD stages. A total of 54 subjects from Alzheimer’s Disease Neuroimaging Initiative (ANDI) database, divided into healthy control (HC), mild cognition impairment (MCI), and AD groups, were included in this study. Network-level (global efficiency and characteristic path length) and nodal (clustering coefficient) metrics were used to capture groupwise difference across HC, MCI, and AD groups. The results showed that almost no significant differences were found according to global efficiency and characteristic path length. However, in terms of clustering coefficient, 52 brain parcels sensitive to AD progression were identified in rs-FC networks built with GIG-ICA, much more than PC (6 parcels) and DTW (3 parcels). This indicates that GIG-ICA is more sensitive to AD progression than PC and DTW. The findings also confirmed that the AD-linked FC alterations mostly appeared in temporal, cingulate, and angular areas, which might contribute to clinical diagnosis of AD. Overall, this study provides insights into the topological properties of rs-FC networks over AD progression, suggesting that FC strength estimation of FC networks cannot be neglected in AD-related graph analysis.