The small-world organization has been hypothesized to reflect a balance between local processing and global integration in the human brain. Previous multimodal imaging studies have consistently demonstrated that the topological architecture of the brain network is disrupted in Alzheimer's disease (AD). However, these studies have reported inconsistent results regarding the topological properties of brain alterations in AD. One potential explanation for these inconsistent results lies with the diverse homogeneity and distinct progressive stages of the AD involved in these studies, which are thought to be critical factors that might affect the results. We investigated the topological properties of brain functional networks derived from resting functional magnetic resonance imaging (fMRI) of carefully selected moderate AD patients and normal controls (NCs). Our results showed that the topological properties were found to be disrupted in AD patients, which showing increased local efficiency but decreased global efficiency. We found that the altered brain regions are mainly located in the default mode network, the temporal lobe and certain subcortical regions that are closely associated with the neuropathological changes in AD. Of note, our exploratory study revealed that the ApoE genotype modulates brain network properties, especially in AD patients.

Mild cognitive impairment (MCI) is often considered a critical time window for predicting early conversion to Alzheimer’s disease (AD). Brain functional connectome data (i.e., functional connections, global and nodal graph metrics) based on resting-state functional magnetic resonance imaging (rs-fMRI) provides numerous information about brain networks and has been used to discriminate normal controls (NCs) from subjects with MCI. In this paper, Student’s t-tests and group-least absolute shrinkage and selection operator (group-LASSO) were used to extract functional connections with significant differences and the most discriminative network nodes, respectively. Based on group-LASSO, the middle temporal, inferior temporal, lingual, posterior cingulate, and middle frontal gyri were the most predominant brain regions for nodal observation in MCI patients. Nodal graph metrics (within-module degree, participation coefficient, and degree centrality) showed the maximum discriminative ability. To effectively combine the multipattern information, we employed the multiple kernel learning support vector machine (MKL-SVM). Combined with functional connectome information, the MKL-SVM achieved a good classification performance (area under the receiving operating characteristic curve = 0.9728). Additionally, the altered brain connectome pattern revealed that functional connectivity was generally decreased in the whole-brain network, whereas graph theory topological attributes of some special nodes in the brain network were increased in MCI patients. Our findings demonstrate that optimal feature selection and combination of all connectome features (i.e., functional connections, global and nodal graph metrics) can achieve good performance in discriminating NCs from MCI subjects. Thus, the combination of functional connections and global and nodal graph metrics of brain networks can predict the occurrence of MCI and contribute to the early clinical diagnosis of AD.

Subjective cognitive decline (SCD) is considered the earliest preclinical stage of Alzheimer’s disease (AD) that precedes mild cognitive impairment (MCI). Effective and accurate diagnosis of SCD is crucial for early detection of and timely intervention in AD. In this study, brain functional connectome (i.e., functional connections and graph theory metrics) based on the resting-state functional magnetic resonance imaging (rs-fMRI) provided multiple information about brain networks and has been used to distinguish individuals with SCD from normal controls (NCs). The consensus connections and the discriminative nodal graph metrics selected by group least absolute shrinkage and selection operator (LASSO) mainly distributed in the prefrontal and frontal cortices and the subcortical regions corresponded to default mode network (DMN) and frontoparietal task control network. Nodal efficiency and nodal shortest path showed the most significant discriminative ability among the selected nodal graph metrics. Furthermore, the comparison results of topological attributes suggested that the brain network integration function was weakened and network segregation function was enhanced in SCD patients. Moreover, the combination of brain connectome information based on multiple kernel-support vector machine (MK-SVM) achieved the best classification performance with 83.33% accuracy, 90.00% sensitivity, and an area under the curve (AUC) of 0.927. The findings of this study provided a new perspective to combine machine learning methods with exploration of brain pathophysiological mechanisms in SCD and offered potential neuroimaging biomarkers for diagnosis of early-stage AD.